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Sample records for curcumin alleviates ethanol-induced

  1. Deletion of circadian gene Per1 alleviates acute ethanol-induced hepatotoxicity in mice

    International Nuclear Information System (INIS)

    Wang, Tao; Yang, Ping; Zhan, Yibei; Xia, Lin; Hua, Zichun; Zhang, Jianfa

    2013-01-01

    The severity of ethanol-induced liver injury is associated with oxidative stress and lipid accumulation in the liver. Core circadian clock is known to mediate antioxidative enzyme activity and lipid metabolism. However, the link between circadian clock and ethanol-induced hepatotoxicity remains unclear. Here we showed that extents of acute ethanol-induced liver injury and steatosis in mice exhibit circadian variations consistent with hepatic expression of Period (Per) genes. Mice lacking clock gene Per1 displayed less susceptible to ethanol-induced liver injury, as evidenced by lower serum transaminase activity and less severe histopathological changes. Ethanol-induced lipid peroxidation was alleviated in Per1−/− mice. However, Per1 deletion had no effect on antioxidants depletion caused by ethanol administration. Ethanol-induced triglycerides (TG) accumulation in the serum and liver was significantly decreased in Per1−/− mice compared with that in wild-type (WT) mice. Analysis of gene expression in the liver revealed peroxisome proliferators activated receptor-gamma (PPARγ) and its target genes related to TG synthesis are remarkably down-regulated in Per1−/− mice. HepG2 cells were treated with ethanol at 150 mM for 3 days. Per1 overexpression augmented lipid accumulation after treatment with ethanol in HepG2 cells, but had no effect on ethanol-induced oxidative stress. Expression of genes related to lipogenesis, including PPARγ and its target genes, was up-regulated in cells overexpressing Per1. In conclusion, these results indicated that circadian rhythms of ethanol-induced hepatotoxicity are controlled by clock gene Per1, and deletion of Per1 protected mice from ethanol-induced liver injury by decreasing hepatic lipid accumulation

  2. Effect of curcumin on ethanol-induced stress on mononuclear cells.

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    Rajakrishnan, V; Shiney, S J; Sudhakaran, P R; Menon, V P

    2002-03-01

    Blood cells in circulation are exposed to a wide variety of stress-causing agents, causing a number of changes including interactions with other cells and the extracellular matrix of the endothelial wall. In order to understand the role of curcumin, an antioxidant principle from Curcuma longa Linn., on blood mononuclear cells from rabbits given ethanol for 30 days and ethanol with curcumin, cells were isolated and an attachment assay was carried out. The monocytes from ethanol-treated rabbits showed a lesser attachment to collagen, the major component of the vessel wall subendothelium, and those from curcumin treated animals along with ethanol showed a higher affinity to collagen, causing an alteration in the attachment of monocyte to collagen due to ethanol-induced stress. Copyright 2002 John Wiley & Sons, Ltd.

  3. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

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    Cui, Ruibing [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Lihui [Shandong Normal University, Jinan, Shandong Province 250012 (China); Luo, Zheng; Guo, Xiaolan [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Ming, E-mail: ymylh@163.com [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China)

    2015-08-15

    Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

  4. Curcumin Alleviates the Functional Gastrointestinal Disorders of Mice In Vivo.

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    Yu, Jing; Xu, Wen-Hua; Sun, Wei; Sun, Yi; Guo, Zhi-Li; Yu, Xiao-Ling

    2017-12-01

    Curcumin is a natural polyphenol extracted from the turmeric rhizome, which has a wide range of biological activities, but until now the effects of curcumin on the gastrointestinal peristalsis have not been fully understood. In vivo study, we observed the effects of curcumin on gastric emptying and intestinal propulsion rates of mice in normal state and in delayed state by atropine (ATR) or nitric oxide precursor L-arginine (L-Arg). An in vitro study explored the direct effects of curcumin on the intestinal contractility, but were studied through measuring spontaneous contraction of isolated jejunum of mice. Our results showed that intragastric administration of curcumin (200 mg/kg/day) for 10-20 days significantly improved gastric emptying and intestinal propulsion rates of mice delayed by ATR. Moreover, intragastric administration of curcumin (200 mg/kg/day) for 15 days also significantly improved mice gastric emptying and intestinal propulsion rates delayed by L-Arg. There was no significant effect on normal gastrointestinal propulsion of mice after intragastric administration of curcumin (200 mg/kg/day) for 1-20 days. When normal isolated jejunum of mice were incubated with curcumin in vitro, the amplitude of the spontaneous contractile waves of jejunum was reduced in a concentration-dependent manner. Moreover, curcumin reduced the amplitude of the contractile waves of jejunum in both contracted and relaxed state induced by acetylcholine or ATR individually. Taken together, our results suggest that curcumin has quite different effects on gastrointestinal peristalsis in vivo and in vitro. Moderate dose of curcumin by intragastric administration for more than 10 days can alleviate the functional gastrointestinal disorders of mice, but cannot affect normal gastrointestinal propulsion.

  5. Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects.

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    Zheng, Bin; Yang, Liu; Wen, Caixia; Huang, Xiuwang; Xu, Chenxia; Lee, Kuan-Han; Xu, Jianhua

    2016-03-15

    L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Combination of Erythromycin and Curcumin Alleviates Staphylococcus aureus Induced Osteomyelitis in Rats

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    Zubin Zhou

    2017-08-01

    Full Text Available Osteomyelitis is commonly caused by Staphylococcus aureus. Both erythromycin and curcumin can suppress S. aureus growth, but their roles in osteomyelitis are barely studied. We aim to explore the activities of erythromycin and curcumin against chronical osteomyelitis induced by methicillin-resistant S. aureus (MRSA. Chronicle implant-induced osteomyelitis was established by MRSA infection in male Wistar rats. Four weeks after bacterial inoculation, rats received no treatment, erythromycin monotherapy, curcumin monotherapy, or erythromycin plus curcumin twice daily for 2 weeks. Bacterial levels, bone infection status, inflammatory signals and side effects were evaluated. Rats tolerated all treatments well, with no death or side effects such as, diarrhea and weight loss. Two days after treatment completion, erythromycin monotherapy did not suppress bacterial growth and had no effect in bone infection, although it reduced serum pro-inflammatory cytokines tumor necrosis factor (TNF-α and interleukin (IL-6. Curcumin monotherapy slightly suppressed bacterial growth, alleviated bone infection and reduced TNF-α and IL-6. Erythromycin and curcumin combined treatment markedly suppressed bacterial growth, substantially alleviated bone infection and reduced TNF-α and IL-6. Combination of erythromycin and curcumin lead a much stronger efficiency against MRSA induced osteomyelitis in rats than monotherapy. Our study suggests that erythromycin and curcumin could be a new combination for treating MRSA induced osteomyelitis.

  7. Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

    International Nuclear Information System (INIS)

    Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min; Xing, Mingyou; Liu, Liegang; Yao, Ping

    2013-01-01

    Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 μmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD

  8. Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Xing, Mingyou [Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Liu, Liegang [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Yao, Ping, E-mail: yaoping@mails.tjmu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China)

    2013-11-15

    Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 μmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD.

  9. Curcumin Alleviates Diabetic Retinopathy in Experimental Diabetic Rats.

    Science.gov (United States)

    Yang, Fang; Yu, Jinqiang; Ke, Feng; Lan, Mei; Li, Dekun; Tan, Ke; Ling, Jiaojiao; Wang, Ying; Wu, Kaili; Li, Dai

    2018-03-29

    To investigate the potential protective effects of curcumin on the retina in diabetic rats. An experimental diabetic rat model was induced by a low dose of streptozotocin combined with a high-energy diet. Rats which had blood glucose levels ≥11.6 mmol/L were used as diabetic rats. The diabetic rats were randomly divided into 3 groups: diabetic rats with no treatment (DM), diabetic rats treated with 100 mg/kg curcumin (DM + Cur 100 mg/kg), and diabetic rats treated with 200 mg/kg curcumin (DM + Cur 200 mg/kg). Curcumin was orally administered daily for 16 weeks. After 16 weeks of administration, the rats were euthanized, and eyes were dissected. Retinal histology was examined, and the thickness of the retina was measured. Ultrastructural changes of retinal ganglion cells, inner layer cells, retinal capillary, and membranous disks were observed by electron microscopy. Malondialdehyde, superoxide dismutase, and total antioxidant capacity were measured by ELISA. Expression levels of vascular endothelial growth factor (VEGF) in retina tissues were examined by immunohistochemical staining and ELISA. Expression levels of Bax and Bcl-2 in retina tissues were determined by immunohistochemical staining and Western blotting. Curcumin reduced the blood glucose levels of diabetic rats and decreased diabetes-induced body weight loss. Curcumin prevented attenuation of the retina in diabetic rats and ameliorated diabetes-induced ultrastructure changes of the retina, including thinning of the retina, apoptosis of the retinal ganglion cells and inner nuclear layer cells, thickening of retinal capillary basement membrane and disturbance of photoreceptor cell membranous disks. We also found that curcumin has a strong antioxidative ability in the retina of diabetic rats. It was observed that curcumin attenuated the expression of VEGF in the retina of diabetic rats. We also discovered that curcumin had an antiapoptotic effect by upregulating the expression of Bcl-2 and downregulating

  10. Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

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    L Xiao

    2017-09-01

    Full Text Available Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2. Such effects might be mediated via protein kinase B (AKT and extracellular signal regulated kinase (ERK pathways. Also, a similar effect in combating TNF-α-induced neuroinflammation was observed in isolated primary neurons. In addition, curcumin protected neurons from TNF-α-triggered excessive reactive oxygen species (ROS production and cellular apoptosis and, accordingly, promoted mRNA expression of the anti-oxidative enzymes haem oxygenase-1, catalase and superoxide dismutase-2. Intriguingly, electronic von Frey test suggested that intraperitoneal injection of curcumin significantly abolished ipsilateral hyperalgesia secondary to disc herniation in mice, for up to 2 weeks post-surgery. Such in vivo pain alleviation could be attributed to the suppression, observed in DRG explant culture, of TNF-α-elicited neuropeptides, such as substance P and calcitonin gene-related peptide. Surprisingly, micro-computed tomography (μCT data suggested that curcumin treatment could promote disc height recovery following disc herniation. Alcian blue/picrosirius red staining confirmed that systemic curcumin administration promoted regeneration of extracellular matrix proteins, visualised by presence of abundant newly-formed collagen and proteoglycan content in herniated disc. Our study provided pre-clinical evidence for expediting this natural, non-toxic pleiotropic agent to become a

  11. Veronicastrum axillare Alleviates Ethanol-Induced Injury on Gastric Epithelial Cells via Downregulation of the NF-kB Signaling Pathway

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    Wei-chun Zhao

    2017-01-01

    Full Text Available We used human gastric epithelial cells (GES-1 line in an ethanol-induced cell damage model to study the protective effect of Veronicastrum axillare and its modulation to NF-κB signal pathway. The goal was to probe the molecular mechanism of V. axillare decoction in the prevention of gastric ulcer and therefore provide guidance in the clinical application of V. axillare on treating injuries from chronic nephritis, pleural effusion, gastric ulcer, and other ailments. The effects of V. axillare-loaded serums on cell viability were detected by MTT assays. Enzyme-linked immunosorbent assay (ELISA and Real-Time PCR methods were used to analyze the protein and mRNA expression of TNF-α, NF-κB, IκBα, and IKKβ. The results showed that V. axillare-loaded serum partially reversed the damaging effects of ethanol and NF-κB activator (phorbol-12-myristate-13-acetate: PMA and increased cell viability. The protein and mRNA expressions of TNF-α, NF-κB, IκBα, and IKKβ were significantly upregulated by ethanol and PMA while they were downregulated by V. axillare-loaded serum. In summary, V. axillare-loaded serum has significantly protective effect on GES-1 against ethanol-induced injury. The protective effect was likely linked to downregulation of TNF-α based NF-κB signal pathway.

  12. Turmeric Extract Rescues Ethanol-Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD).

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    Muralidharan, Pooja; Connors, Craig T; Mohammed, Arooj S; Sarmah, Swapnalee; Marrs, Kathleen; Marrs, James A; Chism, Grady W

    2017-09-01

    Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol-induced developmental defect using zebrafish as a model was determined. Ethanol-induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol-induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol-treated embryos. The mechanism underlying the rescue remains to be determined. © 2017 Institute of Food Technologists®.

  13. Curcumin Requires Tumor Necrosis Factor α Signaling to Alleviate Cognitive Impairment Elicited by Lipopolysaccharide

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    E.M. Kawamoto

    2012-05-01

    Full Text Available A decline in cognitive ability is a typical feature of the normal aging process, and of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. Although their etiologies differ, all of these disorders involve local activation of innate immune pathways and associated inflammatory cytokines. However, clinical trials of anti-inflammatory agents in neurodegenerative disorders have been disappointing, and it is therefore necessary to better understand the complex roles of the inflammatory process in neurological dysfunction. The dietary phytochemical curcumin can exert anti-inflammatory, antioxidant and neuroprotective actions. Here we provide evidence that curcumin ameliorates cognitive deficits associated with activation of the innate immune response by mechanisms requiring functional tumor necrosis factor α receptor 2 (TNFR2 signaling. In vivo, the ability of curcumin to counteract hippocampus-dependent spatial memory deficits, to stimulate neuroprotective mechanisms such as upregulation of BDNF, to decrease glutaminase levels, and to modulate N-methyl-D-aspartate receptor levels was absent in mice lacking functional TNFRs. Curcumin treatment protected cultured neurons against glutamate-induced excitotoxicity by a mechanism requiring TNFR2 activation. Our results suggest the possibility that therapeutic approaches against cognitive decline designed to selectively enhance TNFR2 signaling are likely to be more beneficial than the use of anti-inflammatory drugs per se.

  14. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

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    Daily, James W; Yang, Mini; Park, Sunmin

    2016-08-01

    Although turmeric and its curcumin-enriched extracts have been used for treating arthritis, no systematic review and meta-analysis of randomized clinical trials (RCTs) have been conducted to evaluate the strength of the research. We systemically evaluated all RCTs of turmeric extracts and curcumin for treating arthritis symptoms to elucidate the efficacy of curcuma for alleviating the symptoms of arthritis. Literature searches were conducted using 12 electronic databases, including PubMed, Embase, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were "turmeric," "curcuma," "curcumin," "arthritis," and "osteoarthritis." A pain visual analogue score (PVAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used for the major outcomes of arthritis. Initial searches yielded 29 articles, of which 8 met specific selection criteria. Three among the included RCTs reported reduction of PVAS (mean difference: -2.04 [-2.85, -1.24]) with turmeric/curcumin in comparison with placebo (P curcumin treatment (mean difference: -15.36 [-26.9, -3.77]; P = .009). Furthermore, there was no significant mean difference in PVAS between turmeric/curcumin and pain medicine in meta-analysis of five studies. Eight RCTs included in the review exhibited low to moderate risk of bias. There was no publication bias in the meta-analysis. In conclusion, these RCTs provide scientific evidence that supports the efficacy of turmeric extract (about 1000 mg/day of curcumin) in the treatment of arthritis. However, the total number of RCTs included in the analysis, the total sample size, and the methodological quality of the primary studies were not sufficient to draw definitive conclusions. Thus, more rigorous and larger studies are needed to confirm the therapeutic efficacy of turmeric for arthritis.

  15. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

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    Daily, James W.; Yang, Mini

    2016-01-01

    Abstract Although turmeric and its curcumin-enriched extracts have been used for treating arthritis, no systematic review and meta-analysis of randomized clinical trials (RCTs) have been conducted to evaluate the strength of the research. We systemically evaluated all RCTs of turmeric extracts and curcumin for treating arthritis symptoms to elucidate the efficacy of curcuma for alleviating the symptoms of arthritis. Literature searches were conducted using 12 electronic databases, including PubMed, Embase, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were “turmeric,” “curcuma,” “curcumin,” “arthritis,” and “osteoarthritis.” A pain visual analogue score (PVAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used for the major outcomes of arthritis. Initial searches yielded 29 articles, of which 8 met specific selection criteria. Three among the included RCTs reported reduction of PVAS (mean difference: −2.04 [−2.85, −1.24]) with turmeric/curcumin in comparison with placebo (P < .00001), whereas meta-analysis of four studies showed a decrease of WOMAC with turmeric/curcumin treatment (mean difference: −15.36 [−26.9, −3.77]; P = .009). Furthermore, there was no significant mean difference in PVAS between turmeric/curcumin and pain medicine in meta-analysis of five studies. Eight RCTs included in the review exhibited low to moderate risk of bias. There was no publication bias in the meta-analysis. In conclusion, these RCTs provide scientific evidence that supports the efficacy of turmeric extract (about 1000 mg/day of curcumin) in the treatment of arthritis. However, the total number of RCTs included in the analysis, the total sample size, and the methodological quality of the primary studies were not sufficient to draw definitive conclusions. Thus, more rigorous and larger studies are needed to confirm the therapeutic efficacy

  16. [Curcumin alleviates early brain injury following subarachnoid hemorrhage in rats by inhibiting JNK/c-Jun signal pathway].

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    Li, Xia; Zhu, Ji

    2018-03-01

    Objective To investigate the inhibitory effect of curcumin on early brain injury following subarachnoid hemorrhage (SAH) by inhibiting JNK/ c-Jun signal pathway. Methods Sixty adult male SD rats were randomly divided into four groups: sham operation group (sham group), SAH group, SAH group treated with 100 mg/(kg.d) curcumin and SAH group treated with 200 mg/(kg.d) curcumin, with 15 rats in each group. Endovascular puncture was used to induce SAH model. Nissl staining was used to test whether neurons were broken. TUNEL staining was used to detect apoptosis. Immunohistochemistry was used to investigate the expression of caspase-3. Western blot analysis was used to detect the expressions of p-JNK, JNK, p-c-Jun, c-Jun, and caspase-3. Results Nissl staining indicated the decrease of Nissl bodies in SAH group, but increase of Nissl bodies in SAH group treated with curcumin. TUNEL staining showed that there were more apoptotic neurons in SAH group compared with sham group, while apoptotic neurons decreased after the treatment with curcumin, more obviously in the group treated with 200 mg/(kg.d) curcumin. The expressions of p-JNK, JNK, p-c-Jun, c-Jun, and caspase-3 were up-regulated in SAH group compared with sham group. However, the expressions of those proteins were down-regulated after the treatment with curcumin, especially by higher-dose curcumin treatment. Conclusion Curcumin might suppress early brain injury after SAH by inhibiting JNK/c-Jun signal pathway and neuron apoptosis.

  17. Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF in a rat model.

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    Hu, Yuan; Tang, Jin-Shu; Hou, Shu-Xun; Shi, Xiu-Xiu; Qin, Jiang; Zhang, Tie-Song; Wang, Xiao-Jing

    2017-11-01

    Curcumin is a natural product with antimutagenic, antitumor, antioxidant and neuroprotective properties. However, to the best of our knowledge, curcumin has yet to be investigated for the treatment of lumbar intervertebral disc degeneration LIDD). The aim of the present study was to investigate whether curcumin can alleviate LIDD through regulating the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, transforming growth factor (TGF)‑β1/2, matrix metalloproteinase (MMP)‑9 and brain‑derived neurotrophic factor (BDNF) in a rat model of LIDD. The results of the present study suggest that pretreatment with curcumin can prevent the development of LIDD in rats. It was revealed that treatment with curcumin significantly reduced interleukin (IL)‑1β and IL‑6, iNOS, COX‑2 and MMP‑9 levels in rats with LIDD. In addition, treatment with curcumin reduced the mRNA expression levels of TGF‑β1 and TGF‑β2, whereas it increased the mRNA expression levels of BDNF in rats with LIDD. In conclusion, the present findings indicate that curcumin may exert protective effects on LIDD development, exerting its action through the regulation of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF.

  18. Lithium protects ethanol-induced neuronal apoptosis

    International Nuclear Information System (INIS)

    Zhong Jin; Yang Xianlin; Yao Weiguo; Lee Weihua

    2006-01-01

    Lithium is widely used for the treatment of bipolar disorder. Recent studies have demonstrated its neuroprotective effect. Ethanol is a potent neurotoxin that is particularly harmful to the developing nervous system. In this study, we evaluated lithium's neuroprotection against ethanol-induced apoptosis. Transient exposure of infant mice to ethanol caused apoptotic cell death in brain, which was prevented significantly by administering a low dose of lithium 15 min later. In cultured cerebellar granule neurons, ethanol-induced apoptosis and activation of caspase-3/9, both of which were prevented by lithium. However, lithium's protection is not mediated by its commonly known inhibition of glycogen synthase3β, because neither ethanol nor lithium has significant effects on the phosphorylation of Akt (ser473) or GSK3β (ser9). In addition, the selective GSK-3β inhibitor SB-415286 was unable to prevent ethanol-induced apoptosis. These data suggest lithium may be used as a potential preventive measure for ethanol-induced neurological deficits

  19. Disruption of Skin Stem Cell Homeostasis following Transplacental Arsenicosis; Alleviation by Combined Intake of Selenium and Curcumin.

    Directory of Open Access Journals (Sweden)

    Shiv Poojan

    Full Text Available Of late, a consirable interest has grown in literature on early development of arsenicosis and untimely death in humans after exposure to iAs in drinking water in utero or during the childhood. The mechanism of this kind of intrauterine arsenic poisoning is not known; however it is often suggested to involve stem cells. We looked into this possibility by investigating in mice the influence of chronic in utero exposure to arsenical drinking water preliminarily on multipotent adult stem cell and progenitor cell counts at the beginning of neonatal age. We found that repeated intake of 42.5 or 85 ppm iAs in drinking water by pregnant BALB/c mice substantially changed the counts of EpASCs, the progenitor cells, and the differentiated cells in epidermis of their zero day old neonates. EpASCs counts decreased considerably and the differentiated/apoptosed cell counts increased extensively whereas the counts of progenitor cell displayed a biphasic effect. The observed trend of response was dose-dependent and statistically significant. These observations signified a disruption in stem cell homeostasis. The disorder was in parallel with changes in expression of biomarkers of stem cell and progenitor (TA cell besides changes in expression of pro-inflammatory and antioxidant molecules namely Nrf2, NFkB, TNF-α, and GSH. The biological monitoring of exposure to iAs and the ensuing transplacental toxicity was verifiable correspondingly by the increase in iAs burden in hair, kidney, skin, liver of nulliparous female mice and the onset of chromosomal aberrations in neonate bone marrow cells. The combined intake of selenite and curcumin in utero was found to prevent the disruption of homeostasis and associated biochemical changes to a great extent. The mechanism of prevention seemed possibly to involve (a curcumin and Keap-1 interaction, (b consequent escalated de novo GSH biosynthesis, and (c the resultant toxicant disposition. These observations are important

  20. Disruption of Skin Stem Cell Homeostasis following Transplacental Arsenicosis; Alleviation by Combined Intake of Selenium and Curcumin.

    Science.gov (United States)

    Poojan, Shiv; Kumar, Sushil; Verma, Vikas; Dhasmana, Anupam; Lohani, Mohtashim; Verma, Mukesh K

    2015-01-01

    Of late, a consirable interest has grown in literature on early development of arsenicosis and untimely death in humans after exposure to iAs in drinking water in utero or during the childhood. The mechanism of this kind of intrauterine arsenic poisoning is not known; however it is often suggested to involve stem cells. We looked into this possibility by investigating in mice the influence of chronic in utero exposure to arsenical drinking water preliminarily on multipotent adult stem cell and progenitor cell counts at the beginning of neonatal age. We found that repeated intake of 42.5 or 85 ppm iAs in drinking water by pregnant BALB/c mice substantially changed the counts of EpASCs, the progenitor cells, and the differentiated cells in epidermis of their zero day old neonates. EpASCs counts decreased considerably and the differentiated/apoptosed cell counts increased extensively whereas the counts of progenitor cell displayed a biphasic effect. The observed trend of response was dose-dependent and statistically significant. These observations signified a disruption in stem cell homeostasis. The disorder was in parallel with changes in expression of biomarkers of stem cell and progenitor (TA) cell besides changes in expression of pro-inflammatory and antioxidant molecules namely Nrf2, NFkB, TNF-α, and GSH. The biological monitoring of exposure to iAs and the ensuing transplacental toxicity was verifiable correspondingly by the increase in iAs burden in hair, kidney, skin, liver of nulliparous female mice and the onset of chromosomal aberrations in neonate bone marrow cells. The combined intake of selenite and curcumin in utero was found to prevent the disruption of homeostasis and associated biochemical changes to a great extent. The mechanism of prevention seemed possibly to involve (a) curcumin and Keap-1 interaction, (b) consequent escalated de novo GSH biosynthesis, and (c) the resultant toxicant disposition. These observations are important with respect to

  1. Molecular pathways underpinning ethanol-induced neurodegeneration

    Directory of Open Access Journals (Sweden)

    Dan eGoldowitz*

    2014-07-01

    Full Text Available While genetics impacts the type and severity of damage following developmental ethanol exposure, little is currently known about the molecular pathways that mediate these effects. Traditionally, research in this area has used a candidate gene approach and evaluated effects on a gene-by-gene basis. Recent studies, however, have begun to use unbiased approaches and genetic reference populations to evaluate the roles of genotype and epigenetic modifications in phenotypic changes following developmental ethanol exposure, similar to studies that evaluated numerous alcohol-related phenotypes in adults. Here, we present work assessing the role of genetics and chromatin-based alterations in mediating ethanol-induced apoptosis in the developing nervous system. Utilizing the expanded family of BXD recombinant inbred mice, animals were exposed to ethanol at postnatal day 7 via subcutaneous injection (5.0 g/kg in 2 doses. Tissue was collected 7 hours after the initial ethanol treatment and analyzed by activated caspase-3 immunostaining to visualize dying cells in the cerebral cortex and hippocampus. In parallel, the levels of two histone modifications relevant to apoptosis, γH2AX and H3K14 acetylation, were examined in the cerebral cortex using protein blot analysis. Activated caspase-3 staining identified marked differences in cell death across brain regions between different mouse strains. Genetic analysis of ethanol susceptibility in the hippocampus led to the identification of a quantitative trait locus on chromosome 12, which mediates, at least in part, strain-specific differential vulnerability to ethanol-induced apoptosis. Furthermore, analysis of chromatin modifications in the cerebral cortex revealed a global increase in γH2AX levels following ethanol exposure, but did not show any change in H3K14 acetylation levels. Together, these findings provide new insights into the molecular mechanisms and genetic contributions underlying ethanol-induced

  2. Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF-κB signaling pathway.

    Science.gov (United States)

    Xu, Yiming; Liu, Ling

    2017-09-01

    Influenza A viruses (IAV) result in severe public health problems with worldwide each year. Overresponse of immune system to IAV infection leads to complications, and ultimately causing morbidity and mortality. Curcumin has been reported to have anti-inflammatory ability. However, its molecular mechanism in immune responses remains unclear. We detected the pro-inflammatory cytokine secretion and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-related protein expression in human macrophages or mice infected by IAV with or without curcumin treatment. We found that the IAV infection caused a dramatic enhancement of pro-inflammatory cytokine productions of human macrophages and mice immune cells. However, curcumin treatment after IAV infection downregulated these cytokines production in a dose-dependent manner. Moreover, the NF-κB has been activated in human macrophages after IAV infection, while administration of curcumin inhibited NF-κB signaling pathway via promoting the expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), and inhibiting the translocation of p65 from cytoplasm to nucleus. In summary, IAV infection could result in the inflammatory responses of immune cells, especially macrophages. Curcumin has the therapeutic potentials to relieve these inflammatory responses through inhibiting the NF-κB signaling pathway. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  3. Ethanol-Induced Changes in PKCε: From Cell to Behavior.

    Science.gov (United States)

    Pakri Mohamed, Rashidi M; Mokhtar, Mohd H; Yap, Ernie; Hanim, Athirah; Abdul Wahab, Norhazlina; Jaffar, Farah H F; Kumar, Jaya

    2018-01-01

    The long-term binge intake of ethanol causes neuroadaptive changes that lead to drinkers requiring higher amounts of ethanol to experience its effects. This neuroadaptation can be partly attributed to the modulation of numerous neurotransmitter receptors by the various protein kinases C (PKCs). PKCs are enzymes that control cellular activities by regulating other proteins via phosphorylation. Among the various isoforms of PKC, PKCε is the most implicated in ethanol-induced biochemical and behavioral changes. Ethanol exposure causes changes to PKCε expression and localization in various brain regions that mediate addiction-favoring plasticity. Ethanol works in conjunction with numerous upstream kinases and second messenger activators to affect cellular PKCε expression. Chauffeur proteins, such as receptors for activated C kinase (RACKs), cause the translocation of PKCε to aberrant sites and mediate ethanol-induced changes. In this article, we aim to review the following: the general structure and function of PKCε, ethanol-induced changes in PKCε expression, the regulation of ethanol-induced PKCε activities in DAG-dependent and DAG-independent environments, the mechanisms underlying PKCε-RACKε translocation in the presence of ethanol, and the existing literature on the role of PKCε in ethanol-induced neurobehavioral changes, with the goal of creating a working model upon which further research can build.

  4. Ethanol-Induced Changes in PKCε: From Cell to Behavior

    Directory of Open Access Journals (Sweden)

    Rashidi M. Pakri Mohamed

    2018-04-01

    Full Text Available The long-term binge intake of ethanol causes neuroadaptive changes that lead to drinkers requiring higher amounts of ethanol to experience its effects. This neuroadaptation can be partly attributed to the modulation of numerous neurotransmitter receptors by the various protein kinases C (PKCs. PKCs are enzymes that control cellular activities by regulating other proteins via phosphorylation. Among the various isoforms of PKC, PKCε is the most implicated in ethanol-induced biochemical and behavioral changes. Ethanol exposure causes changes to PKCε expression and localization in various brain regions that mediate addiction-favoring plasticity. Ethanol works in conjunction with numerous upstream kinases and second messenger activators to affect cellular PKCε expression. Chauffeur proteins, such as receptors for activated C kinase (RACKs, cause the translocation of PKCε to aberrant sites and mediate ethanol-induced changes. In this article, we aim to review the following: the general structure and function of PKCε, ethanol-induced changes in PKCε expression, the regulation of ethanol-induced PKCε activities in DAG-dependent and DAG-independent environments, the mechanisms underlying PKCε-RACKε translocation in the presence of ethanol, and the existing literature on the role of PKCε in ethanol-induced neurobehavioral changes, with the goal of creating a working model upon which further research can build.

  5. Gastrointestinal protective effect of dietary spices during ethanol-induced oxidant stress in experimental rats.

    Science.gov (United States)

    Prakash, Usha N S; Srinivasan, Krishnapura

    2010-04-01

    Spices are traditionally known to have digestive stimulant action and to cure digestive disorders. In this study, the protective effect of dietary spices with respect to activities of antioxidant enzymes in gastric and intestinal mucosa was examined. Groups of Wistar rats were fed for 8 weeks with diets containing black pepper (0.5%), piperine (0.02%), red pepper (3.0%), capsaicin (0.01%), and ginger (0.05%). All these spices significantly enhanced the activities of antioxidant enzymes--superoxide dismutase, catalase, glutathione reductase, and glutathione-S-transferase--in both gastric and intestinal mucosa, suggesting a gastrointestinal protective role for these spices. In a separate study, these dietary spices were found to alleviate the diminished activities of antioxidant enzymes in gastric and intestinal mucosa under conditions of ethanol-induced oxidative stress. The gastroprotective effect of the spices was also reflected in their positive effect on mucosal glycoproteins, thereby lowering mucosal injury. The amelioration of the ethanol-induced decrease in the activities of antioxidant enzymes in gastric and intestinal mucosa by dietary spices suggests their beneficial gastrointestinal protective role. This is the first report on the gastrointestinal protective potential of dietary spices.

  6. Antiulcerogenic benefits of herbal ingredients in ethanol-induced ...

    African Journals Online (AJOL)

    Antiulcerogenic benefits of herbal ingredients in ethanol-induced animal models. ... Although therapeutic approaches are widely available, preventive regimens are limited. Numerous studies have demonstrated that herbal ... gastric ulcer. Key words: Herbal Medicines, Gastric ulcer, Prevention, Animal models, Alcohol ...

  7. Ethanol induces rotational behavior in 6-hydroxydopamine lesioned mice

    Energy Technology Data Exchange (ETDEWEB)

    Silverman, P.B.

    1987-03-09

    Mice with unilateal striatal lesions created by 6-hydroxydopamine (6HDA) injection were screened for rotational (circling) behavior in response to injection of amphetamine and apomorphine. Those that rotated ipsilaterally in response to amphetamine and contralaterally in response to apomorphine were subsequently challenged with 1 to 3 g/kg (i.p.) ethanol. Surprisingly, ethanol induced dose related contralateral (apomorphine-like) rotation which, despite gross intoxication, was quite marked in most animals. No significant correlation was found between the number of turns made following ethanol and made after apomorphine or amphetamine. 14 references, 2 figures, 1 table.

  8. Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

    Directory of Open Access Journals (Sweden)

    Ravi Varatharajalu

    2016-01-01

    Full Text Available Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories from ω-3 polyunsaturated fatty acids (PUFA and Lieber-deCarli high menhaden (13.8% of total calories from ω-3 PUFA alcohol-liquid (5% diets supplemented with or without curcumin (150 mg/kg/day for 8 weeks. Treatment with curcumin protected against high ω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1 mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to high ω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with high ω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and high ω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis.

  9. Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity

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    Brigitte Gonthier

    2012-01-01

    Full Text Available Aims. 3,5,4′-Trihydroxy-trans-stilbene, a natural polyphenolic compound present in wine and grapes and better known as resveratrol, has free radical scavenging properties and is a potent protector against oxidative stress induced by alcohol metabolism. Today, the mechanism by which ethanol exerts its toxicity is still not well understood, but it is generally considered that free radical generation plays an important role in the appearance of structural and functional alterations in cells. The aim of this study was to evaluate the protective action of resveratrol against ethanol-induced brain cell injury. Methods. Primary cultures of rat astrocytes were exposed to ethanol, with or without a pretreatment with resveratrol. We examined the dose-dependent effects of this resveratrol pretreatment on cytotoxicity and genotoxicity induced by ethanol. Cytotoxicity was assessed using the MTT reduction test. Genotoxicity was evidenced using single cell gel electrophoresis. In addition, DNA staining with fluorescent dyes allowed visualization of nuclear damage using confocal microscopy. Results. Cell pretreatment with low concentrations of trans-resveratrol (0.1–10 μM slowed down cell death and DNA damage induced by ethanol exposure, while higher concentrations (50–100 μM enhanced these same effects. No protection by cis-resveratrol was observed. Conclusion. Protection offered by trans-resveratrol against ethanol-induced neurotoxicity was only effective for low concentrations of this polyphenol.

  10. Ethanol-induced conditioned taste avoidance: reward or aversion?

    Science.gov (United States)

    Liu, Chuang; Showalter, John; Grigson, Patricia Sue

    2009-03-01

    Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue. The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus. In Experiment 1, fluid-deprived Lewis and Fischer rats were given 5-minute access to 0.15% saccharin and then injected with saline or a range of doses of ethanol (0.5, 0.75, 1.0, or 1.5 g/kg). There was a total of 6 such pairings. In Experiments 2 and 3, Sprague-Dawley rats received bilateral electrophysiologically guided lesions of the gustatory thalamus. After recovery, suppression of intake of the saccharin cue was evaluated following repeated daily pairings with either a high (1.5 g/kg) or a low (0.75 g/kg) dose of ethanol. Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol. The results suggest that the suppressive effects of ethanol on CS intake are mediated by both

  11. Effects of curcumin on HDL functionality.

    Science.gov (United States)

    Ganjali, Shiva; Blesso, Christopher N; Banach, Maciej; Pirro, Matteo; Majeed, Muhammed; Sahebkar, Amirhossein

    2017-05-01

    Curcumin, a bioactive polyphenol, is a yellow pigment of the Curcuma longa (turmeric) plant. Curcumin has many pharmacologic effects including antioxidant, anti-carcinogenic, anti-obesity, anti-angiogenic and anti-inflammatory properties. Recently, it has been found that curcumin affects lipid metabolism, and subsequently, may alleviate hyperlipidemia and atherosclerosis. Plasma HDL cholesterol (HDL-C) is an independent negative risk predictor of cardiovascular disease (CVD). However, numerous clinical and genetic studies have yielded disappointing results about the therapeutic benefit of raising plasma HDL-C levels. Therefore, research efforts are now focused on improving HDL functionality, independent of HDL-C levels. The quality of HDL particles can vary considerably due to heterogeneity in composition. Consistent with its complexity in composition and metabolism, a wide range of biological activities is reported for HDL, including antioxidant, anti-glycation, anti-inflammatory, anti-thrombotic, anti-apoptotic and immune modulatory activities. Protective properties of curcumin may influence HDL functionality; therefore, we reviewed the literature to determine whether curcumin can augment HDL function. In this review, we concluded that curcumin may modulate markers of HDL function, such as apo-AI, CETP, LCAT, PON1, MPO activities and levels. Curcumin may subsequently improve conditions in which HDL is dysfunctional and may have potential as a therapeutic drug in future. Further clinical trials with bioavailability-improved formulations of curcumin are warranted to examine its effects on lipid metabolism and HDL function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. The turmeric protective properties at ethanol-induced behavioral disorders.

    Directory of Open Access Journals (Sweden)

    Goldina I.A.

    2017-03-01

    Full Text Available The aim of the study was to determine the effect of mechanically modified turmeric extract on the parameters of orienting-exploratory behavior in mice with chronic ethanol consumption. Material and methods. Mice behavior was assessed in the "open field" test. In the both control groups the animals received water or 10% ethanol solution; in the test group — turmeric extract in 10% ethanol solution. Amount of blood mononuclear cells, thymocytes, and splenocytes were estimated. Results. Analysis of the behavioral parameters in animals after chronic exposure to ethanol showed suppression of motor and exploratory components of the behavior. In mice that received both ethanol and turmeric extract recorded behavior parameters were significantly higher than in the group of animals who received ethanol only. It was shown that the turmeric extract enhances the amount of blood immune cells. Conclusion. Mechanically modified turmeric extract possesses protective properties against ethanol-induced behavioral disorders.

  13. Anti-angiogenic effect of curcumin, curcumin ethylenediamine derivative and curcumin ethylenediamine manganese complex

    OpenAIRE

    SUNTORNSUK, Leena; Koizumi, Keiichi; Saitoh, Yurika; Nakamura, ElianeShizuka; KAMMASUD, Naparat; VAJARAGUPTA, Opa; Saiki, Ikuo

    2004-01-01

    We investigated the anti-angiogenic effect of curcumin, curcumin ethylenediamine derivative (curcumin ED) and curcumin ethylenediamine manganese complex (curcumin EDMn) through the inhibition of the formation of tube-like structures by human umbilical vascular endothelial cells (HUVEC). Curcumin, curcumin ED, curcumin EDMn did not show cytotoxicity to HUVEC at concentrations equal and lower than 10 μM. At the concentration of 10 μM,curcumin, curcumin ED and curcumin EDMn inhibited the tube fo...

  14. Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver

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    Tao Zeng

    2018-04-01

    Full Text Available Protein kinase B (PKB/Akt plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD. Previous studies suggest that cytochrome P4502E1 (CYP2E1 plays causal roles in the pathogenesis of alcoholic fatty liver (AFL. We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis. In this study, we found that chronic ethanol-induced hepatic steatosis was accompanied with reduced phosphorylation of Akt at Thr308 in mice liver. Chronic ethanol exposure had no effects on the protein levels of phosphatidylinositol 3 kinase (PI3K and phosphatase and tensin homologue deleted on chromosome ten (PTEN, and led to a slight decrease of phosphoinositide-dependent protein kinase 1 (PDK-1 protein level. Ethanol exposure resulted in increased levels of malondialdehyde (MDA and 4-hydroxynonenal (4-HNE-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ, an efficient CYP2E1 inhibitor. Interestingly, N-acetyl-L-cysteine (NAC significantly attenuated chronic ethanol-induced hepatic fat accumulation and the decline of Akt phosphorylation at Thr308. In the in vitro studies, Akt phosphorylation was suppressed in CYP2E1-expressing HepG2 (CYP2E1-HepG2 cells compared with the negative control HepG2 (NC-HepG2 cells, and 4-HNE treatment led to significant decrease of Akt phosphorylation at Thr308 in wild type HepG2 cells. Lastly, pharmacological activation of Akt by insulin-like growth factor-1 (IGF-1 significantly alleviated chronic ethanol-induced fatty liver in mice. Collectively, these results indicate that CYP2E1-induced oxidative stress may be responsible for ethanol-induced suppression of Akt phosphorylation and pharmacological modulation of Akt in liver may be an effective strategy for the treatment of ethanol-induced fatty liver. Keywords

  15. Curcumin improves alcoholic fatty liver by inhibiting fatty acid biosynthesis.

    Science.gov (United States)

    Guo, Chang; Ma, Jingfan; Zhong, Qionghong; Zhao, Mengyuan; Hu, Tianxing; Chen, Tong; Qiu, Longxin; Wen, Longping

    2017-08-01

    Alcoholic fatty liver is a threat to human health. It has been long known that abstinence from alcohol is the most effective therapy, other effective therapies are not available for the treatment in humans. Curcumin has a great potential for anti-oxidation and anti-inflammation, but the effect on metabolic reconstruction remains little known. Here we performed metabolomic analysis by gas chromatography/mass spectrometry and explored ethanol pathogenic insight as well as curcumin action pattern. We identified seventy-one metabolites in mouse liver. Carbohydrates and lipids were characteristic categories. Pathway analysis results revealed that ethanol-induced pathways including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis and pentose and glucuronate interconversions were suppressed by curcumin. Additionally, ethanol enhanced galactose metabolism and pentose phosphate pathway. Glyoxylate and dicarboxylate metabolism and pyruvate metabolism were inhibited in mice fed ethanol diet plus curcumin. Stearic acid, oleic acid and linoleic acid were disease biomarkers and therapical biomarkers. These results reflect the landscape of hepatic metabolism regulation. Our findings illustrate ethanol pathological pathway and metabolic mechanism of curcumin therapy. Copyright © 2017. Published by Elsevier Inc.

  16. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation

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    Abdulrahman Al Asmari

    Full Text Available Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA, myeloperoxidase activity (MPO, expression of nuclear factor kappa B (NF-κB p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion (P < 0.001 and acidity (P < 0.0001 and gastric ulcer index scores (P < 0.001. and augmented the gastric mucosal defense. Vanillin significantly restored the depleted gastric wall mucus levels (P < 0.0001 induced by ethanol and also significantly attenuated ethanol induced inflammation and oxidative stress by the suppression of gastric MPO activity (P < 0.001, reducing the expression of NF-κB p65 and the increased MDA levels (P < 0.001. Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol.Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture. Keywords: Gastric ulcers, Pylorus ligation, Ethanol, Vanillin, Inflammation, Oxidative stress

  17. Dietary fructose augments ethanol-induced liver pathology.

    Science.gov (United States)

    Thomes, Paul G; Benbow, Jennifer H; Brandon-Warner, Elizabeth; Thompson, Kyle J; Jacobs, Carl; Donohue, Terrence M; Schrum, Laura W

    2017-05-01

    Certain dietary components when combined with alcohol exacerbate alcohol-induced liver injury (ALI). Here, we tested whether fructose, a major ingredient of the western diet, enhances the severity of ALI. We fed mice ethanol for 8 weeks in the following Lieber-DeCarli diets: (a) Regular (contains olive oil); (b) corn oil (contains corn oil); (c) fructose (contains fructose and olive oil) and (d) corn+fructose (contains fructose and corn oil). We compared indices of metabolic function and liver pathology among the different groups. Mice fed fructose-free and fructose-containing ethanol diets exhibited similar levels of blood alcohol, blood glucose and signs of disrupted hepatic insulin signaling. However, only mice given fructose-ethanol diets showed lower insulin levels than their respective controls. Compared with their respective pair-fed controls, all ethanol-fed mice exhibited elevated levels of serum ALT; the inflammatory cytokines TNF-α, MCP-1 and MIP-2; hepatic lipid peroxides and triglycerides. All the latter parameters were significantly higher in mice given fructose-ethanol diets than those fed fructose-free ethanol diets. Mice given fructose-free or fructose-containing ethanol diets each had higher levels of hepatic lipogenic enzymes than controls. However, the level of the lipogenic enzyme fatty acid synthase (FAS) was significantly higher in livers of mice given fructose control and fructose-ethanol diets than in all other groups. Our findings indicate that dietary fructose exacerbates ethanol-induced steatosis, oxidant stress, inflammation and liver injury, irrespective of the dietary fat source, to suggest that inclusion of fructose in or along with alcoholic beverages increases the risk of more severe ALI in heavy drinkers. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Potentials of Curcumin as an Antidepressant

    Directory of Open Access Journals (Sweden)

    S.K. Kulkarni

    2009-01-01

    Full Text Available Major depression, a debilitating psychiatric disorder, is predicted to be the second most prevalent human illness by the year 2020. Various antidepressants, ranging from monoamine oxidase inhibitors to recently developed dual reuptake inhibitors, are prescribed for alleviating the symptoms of depression. Despite the availability of these blockbuster molecules, approximately 30% of depressed patients do not respond to the existing drug therapies and the remaining 70% fails to achieve complete remission. Moreover, antidepressants are associated with a plethora of side effects and drug-drug/drug-food interactions. In this context, novel approaches are being tried to find more efficacious and safer drugs for the treatment of major depression. Curcumin is one such molecule that has shown promising efficacy in various animal models of major depression. Although the mechanism of the antidepressant effect of curcumin is not fully understood, it is hypothesized to act through inhibiting the monoamine oxidase enzyme and modulating the release of serotonin and dopamine. Moreover, evidences have shown that curcumin enhances neurogenesis, notably in the frontal cortex and hippocampal regions of the brain. The use of curcumin in clinics for the treatment of major depression is limited due to its poor gastrointestinal absorption. The present review attempts to discuss the pharmacological profile along with molecular mechanisms of the antidepressant effect of curcumin in animal models of depression. A need for clinical trials in order to explore the antidepressant efficacy and safety profile of curcumin is emphasized.

  19. Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.

    Science.gov (United States)

    Tandon, Shashank; Keefe, Kristen A; Taha, Sharif A

    2017-02-15

    The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg -1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced

  20. Ginger extract mitigates ethanol-induced changes of alpha and beta - myosin heavy chain isoforms gene expression and oxidative stress in the heart of male wistar rats.

    Science.gov (United States)

    Shirpoor, Alireza; Zerehpoosh, Mitra; Ansari, Mohammad Hasan Khadem; Kheradmand, Fatemeh; Rasmi, Yousef

    2017-09-01

    The association between ethanol consumption and heart abnormalities, such as chamber dilation, myocyte damage, ventricular hypertrophy, and hypertension is well known. However, underlying molecular mediators involved in ethanol-induced heart abnormalities remain elusive. The aim of this study was to investigate the effect of chronic ethanol exposure on alpha and beta - myosin heavy chain (MHC) isoforms gene expression transition and oxidative stress in rats' heart. It was also planned to find out whether ginger extract mitigated the abnormalities induced by ethanol in rats' heart. Male wistar rats were divided into three groups of eight animals as follows: Control, ethanol, and ginger extract treated ethanolic (GETE) groups. After six weeks of treatment, the results revealed a significant increase in the β-MHC gene expression, 8- OHdG amount, and NADPH oxidase level. Furthermore, a significant decrease in the ratio of α-MHC/β-MHC gene expression to the amount of paraoxonase enzyme in the ethanol group compared to the control group was found. The consumption of Ginger extract along with ethanol ameliorated the changes in MHC isoforms gene expression and reduced the elevated amount of 8-OHdG and NADPH oxidase. Moreover, compared to the consumption of ethanol alone, it increased the paraoxonase level significantly. These findings indicate that ethanol-induced heart abnormalities may in part be associated with MHC isoforms changes mediated by oxidative stress, and that these effects can be alleviated by using ginger extract as an antioxidant molecule. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation.

    Science.gov (United States)

    Al Asmari, Abdulrahman; Al Shahrani, Hamoud; Al Masri, Nasser; Al Faraidi, Ahmed; Elfaki, Ibrahim; Arshaduddin, Mohammed

    2016-01-01

    Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA), myeloperoxidase activity (MPO), expression of nuclear factor kappa B (NF-κB) p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion ( P  Vanillin significantly restored the depleted gastric wall mucus levels ( P  Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol. Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture.

  2. Curcumin Nanoparticle Therapy for Gulf War Illness

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0480 TITLE: Curcumin Nanoparticle Therapy for Gulf War Illness PRINCIPAL INVESTIGATOR: Ashok K. Shetty, Ph.D...Nanoparticle Therapy for Gulf War Illness 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0480 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Ashok K...biodegradable polymer nanosystems (nCUR) for alleviating cognitive, memory and mood impairments in a rat model of gulf war illness (GWI). Specific

  3. Curcumin: Reintroduced Therapeutic Agent from Traditional Medicine for Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hamid Reza Rahimi

    2015-03-01

    Full Text Available Alcoholic liver disease (ALD is the main cause of chronic liver disease across the world and can lead to fibrosis and cirrhosis. The etiopathogenesis of ALD is related to ethanol-induced oxidative stress, glutathione reduction, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. Curcumin is an active ingredient of the rhizome of turmeric. The substance is shown to have minor adverse effects. As the substance possess low bioavailability in free formulation, different strategies has been conducted to improve its bioavailability which resulted in production of nanomiscels and nanoparticles. Curcumin can provide protection for the liver against toxic effects of alcohol use. Several studies showed curcumin blocks endotoxin-mediated activation of NF-κB and suppresses the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. According to the molecular studies, curcumin inhibits NF-κB signaling pathway, regulates cytokines production and modulates immune response. It has been shown that curcumin can suppress gene expression, especially cytokines genes resulting in down-regulation of tumor necrosis factor-α (TNF-α, interleukin 1 (IL-1, IL-6, IL-8, adhesion molecules (ICAM, VCAM and C-reactive protein. Hence, curcumin can have therapeutic effects on the majority of chronic inflammatory diseases such as asthma, bronchitis, inflammatory bowel disease, rheumatoid arthritis, ALD, fatty liver, and allergy.

  4. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    International Nuclear Information System (INIS)

    Li, Weifeng; Huang, Huimin; Niu, Xiaofeng; Fan, Ting; Mu, Qingli; Li, Huani

    2013-01-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue

  5. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage?

    International Nuclear Information System (INIS)

    Wallace, J.L.; Beck, P.L.; Morris, G.P.

    1988-01-01

    The role of leukotriene (LT) C 4 as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis and agents that have previously been shown to reduce ethanol-induced damage prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC 4 synthesis. LTC 4 synthesis could be reduced significantly by pretreatment with L651,392 or dexamethosone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. Furthermore, changes in LBT 4 synthesis paralleled the changes in LTC 4 synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. These studies confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC 4 synthesis does not confer protection to the mucosa, suggesting that LTC 4 does not play an important role in the etiology of ethanol-induced gastric damage

  6. Lithium blocks ethanol-induced modulation of protein kinases in the developing brain

    International Nuclear Information System (INIS)

    Chakraborty, Goutam; Saito, Mitsuo; Mao, Rui-Fen; Wang, Ray; Vadasz, Csaba; Saito, Mariko

    2008-01-01

    Lithium has been shown to be neuroprotective against various insults including ethanol exposure. We previously reported that ethanol-induced apoptotic neurodegeneration in the postnatal day 7 (P7) mice is associated with decreases in phosphorylation levels of Akt, glycogen synthase kinase-3β (GSK-3β), and AMP-activated protein kinase (AMPK), and alteration in lipid profiles in the brain. Here, P7 mice were injected with ethanol and lithium, and the effects of lithium on ethanol-induced alterations in phosphorylation levels of protein kinases and lipid profiles in the brain were examined. Immunoblot and immunohistochemical analyses showed that lithium significantly blocked ethanol-induced caspase-3 activation and reduction in phosphorylation levels of Akt, GSK-3β, and AMPK. Further, lithium inhibited accumulation of cholesterol ester (ChE) and N-acylphosphatidylethanolamine (NAPE) triggered by ethanol in the brain. These results suggest that Akt, GSK-3β, and AMPK are involved in ethanol-induced neurodegeneration and the neuroprotective effects of lithium by modulating both apoptotic and survival pathways

  7. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Fan, Ting; Mu, Qingli; Li, Huani

    2013-10-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue.

  8. Curcuma aromatica Water Extract Attenuates Ethanol-Induced Gastritis via Enhancement of Antioxidant Status

    Directory of Open Access Journals (Sweden)

    Woo-Young Jeon

    2015-01-01

    Full Text Available Curcuma aromatica is an herbal medicine and traditionally used for the treatment of various diseases in Asia. We investigated the effects of C. aromatica water extract (CAW in the stomach of rats with ethanol-induced gastritis. Gastritis was induced in rats by intragastric administration of 5 mL/kg body weight of absolute ethanol. The CAW groups were given 250 or 500 mg of extract/kg 2 h before administration of ethanol, respectively. To determine the antioxidant effects of CAW, we determined the level of lipid peroxidation, the level of reduced glutathione (GSH, the activities of catalase, degree of inflammation, and mucus production in the stomach. CAW reduced ethanol-induced inflammation and loss of epithelial cells and increased the mucus production in the stomach. CAW reduced the increase in lipid peroxidation associated with ethanol-induced gastritis (250 and 500 mg/kg, p<0.01, resp. and increased mucosal GSH content (500 mg/kg, p<0.01 and the activity of catalase (250 and 500 mg/kg, p<0.01, resp.. CAW increased the production of prostaglandin E2. These findings suggest that CAW protects against ethanol-induced gastric mucosa injury by increasing antioxidant status. We suggest that CAW could be developed for the treatment of gastritis induced by alcohol.

  9. Mitochondrial permeability transition pore inhibitors prevent ethanol-induced neuronal death in mice.

    Science.gov (United States)

    Lamarche, Frederic; Carcenac, Carole; Gonthier, Brigitte; Cottet-Rousselle, Cecile; Chauvin, Christiane; Barret, Luc; Leverve, Xavier; Savasta, Marc; Fontaine, Eric

    2013-01-18

    Ethanol induces brain injury by a mechanism that remains partly unknown. Mitochondria play a key role in cell death processes, notably through the opening of the permeability transition pore (PTP). Here, we tested the effect of ethanol and PTP inhibitors on mitochondrial physiology and cell viability both in vitro and in vivo. Direct addition of ethanol up to 100 mM on isolated mouse brain mitochondria slightly decreased oxygen consumption but did not affect PTP regulation. In comparison, when isolated from ethanol-treated (two doses of 2 g/kg, 2 h apart) 7-day-old mouse pups, brain mitochondria displayed a transient decrease in oxygen consumption but no change in PTP regulation or H2O2 production. Conversely, exposure of primary cultured astrocytes and neurons to 20 mM ethanol for 3 days led to a transient PTP opening in astrocytes without affecting cell viability and to a permanent PTP opening in 10 to 20% neurons with the same percentage of cell death. Ethanol-treated mouse pups displayed a widespread caspase-3 activation in neurons but not in astrocytes and dramatic behavioral alterations. Interestingly, two different PTP inhibitors (namely, cyclosporin A and nortriptyline) prevented both ethanol-induced neuronal death in vivo and ethanol-induced behavioral modifications. We conclude that PTP opening is involved in ethanol-induced neurotoxicity in the mouse.

  10. Curcumin and aging

    Science.gov (United States)

    Curcumin has been used commonly as a spice, food additive, and an herbal medicine worldwide. Known as a bioactive polyphenolic, curcumin has a broad range of beneficial properties to human health. Recently, active research on curcumin with respect to aging and related traits in model organisms has d...

  11. Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats

    Science.gov (United States)

    Chen, Sheng-Hsuan; Liang, Yu-Chih; Chao, Jane CJ; Tsai, Li-Hsueh; Chang, Chun-Chao; Wang, Chia-Chi; Pan, Shiann

    2005-01-01

    AIM: To evaluate the preventive effect of Ginkgo biloba extract (GbE) on ethanol-induced gastric mucosal injuries in rats. METHODS: Female Wistar albino rats were used for the studies. We randomly divided the rats for each study into five subgroups: normal control, experimental control, and three experimental groups. The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach. We gave GbE 8.75, 17.5, 26.25 mg/kg intravenously to the experimental groups respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45 min later. The gastric ulcers, gastric mucus and the content of non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in gastric mucosa were evaluated. The amount of gastric juice and its acidity were also measured. RESULTS: The findings of our study are as follows: (1) GbE pretreatment was found to provide a dose-dependent protection against the ethanol-induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose-dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH contents and increase in the lipid peroxidation (increase MDA) in gastric tissue; (3) gastric ulcer induced by ethanol produced an increase in JNK activity in gastric mucosa which also significantly inhibited by pretreatment with GbE; and (4) GbE alone had no inhibitory effect on gastric secretion in pylorus-ligated rats. CONCLUSION: The finding of this study showed that GbE significantly inhibited the ethanol-induced gastric lesions in rats. We suggest that the preventive effect of GbE may be mediated through: (1) inhibition of lipid peroxidation; (2) preservation of gastric mucus and NP-SH; and (3) blockade of cell apoptosis. PMID:15968732

  12. PRENATAL ETHANOL EXPOSURE LEADS TO GREATER ETHANOL-INDUCED APPETITIVE REINFORCEMENT

    Science.gov (United States)

    Pautassi, Ricardo M.; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.

    2012-01-01

    Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of this effect of prenatal ethanol on the sensitivity to ethanol’s reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol’s aversive consequences. The present study assessed ethanol-induced second-order conditioned place preference (CPP) and aversion and ethanol-induced conditioned taste aversion (CTA) in infant rats prenatally exposed to ethanol (2.0 g/kg) or vehicle (water) or left untreated. The involvement of the κ opioid receptor system in ethanol-induced CTA was also explored. When place conditioning occurred during the ascending limb of the blood-ethanol curve (Experiment 1), the pups exposed to ethanol in utero exhibited greater CPP than untreated controls, with a shift to the right of the dose-response curve. Conditioning during a later phase of intoxication (30–45 min post-administration; Experiment 2) resulted in place aversion in control pups exposed to vehicle during late gestation but not in pups that were exposed to ethanol in utero. Ethanol induced a reliable and similar CTA (Experiment 3) in the pups treated with vehicle or ethanol during gestation, and CTA was insensitive to κ antagonism. These results suggest that brief exposure to a moderate ethanol dose during late gestation promotes ethanol-mediated reinforcement and alters the expression of conditioned aversion by ethanol. This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance. PMID:22698870

  13. Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain.

    Science.gov (United States)

    Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Lee, Hae Young; Koh, Phil Ok; Kim, Myeong Ok

    2011-12-01

    Exposure to alcohol during the early stages of brain development can lead to neurological disorders in the CNS. Apoptotic neurodegeneration due to ethanol exposure is a main feature of alcoholism. Exposure of developing animals to alcohol (during the growth spurt period in particular) elicits apoptotic neuronal death and causes fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS). A single episode of ethanol intoxication (at 5 g/kg) in a seven-day-old developing rat can activate the apoptotic cascade, leading to widespread neuronal death in the brain. In the present study, we investigated the potential protective effect of pyruvate against ethanol-induced neuroapoptosis. After 4h, a single dose of ethanol induced upregulation of Bax, release of mitochondrial cytochrome-c into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1), all of which promote apoptosis. These effects were all reversed by co-treatment with pyruvate at a well-tolerated dosage (1000 mg/kg). Histopathology performed at 24 and 48 h with Fluoro-Jade-B and cresyl violet stains showed that pyruvate significantly reduced the number of dead cells in the cerebral cortex, hippocampus and thalamus. Immunohistochemical analysis at 24h confirmed that ethanol-induced cell death is both apoptotic and inhibited by pyruvate. These findings suggest that pyruvate treatment attenuates ethanol-induced neuronal cell loss in the developing rat brain and holds promise as a safe therapeutic and neuroprotective agent in the treatment of neurodegenerative disorders in newborns and infants. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Ghrelin knockout mice show decreased voluntary alcohol consumption and reduced ethanol-induced conditioned place preference.

    Science.gov (United States)

    Bahi, Amine; Tolle, Virginie; Fehrentz, Jean-Alain; Brunel, Luc; Martinez, Jean; Tomasetto, Catherine-Laure; Karam, Sherif M

    2013-05-01

    Recent work suggests that stomach-derived hormone ghrelin receptor (GHS-R1A) antagonism may reduce motivational aspects of ethanol intake. In the current study we hypothesized that the endogenous GHS-R1A agonist ghrelin modulates alcohol reward mechanisms. For this purpose ethanol-induced conditioned place preference (CPP), ethanol-induced locomotor stimulation and voluntary ethanol consumption in a two-bottle choice drinking paradigm were examined under conditions where ghrelin and its receptor were blocked, either using ghrelin knockout (KO) mice or the specific ghrelin receptor (GHS-R1A) antagonist "JMV2959". We showed that ghrelin KO mice displayed lower ethanol-induced CPP than their wild-type (WT) littermates. Consistently, when injected during CPP-acquisition, JMV2959 reduced CPP-expression in C57BL/6 mice. In addition, ethanol-induced locomotor stimulation was lower in ghrelin KO mice. Moreover, GHS-R1A blockade, using JMV2959, reduced alcohol-stimulated locomotion only in WT but not in ghrelin KO mice. When alcohol consumption and preference were assessed using the two-bottle choice test, both genetic deletion of ghrelin and pharmacological antagonism of the GHS-R1A (JMV2959) reduced voluntary alcohol consumption and preference. Finally, JMV2959-induced reduction of alcohol intake was only observed in WT but not in ghrelin KO mice. Taken together, these results suggest that ghrelin neurotransmission is necessary for the stimulatory effect of ethanol to occur, whereas lack of ghrelin leads to changes that reduce the voluntary intake as well as conditioned reward by ethanol. Our findings reveal a major, novel role for ghrelin in mediating ethanol behavior, and add to growing evidence that ghrelin is a key mediator of the effects of multiple abused drugs. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Ethanol-induced increase in portal blood glow: Role of adenosine

    International Nuclear Information System (INIS)

    Orrego, H.; Carmichael, F.J.; Saldivia, V.; Giles, H.G.; Sandrin, S.; Israel, Y.

    1988-01-01

    The mechanism by which ethanol induces an increase in portal vein blood flow was studied in rats using radiolabeled microspheres. Ethanol by gavage resulted in an increase of 50-70% in portal vein blood flow. The ethanol-induced increase in portal blood flow was suppressed by the adenosine receptor blocker 8-phenyltheophylline. By itself, 8-phenyltheophylline was without effect on cardiac output or portal blood flow. Adenosine infusion resulted in a dose-dependent increase in portal blood flow. This adenosine-induced increase in portal blood flow was inhibited by 8-phenyltheophylline in a dose-dependent manner. Both alcohol and adenosine significantly reduced preportal vascular resistance by 40% and 60%, respectively. These effects were fully suppressed by 8-phenyltheophylline. It is concluded that adenosine is a likely candidate to mediate the ethanol-induced increase in portal vein blood flow. It is suggested that an increase in circulating acetate and liver hypoxia may mediate the effects of alcohol by increasing tissue and interstitial adenosine levels

  16. Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in the Developing Cerebellum.

    Science.gov (United States)

    Li, Hui; Chen, Jian; Qi, Yuanlin; Dai, Lu; Zhang, Mingfang; Frank, Jacqueline A; Handshoe, Jonathan W; Cui, Jiajun; Xu, Wenhua; Chen, Gang

    2015-08-01

    Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal alcohol spectrum disorders. The cerebellum is one of the brain areas that are most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains unclear. Our previous in vitro studies have shown that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol exposure and ethanol activates PKR through association with its intracellular activator RAX. However, the role of PKR and its interaction with RAX in vivo have not been investigated. In the current study, by utilizing N-PKR-/- mice, C57BL/6J mice with a deficient RAX-binding domain in PKR, we determined the critical role of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing cerebellum. Our data indicate that while N-PKR-/- mice have a similar BAC profile as wild-type mice, ethanol induces less brain/body mass reduction as well as cerebellar neuronal loss. In addition, ethanol promotes interleukin-1β (IL-1β) secretion, and IL-1β is a master cytokine regulating inflammatory response. Importantly, ethanol-promoted IL-1β secretion is inhibited in the developing cerebellum of N-PKR-/- mice. Thus, RAX/PKR interaction and PKR activation regulate ethanol neurotoxicity in the developing cerebellum, which may involve ethanol-induced neuroinflammation. Further, PKR could be a possible target for pharmacological intervention to prevent or treat fetal alcohol spectrum disorder (FASD).

  17. Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain

    Directory of Open Access Journals (Sweden)

    Mariko Saito

    2016-08-01

    Full Text Available Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD. While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy. Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7 mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain.

  18. [Neuroprotective effects of curcumin].

    Science.gov (United States)

    Li, Yong; Wang, Pengwen

    2009-12-01

    Traditionally, turmeric has been put to use as a food additive and herbal medicine in Asia. Curcumin is an active principle of the perennial herb curcuma longa (commonly known as turmeric). Recent evidence suggests that curcumin has activities with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and antiprotein-aggregate activities. In the current review, we provide the newly evidence for the potential role of curcumin in the neuroprotective effects of neurodegenerative diseases like Alzheimer's disease (AD).

  19. Fractalkine is a "find-me" signal released by neurons undergoing ethanol-induced apoptosis.

    Science.gov (United States)

    Sokolowski, Jennifer D; Chabanon-Hicks, Chloe N; Han, Claudia Z; Heffron, Daniel S; Mandell, James W

    2014-01-01

    Apoptotic neurons generated during normal brain development or secondary to pathologic insults are efficiently cleared from the central nervous system. Several soluble factors, including nucleotides, cytokines, and chemokines are released from injured neurons, signaling microglia to find and clear debris. One such chemokine that serves as a neuronal-microglial communication factor is fractalkine, with roles demonstrated in several models of adult neurological disorders. Lacking, however, are studies investigating roles for fractalkine in perinatal brain injury, an important clinical problem with no effective therapies. We used a well-characterized mouse model of ethanol-induced apoptosis to assess the role of fractalkine in neuronal-microglial signaling. Quantification of apoptotic debris in fractalkine-knockout (KO) and CX3CR1-KO mice following ethanol treatment revealed increased apoptotic bodies compared to wild type mice. Ethanol-induced injury led to release of soluble, extracellular fractalkine. The extracellular media harvested from apoptotic brains induces microglial migration in a fractalkine-dependent manner that is prevented by neutralization of fractalkine with a blocking antibody or by deficiency in the receptor, CX3CR1. This suggests fractalkine acts as a "find-me" signal, recruiting microglial processes toward apoptotic cells to promote their clearance. Next, we aimed to determine whether there are downstream alterations in cytokine gene expression due to fractalkine signaling. We examined mRNA expression in fractalkine-KO and CX3CR1-KO mice after alcohol-induced apoptosis and found differences in cytokine production in the brains of these KOs by 6 h after ethanol treatment. Collectively, this suggests that fractalkine acts as a "find me" signal released by apoptotic neurons, and subsequently plays a critical role in modulating both clearance and inflammatory cytokine gene expression after ethanol-induced apoptosis.

  20. Fractalkine is a "find-me" signal released by neurons undergoing ethanol-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Jennifer D Sokolowski

    2014-11-01

    Full Text Available Apoptotic neurons generated during normal brain development or secondary to pathologic insults are efficiently cleared from the central nervous system. Several soluble factors, including nucleotides, cytokines, and chemokines are released from injured neurons, signaling microglia to find and clear debris. One such chemokine that serves as a neuronal-microglial communication factor is fractalkine, with roles demonstrated in several models of adult neurological disorders. Lacking, however, are studies investigating roles for fractalkine in perinatal brain injury, an important clinical problem with no effective therapies. We used a well-characterized mouse model of ethanol-induced apoptosis to assess the role of fractalkine in neuronal-microglial signaling. Quantification of apoptotic debris in fractalkine-knockout and CX3CR1-knockout mice following ethanol treatment revealed increased apoptotic bodies compared to wild type mice. Ethanol-induced injury led to release of soluble, extracellular fractalkine. The extracellular media harvested from apoptotic brains induces microglial migration in a fractalkine-dependent manner that is prevented by neutralization of fractalkine with a blocking antibody or by deficiency in the receptor, CX3CR1. This suggests fractalkine acts as a ‘find-me’ signal, recruiting microglial processes toward apoptotic cells to promote their clearance. Next, we aimed to determine whether there are downstream alterations in cytokine gene expression due to fractalkine signaling. We examined mRNA expression in fractalkine-knockout and CX3CR1-knockout mice after alcohol-induced apoptosis and found differences in cytokine production in the brains of these knockouts by 6 hours after ethanol treatment. Collectively, this suggests that fractalkine acts as a ‘find me’ signal released by apoptotic neurons, and subsequently plays a critical role in modulating both phagocytic clearance and inflammatory cytokine gene expression after

  1. Alpha7 nicotinic receptor mediated protection against ethanol-induced cytotoxicity in PC12 cells.

    Science.gov (United States)

    Li, Y; King, M A; Grimes, J; Smith, N; de Fiebre, C M; Meyer, E M

    1999-01-16

    Ethanol caused a concentration-dependent loss of PC12 cells over a 24 h interval, accompanied by an increase in intracellular calcium. The specific alpha7 nicotinic receptor partial agonist DMXB attenuated both of these ethanol-induced actions at a concentration (3 microM) found previously to protect against apoptotic and necrotic cell loss. The alpha7 nicotinic receptor antagonist methylylaconitine blocked the neuroprotective action of DMXB when applied with but not 30 min after the agonist. These results indicate that activation of alpha7 nicotinic receptors may be therapeutically useful in preventing ethanol-neurotoxicity. Copyright 1999 Elsevier Science B.V.

  2. Autophagy Protects against CYP2E1/Chronic Ethanol-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Yongke Lu

    2015-10-01

    Full Text Available Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver injury in a chronic ethanol-fed mouse model. Wild type (WT, CYP2E1 knockout (KO or CYP2E1 humanized transgenic knockin (KI, mice were fed an ethanol liquid diet or control dextrose diet for four weeks. In the last week, some mice received either saline or 3-methyladenine (3-MA, an inhibitor of autophagy, or rapamycin, which stimulates autophagy. Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury. Treatment with 3-MA enhanced the ethanol-induced fat accumulation in WT mice and caused necrosis in the KI mice; little or no effect was found in the ethanol-fed KO mice or any of the dextrose-fed mice. 3-MA treatment further lowered the ethanol-decrease in hepatic GSH levels and further increased formation of TBARS in WT and KI mice, whereas rapamycin blunted these effects of ethanol. Neither 3-MA nor rapamycin treatment affected CYP2E1 catalytic activity or content or the induction CYP2E1 by ethanol. The 3-MA treatment decreased levels of Beclin-1 and Atg 7 but increased levels of p62 in the ethanol-fed WT and KI mice whereas rapamycin had the opposite effects, validating inhibition and stimulation of autophagy, respectively. These

  3. Modulation of gut microbiota contributes to curcumin-mediated attenuation of hepatic steatosis in rats.

    Science.gov (United States)

    Feng, Wenhuan; Wang, Hongdong; Zhang, Pengzi; Gao, Caixia; Tao, Junxian; Ge, Zhijuan; Zhu, Dalong; Bi, Yan

    2017-07-01

    Structural disruption of gut microbiota contributes to the development of non-alcoholic fatty liver disease (NAFLD) and modulating the gut microbiota represents a novel strategy for NAFLD prevention. Although previous studies have demonstrated that curcumin alleviates hepatic steatosis, its effect on the gut microbiota modulation has not been investigated. Next generation sequencing and multivariate analysis were utilized to evaluate the structural changes of gut microbiota in a NAFLD rat model induced by high fat-diet (HFD) feeding. We found that curcumin attenuated hepatic ectopic fat deposition, improved intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD-fed rats. More importantly, curcumin dramatically shifted the overall structure of the HFD-disrupted gut microbiota toward that of lean rats fed a normal diet and altered the gut microbial composition. The abundances of 110 operational taxonomic units (OTUs) were altered by curcumin. Seventy-six altered OTUs were significantly correlated with one or more hepatic steatosis associated parameters and designated 'functionally relevant phylotypes'. Thirty-six of the 47 functionally relevant OTUs that were positively correlated with hepatic steatosis associated parameters were reduced by curcumin. These results indicate that curcumin alleviates hepatic steatosis in part through stain-specific impacts on hepatic steatosis associated phylotypes of gut microbiota in rats. Compounds with antimicrobial activities should be further investigated as novel adjunctive therapies for NAFLD. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Curcumin and neurodegenerative diseases

    Science.gov (United States)

    Monroy, Adriana; Lithgow, Gordon J.; Alavez, Silvestre

    2013-01-01

    Over the last ten years curcumin has been reported to be effective against a wide variety of diseases and is characterized as having anti-carcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, and anti-infectious properties. Recent studies performed in both vertebrate and invertebrate models have been conducted to determine whether curcumin was also neuroprotective. The efficacy of curcumin in several pre-clinical trials for neurodegenerative diseases has created considerable excitement mainly due to its lack of toxicity and low cost. This suggests that curcumin could be a worthy candidate for nutraceutical intervention. Since aging is a common risk factor for neurodegenerative diseases, it is possible that some compounds that target aging mechanisms could also prevent these kinds of diseases. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent aging-associated changes in cellular proteins that lead to protein insolubility and aggregation. This loss in protein homeostasis is associated with several age-related diseases. Recently, curcumin has been found to help maintain protein homeostasis and extend lifespan in the model invertebrate Caenorhabditis elegans. Here, we review the evidence from several animal models that curcumin improves healthspan by preventing or delaying the onset of various neurodegenerative diseases. PMID:23303664

  5. Curcumin in inflammatory diseases.

    Science.gov (United States)

    Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

    2013-01-01

    Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  6. Alpha 7 nicotinic acetylcholine receptor-mediated protection against ethanol-induced neurotoxicity.

    Science.gov (United States)

    de Fiebre, NancyEllen C; de Fiebre, Christopher M

    2003-11-01

    The alpha(7)-selective nicotinic partial agonist 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB) was examined for its ability to modulate ethanol-induced neurotoxicity in primary cultures of rat neurons. Primary cultures of hippocampal neurons were established from Long-Evans, embryonic day (E)-18 rat fetuses and maintained for 7 days. Ethanol (0-150 mM), DMXB (0-56 microM), or both were subsequently co-applied to cultures. Ethanol was added two additional times to the cultures to compensate for evaporation. After 5 days, neuronal viability was assessed with the MTT cell proliferation assay. Results demonstrated that ethanol reduces neuronal viability in a concentration-dependent fashion and that DMXB protects against this ethanol-induced neurotoxicity, also in a concentration-dependent fashion. These results support the suggestion that nicotinic partial agonists may be useful in treating binge drinking-induced neurotoxicity and may provide clues as to why heavy drinkers are usually smokers.

  7. Protective effect of arctigenin on ethanol-induced neurotoxicity in PC12 cells.

    Science.gov (United States)

    Huang, Jia; Xiao, Lan; Wei, Jing-Xiang; Shu, Ya-Hai; Fang, Shi-Qi; Wang, Yong-Tang; Lu, Xiu-Min

    2017-04-01

    As a neurotropic substance, ethanol can damage nerve cells through an increase in the production of free radicals, interference of neurotrophic factor signaling pathways, activation of endogenous apoptotic signals and other molecular mechanisms. Previous studies have revealed that a number of natural drugs extracted from plants offer protection of nerve cells from damage. Among these, arctigenin (ATG) is a lignine extracted from Arctium lappa (L.), which has been found to exert a neuroprotective effect on scopolamine‑induced memory deficits in mice with Alzheimer's disease and glutamate-induced neurotoxicity in primary neurons. As a result, it may offer beneficial effects on ethanol-induced neurotoxicity. However, the effects of ATG on ethanol‑induced nerve damage remain to be elucidated. To address this issue, the present study used rat pheochromocytoma PC12 cells to investigate the neuroprotective effects of ATG on ethanol-induced cell damage by performing an MTT reduction assay, cell cycle analysis, Hoechst33342/propidium iodide fluorescence staining and flow cytometry to examine apoptosis. The results showed that 10 µM ATG effectively promoted the proliferation of damaged cells, and increased the distribution ratio of the cells at the G2/M and S phases (P<0.05). In addition, the apoptosis and necrosis of the PC12 cells were significantly decreased following treatment with ATG. Therefore, it was concluded that 10 µM ATG had a protective effect on ethanol‑induced injury in PC12 cells.

  8. Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage.

    Science.gov (United States)

    Müller, Liz Girardi; Pase, Camila Simonetti; Reckziegel, Patrícia; Barcelos, Raquel C S; Boufleur, Nardeli; Prado, Ana Cristina P; Fett, Roseane; Block, Jane Mara; Pavanato, Maria Amália; Bauermann, Liliane F; da Rocha, João Batista Teixeira; Burger, Marilise Escobar

    2013-01-01

    The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4±1.9 mg GAE/g), condensed tannins (58.4±2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe(2+)-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE+Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption. Copyright © 2011 Elsevier GmbH. All rights reserved.

  9. Vitamin-C protect ethanol induced apoptotic neuro degeneration in postnatal rat brain

    International Nuclear Information System (INIS)

    Naseer, M.I.; Najeebullah; Ikramullah; Zubair, H.; Hassan, M.; Yang, B.C.

    2010-01-01

    Objective: To evaluate ethanol effects to induced activation of caspsae-3, and to observe the protective effects of Vitamin C (vit-C) on ethanol-induced apoptotic neuro degeneration in rat cortical area of brain. Methodology: Administration of a single dose of ethanol in 7-d postnatal (P7) rats triggers activation of caspase-3 and widespread apoptotic neuronal death. Western blot analysis, cells counting and Nissl staining were used to elucidate possible protective effect of vit-C against ethanol-induced apoptotic neuro degeneration in brain. Results: The results showed that ethanol significantly increased caspase-3 expression and neuronal apoptosis. Furthermore, the co-treatment of vit-C along with ethanol showed significantly decreased expression of caspase-3 as compare to control group. Conclusion: Our findings indicate that vit-C can prevent some of the deleterious effect of ethanol on developing rat brain when given after ethanol exposure and can be used as an effective protective agent for Fetal Alcohol Syndrome (FAS). (author)

  10. In vitro/vivo drug release and anti-diabetic cardiomyopathy properties of curcumin/PBLG-PEG-PBLG nanoparticles.

    Science.gov (United States)

    Tong, Fei; Chai, Rongkui; Jiang, Haiying; Dong, Bo

    2018-01-01

    The objective of this study was to survey the therapeutic function of curcumin-encapsulated poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gammabenzyl l-glutamate) (PBLG-PEG-PBLG) (P) on diabetic cardiomyopathy (DCM) via cross regulation effect of calcium-sensing receptor (CaSR) and endogenous cystathionine-γ-lyase (CSE)/hydrogen sulfide (H 2 S). Diabetic rats were preconditioned with 20 mg/kg curcumin or curcumin/P complex continuously for 8 weeks. The blood and myocardiums were collected, the level of serum H 2 S was observed, and the [Ca 2+ ] i content was measured in myocardial cells, and hematoxylin-eosin, CaSR, CSE, and calmodulin (CaM) expression were detected. Both curcumin and curcumin/P pretreatment alleviated pathological morphological damage of myocardium, increased H 2 S and [Ca 2+ ] i levels, and upregulated the expression of CaSR, CSE, and CaM as compared to DCM group, while curcumin/P remarkably augmented this effect. PBLG-PEG-PBLG could improve water-solubility and bioactivity of curcumin and curcumin/PBLG-PEG-PBLG significantly alleviated diabetic cardiomyopathy.

  11. Memantine Can Reduce Ethanol-Induced Caspase-3 Activity and Apoptosis in H4 Cells by Decreasing Intracellular Calcium.

    Science.gov (United States)

    Wang, Xiaolong; Chen, Jiajun; Wang, Hongbo; Yu, Hao; Wang, Changliang; You, Jiabin; Wang, Pengfei; Feng, Chunmei; Xu, Guohui; Wu, Xu; Zhao, Rui; Zhang, Guohua

    2017-08-01

    Caspase-3 activation and apoptosis are associated with various neurodegenerative disorders. Calcium activation is an important factor in promoting apoptosis. We, therefore, assessed the role of intracellular calcium in ethanol-induced activation of caspase-3 in H4 human neuroglioma cells and the protective effect of the NMDA receptor antagonist, memantine, on ethanol-induced apoptosis in H4 cells. H4 cells were treated with 100 mM EtOH (in culture medium) for 2 days. For interaction studies, cells were treated with memantine (4 μM), EDTA (1 mM), or BAPTA-AM (10 μM) before treatment with EtOH. Knockdown of the gene encoding the NR1 subunit of the NMDA receptor was performed using RNAi. Apoptosis was detected by Annexin V-FITC/PI staining and flow cytometry. Cell viability was detected using an MTS cell proliferation kit. Fluorescence dual wavelength spectrophotometry was used to determine the intracellular calcium concentration. The levels of NR1, caspase-3, IP3R1, and SERCA1 proteins were detected by western blotting. NR1, IP3R1, and SERCA1 mRNA levels were detected by qPCR. We observed increased expression of NR1, IP3R1, SERCA1, and increased intracellular levels of calcium ions in H4 cells exposed to ethanol. In addition, the calcium chelators, EDTA and BAPTA, and RNAi disruption of the NMDA receptor reduced ethanol-induced caspase-3 activation in H4 cells. Memantine treatment reduced the ethanol-induced increase of intracellular calcium, caspase-3 activation, apoptosis, and the ethanol-induced decrease in cell viability. Our results indicate that ethanol-induced caspase-3 activation and apoptosis are likely to be dependent on cytosolic calcium levels and that they can be reduced by memantine treatment.

  12. miR-217 Regulates Ethanol-Induced Hepatic Inflammation by Disrupting Sirtuin 1–Lipin-1 Signaling

    OpenAIRE

    Yin, Huquan; Liang, Xiaomei; Jogasuria, Alvin; Davidson, Nicholas O.; You, Min

    2015-01-01

    Ethanol-mediated injury, combined with gut-derived lipopolysaccharide (LPS), provokes generation of proinflammatory cytokines in Kupffer cells, causing hepatic inflammation. Among the mediators of these effects, miR-217 aggravates ethanol-induced steatosis in hepatocytes. However, the role of miR-217 in ethanol-induced liver inflammation process is unknown. Here, we examined the role of miR-217 in the responses to ethanol, LPS, or a combination of ethanol and LPS in RAW 264.7 macrophages and ...

  13. Molecular Mechanisms of Curcumin Renoprotection in Experimental Acute Renal Injury

    Directory of Open Access Journals (Sweden)

    Youling Fan

    2017-12-01

    Full Text Available As a highly perfused organ, the kidney is especially sensitive to ischemia and reperfusion. Ischemia-reperfusion (IR-induced acute kidney injury (AKI has a high incidence during the perioperative period in the clinic and is an important link in ischemic acute renal failure (IARF. Therefore, IR-induced AKI has important clinical significance and it is necessary to explore to develop drugs to prevent and alleviate IR-induced AKI. Curcumin [diferuloylmethane, 1,7-bis(4-hydroxy-3-methoxiphenyl-1,6-heptadiene-3,5-dione] is a polyphenol compound derived from Curcuma longa (turmeric and was shown to have a renoprotective effect on ischemia-reperfusion injury (IRI in a previous study. However, the specific mechanisms underlying the protective role of curcumin in IR-induced AKI are not completely understood. APPL1 is a protein coding gene that has been shown to be involved in the crosstalk between the adiponectin-signaling and insulin-signaling pathways. In the study, to investigate the molecular mechanisms of curcumin effects in kidney ischemia/reperfusion model, we observed the effect of curcumin in experimental models of IR-induced AKI and we found that curcumin treatment significantly increased the expression of APPL1 and inhibited the activation of Akt after IR treatment in the kidney. Our in vitro results showed that apoptosis of renal tubular epithelial cells was exacerbated with hypoxia-reoxygenation (HR treatment compared to sham control cells. Curcumin significantly decreased the rate of apoptosis in renal tubular epithelial cells with HR treatment. Moreover, knockdown of APPL1 activated Akt and subsequently aggravated apoptosis in HR-treated renal tubular epithelial cells. Conversely, inhibition of Akt directly reversed the effects of APPL1 knockdown. In summary, our study demonstrated that curcumin mediated upregulation of APPL1 protects against ischemia reperfusion induced AKI by inhibiting Akt phosphorylation.

  14. Targets of curcumin

    Science.gov (United States)

    Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

    2010-01-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

  15. The targets of curcumin.

    Science.gov (United States)

    Zhou, Hongyu; Beevers, Christopher S; Huang, Shile

    2011-03-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here.

  16. Curcumin nanodisks: formulation and characterization

    OpenAIRE

    Ghosh, Mistuni; Singh, Amareshwar T. K.; Xu, Wenwei; Sulchek, Todd; Gordon, Leo I.; Ryan, Robert O.

    2010-01-01

    Nanodisks (ND) are nanoscale, disk-shaped phospholipid bilayers whose edge is stabilized by apolipoproteins. In the present study, ND were formulated with the bioactive polyphenol, curcumin, at a 6:1 phospholipid:curcumin molar ratio. Atomic force microscopy revealed that curcumin-ND are particles with diameters

  17. Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Xiao J

    2016-03-01

    Full Text Available Jie Xiao, Xi Sheng, Xinyu Zhang, Mengqi Guo, Xiaoping JiKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaAbstract: Curcumin, a polyphenolic compound derived from turmeric, protects against myocardial injury by alleviating oxidative stress, inflammation, apoptosis, and fibrosis. However, the role of curcumin and its mechanism of action on interstitial fibrosis after myocardial infarction (MI are poorly understood. To clarify, MI was induced by a permanent ligation of the left anterior descending coronary artery in adult mice, and the effects of curcumin were evaluated 4 weeks after the MI event. In vitro, we treated cardiac fibroblasts (CFs with Ang II, and investigated the anti-fibrotic mechanism of curcumin. Our results showed that curcumin significantly attenuated collagen deposition in vivo and inhibited CF proliferation and migration, and MMP expression. In addition, we found that the down-regulation of SIRT1 after MI was attenuated by curcumin pretreatment, which indicated that the activation of SIRT1 might be involved in the protective action of curcumin. This hypothesis was confirmed by genetic inhibition of SIRT1 (siRNA-SIRT1 in Ang II-treated CFs. Our results provide new insights into the mechanism underlying the anti-fibrotic effects of curcumin in the heart.Keywords: curcumin, myocardial infarction, angiotensin II, cardiac fibroblasts, fibrosis, SIRT1

  18. Possible mechanisms of action of Caesalpinia pyramidalis against ethanol-induced gastric damage.

    Science.gov (United States)

    Diniz, Polyana B F; Ribeiro, Ana Roseli S; Estevam, Charles S; Bani, Cristiane C; Thomazzi, Sara M

    2015-06-20

    Caesalpinia pyramidalis Tul. (Fabaceae), known as "catingueira", is an endemic tree of the Northeast region of Brazil. This plant, mainly inner bark and flowers, has been used in traditional medicine to treat gastritis, heartburn, indigestion, stomachache, dysenteries, and diarrheas. The ethanol extract of C. pyramidalis inner bark was used in rats via oral route, at the doses of 30, 100, and 300 mg/kg, in the ethanol-induced ulcer model and some of the mechanisms underlying to the gastroprotective effect of this plant investigated. The ethanol extract of C. pyramidalis inner bark (100 mg/kg) produced reduction (P process with imbalance between pro-inflammatory and anti-inflammatory mediators, supporting the popular usage of this plant. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Ameliorative effect of Opuntia ficus indica juice on ethanol-induced oxidative stress in rat erythrocytes.

    Science.gov (United States)

    Alimi, Hichem; Hfaeidh, Najla; Bouoni, Zouhour; Sakly, Mohsen; Rhouma, Khémais Ben

    2013-05-01

    The aim of the present study was to investigate the efficacy of Opuntia ficus indica f. inermis fruit juice (OFIj) on reversing oxidative damages induced by chronic ethanol intake in rat erythrocytes. OFIj was firstly analyzed with HPLC for phenolic and flavonoids content. Secondly, 40 adult male Wistar rats were equally divided into five groups and treated for 90 days as follows: control (C), ethanol-only 3 g/kg body weight (b.w) (E), low dose of OFIj 2 ml/100 g b.w+ethanol (Ldj+E), high dose of OFIj 4 ml/100 g b.w+ethanol (Hdj+E), and only a high dose of OFIj 4 ml/100g b.w (Hdj). HPLC analysis indicated high concentrations of phenolic acids and flavonoids in OFIj. Ethanol treatment markedly decreased the activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and the level of reduced glutathione (GSH). Changes in the erythrocyte's antioxidant ability were accompanied by enhanced oxidative modification of lipids (increase of malondialdeyde level) and proteins (increase in carbonyl groups). Interestingly, pre-administration of either 2 ml/100 g b.w or 4 ml/100 g b.w of OFIj to ethanol-intoxicated rats significantly reversed decreases in enzymatic as well as non enzymatic antioxidants parameters in erythrocytes. Also, the administration of OFIj significantly protected lipids and proteins against ethanol-induced oxidative modifications in rat erythrocytes. The beneficial effect of OFIj can result from the inhibition of ethanol-induced free radicals chain reactions in rat erythrocytes or from the enhancement of the endogenous antioxidants activities. Copyright © 2011 Elsevier GmbH. All rights reserved.

  20. Participation of the cholinergic system in the ethanol-induced suppression of paradoxical sleep in rats

    Directory of Open Access Journals (Sweden)

    L.A. Papale

    2008-09-01

    Full Text Available Sleep disturbance is among the many consequences of ethanol abuse in both humans and rodents. Ethanol consumption can reduce REM or paradoxical sleep (PS in humans and rats, respectively. The first aim of this study was to develop an animal model of ethanol-induced PS suppression. This model administered intragastrically (by gavage to male Wistar rats (3 months old, 200-250 g 0.5 to 3.5 g/kg ethanol. The 3.5 g/kg dose of ethanol suppressed the PS stage compared with the vehicle group (distilled water during the first 2-h interval (0-2 h; 1.3 vs 10.2; P < 0.001. The second aim of this study was to investigate the mechanisms by which ethanol suppresses PS. We examined the effects of cholinergic drug pretreatment. The cholinergic system was chosen because of the involvement of cholinergic neurotransmitters in regulating the sleep-wake cycle. A second set of animals was pretreated with 2.5, 5.0, and 10 mg/kg pilocarpine (cholinergic agonist or atropine (cholinergic antagonist. These drugs were administered 1 h prior to ethanol (3.5 g/kg or vehicle. Treatment with atropine prior to vehicle or ethanol produced a statistically significant decrease in PS, whereas pilocarpine had no effect on minutes of PS. Although the mechanism by which ethanol induces PS suppression is not fully understood, these data suggest that the cholinergic system is not the only system involved in this interaction.

  1. Ethanol induced hepatic mitochondrial dysfunction is attenuated by all trans retinoic acid supplementation.

    Science.gov (United States)

    Nair, Saritha S; Prathibha, P; Rejitha, S; Indira, M

    2015-08-15

    Alcoholics have reduced vitamin A levels in serum since vitamin A and ethanol share the same metabolic pathway. Vitamin A supplementation has an additive effect on ethanol induced toxicity. Hence in this study, we assessed the impact of supplementation of all trans retinoic acid (ATRA), an active metabolite of vitamin A on ethanol induced disruptive alterations in liver mitochondria. Male Sprague Dawley rats were grouped as follows: I: Control; II: Ethanol (4 g/kg b.wt./day); III: ATRA (100 μg/kg b.wt./day); and IV: Ethanol (4 g/kg b.wt./day)+ATRA (100 μg/kg b.wt./day). Duration of the experiment was 90 days, after which the animals were sacrificed for the study. The key enzymes of energy metabolism, reactive oxygen species, mitochondrial membrane potential and hepatic mRNA expressions of Bax, Bcl-2, c-fos and c-jun were assessed. Ethanol administration increased the reactive oxygen species generation in mitochondria. It also decreased the activities of the enzymes of citric acid cycle and oxidative phosphorylation. ATP content and mitochondrial membrane potential were decreased and cytosolic cytochrome c was increased consequently enhancing apoptosis. All these alterations were altered significantly on ATRA supplementation along with ethanol. These results were reinforced by our histopathological studies. ATRA supplementation to ethanol fed rats, led to reduction in oxidative stress, decreased calcium overload in the matrix and increased mitochondrial membrane potential, which might have altered the mitochondrial energy metabolism and elevated ATP production thereby reducing the apoptotic alterations. Hence ATRA supplementation seemed to be an effective intervention against alcohol induced mitochondrial dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The H2O2 scavenger ebselen decreases ethanol-induced locomotor stimulation in mice.

    Science.gov (United States)

    Ledesma, Juan Carlos; Font, Laura; Aragon, Carlos M G

    2012-07-01

    In the brain, the enzyme catalase by reacting with H(2)O(2) forms Compound I (catalase-H(2)O(2) system), which is the main system of central ethanol metabolism to acetaldehyde. Previous research has demonstrated that acetaldehyde derived from central-ethanol metabolism mediates some of the psychopharmacological effects produced by ethanol. Manipulations that modulate central catalase activity or sequester acetaldehyde after ethanol administration modify the stimulant effects induced by ethanol in mice. However, the role of H(2)O(2) in the behavioral effects caused by ethanol has not been clearly addressed. The present study investigated the effects of ebselen, an H(2)O(2) scavenger, on ethanol-induced locomotion. Swiss RjOrl mice were pre-treated with ebselen (0-50mg/kg) intraperitoneally (IP) prior to administration of ethanol (0-3.75g/kg; IP). In another experiment, animals were pre-treated with ebselen (0 or 25mg/kg; IP) before caffeine (15mg/kg; IP), amphetamine (2mg/kg; IP) or cocaine (10mg/kg; IP) administration. Following these treatments, animals were placed in an open field to measure their locomotor activity. Additionally, we evaluated the effect of ebselen on the H(2)O(2)-mediated inactivation of brain catalase activity by 3-amino-1,2,4-triazole (AT). Ebselen selectively prevented ethanol-induced locomotor stimulation without altering the baseline activity or the locomotor stimulating effects caused by caffeine, amphetamine and cocaine. Ebselen reduced the ability of AT to inhibit brain catalase activity. Taken together, these data suggest that a decline in H(2)O(2) levels might result in a reduction of the ethanol locomotor-stimulating effects, indicating a possible role for H(2)O(2) in some of the psychopharmacological effects produced by ethanol. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

    Science.gov (United States)

    The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

  4. Antioxidant Mechanism is Involved in the Gastroprotective Effects of Ozonized Sunflower Oil in Ethanol-Induced Ulcers in Rats

    Directory of Open Access Journals (Sweden)

    Zullyt B. Zamora Rodríguez

    2007-01-01

    In summary, our results demonstrate that OSO pretreatment exerts protective effects in ethanol-induced gastric ulcers in rats. Furthermore, these results provide evidence that these protective effects of OSO are mediated at least partially by stimulation of some important antioxidant enzymes such as SOD and GSH-Px, which are scavengers of ROS and therefore prevent gastric injury induced by them.

  5. Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine.

    Science.gov (United States)

    Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Silberring, Jerzy; Kotlinska, Jolanta H

    2016-07-01

    The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour. © The Author(s) 2016.

  6. Brain catalase activity inhibition as well as opioid receptor antagonism increases ethanol-induced HPA axis activation.

    Science.gov (United States)

    Pastor, Raúl; Sanchis-Segura, Carles; Aragon, Carlos M G

    2004-12-01

    Growing evidence indicates that brain catalase activity is involved in the psychopharmacological actions of ethanol. Recent data suggest that participation of this enzymatic system in some ethanol effects could be mediated by the endogenous opioid system. The present study assessed whether brain catalase has a role in ethanol-induced activation of the HPA axis, a neuroendocrine system modulated by the endogenous opioid neurotransmission. Swiss male mice received an intraperitoneal injection of the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg), and 0 to 20 hr after this administration, animals received an ethanol (0-4 g/kg; intraperitoneally) challenge. Thirty, 60, or 120 min after ethanol administration, plasma corticosterone levels were determined immunoenzymatically. In addition, we tested the effects of 45 mg/kg of cyanamide (another catalase inhibitor) and 0 to 2 mg/kg of naltrexone (nonselective opioid receptor antagonist) on ethanol-induced enhancement in plasma corticosterone values. The present study revealed that AT boosts ethanol-induced increase in plasma corticosterone levels in a dose- and time-dependent manner. However, it did not affect corticosterone values when measured after administration of saline, cocaine (4 mg/kg, intraperitoneally), or morphine (30 mg/kg, intraperitoneally). The catalase inhibitor cyanamide (45 mg/kg, intraperitoneally) also increased ethanol-related plasma corticosterone levels. These effects of AT and cyanamide on ethanol-induced corticosterone values were observed under treatment conditions that decreased significantly brain catalase activity. Indeed, a significant correlation between effects of catalase manipulations on both variables was found. Finally, we found that the administration of naltrexone enhanced the levels of plasma corticosterone after the administration of saline or ethanol. This study shows that the inhibition of brain catalase increases ethanol-induced plasma corticosterone levels. Results are

  7. Curcumin and autoimmune disease.

    Science.gov (United States)

    Bright, John J

    2007-01-01

    The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

  8. Curcumin is a potent modulator of microglial gene expression and migration

    Directory of Open Access Journals (Sweden)

    Aslanidis Alexander

    2011-09-01

    Full Text Available Abstract Background Microglial cells are important effectors of the neuronal innate immune system with a major role in chronic neurodegenerative diseases. Curcumin, a major component of tumeric, alleviates pro-inflammatory activities of these cells by inhibiting nuclear factor kappa B (NFkB signaling. To study the immuno-modulatory effects of curcumin on a transcriptomic level, DNA-microarray analyses were performed with resting and LPS-challenged microglial cells after short-term treatment with curcumin. Methods Resting and LPS-activated BV-2 cells were stimulated with curcumin and genome-wide mRNA expression patterns were determined using DNA-microarrays. Selected qRT-PCR analyses were performed to confirm newly identified curcumin-regulated genes. The migration potential of microglial cells was determined with wound healing assays and transwell migration assays. Microglial neurotoxicity was estimated by morphological analyses and quantification of caspase 3/7 levels in 661W photoreceptors cultured in the presence of microglia-conditioned medium. Results Curcumin treatment markedly changed the microglial transcriptome with 49 differentially expressed transcripts in a combined analysis of resting and activated microglial cells. Curcumin effectively triggered anti-inflammatory signals as shown by induced expression of Interleukin 4 and Peroxisome proliferator activated receptor α. Several novel curcumin-induced genes including Netrin G1, Delta-like 1, Platelet endothelial cell adhesion molecule 1, and Plasma cell endoplasmic reticulum protein 1, have been previously associated with adhesion and cell migration. Consequently, curcumin treatment significantly inhibited basal and activation-induced migration of BV-2 microglia. Curcumin also potently blocked gene expression related to pro-inflammatory activation of resting cells including Toll-like receptor 2 and Prostaglandin-endoperoxide synthase 2. Moreover, transcription of NO synthase 2 and

  9. Curcumin is a potent modulator of microglial gene expression and migration

    Science.gov (United States)

    2011-01-01

    Background Microglial cells are important effectors of the neuronal innate immune system with a major role in chronic neurodegenerative diseases. Curcumin, a major component of tumeric, alleviates pro-inflammatory activities of these cells by inhibiting nuclear factor kappa B (NFkB) signaling. To study the immuno-modulatory effects of curcumin on a transcriptomic level, DNA-microarray analyses were performed with resting and LPS-challenged microglial cells after short-term treatment with curcumin. Methods Resting and LPS-activated BV-2 cells were stimulated with curcumin and genome-wide mRNA expression patterns were determined using DNA-microarrays. Selected qRT-PCR analyses were performed to confirm newly identified curcumin-regulated genes. The migration potential of microglial cells was determined with wound healing assays and transwell migration assays. Microglial neurotoxicity was estimated by morphological analyses and quantification of caspase 3/7 levels in 661W photoreceptors cultured in the presence of microglia-conditioned medium. Results Curcumin treatment markedly changed the microglial transcriptome with 49 differentially expressed transcripts in a combined analysis of resting and activated microglial cells. Curcumin effectively triggered anti-inflammatory signals as shown by induced expression of Interleukin 4 and Peroxisome proliferator activated receptor α. Several novel curcumin-induced genes including Netrin G1, Delta-like 1, Platelet endothelial cell adhesion molecule 1, and Plasma cell endoplasmic reticulum protein 1, have been previously associated with adhesion and cell migration. Consequently, curcumin treatment significantly inhibited basal and activation-induced migration of BV-2 microglia. Curcumin also potently blocked gene expression related to pro-inflammatory activation of resting cells including Toll-like receptor 2 and Prostaglandin-endoperoxide synthase 2. Moreover, transcription of NO synthase 2 and Signal transducer and activator

  10. Curcumin Promotes A-beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila

    Science.gov (United States)

    Caesar, Ina; Jonson, Maria; Nilsson, K. Peter R.; Thor, Stefan; Hammarström, Per

    2012-01-01

    The pathology of Alzheimer's disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-β (Aβ) peptide and intraneuronal accumulation of tangles comprised of hyperphosphorylated Tau protein. For several years, the natural compound curcumin has been proposed to be a candidate for enhanced clearance of toxic Aβ amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate Aβ toxicity in transgenic Drosophila. The longevity as well as the locomotor activity of five different AD model genotypes, measured relative to a control line, showed up to 75% improved lifespan and activity for curcumin fed flies. In contrast to the majority of studies of curcumin effects on amyloid we did not observe any decrease in the amount of Aβ deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to Aβ deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of Aβ1–42 in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant Aβ1–42. Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of Aβ, resulting in a reduced neurotoxicity in Drosophila. PMID:22348084

  11. Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice.

    Science.gov (United States)

    Yuan, Jichao; Liu, Wei; Zhu, Haitao; Zhang, Xuan; Feng, Yang; Chen, Yaxing; Feng, Hua; Lin, Jiangkai

    2017-01-01

    Early brain injury, one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. We induced SAH in mice via endovascular perforation, administered curcumin 15 min after surgery and evaluated neurologic scores, brain water content, Evans blue extravasation, Western blot assay results, and immunohistochemical analysis results 24 h after surgery. Curcumin significantly improved neurologic scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. At last, curcumin treatment increased the expression of the tight junction proteins zonula occludens-1 and occludin in treated mice compared with vehicle-treated and sample SAH mice. We demonstrated that curcumin inhibits microglial activation and matrix metallopeptidase-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Curcumin Protects against Cadmium-Induced Vascular Dysfunction, Hypertension and Tissue Cadmium Accumulation in Mice

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    Upa Kukongviriyapan

    2014-03-01

    Full Text Available Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L in drinking water for eight weeks. Curcumin (50 or 100 mg/kg was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd.

  13. Dissolution enhancement of curcumin via curcumin-prebiotic inulin nanoparticles.

    Science.gov (United States)

    Fares, Mohammad M; Salem, Mu'taz Sheikh

    2015-01-01

    Dissolution enhancement of curcumin via prebiotic inulin designed to orally deliver poorly water-soluble curcumin at duodenum low acidity (pH 5.5) was investigated. Different prebiotic inulin-curcumin nanoparticles were synthesized in ethanol-water binary system at different pre-adjusted pH values. Characterization via FTIR, XRD and TGA revealed the formation of curcumin-inulin conjugates, whereas surface morphology via SEM and TEM techniques implied the formation of nanoparticle beads and nanoclusters. Prebiotic inulin-curcumin nanoparticles prepared at pH 7.0 demonstrated a maximum curcumin dissolution enhancement of ≈90% with respect to 30% for curcumin alone at pH 5.5. Power law constant values were in accordance with dissolution enhancement investigations. All samples show Fickian diffusion mechanism. XRD investigations confirm that inulin maintain its crystalline structure in curcumin-inulin conjugate structure, which confirms that it can exert successfully its prebiotic role in the gastrointestinal (GI) tract. Therefore, the use of curcumin-inulin nanoparticles can perform dual-mission in the GI tract at the duodenum environment; release of 90% of curcumin followed by prebiotic activity of inulin, which will probably play a significant role in cancer therapeutics for the coming generations.

  14. Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons

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    Ullah Ikram

    2012-01-01

    Full Text Available Abstract Background Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met and thymoquinone (TQ during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD 17.5. Results We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca2+]c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (ΔψM, which is typically lowered by ethanol exposure. Increased cytosolic free [Ca2+]c and lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2, increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death. Conclusion These findings suggested that Met and TQ are strong protective agents against ethanol-induced

  15. Ethanol induced antidepressant-like effect in the mouse forced swimming test: modulation by serotonergic system.

    Science.gov (United States)

    Jain, Nishant S; Kannamwar, Uday; Verma, Lokesh

    2017-02-01

    The present investigation explored the modulatory role of serotonergic transmission in the acute ethanol-induced effects on immobility time in the mouse forced swim test (FST). Acute i.p. administration of ethanol (20% w/v, 2 or 2.5 g/kg, i.p.) decreased the immobility time in FST of mice, indicating its antidepressant-like effect while lower doses of ethanol (1, 1.5 g/kg, i.p.) were devoid of any effect in the FST. The mice pre-treated with a sub-effective dose of 5-HT 2A agonist, DOI (10 μg/mouse, i.c.v.) or 5-HT 1A receptor antagonist, WAY 100635 (0.1 μg/mouse, i.c.v.) but not with the 5-HT 2A/2C antagonist, ketanserin (1.5 μg/mouse, i.c.v.) exhibited a synergistic reduction in the immobility time induced by sub-effective dose of ethanol (1.5 g/kg, i.p.). On the other hand, ethanol (2.5 g/kg, i.p.) failed to decrease the immobility time in mice, pre-treated with 5-HT 1A agonist, 8-OH-DPAT (0.1 μg/mouse, i.c.v.) or ketanserin (1.5 μg/mouse, i.c.v.). In addition, pre-treatment with a 5-HT neuronal synthesis inhibitor, p-CPA (300 mg/kg, i.p. × 3 days) attenuated the anti-immobility effect ethanol (2.5 g/kg, i.p.) in mouse FST. Thus, the results of the present study points towards the essentiality of the central 5-HT transmission at the synapse for the ethanol-induced antidepressant-like effect in the FST wherein the regulatory role of the 5-HT 1A receptor or contributory role of the 5-HT 2A/2C receptor-mediated mechanism is proposed in the anti-immobility effect of acute ethanol in mouse FST.

  16. Synthesis and Evaluation of the Anti-Oxidant Capacity of Curcumin Glucuronides, the Major Curcumin Metabolites

    OpenAIRE

    Choudhury, Ambar K.; Raja, Suganya; Mahapatra, Sanjata; Nagabhushanam, Kalyanam; Majeed, Muhammed

    2015-01-01

    Curcumin metabolites namely curcumin monoglucuronide and curcumin diglucuronide were synthesized using an alternative synthetic approach. The anti-oxidant potential of these curcumin glucuronides was compared with that of curcumin using DPPH scavenging method and Oxygen Radical Absorbance Capacity (ORAC) assay. The results show that curcumin monoglucuronide exhibits 10 fold less anti-oxidant activity (DPPH method) and the anti-oxidant capacity of curcumin diglucuronide is highly attenuated co...

  17. Curcumin attenuates beta-amyloid-induced neuroinflammation via activation of peroxisome proliferator-activated receptor-gamma function in a rat model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Zun-Jing Liu

    2016-08-01

    Full Text Available Neuroinflammation is known to have a pivotal role in the pathogenesis of Alzheimer’s disease (AD, and curcumin has been reported to have therapeutical effects on AD because of its anti-inflammatory effects. Curcumin is not only a potent PPARγ agonist, but also has neuroprotective effects on cerebral ischemic injury. However, whether PPARγ activated by curcumin is responsible for the anti-neuroinflammation and neuroprotection on AD remains unclear, and needs to be further investigated. Here, using both APP/PS1 transgenic mice and beta-amyloid-induced neuroinflammation in mixed neuronal/glial cultures, we showed that curcumin significantly alleviated spatial memory deficits in APP/PS1 mice and promoted cholinergic neuronal function in vivo and in vitro. Curcumin also reduced the activation of microglia and astrocytes, as well as cytokine production and inhibited nuclear factor kappa B (NF-κB signaling pathway, suggesting the beneficial effects of curcumin on AD are attributable to the suppression of neuroinflammation. Attenuation of these beneficial effects occurred when co-administrated with PPARγ antagonist GW9662 or silence of PPARγ gene expression, indicating that PPARγ might be involved in anti-inflammatory effects. Circular dichroism and co-immunoprecipitation analysis showed that curcumin directly bound to PPARγ and increased the transcriptional activity and protein levels of PPARγ. Taking together, these data suggested that PPARγ might be a potential target of curcumin, acting to alleviate neuroinflammation and improve neuronal function in AD.

  18. Mitigation of postnatal ethanol-induced neuroinflammation ameliorates trace fear memory deficits in juvenile rats.

    Science.gov (United States)

    Goodfellow, Molly J; Shin, Youn Ju; Lindquist, Derick H

    2018-02-15

    Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naïve controls (NC) over postnatal days (PD) 4-9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol-induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Red sorrel (Hibiscus Sabdariffa) prevents the ethanol-induced deficits of Purkinje cells in the cerebellum.

    Science.gov (United States)

    Suryanti, S; Partadiredja, G; Atthobari, J

    2015-01-01

    The present study is aimed at investigating the possible protective effects of H. sabdariffa on ethanol-elicited deficits of motor coordination and estimated total number of the Purkinje cells of the cerebellums of adolescent male Wistar rats. Forty male Wistar rats aged 21 days were divided into five groups. Na/wtr group was given water orally and injected with normal saline intra peritoneally (ip). Eth/wtr group was given water orally and ethanol (ip). Another three experimental groups (Eth/Hsab) were given different dosages of H. sabdariffa and ethanol (ip). All groups were treated intermittently for the total period of treatment of two weeks. The motor coordination of rats was tested prior and subsequent to the treatments. The rats were euthanized, and their cerebellums were examined. The total number of Purkinje cells was estimated using physical fractionator method. Upon revolving drum test, the number of falls of rats increased following ethanol treatment. There was no significant difference between the total number of falls prior and subsequent to treatment in all Eth/Hsab groups. The estimated total number of Purkinje cells in Eth/Hsab groups was higher than in Eth/wtr group. H. sabdariffa may prevent the ethanol-induced deficits of motor coordination and estimated total number of Purkinje cells of the cerebellums in adolescent rats (Tab. 3, Fig. 1, Ref. 42).

  20. Ethanol-induced activation of adenine nucleotide turnover. Evidence for a role of acetate

    International Nuclear Information System (INIS)

    Puig, J.G.; Fox, I.H.

    1984-01-01

    Consumption of alcohol causes hyperuricemia by decreasing urate excretion and increasing its production. Our previous studies indicate that ethanol administration increases uric acid production by increasing ATP degradation to uric acid precursors. To test the hypothesis that ethanol-induced increased urate production results from acetate metabolism and enhanced adenosine triphosphate turnover, we gave intravenous sodium acetate, sodium chloride and ethanol (0.1 mmol/kg per min for 1 h) to five normal subjects. Acetate plasma levels increased from 0.04 +/- 0.01 mM (mean +/- SE) to peak values of 0.35 +/- 0.07 mM and to 0.08 +/- 0.01 mM during acetate and ethanol infusions, respectively. Urinary oxypurines increased to 223 +/- 13% and 316 +/- 44% of the base-line values during acetate and ethanol infusions, respectively. Urinary radioactivity from the adenine nucleotide pool labeled with [8-14C] adenine increased to 171 +/- 27% and to 128 +/- 8% of the base-line values after acetate and ethanol infusions. These data indicate that both ethanol and acetate increase purine nucleotide degradation by enhancing the turnover of the adenine nucleotide pool. They support the hypothesis that acetate metabolism contributes to the increased production of urate associated with ethanol intake

  1. The Protective Role of Zinc Sulphate on Ethanol -Induced Liver and Kidney Damages in Rats

    International Nuclear Information System (INIS)

    Al-Damegh, Mona Abdalla

    2007-01-01

    Around the world more and more people suffer from alcoholism. Addiction problems, alcoholism and excessive use of drugs both medical and nonmedical, are major causes of liver and kidney damage in adults. The purpose of this study was to investigate on the protective role of zinc sulphate on liver and kidney in rats with acute alcoholism. Wistar albino rats were divided into four groups. Group I; control group, group 2; given only Zinc Sulphate (100 mg/kg/day for 3days), group 3; rats given absolute ethanol (1 ml of absolute ethanol administrated by gavage technique to each rat), group 4 given Zinc sulphate prior to the administration of absolute ethanol. The results of this study revealed that acute ethanol exposure caused degenerative morphological changes in the liver and kidney. Significant difference were found in the levels of serum, liver, kidney super oxide dismutase(SOD), catalase (CAT), nitric oxide(NO), and malondialdehyde (MDA) in the ethanol group compared to the control group. Moreover ,serum urea, creatnine, uric acid, alkaline phoshpatase and transaminases activities (GOTand GPT) were increased in the ethanol group compared to the control group. On the other hand,administration of zinc sulphate in the ethanol group caused a significant decrease in the degenerative changes, lipid peroxidation, antioxidant enzymes, and nitric oxide in serum, liver, and kidney. It can be concluded that zinc Sulphate has a protective role on the ethanol induced liver and kidney injury. In addition ,nitric oxide is involved in the mechanism of acute alcohol intoxication. (author)

  2. Involvement of brain catalase activity in the acquisition of ethanol-induced conditioned place preference.

    Science.gov (United States)

    Font, Laura; Miquel, Marta; Aragon, Carlos M G

    2008-03-18

    It has been suggested that some of the behavioral effects produced by ethanol are mediated by its first metabolite, acetaldehyde. The present research addressed the hypothesis that catalase-dependent metabolism of ethanol to acetaldehyde in the brain is an important step in the production of ethanol-related affective properties. Firstly, we investigated the contribution of brain catalase in the acquisition of ethanol-induced conditioned place preference (CPP). Secondly, the specificity of the catalase inhibitor 3-amino-1,2,4-triazole (AT) was evaluated with morphine- and cocaine-induced CPP. Finally, to investigate the role of catalase in the process of relapse to ethanol seeking caused by re-exposure to ethanol, after an initial conditioning and extinction, mice were primed with saline and ethanol or AT and ethanol and tested for reinstatement of CPP. Conditioned place preference was blocked in animals treated with AT and ethanol. Morphine and cocaine CPP were unaffected by AT treatment. However, the reinstatement of place preference was not modified by catalase inhibition. Taken together, the results of the present study indicate that the brain catalase-H(2)O(2) system contributes to the acquisition of affective-dependent learning induced by ethanol, and support the involvement of centrally-formed acetaldehyde in the formation of positive affective memories produced by ethanol.

  3. Gastroprotective effect of esculin on ethanol-induced gastric lesion in mice.

    Science.gov (United States)

    Li, Weifeng; Wang, Yu; Wang, Xiumei; Zhang, Hailin; He, Zehong; Zhi, Wenbing; Liu, Fang; Niu, Xiaofeng

    2017-04-01

    The gastroprotective effect of esculin was investigated in a mouse model of ethanol-induced gastric lesion. Administration of esculin at doses of 5, 10, and 20 mg/kg body weight prior to ethanol ingestion led to significant gastroprotection compared with untreated mice. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations, lesion index, and myeloperoxidase (MPO) activity. Pretreatment with esculin significantly reduced macroscopic and histopathological damage, gastric lesion index, and MPO activity in a dose-dependent manner. Moreover, esculin significantly reduced nitric oxide (NO) production, inducible NO synthase (iNOS) levels, and nuclear factor-kappa B (NF-κB) p65 protein expression in gastric tissues after ethanol challenge. Analysis of inflammatory cytokines indicated that esculin pretreatment markedly suppressed the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in ethanol-treated mice. The results demonstrate a protective effect of esculin against gastric injury and suggest that the underlying mechanism might be associated with inhibition of NF-κB activation, which subsequently reduces expression of iNOS, TNF-α, and IL-6. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  4. Curcumin (Turmeric) and cancer.

    Science.gov (United States)

    Unlu, Ahmet; Nayir, Erdinc; Dogukan Kalenderoglu, Muhammed; Kirca, Onder; Ozdogan, Mustafa

    2016-01-01

    Curcumin is a substance obtained from the root of the turmeric plant, which has the feature of being a yellow or orange pigment. It is also the main component of curry powder commonly used in Asian cuisine. Curcumin, a substance that has had an important place in traditional Indian and Chinese medicines for thousands of years, has been the center of interest for scientific studies especially in the field of cancer treatment for several years. Laboratory studies have presented some favorable results in terms of curcumin's antioxidant, antiinflammatory and anticancer properties in particular. However, since such findings have yet to be confirmed in clinical studies, its effect on humans is not clearly known. Therefore, when its advantages in terms of toxicity, cost and availability as well as the favorable results achieved in laboratory studies are considered, it would not be wrong to say that curcumin is a substance worth being studied. However, for now the most correct approach is to abstain from its use for medical purposes due to lack of adequate reliable evidence obtained from clinical studies, and because of its potential to interfere with other drugs.

  5. Silencing of cytosolic NADP+-dependent isocitrate dehydrogenase gene enhances ethanol-induced toxicity in HepG2 cells.

    Science.gov (United States)

    Yang, Eun Sun; Lee, Su-Min; Park, Jeen-Woo

    2010-07-01

    It has been shown that acute and chronic alcohol administrations increase the production of reactive oxygen species, lower cellular antioxidant levels and enhance oxidative stress in many tissues. We recently reported that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) functions as an antioxidant enzyme by supplying NADPH to the cytosol. Upon exposure to ethanol, IDPc was susceptible to the loss of its enzyme activity in HepG2 cells. Transfection of HepG2 cells with an IDPc small interfering RNA noticeably downregulated IDPc and enhanced the cells' vulnerability to ethanol-induced cytotoxicity. Our results suggest that suppressing the expression of IDPc enhances ethanol-induced toxicity in HepG2 cells by further disruption of the cellular redox status.

  6. The ethanol-induced stimulation of rat duodenal mucosal bicarbonate secretion in vivo is critically dependent on luminal Cl-.

    Directory of Open Access Journals (Sweden)

    Anna Sommansson

    Full Text Available Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v. did not change the secretory response to ethanol, while removing Cl- from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v. but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl- and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.

  7. Multifunctional Curcumin Mediate Multitherapeutic Effects.

    Science.gov (United States)

    Shehzad, Adeeb; Qureshi, Munibah; Anwar, Muhammad Nabeel; Lee, Young Sup

    2017-09-01

    Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases. Numerous studies have shown that curcumin modulate multiple molecular targets and can be translated to the clinics for multiple therapeutic processes. There is compelling evidence that curcumin can block cell proliferation, invasion, and angiogenesis as well as reduced the prolonged survival of cancer cells. Curcumin mediates anti-inflammatory effect through downregulation of inflammatory cytokines, transcription factors, protein kinases, and enzymes that promote inflammation and development of chronic diseases. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways by activating caspase cascades. Curcumin is a safe and nontoxic drug that has been reported to be well tolerated. Available clinical trials support the potential role of curcumin for treatment of various inflammatory disorders. However, curcumin's efficacy is hindered by poor absorption and low bioavailability, which limit its translation into clinics. This review outlines the potential pharmacological and clinical role of curcumin, which provide a gateway for the beneficial role of plant isolated compounds in treatment of various inflammatory diseases and cancer. © 2017 Institute of Food Technologists®.

  8. Comparison between the efficacies of curcumin and puerarin in C57BL/6 mice with steatohepatitis induced by a methionine- and choline-deficient diet.

    Science.gov (United States)

    Wang, Yunliang; Li, Jian; Zhuge, Li; Su, Dongmei; Yang, Meijuan; Tao, Shiying; Li, Junxiang

    2014-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease, which features an abnormal accumulation of lipids inside hepatocytes. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Curcumin and puerarin are herbal products widely used in Asia, which are believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. In this study, mice models of steatohepatitis induced by a methionine- and choline-deficient diet (MCD) were established to compare the pharmacological actions of curcumin and puerarin. The results showed that curcumin and puerarin exerted inhibitory effects against MCD-induced steatohepatitis in mice. Briefly, curcumin and puerarin significantly downregulated the levels of tumor necrosis factor-α in the blood serum of mice (PMCD group). In addition, the levels of triglycerides, total cholesterol and low density lipoproteins in the serum were significantly reduced by puerarin treatment (PMCD group). The concentration of interleukin-6 was downregulated by curcumin only (PMCD group). Curcumin and puerarin significantly increased the levels of peroxisome proliferator-activated receptor-γ (PPARγ; PMCD group). Moreover, increased nuclear factor-κB (NF-κB) was markedly attenuated by curcumin (PMCD group). In conclusion, curcumin and puerarin appear to exert different actions against steatohepatitis. It is possible that puerarin regulated lipid metabolism in the 'first hit' stage through the PPARγ pathway, while curcumin inhibited the inflammatory response in the 'second hit' stage through the NF-κB pathway.

  9. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.

    Directory of Open Access Journals (Sweden)

    Hany H Arab

    Full Text Available Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o. attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO and tumor necrosis factor-α (TNF-α levels along with nuclear factor kappa B (NF-κB p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10 levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH, glutathione peroxidase (GPx and the total antioxidant capacity (TAC. With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2 in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2 and nitric oxide (NO. Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.

  10. Methyl and isopropyl N-methylanthranilates attenuate diclofenac- and ethanol-induced gastric lesions in rats.

    Science.gov (United States)

    Radulović, Niko S; Jovanović, Ivan; Ilić, Ivan R; Randjelović, Pavle J; Stojanović, Nikola M; Miltojević, Ana B

    2013-11-19

    Two natural alkaloids, methyl (M) and isopropyl (I) N-methylanthranilates, with recently demonstrated significant pharmacological activities, were assayed for their possible overall effect on intact gastric mucosa and their protective properties towards the onset of gastric lesions induced by diclofenac (a non-steroidal anti-inflammatory drug, NSAID) or ethanol. The influence of I and M on gastric mucosa integrity was assessed by oral administration in doses of 200mg/kg. The gastroprotective action of I and M in doses of 50, 100 and 200mg/kg was analyzed in the diclofenac and ethanol-induced gastric lesion models in rats. After the treatment, the stomachs of the animals were analyzed (captured by a digital camera). Ulcer scoring, morphometric and histopathological analyses of the stomachs were done. The oral application of these compounds on their own, even in quite high doses (200mg/kg) did not induce gastric lesions. Both alkaloids exerted a very strong antiulcer activity, even in low doses (50mg/kg), by decreasing the number of lesions caused by the application of either diclofenac or ethanol, eliminating them completely or reducing them to a form of mucosal hyperemia. Their possible mechanism of action was discussed and due to their many positive properties including anxiolytic, antidepressant, antinociceptive, anti-inflammatory and gastroprotective activities, as well as a cheap and simple synthetic route for their preparation, methyl and isopropyl N-methylanthranilates, both alike, might represent a cost effective alternative sought for in the treatment of peptic ulcers and/or new safer NSAIDs for pain management. © 2013.

  11. Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress.

    Science.gov (United States)

    Ozel Turkcu, Ummuhani; Bilgihan, Ayşe; Biberoglu, Gursel; Mertoglu Caglar, Oznur

    2010-06-01

    Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.

  12. Ganoderma Lucidum Pharmacopuncture for Teating Ethanol-induced Chronic Gastric Ulcers in Rats

    Directory of Open Access Journals (Sweden)

    Jae-Heung Park

    2015-03-01

    Full Text Available Objectives: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP on chronic gastric ulcers in rats. Methods: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 (中脘 and ST36 (足三里 were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. Results: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX, B-cell lymphoma 2 (Bcl-2 and Transforming growth factor-beta 1 (TGF-β1. Conclusion: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer.

  13. PPARβ/δ modulates ethanol-induced hepatic effects by decreasing pyridoxal kinase activity

    International Nuclear Information System (INIS)

    Goudarzi, Maryam; Koga, Takayuki; Khozoie, Combiz; Mak, Tytus D.; Kang, Boo-Hyon; Jr, Albert J. Fornace; Peters, Jeffrey M.

    2013-01-01

    Because of the significant morbidity and lethality caused by alcoholic liver disease (ALD), there remains a need to elucidate the regulatory mechanisms that can be targeted to prevent and treat ALD. Toward this goal, minimally invasive biomarker discovery represents an outstanding approach for these purposes. The mechanisms underlying ALD include hepatic lipid accumulation. As the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) has been shown to inhibit steatosis, the present study examined the role of PPARβ/δ in ALD coupling metabolomic, biochemical and molecular biological analyses. Wild-type and Pparβ/δ-null mice were fed either a control or 4% ethanol diet and examined after 4–7 months of treatment. Ethanol fed Pparβ/δ-null mice exhibited steatosis after short-term treatment compared to controls, the latter effect appeared to be due to increased activity of sterol regulatory element binding protein 1c (SREBP1c). The wild-type and Pparβ/δ-null mice fed the control diet showed clear differences in their urinary metabolomic profiles. In particular, metabolites associated with arginine and proline metabolism, and glycerolipid metabolism, were markedly different between genotypes suggesting a constitutive role for PPARβ/δ in the metabolism of these amino acids. Interestingly, urinary excretion of taurine was present in ethanol-fed wild-type mice but markedly lower in similarly treated Pparβ/δ-null mice. Evidence suggests that PPARβ/δ modulates pyridoxal kinase activity by altering K m , consistent with the observed decreased in urinary taurine excretion. These data collectively suggest that PPARβ/δ prevents ethanol-induced hepatic effects by inhibiting hepatic lipogenesis, modulation of amino acid metabolism, and altering pyridoxal kinase activity

  14. The effects of nicotine on ethanol-induced conditioned taste aversions in Long-Evans rats.

    Science.gov (United States)

    Rinker, Jennifer A; Busse, Gregory D; Roma, Peter G; Chen, Scott A; Barr, Christina S; Riley, Anthony L

    2008-04-01

    Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter of which is reportedly affected by polydrug use. Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine's impact on ethanol's aversive effects within a conditioned taste aversion design. Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment 2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment 3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally, nicotine's effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined. Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination. These data demonstrate that nicotine may interact with ethanol, increasing ethanol's aversive effects. Although the rewarding effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered nicotine. It is more likely attributable to nicotine-related changes in ethanol's rewarding effects.

  15. Shuidouchi (Fermented Soybean Fermented in Different Vessels Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury

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    Huayi Suo

    2015-11-01

    Full Text Available Shuidouchi (Natto is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein, and GVFS (glass vessel fermented Shuidouchi had the highest isoflavone levels among Shuidouchi samples fermented in different vessels. After treatment with GVFS, the gastric mucosal injury was reduced as compared to the control mice. The gastric secretion volume (0.47 mL and pH of gastric juice (3.1 of GVFS treated gastric mucosal injury mice were close to those of ranitidine-treated mice and normal mice. Shuidouchi could decrease serum motilin (MTL, gastrin (Gas level and increase somatostatin (SS, vasoactive intestinal peptide (VIP level, and GVFS showed the strongest effects. GVFS showed lower IL-6, IL-12, TNF-α and IFN-γ cytokine levels than other vessel fermented Shuidouchi samples, and these levels were higher than those of ranitidine-treated mice and normal mice. GVFS also had higher superoxide dismutase (SOD, nitric oxide (NO and malonaldehyde (MDA contents in gastric tissues than other Shuidouchi samples. Shuidouchi could raise IκB-α, EGF, EGFR, nNOS, eNOS, Mn-SOD, Gu/Zn-SOD, CAT mRNA expressions and reduce NF-κB, COX-2, iNOS expressions as compared to the control mice. GVFS showed the best treatment effects for gastric mucosal injuries, suggesting that glass vessels could be used for Shuidouchi fermentation in functional food manufacturing.

  16. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis

    OpenAIRE

    Jain, S. K.; Gill, M. S.; Pawar, H. S.; Suresh, Sarasija

    2014-01-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; st...

  17. Encapsulated Curcumin for Transdermal Administration

    African Journals Online (AJOL)

    Purpose: To develop a proniosomal carrier system of curcumin for transdermal delivery. Methods: Proniosomes of curcumin were prepared by encapsulation of the drug in a mixture of Span 80, cholesterol and diethyl ether by ether injection method, and then investigated as a transdermal drug delivery system (TDDS).

  18. Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway.

    Science.gov (United States)

    Cui, Qunli; Li, Xin; Zhu, Hongcan

    2016-02-01

    Parkinson's disease (PD) is an age-related complex neurodegenerative disease that affects ≤ 80% of dopaminergic neurons in the substantia nigra pars compacta (SNpc). It has previously been suggested that mitochondrial dysfunction, oxidative stress and oxidative damage underlie the pathogenesis of PD. Curcumin, which is a major active polyphenol component extracted from the rhizomes of Curcuma longa (Zingiberaceae), has been reported to exert neuroprotective effects on an experimental model of PD. The present study conducted a series of in vivo experiments, in order to investigate the effects of curcumin on behavioral deficits, oxidative damage and related mechanisms. The results demonstrated that curcumin was able to significantly alleviate motor dysfunction and increase suppressed tyrosine hydroxylase (TH) activity in the SNpc of rotenone (ROT)-injured rats. Biochemical measurements indicated that rats pretreated with curcumin exhibited increased glutathione (GSH) levels, and reduced reactive oxygen species activity and malondialdehyde content. Mechanistic studies demonstrated that curcumin significantly restored the expression levels of heme oxygenase-1 and quinone oxidoreductase 1, thus ameliorating ROT-induced damage in vivo, via the phosphorylation of Akt and nuclear factor erythroid 2-related factor 2 (Nrf2). Further studies indicated that the Akt/Nrf2 signaling pathway was associated with the protective role of curcumin in ROT-treated rats. Inhibiting the Akt/Nrf2 pathway using a lentiviral vector containing Nrf2-specific short hairpin RNA, or the phosphoinositide 3-kinase inhibitor LY294002, markedly reduced the expression levels of TH and GSH, ultimately attenuating the neuroprotective effects of curcumin against oxidative damage. These results indicated that curcumin was able to significantly ameliorate ROT-induced dopaminergic neuronal oxidative damage in the SNpc of rats via activation of the Akt/Nrf2 signaling pathway.

  19. Curcumin attenuates sepsis-induced acute organ dysfunction by preventing inflammation and enhancing the suppressive function of Tregs.

    Science.gov (United States)

    Chen, Longwang; Lu, Yang; Zhao, Linjun; Hu, Lili; Qiu, Qiaomeng; Zhang, Zhuoling; Li, Mengfang; Hong, Guangliang; Wu, Bing; Zhao, Guangju; Lu, Zhongqiu

    2018-05-17

    Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP). Inflammatory tissue injury was evaluated by histological observation. Magnetic microbeads were used to isolate splenic CD4 + CD25 + regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. The levels of Foxp3 were detected by Western blot and real-time PCR and cytokine levels were determined by enzyme-linked immunosorbent assay. We found that the administration of curcumin significantly alleviated inflammatory injury of the lung and kidney in septic mice. The suppressive function of Treg cells was enhanced and the plasma levels of IL-10 increased after treatment with curcumin. Furthermore, the secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with curcumin and administration with curcumin could improve survival after CLP. These data suggest that curcumin could be used as a potential therapeutic agent for sepsis. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Lactobacillus fermentum Suo Attenuates HCl/Ethanol Induced Gastric Injury in Mice through Its Antioxidant Effects

    Directory of Open Access Journals (Sweden)

    Huayi Suo

    2016-03-01

    Full Text Available The purpose of the study was to determine the inhibitory effects of Lactobacillus fermentum Suo (LF-Suo on HCl/ethanol induced gastric injury in ICR (Institute for Cancer Research mice and explain the mechanism of these effects through the molecular biology activities of LF-Suo. The studied mice were divided into four groups: healthy, injured, LF-Suo-L and LF-Suo-H group. After the LF-Suo intragastric administration, the gastric injury area was reduced compared to the injured group. The serum MOT (motilin, SP (substance P, ET (endothelin levels of LF-Suo treated mice were lower, and SS (somatostatin, VIP (vasoactive intestinal peptide levels were higher than the injured group mice. The cytokine IL-6 (interleukin 6, IL-12 (interleukin 12, TNF-α (tumor necrosis factor-α and IFN-γ (interferon-γ serum levels were decreased after the LF-Suo treatment. The gastric tissues SOD (superoxide dismutase, GSH-Px (glutathione peroxidase, NO (nitric oxide and activities of LF-Suo treated mice were increased and MDA (malondialdehyde activity was decreased compared to the injured group mice. By the RT-PCR assay, LF-Suo raised the occludin, EGF (epidermal growth factor, EGFR (epidermal growth factor receptor, VEGF (vascular endothelial growth factor, Fit-1 (fms-like tyrosine kinase-1, IκB-α (inhibitor kappaB-α, nNOS (neuronal nitric oxide synthase, eNOS (endothelial nitric oxide synthase, Mn-SOD, Cu/Zn-SOD, CAT (catalase mRNA or protein expressions and reduced the COX-2, NF-κB (nuclear factor kappaB, and iNOS (inducible nitric oxide synthase expressions in gastric tissues compared to the gastric injured group mice. A high concentration (1.0 × 109 CFU/kg b.w. of LF-Suo treatment showed stronger anti-gastric injury effects compared to a low concentration of (0.5 × 109 CFU/kg b.w. of LF-Suo treatment. LF-Suo also showed strong survival in pH 3.0 man-made gastric juice and hydrophobic properties. These results indicate that LF-Suo has potential use as

  1. Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol-induced gastric ulcers

    Directory of Open Access Journals (Sweden)

    Albaayit SFA

    2016-06-01

    Full Text Available Shaymaa Fadhel Abbas Albaayit,1,2 Yusuf Abba,3 Rasedee Abdullah,4 Noorlidah Abdullah1 1Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq; 3Department of Veterinary Pathology and Microbiology, 4Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Clausena excavata is a natural herb with both antioxidant and anti-inflammatory properties. It has been used for decades in folkloric practice for the amelioration of various ailments. In this study, the gastroprotective activity of methanolic extract of C. excavata leaves (MECE was determined in the Sprague Dawley rat ethanol-induced gastric ulcer model. Rats were pretreated with a single dose of vehicle (5% Tween 20, 20 mg/mL omeprazole, 400 and 200 mg/mL of MECE dissolved in 5% Tween 20. Ulcer was induced with 5 mL/kg of ethanol and stomach tissue was obtained after 1 hour. Histological examination was done on hematoxylin and eosin, periodic acid-Schiff, and immunochemically stained gastric mucosal tissues. Prostaglandin E2, superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation levels of the gastric tissue homogenates were also determined. Significantly (P<0.05 smaller ulcer areas, less intense edema, and fewer leukocytes’ infiltration were observed in MECE- and omeprazole-treated than in untreated gastric mucosa with ulcer. The gastric pH, mucus production, superoxide dismutase, catalase, and glutathione peroxidase contents increased, while the lipid peroxidation content decreased as a result of MECE treatment. Bcl-2-associated X protein was underexpressed, while heat shock protein 70 and transforming growth factor-beta protein were overexpressed in the ulcerated gastric mucosa tissues treated with omeprazole and MECE. Similarly, there was a reduction in

  2. Gastroprotective effect of diligustilide isolated from roots of Ligusticum porteri coulter & rose (Apiaceae) on ethanol-induced lesions in rats.

    Science.gov (United States)

    Velázquez-Moyado, Josué A; Martínez-González, Alejandro; Linares, Edelmira; Bye, Robert; Mata, Rachel; Navarrete, Andrés

    2015-11-04

    The rhizome of Ligusticum porteri Coulter& Rose (LP) has been traditionally used by the ethnic group Raramuri in the North of México for treatment of diabetes, tuberculosis, stomachaches, diarrhea and ritual healing ceremonies. It is use as antiulcer remedy has been extended to all Mexico. To evaluate the gastroprotective activity of LP organic extracts and the major natural product diligustilide (DLG),using as experimental model the inhibition of the ethanol-induced lesions in rats. Gastric ulcers were induced by intragastric instillation of absolute ethanol (1 mL). We tested the gastroprotective activity of the organic extracts of LP and the pure compound DLG. The ulcer index (UI) was determined to measure the activity. In order to elucidate the action mechanism of DLG the animals were treated with L-NAME, N-ethylmalemide, Forskolin, 2',5'-dideoxyadenosine, Indomethacin, Glibenclameide, Diazoxide, NaHS and DL-Propargylglycine. The pylorus-ligated rat model was used to measure gastric secretion. The oral administration of organic extracts of Ligusticum porteri showed gastroprotective effect at 30 mg/Kg on ethanol induced gastric lesions; hexane and dichloromethane extracts were the most active. DLG was the major compound in the hexane extract. This compound at 10 mg/kg prevented significantly the gastric injuries induced by ethanol. The alkylation of endogenous non-protein-SH groups with N-ethylmaleimide abolished the gastroprotective effect of DLG and blocking the formation of endogenous prostaglandins by the pretreatment with indomethacin attenuated the gastroprotective effect of DLG. The gastroprotective activity demonstrated in this study tends to support the ethnomedical use of Ligusticum porteri roots. DLG, isolated as major compound of this medicinal plant has a clear gastroprotective effect on the ethanol-induced gastric lesions. The results suggest that the antiulcer activity of DLG depends on the participation of the endogenous non-protein -SH groups

  3. Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat

    Directory of Open Access Journals (Sweden)

    Han JH

    2015-06-01

    Full Text Available Jin-hong Han,1,2 Hong-zhao Tian,2 Yang-yang Lian,1 Yi Yu,1 Cheng-biao Lu,2 Xin-min Li,3 Rui-ling Zhang,1 Haiyun Xu4 1The Second Affiliated Hospital of Xinxiang Medical University, 2School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 3Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 4The Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Quetiapine, an atypical antipsychotic, has been employed to treat alcoholic patients with comorbid psychopathology. It was shown to scavenge hydroxyl radicals and to protect cultured cells from noxious effects of oxidative stress, a pathophysiological mechanism involved in the toxicity of alcohol. This study compared the redox status of the liver and the brain regions of prefrontal cortex, hippocampus, and cerebellum of rats treated with or without ethanol and quetiapine. Ethanol administration for 1 week induced oxidative stress in the liver and decreased the activity of glutathione peroxidase and total antioxidant capacity (TAC there. Coadministration of quetiapine did not protect glutathione peroxidase and TAC in the liver against the noxious effect of ethanol, thus was unable to mitigate the ethanol-induced oxidative stress there. The ethanol-induced alteration in the redox status in the prefrontal cortex is mild, whereas the hippocampus and cerebellum are more susceptible to ethanol intoxication. For all the examined brain regions, coadministration of quetiapine exerted effective protection on the antioxidants catalase and total superoxide dismutase and on the TAC, thus completely blocking the ethanol-induced oxidative stress in these brain regions. These protective effects may explain the clinical observations that quetiapine reduced psychiatric symptoms intensity and maintained a good level of tolerability in chronic alcoholism with

  4. Microglial-derived miRNA let-7 and HMGB1 contribute to ethanol-induced neurotoxicity via TLR7.

    Science.gov (United States)

    Coleman, Leon G; Zou, Jian; Crews, Fulton T

    2017-01-25

    Toll-like receptor (TLR) signaling is emerging as an important component of neurodegeneration. TLR7 senses viral RNA and certain endogenous miRNAs to initiate innate immune responses leading to neurodegeneration. Alcoholism is associated with hippocampal degeneration, with preclinical studies linking ethanol-induced neurodegeneration with central innate immune induction and TLR activation. The endogenous miRNA let-7b binds TLR7 to cause neurodegeneration. TLR7 and other immune markers were assessed in postmortem human hippocampal tissue that was obtained from the New South Wales Tissue Bank. Rat hippocampal-entorhinal cortex (HEC) slice culture was used to assess specific effects of ethanol on TLR7, let-7b, and microvesicles. We report here that hippocampal tissue from postmortem human alcoholic brains shows increased expression of TLR7 and increased microglial activation. Using HEC slice culture, we found that ethanol induces TLR7 and let-7b expression. Ethanol caused TLR7-associated neuroimmune gene induction and initiated the release let-7b in microvesicles (MVs), enhancing TLR7-mediated neurotoxicity. Further, ethanol increased let-7b binding to the danger signaling molecule high mobility group box-1 (HMGB1) in MVs, while reducing let-7 binding to classical chaperone protein argonaute (Ago2). Flow cytometric analysis of MVs from HEC media and analysis of MVs from brain cell culture lines found that microglia were the primary source of let-7b and HMGB1-containing MVs. Our results identify that ethanol induces neuroimmune pathology involving the release of let-7b/HMGB1 complexes in microglia-derived microvesicles. This contributes to hippocampal neurodegeneration and may play a role in the pathology of alcoholism.

  5. Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

    Directory of Open Access Journals (Sweden)

    Rui Guo

    2010-01-01

    Full Text Available Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH.ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p. for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways were examined.Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2 (*-. Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF.Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

  6. miR-217 regulates ethanol-induced hepatic inflammation by disrupting sirtuin 1-lipin-1 signaling.

    Science.gov (United States)

    Yin, Huquan; Liang, Xiaomei; Jogasuria, Alvin; Davidson, Nicholas O; You, Min

    2015-05-01

    Ethanol-mediated injury, combined with gut-derived lipopolysaccharide (LPS), provokes generation of proinflammatory cytokines in Kupffer cells, causing hepatic inflammation. Among the mediators of these effects, miR-217 aggravates ethanol-induced steatosis in hepatocytes. However, the role of miR-217 in ethanol-induced liver inflammation process is unknown. Here, we examined the role of miR-217 in the responses to ethanol, LPS, or a combination of ethanol and LPS in RAW 264.7 macrophages and in primary Kupffer cells. In macrophages, ethanol substantially exacerbated LPS-mediated induction of miR-217 and production of proinflammatory cytokines compared with LPS or ethanol alone. Consistently, ethanol administration to mice led to increases in miR-217 abundance and increased production of inflammatory cytokines in isolated primary Kupffer cells exposed to the combination of ethanol and LPS. miR-217 promoted combined ethanol and LPS-mediated inhibition of sirtuin 1 expression and activity in macrophages. Moreover, miR-217-mediated sirtuin 1 inhibition was accompanied by increased activities of two vital inflammatory regulators, NF-κB and the nuclear factor of activated T cells c4. Finally, adenovirus-mediated overexpression of miR-217 led to steatosis and inflammation in mice. These findings suggest that miR-217 is a pivotal regulator involved in ethanol-induced hepatic inflammation. Strategies to inhibit hepatic miR-217 could be a viable approach in attenuating alcoholic hepatitis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

    Science.gov (United States)

    Guo, Rui; Ren, Jun

    2010-01-18

    Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH). ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways) were examined. Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2) (*-). Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF. Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

  8. Carbon Monoxide (CO Released from Tricarbonyldichlororuthenium (II Dimer (CORM-2 in Gastroprotection against Experimental Ethanol-Induced Gastric Damage.

    Directory of Open Access Journals (Sweden)

    Katarzyna Magierowska

    Full Text Available The physiological gaseous molecule, carbon monoxide (CO becomes a subject of extensive investigation due to its vasoactive activity throughout the body but its role in gastroprotection has been little investigated. We determined the mechanism of CO released from its donor tricarbonyldichlororuthenium (II dimer (CORM-2 in protection of gastric mucosa against 75% ethanol-induced injury. Rats were pretreated with CORM-2 30 min prior to 75% ethanol with or without 1 non-selective (indomethacin or selective cyclooxygenase (COX-1 (SC-560 and COX-2 (celecoxib inhibitors, 2 nitric oxide (NO synthase inhibitor L-NNA, 3 ODQ, a soluble guanylyl cyclase (sGC inhibitor, hemin, a heme oxygenase (HO-1 inductor or zinc protoporphyrin IX (ZnPPIX, an inhibitor of HO-1 activity. The CO content in gastric mucosa and carboxyhemoglobin (COHb level in blood was analyzed by gas chromatography. The gastric mucosal mRNA expression for HO-1, COX-1, COX-2, iNOS, IL-4, IL-1β was analyzed by real-time PCR while HO-1, HO-2 and Nrf2 protein expression was determined by Western Blot. Pretreatment with CORM-2 (0.5-10 mg/kg dose-dependently attenuated ethanol-induced lesions and raised gastric blood flow (GBF but large dose of 100 mg/kg was ineffective. CORM-2 (5 mg/kg and 50 mg/kg i.g. significantly increased gastric mucosal CO content and whole blood COHb level. CORM-2-induced protection was reversed by indomethacin, SC-560 and significantly attenuated by celecoxib, ODQ and L-NNA. Hemin significantly reduced ethanol damage and raised GBF while ZnPPIX which exacerbated ethanol-induced injury inhibited CORM-2- and hemin-induced gastroprotection and the accompanying rise in GBF. CORM-2 significantly increased gastric mucosal HO-1 mRNA expression and decreased mRNA expression for iNOS, IL-1β, COX-1 and COX-2 but failed to affect HO-1 and Nrf2 protein expression decreased by ethanol. We conclude that CORM-2 released CO exerts gastroprotection against ethanol-induced gastric

  9. Anti-oxidant and anti-inflammatory effects of hydrogen-rich water alleviate ethanol-induced fatty liver in mice.

    Science.gov (United States)

    Lin, Ching-Pin; Chuang, Wen-Chen; Lu, Fung-Jou; Chen, Chih-Yen

    2017-07-21

    To investigate the effects of hydrogen-rich water (HRW) treatment on prevention of ethanol (EtOH)-induced early fatty liver in mice. In vitro reduction of hydrogen peroxide by HRW was determined with a chemiluminescence system. Female mice were randomly divided into five groups: control, EtOH, EtOH + silymarin, EtOH + HRW and EtOH + silymarin + HRW. Each group was fed a Lieber-DeCarli liquid diet containing EtOH or isocaloric maltose dextrin (control diet). Silymarin was used as a positive control to compare HRW efficacy against chronic EtOH-induced hepatotoxicity. HRW was freshly prepared and given at a dosage of 1.2 mL/mouse trice daily. Blood and liver tissue were collected after chronic-binge liquid-diet feeding for 12 wk. The in vitro study showed that HRW directly scavenged hydrogen peroxide. The in vivo study showed that HRW increased expression of acyl ghrelin, which was correlated with food intake. HRW treatment significantly reduced EtOH-induced increases in serum alanine aminotransferase, aspartate aminotransferase, triglycerol and total cholesterol levels, hepatic lipid accumulation and inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. HRW attenuated malondialdehyde level, restored glutathione depletion and increased superoxide dismutase, glutathione peroxidase and catalase activities in the liver. Moreover, HRW reduced TNF-α and IL-6 levels but increased IL-10 and IL-22 levels. HRW protects against chronic EtOH-induced liver injury, possibly by inducing acyl ghrelin to suppress the pro-inflammatory cytokines TNF-α and IL-6 and induce IL-10 and IL-22, thus activating antioxidant enzymes against oxidative stress.

  10. Prospective of curcumin, a pleiotropic signalling molecule from Curcuma longa in the treatment of Glioblastoma.

    Science.gov (United States)

    Luthra, Pratibha Mehta; Lal, Neetika

    2016-02-15

    GBM (Glioblastoma) is the most malignant human brain tumor with median survival of one year. The treatment involves surgery, radiotherapy and adjuvant chemotherapy mostly with the alkylation agents such as temozolomide (TMZ). Dietary polyphenol curcumin, isolated from the rhizome of the Curcuma longa (turmeric), has emerged as remarkable anti-cancer agent in the treatment of various peripheral cancers such as blood, lymphomas, multiple myeloma, melanoma as well as skin, lung, prostate, breast, ovarian, bladder, liver, gastrointestinal tract, pancreatic and colorectal epithelial cancers with a pleiotropic mode of action and also showed promise in alleviation of GBM. In this review, the mechanism of anticancer effect of curcumin in GBM has been discussed extensively. The clinical safety and pharmacokinetics of curcumin has been scrutinized to combat the challenges for the treatment of GBM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Protective effects of resveratrol on ethanol-induced apoptosis in embryonic stem cells and disruption of embryonic development in mouse blastocysts

    International Nuclear Information System (INIS)

    Huang, L.-H.; Shiao, N.-H.; Hsuuw, Y.-D.; Chan, W.-H.

    2007-01-01

    Previous studies have established that ethanol induces apoptosis, but the precise molecular mechanisms are currently unclear. Here, we show that 0.3-1.0% (w/v) ethanol induces apoptosis in mouse blastocysts and that resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties, prevents ethanol-induced apoptosis and inhibition of cell proliferation. Moreover, ethanol-treated blastocysts show normal levels of implantation on culture dishes in vitro but a reduced ability to reach the later stages of embryonic development. Pretreatment with resveratrol prevented ethanol-induced disruption of embryonic development in vitro and in vivo. In an in vitro cell-based assay, we further found that ethanol increases the production of reactive oxygen species in ESC-B5 embryonic stem cells, leading to an increase in the intracellular concentrations of cytoplasmic free Ca 2+ and NO, loss of mitochondrial membrane potential, mitochondrial release of cytochrome c, activation of caspase-9 and -3, and apoptosis. These changes were blocked by pretreatment with resveratrol. Based on these results, we propose a model for the protective effect of resveratrol on ethanol-induced cell injury in blastocysts and ESC-B5 cells

  12. Nicotinamide Inhibits Ethanol-Induced Caspase-3 and PARP-1 Over-activation and Subsequent Neurodegeneration in the Developing Mouse Cerebellum.

    Science.gov (United States)

    Ieraci, Alessandro; Herrera, Daniel G

    2018-06-01

    Fetal alcohol spectrum disorder (FASD) is the principal preventable cause of mental retardation in the western countries resulting from alcohol exposure during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in immature neurons during the brain growth spurt period. The cerebellum is one of the brain areas that are most sensitive to ethanol neurotoxicity. Currently, there is no effective treatment that targets the causes of these disorders and efficient treatments to counteract or reverse FASD are desirable. In this study, we investigated the effects of nicotinamide on ethanol-induced neuronal cell death in the developing cerebellum. Subcutaneous administration of ethanol in postnatal 4-day-old mice induced an over-activation of caspase-3 and PARP-1 followed by a massive neurodegeneration in the developing cerebellum. Interestingly, treatment with nicotinamide, immediately or 2 h after ethanol exposure, diminished caspase-3 and PARP-1 over-activation and reduced ethanol-induced neurodegeneration. Conversely, treatment with 3-aminobenzadine, a specific PARP-1 inhibitor, was able to completely block PARP-1 activation, but not caspase-3 activation or ethanol-induced neurodegeneration in the developing cerebellum. Our results showed that nicotinamide reduces ethanol-induced neuronal cell death and inhibits both caspase-3 and PARP-1 alcohol-induced activation in the developing cerebellum, suggesting that nicotinamide might be a promising and safe neuroprotective agent for treating FASD and other neurodegenerative disorders in the developing brain that shares similar cell death pathways.

  13. The Protective Effect of Hydroalcoholic Extract of Zingiber officinale Roscoe (Ginger) on Ethanol-Induced Reproductive Toxicity in Male Rats.

    Science.gov (United States)

    Akbari, Abolfazl; Nasiri, Khadijeh; Heydari, Mojtaba; Mosavat, Seyed Hamdollah; Iraji, Aida

    2017-10-01

    This study was conducted to evaluate the prophylactic effect of ginger extract on ethanol-induced reproductive toxicity in male rats. Twenty-eight adult male Sprague-Dawley rats were randomly divided into 4 groups and treated daily for 28 days as follows: control, control-ginger (1 g/kg of body weight [BW]/day by gavage), ethanol group (ethanol 4 g/kg of BW/day by gavage), and ginger-ethanol group. At the end of the experiment, all the rats were sacrificed and their testes were removed and used for measurement of the total homocysteine (tHcy), trace elements, antioxidant enzymes activity, and malondialdehyde (MDA). The results in the ethanol group indicate that ethanol decreased antioxidant enzymes activity and increased MDA and tHcy compared with the control groups ( P < .05). In ginger-ethanol group, ginger improved antioxidant enzymes activity and reduced tHcy and MDA compared to ethanol group ( P < .05). It can be concluded that ginger protects the ethanol-induced testicular damage and improves the hormonal levels, trace elements, antioxidant enzymes activity, and decreases tHcy and MDA.

  14. Sodium selenite/selenium nanoparticles (SeNPs) protect cardiomyoblasts and zebrafish embryos against ethanol induced oxidative stress.

    Science.gov (United States)

    Kalishwaralal, Kalimuthu; Jeyabharathi, Subhaschandrabose; Sundar, Krishnan; Muthukumaran, Azhaguchamy

    2015-10-01

    Alcoholic cardiomyopathy is the damage caused to the heart muscles due to high level of alcohol consumption resulting in enlargement and inflammation of the heart. Selenium is an important trace element that is beneficial to human health. Selenium protects the cells by preventing the formation of free radicals in the body. In the present study, protein mediated synthesis of SeNPs was investigated. Two different sizes of SeNPs were synthesized using BSA and keratin. The synthesized SeNPs were characterized by scanning electron microscopy (SEM) with elemental composition analysis Energy Dispersive X-ray spectroscopy(EDX) and X-ray diffraction (XRD). This study demonstrates the in vitro and in vivo antioxidative effects of sodium selenite and SeNPs. Further selenium and SeNPs were evaluated for their ability to protect against 1% ethanol induced oxidative stress in H9C2 cell line. The selenium and SeNPs were found to reduce the 1% ethanol-induced oxidative damage through scavenging intracellular reactive oxygen species. The selenium and SeNPs could also prevent pericardial edema induced ethanol treatment and reduced apoptosis and cell death in zebrafish embryos. The results indicate that selenium and SeNPs could potentially be used as an additive in alcoholic beverage industry to control the cardiomyopathy. Copyright © 2015 Elsevier GmbH. All rights reserved.

  15. Ecklonia cava Polyphenol Has a Protective Effect against Ethanol-Induced Liver Injury in a Cyclic AMP-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Haruka Yamashita

    2015-06-01

    Full Text Available Previously, we showed that Ecklonia cava polyphenol (ECP treatment suppressed ethanol-induced increases in hepatocyte death by scavenging intracellular reactive oxygen species (ROS and maintaining intracellular glutathione levels. Here, we examined the effects of ECP on the activities of alcohol-metabolizing enzymes and their regulating mechanisms in ethanol-treated hepatocytes. Isolated hepatocytes were incubated with or without 100 mM ethanol. ECP was dissolved in dimethylsulfoxide. ECP was added to cultured cells that had been incubated with or without ethanol. The cells were incubated for 0–24 h. In cultured hepatocytes, the ECP treatment with ethanol inhibited cytochrome P450 2E1 (CYP2E1 expression and activity, which is related to the production of ROS when large quantities of ethanol are oxidized. On the other hand, ECP treatment with ethanol increased the activity of alcohol dehydrogenase (ADH and aldehyde dehydrogenase. These changes in activities of CYP2E1 and ADH were suppressed by treatment with H89, an inhibitor of protein kinase A. ECP treatment with ethanol enhanced cyclic AMP concentrations compared with those of control cells. ECP may be a candidate for preventing ethanol-induced liver injury via regulating alcohol metabolic enzymes in a cyclic AMP-dependent manner.

  16. Stabilization of Nrf2 protein by D3T provides protection against ethanol-induced apoptosis in PC12 cells.

    Directory of Open Access Journals (Sweden)

    Jian Dong

    2011-02-01

    Full Text Available Previous studies have demonstrated that maternal ethanol exposure induces a moderate increase in Nrf2 protein expression in mouse embryos. Pretreatment with the Nrf2 inducer, 3H-1, 2-dithiole-3-thione (D3T, significantly increases the Nrf2 protein levels and prevents apoptosis in ethanol-exposed embryos. The present study, using PC12 cells, was designed to determine whether increased Nrf2 stability is a mechanism by which D3T enhances Nrf2 activation and subsequent antioxidant protection. Ethanol and D3T treatment resulted in a significant accumulation of Nrf2 protein in PC 12 cells. CHX chase analysis has shown that ethanol treatment delayed the degradation of Nrf2 protein in PC12 cells. A significantly greater decrease in Nrf2 protein degradation was observed in the cells treated with D3T alone or with both ethanol and D3T. In addition, D3T treatment significantly reduced ethanol-induced apoptosis. These results demonstrate that the stabilization of Nrf2 protein by D3T confers protection against ethanol-induced apoptosis.

  17. Ascorbic acid supplementation enhances recovery from ethanol induced inhibition of Leydig cell steroidogenesis than abstention in male guinea pigs.

    Science.gov (United States)

    Radhakrishnakartha, Harikrishnan; Appu, Abhilash Puthuvelvippel; Indira, Madambath

    2014-01-15

    The impact of ascorbic acid supplementation against ethanol induced Leydig cell toxicity was studied in guinea pigs. Male guinea pigs were exposed to ethanol (4g/kgb.wt.) for 90 days. After 90 days, ethanol administration was completely stopped and animals in the ethanol group were divided into abstention group and ascorbic acid supplemented group (25mg/100gb.wt.) and those in control group were maintained as control and control+ascorbic acid group. Ethanol administration reduced the serum testosterone and LH (luteinising hormone) levels and elevated estradiol levels. Cholesterol levels in Leydig cell were increased whereas the mRNA and protein expressions of StAR (steroidogenic acute regulatory) protein, cytochrome P450scc (cytochrome p450side chain cleavage enzyme), 3β-HSD (3β-hydroxysteroid dehydrogenase), 17β-HSD (17β-hydroxysteroid dehydrogenase) and LH receptor were drastically reduced. Administration of ascorbic acid resulted in alteration of all these parameters indicating enhanced recovery from ethanol induced inhibition of Leydig cell steroidogenesis. Although abstention could also reduce the inhibition of steroidogenesis, this was lesser in comparison with ascorbic acid supplemented group. © 2013 Published by Elsevier B.V.

  18. Curcumin Reverse Methicillin Resistance in Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Su-Hyun Mun

    2014-11-01

    Full Text Available Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., was shown to possess superior potency to resensitize methicillin-resistant Staphylococcus aureus (MRSA to antibiotics. Previous studies have shown the synergistic activity of curcumin with β-lactam and quinolone antibiotics. Further, to understand the anti-MRSA mechanism of curcumin, we investigated the potentiated effect of curcumin by its interaction in diverse conditions. The mechanism of anti-MRSA action of curcumin was analyzed by the viability assay in the presence of detergents, ATPase inhibitors and peptidoglycan (PGN from S. aureus, and the PBP2a protein level was analyzed by western blotting. The morphological changes in the curcumin-treated MRSA strains were investigated by transmission electron microscopy (TEM. We analyzed increased susceptibility to MRSA isolates in the presence of curcumin. The optical densities at 600 nm (OD600 of the suspensions treated with the combinations of curcumin with triton X-100 and Tris were reduced to 63% and 59%, respectively, compared to curcumin without treatment. N,N'-dicyclohexylcarbodiimide (DCCD and sodium azide (NaN3 were reduced to 94% and 55%, respectively. When peptidoglycan (PGN from S. aureus was combined with curcumin, PGN (0–125 μg/mL gradually blocked the antibacterial activity of curcumin (125 μg/mL; however, at a concentration of 125 µg/mL PGN, it did not completely block curcumin. Curcumin has a significant effect on the protein level of PBP2a. The TEM images of MRSA showed damage of the cell wall, disruption of the cytoplasmic contents, broken cell membrane and cell lysis after the treatment of curcumin. These data indicate a remarkable antibacterial effect of curcumin, with membrane permeability enhancers and ATPase inhibitors, and curcumin did not directly bind to PGN on the cell wall. Further, the antimicrobial action of curcumin involved in the PBP2a-mediated resistance mechanism was

  19. Chemopreventive properties of curcumin analogues ...

    African Journals Online (AJOL)

    Chemopreventive properties of curcumin analogues, ... These compounds .... using microscope with 400 × magnification. APC ... Figure 3: Microscopic images of rat colorectal tissue stained with APC rabbit polyclonal antibody with different.

  20. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis.

    Science.gov (United States)

    Jain, S K; Gill, M S; Pawar, H S; Suresh, Sarasija

    2014-09-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (Parthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.

  1. Therapeutic actions of curcumin in bone disorders

    OpenAIRE

    Rohanizadeh, Ramin; Deng, Yi; Verron, Elise

    2016-01-01

    Curcumin is the active component of turmeric extract derived from the Curcuma longa plant. In the last decade, curcumin has raised a considerable interest in medicine owing to its negligible toxicity and multiple therapeutic actions including anti-cancer, anti-inflammatory and anti-microbial activities. Among the various molecular targets of curcumin, some are involved in bone remodeling, which strongly suggests that curcumin can affect the skeletal system. The review sheds light on the curre...

  2. Advances in clinical study of curcumin.

    Science.gov (United States)

    Yang, Chunfen; Su, Xun; Liu, Anchang; Zhang, Lin; Yu, Aihua; Xi, Yanwei; Zhai, Guangxi

    2013-01-01

    Curcumin has been estimated as a potential agent for many diseases and attracted great attention owing to its various pharmacological activities, including anti-cancer, and anti-inflammatory. Now curcumin is being applied to a number of patients with breast cancer, rheumatoid arthritis, Alzheimer's disease, colorectal cancer, psoriatic, etc. Several clinical trials have stated that curcumin is safe enough and effective. The objective of this article was to summarize the clinical studies of curcumin, and give a reference for future studies.

  3. Piperine Augments the Protective Effect of Curcumin Against Lipopolysaccharide-Induced Neurobehavioral and Neurochemical Deficits in Mice.

    Science.gov (United States)

    Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Sharma, Yogita; Saroha, Babita; Datusalia, Ashok Kumar; Bezbaruah, Babul Kumar

    2016-06-01

    The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits.

  4. Pharmacokinetics of Curcumin Diethyl Disuccinate, a Prodrug of Curcumin, in Wistar Rats.

    Science.gov (United States)

    Bangphumi, Kunan; Kittiviriyakul, Chuleeporn; Towiwat, Pasarapa; Rojsitthisak, Pornchai; Khemawoot, Phisit

    2016-12-01

    Curcumin is the major bioactive component of turmeric, but has poor oral bioavailability that limits its clinical applications. To improve the in vitro solubility and alkaline stability, we developed a prodrug of curcumin by succinylation to obtain curcumin diethyl disuccinate, with the goal of improving the oral bioavailability of curcumin. The in vivo pharmacokinetic profile of curcumin diethyl disuccinate was compared with that of curcumin in male Wistar rats. Doses of curcumin 20 mg/kg intravenous or 40 mg/kg oral were used as standard regimens for comparison with the prodrug at equivalent doses in healthy adult rats. Blood, tissues, urine, and faeces were collected from time zero to 48 h after dosing to determine the prodrug level, curcumin level and a major metabolite by liquid chromatography-tandem spectrometry. The absolute oral bioavailability of curcumin diethyl disuccinate was not significantly improved compared with curcumin, with both compounds having oral bioavailability of curcumin less than 1 %. The major metabolic pathway of the prodrug was rapid hydrolysis to obtain curcumin, followed by glucuronidation. Interestingly, curcumin diethyl disuccinate gave superior tissue distribution with higher tissue to plasma ratio of curcumin and curcumin glucuronide in several organs after intravenous dosing at 1 and 4 h. The primary elimination route of curcumin glucuronide occurred via biliary and faecal excretion, with evidence of an entry into the enterohepatic circulation. Curcumin diethyl disuccinate did not significantly improve the oral bioavailability of curcumin due to first pass metabolism in the gastrointestinal tract. Further studies on reduction of first pass metabolism are required to optimise delivery of curcumin using a prodrug approach.

  5. PARP Inhibition Prevents Ethanol-Induced Neuroinflammatory Signaling and Neurodegeneration in Rat Adult-Age Brain Slice Cultures

    Science.gov (United States)

    Tajuddin, Nuzhath; Kim, Hee-Yong

    2018-01-01

    Using rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures, we examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol’s brain inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks, PARP (principally PARP1 in the brain) promotes DNA repair via poly [ADP-ribose] (PAR) products, but PARP overactivation triggers regulated neuronal necrosis (e.g., parthanatos). Previously, we found that brain PARP1 levels were upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP inhibitor PJ34 abrogated slice neurodegeneration. Binged HEC slices also exhibited increased Ca+2-dependent phospholipase A2 (PLA2) isoenzymes (cPLA2 IVA and sPLA2 IIA) that mobilize proinflammatory ω6 arachidonic acid (ARA). We now find in 4-day–binged HEC slice cultures (100 mM ethanol) that PARP1 elevations after two overnight binges precede PAR, cPLA2, and sPLA2 enhancements by 1 day and high-mobility group box-1 (HMGB1), an ethanol-responsive alarmin that augments proinflammatory cytokines via toll-like receptor-4 (TLR4), by 2 days. After verifying that PJ34 effectively blocks PARP activity (↑PAR), we demonstrated that, like PJ34, three other PARP inhibitors—olaparib, veliparib, and 4-aminobenzamide—provided neuroprotection from ethanol. Importantly, PJ34 and olaparib also prevented ethanol’s amplification of the PLA2 isoenzymes, and two PLA2 inhibitors were neuroprotective—thus coupling PARP to PLA2, with PLA2 activity promoting neurodegeneration. Also, PJ34 and olaparib blocked ethanol-induced HMGB1 elevations, linking brain PARP induction to TLR4 activation. The results provide evidence in adult brains that induction of PARP1 may mediate dual neuroinflammatory pathways (PLA2→phospholipid→ARA and HMGB1→TLR4→proinflammatory cytokines) that are complicit in binge ethanol-induced neurodegeneration. PMID:29339456

  6. Hepato- and neuro-protective effects of watermelon juice on acute ethanol-induced oxidative stress in rats

    Directory of Open Access Journals (Sweden)

    Omolola R. Oyenihi

    Full Text Available Chronic and acute alcohol exposure has been extensively reported to cause oxidative stress in hepatic and extra-hepatic tissues. Watermelon (Citrullus lanatus is known to possess various beneficial properties including; antioxidant, anti-inflammatory, analgesic, anti-diabetic, anti-ulcerogenic effects. However, there is a lack of pertinent information on its importance in acute alcohol-induced hepato- and neuro-toxicity. The present study evaluated the potential protective effects of watermelon juice on ethanol-induced oxidative stress in the liver and brain of male Wistar rats. Rats were pre-treated with the watermelon juice at a dose of 4 ml/kg body weight for a period of fifteen days prior to a single dose of ethanol (50%; 12 ml/kg body weight. Ethanol treatment reduced body weight gain and significantly altered antioxidant status in the liver and brain. This is evidenced by the significant elevation of malondialdehyde (MDA concentration; depletion in reduced glutathione (GSH levels and an increased catalase (CAT activity in the brain and liver. There was no significant difference in the activity of glutathione peroxidase (GPX in the liver and brain.Oral administration of watermelon juice for fifteen (15 days prior to ethanol intoxication, significantly reduced the concentration of MDA in the liver and brain of rats. In addition, water melon pre-treatment increased the concentration of GSH and normalized catalase activity in both tissues in comparison to the ethanol control group. Phytochemical analysis revealed the presence of phenol, alkaloids, saponins, tannins and steroids in watermelon juice. Our findings indicate that watermelon juice demonstrate anti-oxidative effects in ethanol-induced oxidation in the liver and brain of rats; which could be associated with the plethora of antioxidant phyto-constituents present there-in. Keywords: Watermelon, Neuro-protective, Hepatoprotective, Ethanol intoxication

  7. Strawberry polyphenols attenuate ethanol-induced gastric lesions in rats by activation of antioxidant enzymes and attenuation of MDA increase.

    Directory of Open Access Journals (Sweden)

    José M Alvarez-Suarez

    Full Text Available BACKGROUND AND AIM: Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. METHODS/PRINCIPAL FINDINGS: Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. CONCLUSIONS: Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in

  8. Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

    Science.gov (United States)

    Alvarez-Suarez, José M.; Dekanski, Dragana; Ristić, Slavica; Radonjić, Nevena V.; Petronijević, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

    2011-01-01

    Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a

  9. Mutation of the inhibitory ethanol site in GABAA ρ1 receptors promotes tolerance to ethanol-induced motor incoordination.

    Science.gov (United States)

    Blednov, Yuri A; Borghese, Cecilia M; Ruiz, Carlos I; Cullins, Madeline A; Da Costa, Adriana; Osterndorff-Kahanek, Elizabeth A; Homanics, Gregg E; Harris, R Adron

    2017-09-01

    Genes encoding the ρ1/2 subunits of GABA A receptors have been associated with alcohol (ethanol) dependence in humans, and ρ1 was also shown to regulate some of the behavioral effects of ethanol in animal models. Ethanol inhibits GABA-mediated responses in wild-type (WT) ρ1, but not ρ1(T6'Y) mutant receptors expressed in Xenopus laevis oocytes, indicating the presence of an inhibitory site for ethanol in the second transmembrane helix. In this study, we found that ρ1(T6'Y) receptors expressed in oocytes display overall normal responses to GABA, the endogenous GABA modulator (zinc), and partial agonists (β-alanine and taurine). We generated ρ1 (T6'Y) knockin (KI) mice using CRISPR/Cas9 to test the behavioral importance of the inhibitory actions of ethanol on this receptor. Both ρ1 KI and knockout (KO) mice showed faster recovery from acute ethanol-induced motor incoordination compared to WT mice. Both KI and KO mutant strains also showed increased tolerance to motor impairment produced by ethanol. The KI mice did not differ from WT mice in other behavioral actions, including ethanol intake and preference, conditioned taste aversion to ethanol, and duration of ethanol-induced loss of righting reflex. WT and KI mice did not differ in levels of ρ1 or ρ2 mRNA in cerebellum or in ethanol clearance. Our findings indicate that the inhibitory site for ethanol in GABA A ρ1 receptors regulates acute functional tolerance to moderate ethanol intoxication. We note that low sensitivity to alcohol intoxication has been linked to risk for development of alcohol dependence in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. A role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of wnt/beta-catenin signaling

    Science.gov (United States)

    The mechanisms by which chronic ethanol intake induces bone loss remain unclear. In females, the skeletal response to ethanol varies depending on physiologic status (viz. cycling, pregnancy, lactation). Ethanol-induced oxidative stress appears to be a key event leading to skeletal toxicity. In the c...

  11. A crucial role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of wnt/beta-catenin signaling

    Science.gov (United States)

    Female skeletal responses to ethanol may vary depending on the physiologic status (viz. cycling, pregnancy, lactation). Nonetheless, ethanol-induced oxidative stress appears to be the key event leading to skeletal toxicity. In the current study, we chronically infused EtOH-containing liquid diets ...

  12. Age-related effects of chronic restraint stress on ethanol drinking, ethanol-induced sedation, and on basal and stress-induced anxiety response.

    Science.gov (United States)

    Fernández, Macarena Soledad; Fabio, María Carolina; Miranda-Morales, Roberto Sebastián; Virgolini, Miriam B; De Giovanni, Laura N; Hansen, Cristian; Wille-Bille, Aranza; Nizhnikov, Michael E; Spear, Linda P; Pautassi, Ricardo Marcos

    2016-03-01

    Adolescents are sensitive to the anxiolytic effect of ethanol, and evidence suggests that they may be more sensitive to stress than adults. Relatively little is known, however, about age-related differences in stress modulation of ethanol drinking or stress modulation of ethanol-induced sedation and hypnosis. We observed that chronic restraint stress transiently exacerbated free-choice ethanol drinking in adolescent, but not in adult, rats. Restraint stress altered exploration patterns of a light-dark box apparatus in adolescents and adults. Stressed animals spent significantly more time in the white area of the maze and made significantly more transfers between compartments than their non-stressed peers. Behavioral response to acute stress, on the other hand, was modulated by prior restraint stress only in adults. Adolescents, unlike adults, exhibited ethanol-induced motor stimulation in an open field. Stress increased the duration of loss of the righting reflex after a high ethanol dose, yet this effect was similar at both ages. Ethanol-induced sleep time was much higher in adult than in adolescent rats, yet stress diminished ethanol-induced sleep time only in adults. The study indicates age-related differences that may increase the risk for initiation and escalation in alcohol drinking. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Modulation of the Proteasome Pathway by Nano-Curcumin and Curcumin in Retinal Pigment Epithelial Cells.

    Science.gov (United States)

    Ramos de Carvalho, J Emanuel; Verwoert, Milan T; Vogels, Ilse M C; Schipper-Krom, Sabine; Van Noorden, Cornelis J F; Reits, Eric A; Klaassen, Ingeborg; Schlingemann, Reinier O

    2018-01-01

    Curcumin has multiple biological effects including the modulation of protein homeostasis by the ubiquitin-proteasome system. The purpose of this study was to assess the in vitro cytotoxic and oxidative effects of nano-curcumin and standard curcumin and characterize their effects on proteasome regulation in retinal pigment epithelial (RPE) cells. Viability, cell cycle progression, and reactive oxygen species (ROS) production were determined after treatment with nano-curcumin or curcumin. Subsequently, the effects of nano-curcumin and curcumin on proteasome activity and the gene and protein expression of proteasome subunits PA28α, α7, β5, and β5i were assessed. Nano-curcumin (5-100 μM) did not show significant cytotoxicity or anti-oxidative effects against H2O2-induced oxidative stress, whereas curcumin (≥10 μM) was cytotoxic and a potent inducer of ROS production. Both nano-curcumin and curcumin induced changes in proteasome-mediated proteolytic activity characterized by increased activity of the proteasome subunits β2 and β5i/β1 and reduced activity of β5/β1i. Likewise, nano-curcumin and curcumin affected mRNA and protein levels of household and immunoproteasome subunits. Nano-curcumin is less toxic to RPE cells and less prone to induce ROS production than curcumin. Both nano-curcumin and curcumin increase proteasome-mediated proteolytic activity. These results suggest that nano-curcumin may be regarded as a proteasome-modulating agent of limited cytotoxicity for RPE cells. The Author(s). Published by S. Karger AG, Basel.

  14. Dendrobium huoshanense polysaccharide prevents ethanol-induced liver injury in mice by metabolomic analysis.

    Science.gov (United States)

    Wang, Xiao-Yu; Luo, Jian-Ping; Chen, Rui; Zha, Xue-Qiang; Pan, Li-Hua

    2015-01-01

    The prevalence of alcohol consumption has increased in modern dietary life and alcoholic liver injury can follow. Dendrobium huoshanense polysaccharide (DHP) is a homogeneous polysaccharide isolated from Dendrobium huoshanense, which possesses hepatoprotection function. In this study, we investigated the metabolic profiles of serum and liver tissues extracts from control, ethanol-treated and DHP\\ethanol-treated mice using a UHPLC/LTQ Orbitrap XL MS-based metabolomics approach. Our results indicated that DHP alleviated early steatosis and inflammation in liver histology and the metabolomic analysis of serum and hepatic tissue revealed that first, ethanol treatment mainly altered phosphatidylcholines (PCs) including PC (13:0) and phosphocholine, arachidonic acid metabolites including 20-ethyl PGF2α and amino acids including L-Proline; Second, DHP supplementation ameliorated the altered metabolic levels particularly involved in phosphocholine and L-Proline. These data suggested that DHP might restore the perturbed metabolism pathways by ethanol exposure to prevent the progression of alcoholic liver injury. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Curcumin: the Indian solid gold.

    Science.gov (United States)

    Aggarwal, Bharat B; Sundaram, Chitra; Malani, Nikita; Ichikawa, Haruyo

    2007-01-01

    Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".

  16. Curcumin Mitigates the Intracellular Lipid Deposit Induced by Antipsychotics In Vitro.

    Directory of Open Access Journals (Sweden)

    Alberto Canfrán-Duque

    Full Text Available First- and second-generation antipsychotics (FGAs and SGAs, respectively, both inhibit cholesterol biosynthesis and impair the intracellular cholesterol trafficking, leading to lipid accumulation in the late endosome/lysosome compartment. In this study we examined if curcumin, a plant polyphenol that stimulates exosome release, can alleviate antipsychotic-induced intracellular lipid accumulation.HepG2 hepatocarcinoma cells were treated with antipsychotics or placebo and DiI-labelled LDL for 18 h and then exposed to curcumin for the last 2 h. Cells and media were collected separately and used for biochemical analyses, electron microscopy and immunocytochemistry. Exosomes were isolated from the incubation medium by ultracentrifugation.Curcumin treatment reduced the number of heterolysosomes and shifted their subcellular localization to the periphery, as revealed by electron microscopy, and stimulated the release of lysosomal β-hexosaminidase and exosome markers flotillin-2 and CD63 into the media. The presence of DiI in exosomes released by cells preloaded with DiI-LDL demonstrated the endolysosomal origin of the microvesicles. Furthermore, curcumin increased the secretion of cholesterol as well as LDL-derived DiI and [3H]-cholesterol, in association with a decrease of intracellular lipids. Thus, the disruption of lipid trafficking induced by FGAs or SGAs can be relieved by curcumin treatment. This polyphenol, however, did not mitigate the reduction of cholesterol esterification induced by antipsychotics.Curcumin stimulates exosome release to remove cholesterol (and presumably other lipids accumulated within the endolysosomal compartment, thereby normalizing intracellular lipid homeostasis. This action may help minimize the adverse metabolic effects of antipsychotic treatment, which should now be evaluated in clinical trials.

  17. Inhibition of enveloped viruses infectivity by curcumin.

    Directory of Open Access Journals (Sweden)

    Tzu-Yen Chen

    Full Text Available Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter than for the pseudorabies virus (approximately 180 nm and the vaccinia virus (roughly 335 × 200 × 200 nm. These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses.

  18. Inhibition of Enveloped Viruses Infectivity by Curcumin

    Science.gov (United States)

    Wen, Hsiao-Wei; Ou, Jun-Lin; Chiou, Shyan-Song; Chen, Jo-Mei; Wong, Min-Liang; Hsu, Wei-Li

    2013-01-01

    Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA) activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB)-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter) than for the pseudorabies virus (approximately 180 nm) and the vaccinia virus (roughly 335 × 200 × 200 nm). These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses. PMID:23658730

  19. Bioavailability of curcumin: problems and promises.

    Science.gov (United States)

    Anand, Preetha; Kunnumakkara, Ajaikumar B; Newman, Robert A; Aggarwal, Bharat B

    2007-01-01

    Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.

  20. Impaired TFEB-mediated Lysosome Biogenesis and Autophagy Promote Chronic Ethanol-induced Liver Injury and Steatosis in Mice.

    Science.gov (United States)

    Chao, Xiaojuan; Wang, Shaogui; Zhao, Katrina; Li, Yuan; Williams, Jessica A; Li, Tiangang; Chavan, Hemantkumar; Krishnamurthy, Partha; He, Xi C; Li, Linheng; Ballabio, Andrea; Ni, Hong-Min; Ding, Wen-Xing

    2018-05-18

    Defects in lysosome function and autophagy contribute to pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes, evaluating the functions transcription factor EB (TFEB), which regulates lysosomal biogenesis. We performed studies with GFP-LC3 mice, mice with liver-specific deletion of transcription factor EB (TFEB), mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB, TFE3 double-knockout mice), and Tfeb flox/flox albumin cre-negative mice (controls). TFEB was overexpressed from adenoviral vectors or knocked down with small interfering RNAs in mouse livers. Mice were placed on diets of chronic ethanol feeding plus an acute binge to induce liver damage (ethanol diet); some mice were also given injections of torin1, an inhibitor of the kinase activity of the mechanistic target of rapamycin (mTOR). Liver tissues were collected and analyzed by immunohistochemistry, immunoblots, and quantitative real-time PCR to monitor lysosome biogenesis. We analyzed levels of TFEB in liver tissues from patients with alcoholic hepatitis and from healthy donors (controls) by immunohistochemistry. Liver tissues from mice on the ethanol diet had lower levels of total and nuclear TFEB, compared with control mice, and hepatocytes had reduced lysosome biogenesis and autophagy. Hepatocytes from mice on the ethanol diet had increased translocation of mTOR into lysosomes, resulting increased mTOR activation. Administration of torin1 increased liver levels of TFEB and reduced steatosis and liver injury induced by ethanol. Mice that overexpressed TFEB in liver developed less-severe ethanol-induced liver injury and had increased lysosomal biogenesis and mitochondrial bioenergetics compared to mice carrying a control vector. Mice with knockdown of TFEB, as well as TFEB, TFE3 double-knockout mice, developed more severe liver injury in response to the

  1. Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors.

    Directory of Open Access Journals (Sweden)

    Carolina R den Hartog

    Full Text Available Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs. In this study, we determined how expression of a mutant GluN1 subunit (F639A that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; i.p. increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg. In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol.

  2. Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors.

    Science.gov (United States)

    den Hartog, Carolina R; Beckley, Jacob T; Smothers, Thetford C; Lench, Daniel H; Holseberg, Zack L; Fedarovich, Hleb; Gilstrap, Meghin J; Homanics, Gregg E; Woodward, John J

    2013-01-01

    Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; i.p.) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol.

  3. Modulation of the Proteasome Pathway by Nano-Curcumin and Curcumin in Retinal Pigment Epithelial Cells

    NARCIS (Netherlands)

    Ramos de Carvalho, J. Emanuel; Verwoert, Milan T.; Vogels, Ilse M. C.; Schipper-Krom, Sabine; van Noorden, Cornelis J. F.; Reits, Eric A.; Klaassen, Ingeborg; Schlingemann, Reinier O.

    2018-01-01

    Curcumin has multiple biological effects including the modulation of protein homeostasis by the ubiquitin-proteasome system. The purpose of this study was to assess the in vitro cytotoxic and oxidative effects of nano-curcumin and standard curcumin and characterize their effects on proteasome

  4. Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson's disease rat.

    Science.gov (United States)

    Yang, Jiaqing; Song, Shilei; Li, Jian; Liang, Tao

    2014-06-01

    Clinically, Parkinson's disease (PD)-related neuronal lesions commonly occur. The purpose of this study is to investigate potential therapeutic effect of curcumin against hippocampal damage of 6-hydroxydopamine (6-OHDA)-PD rat model. These results showed that curcumin significantly increased the body weight of 6-OHDA-impaired rats (Pcurcumin-treated PD rats were effectively ameliorated as shown in open field test (Pcurcumin increased the contents of monoaminergic neurotransmitters (PCurcumin effectively alleviated the 6-OHDA-induced hippocampal damage as observed in hematoxylin-eosin (H&E) staining. Furthermore, curcumin obviously up-regulated hippocampal brain derived neurotrophic factor (BDNF), TrkB, phosphatidylinositide 3-kinases (PI3K) protein expressions, respectively as shown in Western blot analysis. These findings demonstrated that curcumin mediated the neuroprotection against 6-OHDA-induced hippocampus neurons in rats, which the underlying mechanism is involved in activating BDNF/TrkB-dependent pathway for promoting neural regeneration of hippocampal tissue. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. Curcumin-Protected PC12 Cells Against Glutamate-Induced Oxidative Toxicity

    Directory of Open Access Journals (Sweden)

    Chi-Huang Chang

    2014-01-01

    Full Text Available Glutamate is a major excitatory neurotransmitter present in the central nervous system. The glutamate/cystine antiporter system xc– connects the antioxidant defense with neurotransmission and behaviour. Overactivation of ionotropic glutamate receptors induces neuronal death, a pathway called excitotoxicity. Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases including cerebral ischemia, Alzheimer’s and Huntington’s disease. Curcuma has a wide spectrum of biological activities regarding neuroprotection and neurocognition. By reducing the oxidative damage, curcumin attenuates a spinal cord ischemia-reperfusion injury, seizures and hippocampal neuronal loss. The rat pheochromocytoma (PC12 cell line exhibits many characteristics useful for the study of the neuroprotection and neurocognition. This investigation was carried out to determine whether the neuroprotective effects of curcumin can be observed via the glutamate-PC12 cell model. Results indicate that glutamate (20 mM upregulated glutathione peroxidase 1, glutathione disulphide, Ca2+ influx, nitric oxide production, cytochrome c release, Bax/Bcl-2 ratio, caspase-3 activity, lactate dehydrogenase release, reactive oxygen species, H2O2, and malondialdehyde; and downregulated glutathione, glutathione reductase, superoxide dismutase and catalase, resulting in enhanced cell apoptosis. Curcumin alleviates all these adverse effects. Conclusively, curcumin can effectively protect PC12 cells against the glutamate-induced oxidative toxicity. Its mode of action involves two pathways: the glutathione-dependent nitric oxide-reactive oxygen species pathway and the mitochondria-dependent nitric oxide-reactive oxygen species pathway.

  6. Guargum and Eudragit ® coated curcumin liquid solid tablets for colon specific drug delivery.

    Science.gov (United States)

    S Kumar, Vrinda; Rijo, John; M, Sabitha

    2018-04-15

    Colorectal cancer, also known as bowel cancer, is the uncontrolled cell growth in the colon or rectum (parts of the large intestine), or in the appendix. The colon specific drug delivery would alleviate the systemic side effects and would assure the safe therapy for colonic disorders with minimum dose and duration of therapy. The liquisolid technique refers to solubilisation of drug in a non-volatile solvent combined with inclusion of appropriate carrier and coating agent required for tableting. Colon specific degradation of natural polymer, guar gum and pH dependant degradative (pH-7) property of eudragit L100 restricts the delivery of curcumin in gastric and intestinal pH. Formulated curcumin liquisolid powder was evaluated for the micrometric properties, solubility and by differential thermal analysis, X ray powder diffraction and scanning electron microscopy. Curcumin loaded liquisolid tablet showed more anticancer activity against HCT-15 compared with free curcumin. Bioavailability study of the coated and uncoated liquisolid tablets were performed using Newzealand white rabbits. The present study concludes that liquisolid technique is a promising alternative for improving oral bioavailability and dissolution rate of water insoluble drug and coating liquisolid tablet with colon sensitive polymers showed site specific release of drug in the colon. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. The Essential Medicinal Chemistry of Curcumin.

    Science.gov (United States)

    Nelson, Kathryn M; Dahlin, Jayme L; Bisson, Jonathan; Graham, James; Pauli, Guido F; Walters, Michael A

    2017-03-09

    Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

  8. Protective effect of N-Acetylcysteine against ethanol-induced gastric ulcer: a pharmacological assessment in mice

    Directory of Open Access Journals (Sweden)

    Ausama Ayoob Jaccob

    2015-06-01

    Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-Acetylcysteine (NAC against ethanol-induced gastric ulcer models in mice. Materials and Methods: Forty-two mice were allocated into six groups consisting of 7 mice each. Groups 1 (normal control and 2 (ulcer control received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg. All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by antisecretory, cytoprotective, histological and biochemical data but the molecular mechanisms behind such protection are complex. [J Intercult Ethnopharmacol 2015; 4(2.000: 90-95

  9. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

    Science.gov (United States)

    Bahi, Amine

    2013-07-01

    Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

  10. Tetrachloro-p-benzoquinone induces hepatic oxidative damage and inflammatory response, but not apoptosis in mouse: The prevention of curcumin

    International Nuclear Information System (INIS)

    Xu, Demei; Hu, Lihua; Su, Chuanyang; Xia, Xiaomin; Zhang, Pu; Fu, Juanli; Wang, Wenchao; Xu, Duo; Du, Hong; Hu, Qiuling; Song, Erqun; Song, Yang

    2014-01-01

    This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS, COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling. - Highlights: • TCBQ-intoxication significantly increased AST and ALT activities. • TCBQ-intoxication induced oxidative stress in mice liver. • TCBQ-intoxication induced inflammatory response in mice liver. • TCBQ-intoxication induced hepatotoxicity is independent of apoptosis. • Curcumin relieved TCBQ-induced liver damage remarkably

  11. Tetrachloro-p-benzoquinone induces hepatic oxidative damage and inflammatory response, but not apoptosis in mouse: The prevention of curcumin

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Demei; Hu, Lihua; Su, Chuanyang; Xia, Xiaomin; Zhang, Pu; Fu, Juanli; Wang, Wenchao; Xu, Duo; Du, Hong; Hu, Qiuling; Song, Erqun; Song, Yang, E-mail: songyangwenrong@hotmail.com

    2014-10-15

    This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS, COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling. - Highlights: • TCBQ-intoxication significantly increased AST and ALT activities. • TCBQ-intoxication induced oxidative stress in mice liver. • TCBQ-intoxication induced inflammatory response in mice liver. • TCBQ-intoxication induced hepatotoxicity is independent of apoptosis. • Curcumin relieved TCBQ-induced liver damage remarkably.

  12. Prevention of ethanol-induced vascular injury and gastric mucosal lesions by sucralfate and its components: possible role of endogenous sulfhydryls

    Energy Technology Data Exchange (ETDEWEB)

    Szabo, S.; Brown, A.

    1987-09-01

    The authors tested the hypothesis that sucralfate, which contains eight sulfate and aluminum molecules on a sucrose and its other components might decrease ethanol-induced vascular injury and hemorrhagic mucosal lesions through a sulfhydryl (SH)-sensitive process. Experiments performed in rats revealed that the entire sucralfate molecule is not a prerequisite for protection against ethanol-induced mucosal vascular injury and erosions. It appears that sulfate and sucrose octasulfate are potent components of sucralfate, although an equimolar amount of sucralfate is at least twice as effective in gastroprotection than its components. The SH alkylator N-ethylmaleimide abolished the gastroprotection by sucralfate, suggesting SH-sensitive process in the mucosal protection which seems to be associated with the prevention of rapidly developing vascular injury in the stomach of rats given ethanol.

  13. Curcuma Contra Cancer? Curcumin and Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Stefanie Kewitz

    2013-01-01

    Full Text Available Curcumin, a phytochemical isolated from curcuma plants which are used as coloring ingredient for the preparation of curry powder, has several activities which suggest that it might be an interesting drug for the treatment or prevention of cancer. Curcumin targets different pathways which are involved in the malignant phenotype of tumor cells, including the nuclear factor kappa B (NFKB pathway. This pathway is deregulated in multiple tumor entities, including Hodgkin's lymphoma (HL. Indeed, curcumin can inhibit growth of HL cell lines and increases the sensitivity of these cells for cisplatin. In this review we summarize curcumin activities with special focus on possible activities against HL cells.

  14. Molecular understanding of curcumin in diabetic nephropathy.

    Science.gov (United States)

    Soetikno, Vivian; Suzuki, Kenji; Veeraveedu, Punniyakoti T; Arumugam, Somasundaram; Lakshmanan, Arun P; Sone, Hirohito; Watanabe, Kenichi

    2013-08-01

    Diabetic nephropathy is characterized by a plethora of signaling abnormalities. Recent trials have suggested that intensive glucose-lowering treatment leads to hypoglycemic events, which can be dangerous. Curcumin is the active ingredient of turmeric, which has been widely used in many countries for centuries to treat numerous diseases. The preventive and therapeutic properties of curcumin are associated with its antioxidant and anti-inflammatory properties. Here, we highlight the renoprotective role of curcumin in diabetes mellitus (DM) with an emphasis on the molecular basis of this effect. We also briefly discuss the numerous approaches that have been undertaken to improve the pharmacokinetics of curcumin. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Lignans from Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidative stress.

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    Kim, Jung Wha; Yang, Heejung; Kim, Hyeon Woo; Kim, Hong Pyo; Sung, Sang Hyun

    2017-01-01

    Bioactivity-guided isolation of Opuntia ficus-indica (Cactaceae) seeds against ethanol-treated primary rat hepatocytes yielded six lignan compounds. Among the isolates, furofuran lignans 4-6, significantly protected rat hepatocytes against ethanol-induced oxidative stress by reducing intracellular reactive oxygen species levels, preserving antioxidative defense enzyme activities, and maintaining the glutathione content. Moreover, 4 dose-dependently induced the heme oxygenase-1 expression in HepG2 cells.

  16. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle.

    Science.gov (United States)

    Simakova, Maria N; Bisen, Shivantika; Dopico, Alex M; Bukiya, Anna N

    2017-12-01

    Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet+atorvastatin group when compared to high CLR diet+placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin's ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Complement and alcoholic liver disease: role of C1q in the pathogenesis of ethanol-induced liver injury in mice.

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    Cohen, Jessica I; Roychowdhury, Sanjoy; McMullen, Megan R; Stavitsky, Abram B; Nagy, Laura E

    2010-08-01

    Complement is involved in the development of alcoholic liver disease in mice; however, the mechanisms for complement activation during ethanol exposure have not been identified. C1q, the recognition subunit of the first complement component, binds to apoptotic cells, thereby activating the classical complement pathway. Because ethanol exposure increases hepatocellular apoptosis, we hypothesized that ethanol-induced apoptosis would lead to activation of complement via the classical pathway. Wild-type and C1qa-/- mice were allowed free access to ethanol-containing diets or pair-fed control diets for 4 or 25 days. Ethanol feeding for 4 days increased apoptosis of Kupffer cells in both wild-type and C1qa-/- mice. Ethanol-induced deposition of C1q and C3b/iC3b/C3c was colocalized with apoptotic Kupffer cells in wild-type, but not C1qa-/-, mice. Furthermore, ethanol-induced increases in tumor necrosis factor-alpha and interleukin-6 expression at this early time point were suppressed in C1q-deficient mice. Chronic ethanol feeding (25 days) increased steatosis, hepatocyte apoptosis, and activity of serum alanine and aspartate aminotransferases in wild-type mice. These markers of hepatocyte injury were attenuated in C1qa-/- mice. In contrast, chronic ethanol (25 days)-induced increases in cytochrome P450 2E1 expression and oxidative stress did not differ between wild-type and C1qa-/- mice. For the first time, these data indicate that ethanol activates the classical complement pathway via C1q binding to apoptotic cells in the liver and that C1q contributes to the pathogenesis of ethanol-induced liver injury. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Striatal modulation of BDNF expression using microRNA124a-expressing lentiviral vectors impairs ethanol-induced conditioned-place preference and voluntary alcohol consumption.

    Science.gov (United States)

    Bahi, Amine; Dreyer, Jean-Luc

    2013-07-01

    Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol-induced conditioned-place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso-lateral striatum (DLS) following alcohol drinking. Then, we identified brain-derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol-induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV-miR124a in the DLS enhances ethanol-induced CPP as well as voluntary alcohol consumption in a two-bottle choice drinking paradigm. Moreover, miR124a-silencer (LV-siR124a) as well as LV-BDNF infusion in the DLS attenuates ethanol-induced CPP as well as voluntary alcohol consumption. Importantly, LV-miR124a, LV-siR124a and LV-BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. A hot water extract of turmeric (Curcuma longa) suppresses acute ethanol-induced liver injury in mice by inhibiting hepatic oxidative stress and inflammatory cytokine production.

    Science.gov (United States)

    Uchio, Ryusei; Higashi, Yohei; Kohama, Yusuke; Kawasaki, Kengo; Hirao, Takashi; Muroyama, Koutarou; Murosaki, Shinji

    2017-01-01

    Turmeric ( Curcuma longa ) is a widely used spice that has various biological effects, and aqueous extracts of turmeric exhibit potent antioxidant activity and anti-inflammatory activity. Bisacurone, a component of turmeric extract, is known to have similar effects. Oxidative stress and inflammatory cytokines play an important role in ethanol-induced liver injury. This study was performed to evaluate the influence of a hot water extract of C. longa (WEC) or bisacurone on acute ethanol-induced liver injury. C57BL/6 mice were orally administered WEC (20 mg/kg body weight; BW) or bisacurone (60 µg/kg BW) at 30 min before a single dose of ethanol was given by oral administration (3·0 g/kg BW). Plasma levels of aspartate aminotransferase and alanine aminotransferase were markedly increased in ethanol-treated mice, while the increase of these enzymes was significantly suppressed by prior administration of WEC. The increase of alanine aminotransferase was also significantly suppressed by pretreatment with bisacurone. Compared with control mice, animals given WEC had higher hepatic tissue levels of superoxide dismutase and glutathione, as well as lower hepatic tissue levels of thiobarbituric acid-reactive substances, TNF-α protein and IL-6 mRNA. These results suggest that oral administration of WEC may have a protective effect against ethanol-induced liver injury by suppressing hepatic oxidation and inflammation, at least partly through the effects of bisacurone.

  20. Physicochemical properties, antioxidant activities and protective effect against acute ethanol-induced hepatic injury in mice of foxtail millet (Setaria italica) bran oil.

    Science.gov (United States)

    Pang, Min; He, Shujian; Wang, Lu; Cao, Xinmin; Cao, Lili; Jiang, Shaotong

    2014-08-01

    This study was designed to investigate physicochemical characterization of the oil extracted from foxtail millet bran (FMBO), and the antioxidant and hepatoprotective effects against acute ethanol-induced hepatic injury in mice. GC-MS analysis revealed that unsaturated fatty acids (UFAs) account for 83.76% of the total fatty acids; in particular, the linoleic acid (C18:2) is the predominant polyunsaturated fatty acid (PUFA), and the compounds of squalene and six phytosterols (or phytostanols) were identified in unsaponifiable matter of FMBO. The antioxidant activity examination of FMBO in vitro showed highly ferric-reducing antioxidant power and scavenging effects against DPPH· and HO· radicals. Furthermore, the protective effect of FMBO against acute hepatic injuries induced by ethanol was verified in mice. In this, intragastric administration with different dosages of FMBO in mice ahead of acute ethanol administration could observably antagonize the ethanol-induced increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and the hepatic malondialdehyde (MDA) levels, respectively, along with enhanced hepatic superoxide dismutase (SOD) levels relative to the control. Hepatic histological changes were also observed and confirmed that FMBO is capable of attenuating ethanol-induced hepatic injury.

  1. Novel dipeptide nanoparticles for effective curcumin delivery

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    Alam S

    2012-08-01

    Full Text Available Shadab Alam,* Jiban J Panda,* Virander S Chauhan International Centre for Genetic Engineering and Biotechnology, New Delhi, India*Both authors contributed equally to this workBackground: Curcumin, the principal curcuminoid of the popular Indian spice turmeric, has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin is a major challenge in its development as a useful drug. To enhance the aqueous solubility and bioavailability of curcumin, attempts have been made to encapsulate it in liposomes, polymeric nanoparticles (NPs, lipid-based NPs, biodegradable microspheres, cyclodextrin, and hydrogels.Methods: In this work, we attempted to entrap curcumin in novel self-assembled dipeptide NPs containing a nonprotein amino acid, α,β-dehydrophenylalanine, and investigated the biological activity of dipeptide-curcumin NPs in cancer models both in vitro and in vivo.Results: Of the several dehydrodipeptides tested, methionine-dehydrophenylalanine was the most suitable one for loading and release of curcumin. Loading of curcumin in the dipeptide NPs increased its solubility, improved cellular availability, enhanced its toxicity towards different cancerous cell lines, and enhanced curcumin’s efficacy towards inhibiting tumor growth in Balb/c mice bearing a B6F10 melanoma tumor.Conclusion: These novel, highly biocompatible, and easy to construct dipeptide NPs with a capacity to load and release curcumin in a sustained manner significantly improved curcumin’s cellular uptake without altering its anticancer or other therapeutic properties. Curcumin-dipeptide NPs also showed improved in vitro and in vivo chemotherapeutic efficacy compared to curcumin alone. Such dipeptide-NPs may also improve the delivery of other potent hydrophobic drug molecules that show poor cellular uptake, bioavailability, and efficacy

  2. Differential contribution of complement receptor C5aR in myeloid and non-myeloid cells in chronic ethanol-induced liver injury in mice.

    Science.gov (United States)

    McCullough, Rebecca L; McMullen, Megan R; Das, Dola; Roychowdhury, Sanjoy; Strainic, Michael G; Medof, M Edward; Nagy, Laura E

    2016-07-01

    Complement is implicated in the development of alcoholic liver disease. C3 and C5 contribute to ethanol-induced liver injury; however, the role of C5a receptor (C5aR) on myeloid and non-myeloid cells to progression of injury is not known. C57BL/6 (WT), global C5aR-/-, myeloid-specific C5aR-/-, and non-myeloid-specific C5aR-/- mice were fed a Lieber-DeCarli diet (32%kcal EtOH) for 25 days. Cultured hepatocytes were challenged with ethanol, TNFα, and C5a. Chronic ethanol feeding increased expression of pro-inflammatory mediators in livers of WT mice; this response was completely blunted in C5aR-/- mice. However, C5aR-/- mice were not protected from other measures of hepatocellular damage, including ethanol-induced increases in hepatic triglycerides, plasma alanine aminotransferase and hepatocyte apoptosis. CYP2E1 and 4-hydroxynonenal protein adducts were induced in WT and C5aR-/- mice. Myeloid-specific C5aR-/- mice were protected from ethanol-induced increases in hepatic TNFα, whereas non-myeloid-specific C5aR-/- displayed increased hepatocyte apoptosis and inflammation after chronic ethanol feeding. In cultured hepatocytes, cytotoxicity induced by challenge with ethanol and TNFα was completely eliminated by treatment with C5a in cells from WT, but not C5aR-/- mice. Further, treatment with C5a enhanced activation of pro-survival signal AKT in hepatocytes challenged with ethanol and TNFα. Taken together, these data reveal a differential role for C5aR during ethanol-induced liver inflammation and injury, with C5aR on myeloid cells contributing to ethanol-induced inflammatory cytokine expression, while non-myeloid C5aR protects hepatocytes from death after chronic ethanol feeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Cytisine modulates chronic voluntary ethanol consumption and ethanol-induced striatal up-regulation of ΔFosB in mice.

    Science.gov (United States)

    Sajja, Ravi Kiran; Rahman, Shafiqur

    2013-06-01

    Chronic administration of ethanol induces persistent accumulation of ΔFosB, an important transcription factor, in the midbrain dopamine system. This process underlies the progression to addiction. Previously, we have shown that cytisine, a neuronal nicotinic acetylcholine receptor (nAChR) partial agonist, reduces various ethanol-drinking behaviors and ethanol-induced striatal dopamine function. However, the effects of cytisine on chronic ethanol drinking and ethanol-induced up-regulation of striatal ΔFosB are not known. Therefore, we examined the effects of cytisine on chronic voluntary ethanol consumption and associated striatal ΔFosB up-regulation in C57BL/6J mice using behavioral and biochemical methods. Following the chronic voluntary consumption of 15% (v/v) ethanol under a 24-h two-bottle choice intermittent access (IA; 3 sessions/week) or continuous access (CA; 24 h/d and 7 d/week) paradigm, mice received repeated intraperitoneal injections of saline or cytisine (0.5 or 3.0 mg/kg). Ethanol and water intake were monitored for 24 h post-treatment. Pretreatment with cytisine (0.5 or 1.5 mg/kg) significantly reduced ethanol consumption and preference in both paradigms at 2 h and 24 h post-treatment. The ΔFosB levels in the ventral and dorsal striatum were determined by Western blotting 18-24 h after the last point of ethanol access. In addition, cytisine (0.5 mg/kg) significantly attenuated up-regulation of ΔFosB in the ventral and dorsal striatum following chronic ethanol consumption in IA and CA paradigms. The results indicate that cytisine modulates chronic voluntary ethanol consumption and reduces ethanol-induced up-regulation of striatal ΔFosB. Further, the data suggest a critical role of nAChRs in chronic ethanol-induced neurochemical adaptations associated with ethanol addiction. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Ibrahim IAA

    2015-12-01

    Full Text Available Ibrahim Abdel Aziz Ibrahim,1 Mahmood Ameen Abdulla,2 Maryam Hajrezaie,2 Ammar Bader,3 Naiyer Shahzad,1 Saeed S Al-Ghamdi,1 Ahmad S Gushash,4 Mohadeseh Hasanpourghadi5 1Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 4College of Arts and Science in Baljurashi, Albaha University, Baljurashi, Saudi Arabia; 5Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Abstract: Monolluma quadrangula (Forssk. Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid–Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the

  5. Clinical utility of curcumin extract.

    Science.gov (United States)

    Asher, Gary N; Spelman, Kevin

    2013-01-01

    Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.

  6. Curcumin Stimulates the Antioxidant Mechanisms in Mouse Skin Exposed to Fractionated γ-Irradiation

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    Ganesh Chandra Jagetia

    2015-01-01

    Full Text Available Fractionated irradiation is one of the important radiotherapy regimens to treat different types of neoplasia. Despite of the immense therapeutic gains accrued by delivering fractionated irradiation to tumors, the radiation burden on skin increases significantly. Low doses of irradiation to skin adversely affect its molecular and metabolic status. The use of antioxidant/s may help to alleviate the radiation-induced changes in the skin and allow delivering a higher dose of radiation to attain better therapeutic gains. Curcumin is an antioxidant and a free radical scavenging dietary supplement, commonly used as a flavoring agent in curries. Therefore, the effect of 100 mg/kg body weight curcumin was studied on the antioxidant status of mice skin exposed to a total dose of 10, 20 and 40 Gy γ-radiation below the rib cage delivered as a single fraction of 2 Gy per day for 5, 10 or 20 days. Skin biopsies from both the curcumin treated or untreated irradiated groups were collected for the biochemical estimations at various post-irradiation times. The irradiation of animals caused a dose dependent decline in the glutathione concentration, glutathione peroxidase, and superoxide dismutase activities and increased the lipid peroxidation in the irradiated skin. Curcumin treatment before irradiation resulted in a significant rise in the glutathione concentration and activities of both the glutathione peroxidase and superoxide dismutase enzymes in mouse skin, whereas lipid peroxidation declined significantly. The present study indicates that curcumin treatment increased the antioxidant status of mouse exposed to different doses of fractionated γ-radiation.

  7. Methanolic extract of Morinda citrifolia L. (noni unripe fruit attenuates ethanol-induced conditioned place preferences in mice

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    Yasmin Khan

    2016-09-01

    Full Text Available Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC, on compulsive ethanol-seeking behaviour using the mouse conditioned place preference (CPP test. CPP was established by injections of ethanol (2g/kg, i.p. in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM, on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3 and 5g/kg and ACAM (300 mg/kg 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction, during which the treatment groups received MMC (1, 3 and 5g/kg, p.o. or ACAM (300 mg/kg, p.o.. Finally, a priming injection of a low dose of ethanol (0.4g/kg, i.p. in the home cage (Reinstatement was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5g/kg, p.o and ACAM (300 mg/kg, p.o. significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

  8. Protective effect of Allium neapolitanum Cyr. versus Allium sativum L. on acute ethanol-induced oxidative stress in rat liver.

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    Nencini, Cristina; Franchi, Gian Gabriele; Cavallo, Federica; Micheli, Lucia

    2010-04-01

    This study investigated the protective effect of Allium neapolitanum Cyr., a spontaneous species of the Italian flora, compared with garlic (Allium sativum L.) on liver injury induced by ethanol in rats. Male albino Wistar rats were orally treated with fresh Allium homogenates (leaves or bulbs, 250 mg/kg) daily for 5 days, whereas controls received vehicle only. At the end of the experimental 5-day period, the animals received an acute ethanol dose (6 mL/kg, i.p.) 2 hours before the last Allium administration and were sacrificed 6 hours after ethanol administration. The activities of catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GR) and the levels of malondialdehyde (MDA), ascorbic acid (AA), and reduced (GSH) and oxidized glutathione in liver tissue were determined. Administration of both Allium species for 5 days (leaves or bulbs) led to no statistical variation of nonenzymatic parameters versus the control group; otherwise Allium treatment caused an increase of GSH and AA levels compared with the ethanol group and a diminution of MDA levels, showing in addition that A. neapolitanum bulb had the best protective effect. Regarding to enzymatic parameters, GR and CAT activities were enhanced significantly compared with the ethanol group, whereas SOD activity showed a trend different from other parameters estimated. However, the treatment with both Allium species followed by acute ethanol administration reestablished the nonenzymatic parameters similar to control values and enhanced the activities of the enzymes measured. These results suggest that fresh Allium homogenates (leaves or bulbs) possess antioxidant properties and provide protection against ethanol-induced liver injury.

  9. Ethanol induces impulsive-like responding in a delay-of-reward operant choice procedure: impulsivity predicts autoshaping.

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    Tomie, A; Aguado, A S; Pohorecky, L A; Benjamin, D

    1998-10-01

    Autoshaping conditioned responses (CRs) are reflexive and targeted motor responses expressed as a result of experience with reward. To evaluate the hypothesis that autoshaping may be a form of impulsive responding, within-subjects correlations between performance on autoshaping and impulsivity tasks were assessed in 15 Long-Evans hooded rats. Autoshaping procedures [insertion of retractable lever conditioned stimulus (CS) followed by the response-independent delivery of food (US)] were followed by testing for impulsive-like responding in a two-choice lever-press operant delay-of-reward procedure (immediate small food reward versus delayed large food reward). Delay-of-reward functions revealed two distinct subject populations. Subjects in the Sensitive group (n=7) were more impulsive-like, increasing immediate reward choices at longer delays for large reward, while those in the Insensitive group (n=8) responded predominantly on only one lever. During the prior autoshaping phase, the Sensitive group had performed more autoshaping CRs, and correlations revealed that impulsive subjects acquired the autoshaping CR in fewer trials. In the Sensitive group, acute injections of ethanol (0, 0.25, 0.50, 1.00, 1.50 g/kg) given immediately before delay-of-reward sessions yielded an inverted U-shaped dose-response curve with increased impulsivity induced by the 0.25, 0.50, and 1.00 g/kg doses of ethanol, while choice strategy of the Insensitive group was not influenced by ethanol dose. Ethanol induced impulsive-like responding only in rats that were flexible in their response strategy (Sensitive group), and this group also performed more autoshaping CRs. Data support the hypothesis that autoshaping and impulsivity are linked.

  10. Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.

    Science.gov (United States)

    Farshori, Nida Nayyar; Al-Sheddi, Ebtsam S; Al-Oqail, Mai M; Hassan, Wafaa H B; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Siddiqui, Maqsood A

    2015-08-01

    The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 μg/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h. After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied. Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol. Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated. Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol. The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells. However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective. The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia. © The Author(s) 2013.

  11. Antioxidants of Phyllanthus emblica L. Bark Extract Provide Hepatoprotection against Ethanol-Induced Hepatic Damage: A Comparison with Silymarin

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    Renuka Chaphalkar

    2017-01-01

    Full Text Available Phyllanthus emblica L. (amla has been used in Ayurveda as a potent rasayan for treatment of hepatic disorders. Most of the pharmacological studies, however, are largely focused on PE fruit, while the rest of the parts of PE, particularly, bark, remain underinvestigated. Therefore, we aimed to investigate the protective effect of the hydroalcoholic extract of Phyllanthus emblica bark (PEE in ethanol-induced hepatotoxicity model in rats. Total phenolic, flavonoid, and tannin content and in vitro antioxidant activities were determined by using H2O2 scavenging and ABTS decolorization assays. Our results showed that PEE was rich in total phenols (99.523±1.91 mg GAE/g, total flavonoids (389.33±1.25 mg quercetin hydrate/g, and total tannins (310±0.21 mg catechin/g, which clearly support its strong antioxidant potential. HPTLC-based quantitative analysis revealed the presence of the potent antioxidants gallic acid (25.05 mg/g and ellagic acid (13.31 mg/g. Moreover, one-month PEE treatment (500 and 1000 mg/kg, p.o. followed by 30-day 70% ethanol (10 mL/kg administration showed hepatoprotection as evidenced by significant restoration of ALT (p<0.01, AST (p<0.001, ALP (p<0.05, and TP (p<0.001 and further confirmed by liver histopathology. PEE-mediated hepatoprotection could be due to its free radical scavenging and antioxidant activity that may be ascribed to its antioxidant components, namely, ellagic acid and gallic acid. Thus, the results of the present study support the therapeutic claims made in Ayurveda about Phyllanthus emblica.

  12. Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

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    Yoshiki Shionoya

    Full Text Available This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB in a canine model. This study involved two experiments-in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow.

  13. Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

    Science.gov (United States)

    Sunada, Katsuhisa; Shigeno, Keiji; Nakada, Akira; Honda, Michitaka; Nakamura, Tatsuo

    2017-01-01

    This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow. PMID:29220373

  14. Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats

    Science.gov (United States)

    Omar, Hanita; Nordin, Noraziah; Hassandarvish, Pouya; Hajrezaie, Maryam; Azizan, Ainnul Hamidah Syahadah; Fadaeinasab, Mehran; Abdul Majid, Nazia; Abdulla, Mahmood Ameen; Mohd Hashim, Najihah; Mohd Ali, Hapipah

    2017-01-01

    prominent gastroprotective potential in rats’ stomach against ethanol-induced ulcer. PMID:28496305

  15. Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Bahi, Amine; Dreyer, Jean-Luc

    2014-01-01

    We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

  16. Ethanol-induced conditioned taste aversion in male sprague-dawley rats: impact of age and stress.

    Science.gov (United States)

    Anderson, Rachel I; Varlinskaya, Elena I; Spear, Linda P

    2010-12-01

    Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed. Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings. This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment. Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption. Copyright © 2010 by the Research Society on Alcoholism.

  17. Inhibition of vascular endothelial growth factor signaling facilitates liver repair from acute ethanol-induced injury in zebrafish

    Directory of Open Access Journals (Sweden)

    Changwen Zhang

    2016-11-01

    Full Text Available Alcoholic liver disease (ALD results from alcohol overconsumption and is among the leading causes of liver-related morbidity and mortality worldwide. Elevated expression of vascular endothelial growth factor (VEGF and its receptors has been observed in ALD, but how it contributes to ALD pathophysiology is unclear. Here, we investigated the impact of VEGF signaling inhibition on an established zebrafish model of acute alcoholic liver injury. Kdrl activity was blocked by chemical inhibitor treatment or by genetic mutation. Exposing 4-day-old zebrafish larvae to 2% ethanol for 24 h induced hepatic steatosis, angiogenesis and fibrogenesis. The liver started self-repair once ethanol was removed. Although inhibiting Kdrl did not block the initial activation of hepatic stellate cells during ethanol treatment, it suppressed their proliferation, extracellular matrix protein deposition and fibrogenic gene expression after ethanol exposure, thus enhancing the liver repair. It also ameliorated hepatic steatosis and attenuated hepatic angiogenesis that accelerated after the ethanol treatment. qPCR showed that hepatic stellate cells are the first liver cell type to increase the expression of VEGF ligand and receptor genes in response to ethanol exposure. Both hepatic stellate cells and endothelial cells, but not hepatic parenchymal cells, expressed kdrl upon ethanol exposure and were likely the direct targets of Kdrl inhibition. Ethanol-induced steatosis and fibrogenesis still occurred in cloche mutants that have hepatic stellate cells but lack hepatic endothelial cells, and Kdrl inhibition suppressed both phenotypes in the mutants. These results suggest that VEGF signaling mediates interactions between activated hepatic stellate cells and hepatocytes that lead to steatosis. Our study demonstrates the involvement of VEGF signaling in regulating sustained liver injuries after acute alcohol exposure. It also provides a proof of principle of using the

  18. Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats.

    Science.gov (United States)

    Omar, Hanita; Nordin, Noraziah; Hassandarvish, Pouya; Hajrezaie, Maryam; Azizan, Ainnul Hamidah Syahadah; Fadaeinasab, Mehran; Abdul Majid, Nazia; Abdulla, Mahmood Ameen; Mohd Hashim, Najihah; Mohd Ali, Hapipah

    2017-01-01

    gastroprotective potential in rats' stomach against ethanol-induced ulcer.

  19. Curcumin derivatives as HIV-1 protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Z.; Li, J.; Craik, C.S.; Ortiz de Montellano, P.R. [Univ. of California, San Francisco, CA (United States)

    1993-12-31

    Curcumin, a non-toxic natural compound from Curcuma longa, has been found to be an HIV-1 protease inhibitor. Some of its derivatives were synthesized and their inhibitory activity against the HIV-1 protease was tested. Curcumin analogues containing boron enhanced the inhibitory activity. At least of the the synthesized compounds irreversibly inhibits the HIV-1 protease.

  20. Molecular mechanisms of curcumin action: gene expression.

    Science.gov (United States)

    Shishodia, Shishir

    2013-01-01

    Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  1. Curcumin as "Curecumin": from kitchen to clinic.

    Science.gov (United States)

    Goel, Ajay; Kunnumakkara, Ajaikumar B; Aggarwal, Bharat B

    2008-02-15

    Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".

  2. Investigation on Curcumin nanocomposite for wound dressing.

    Science.gov (United States)

    Venkatasubbu, G Devanand; Anusuya, T

    2017-05-01

    Curcuma longa (turmeric) has a long history of use in medicine as a treatment for inflammatory conditions. The primary active constituent of turmeric and the one responsible for its vibrant yellow color is curcumin. Curcumin is used for treatment of wound and inflammation. It had antimicrobial and antioxidant property. It has low intrinsic toxicity and magnificent properties like with comparatively lesser side-effects. Cotton cloth is one of the most successful wound dressings which utilize the intrinsic properties of cotton fibers. Modern wound dressings, however, require other properties such as antibacterial and moisture maintaining capabilities. In this study, conventional cotton cloth was coated with Curcumin composite for achieving modern wound dressing properties. Curcumin nanocomposite is characterized. The results show that coated cotton cloth with Curcumin nanocomposite has increased drying time (74%) and water absorbency (50%). Furthermore, they show antibacterial efficiency against bacterial species present in wounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. New perspectives of curcumin in cancer prevention

    Science.gov (United States)

    Park, Wungki; Amin, A.R.M Ruhul; Chen, Zhuo Georgia; Shin, Dong M.

    2013-01-01

    Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications. PMID:23466484

  4. Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice

    Science.gov (United States)

    Zhongfa, Liu; Chiu, Ming; Wang, Jiang; Chen, Wei; Yen, Winston; Fan-Havard, Patty; Yee, Lisa D.; Chan, Kenneth K.

    2012-01-01

    Purpose Curcumin has shown a variety of biological activity for various human diseases including cancer in preclinical setting. Its poor oral bioavailability poses significant pharmacological barriers to its clinical application. Here, we established a practical nano-emulsion curcumin (NEC) containing up to 20% curcumin (w/w) and conducted the pharmacokinetics of curcuminoids and curcumin metabolites in mice. Methods This high loading NEC was formulated based on the high solubility of curcumin in polyethylene glycols (PEGs) and the synergistic enhancement of curcumin absorption by PEGs and Cremophor EL. The pharmacokinetics of curcuminoids and curcumin metabolites was characterized in mice using a LC–MS/MS method, and the pharmacokinetic parameters were determined using WinNonlin computer software. Results A tenfold increase in the AUC0→24h and more than 40-fold increase in the Cmax in mice were observed after an oral dose of NEC compared with suspension curcumin in 1% methylcellulose. The plasma pharmacokinetics of its two natural congeners, demethoxycurcumin and bisdemethoxycurcumin, and three metabolites, tetrahydrocurcumin (THC), curcumin-O-glucuronide, and curcumin-O-sulfate, was characterized for the first time in mice after an oral dose of NEC. Conclusion This oral absorption enhanced NEC may provide a practical formulation to conduct the correlative study of the PK of curcuminoids and their pharmacodynamics, e.g., hypomethylation activity in vivo. PMID:21968952

  5. Cooking enhances curcumin anti-cancerogenic activity through pyrolytic formation of "deketene curcumin".

    Science.gov (United States)

    Dahmke, Indra N; Boettcher, Stefan P; Groh, Matthias; Mahlknecht, Ulrich

    2014-05-15

    Curcumin is widely used in traditional Asian kitchen as a cooking ingredient. Despite its low bioavailability, epidemiological data, on low cancer incidence in Asia, suggest beneficial health effects of this compound. Therefore, the question arose whether cooking modifies the anti-cancerogenic effects of curcumin. To evaluate this, we pyrolysed curcumin with and without coconut fat or olive oil, and analysed the products by high-performance liquid chromatography (HPLC). A number of more hydrophilic curcumin isoforms and decomposition products, including a compound later identified by nuclear magnetic resonance spectroscopy (NMR) as "deketene curcumin" (1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one), formerly described as a synthetic curcumin derivative, were detected. Additionally, we proved that deketene curcumin, compared to curcumin, exhibits higher toxicity on B78H1 melanoma cells resulting in G2 arrest. In conclusion, deketene curcumin is formed as a consequence of pyrolysis during common household cooking, showing stronger anti-cancer effects than curcumin. Moreover, we propose a chemical reaction-pathway for this process. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Lychee (Litchi chinensis Sonn.) Pulp Phenolic Extract Provides Protection against Alcoholic Liver Injury in Mice by Alleviating Intestinal Microbiota Dysbiosis, Intestinal Barrier Dysfunction, and Liver Inflammation.

    Science.gov (United States)

    Xiao, Juan; Zhang, Ruifen; Zhou, Qiuyun; Liu, Lei; Huang, Fei; Deng, Yuanyuan; Ma, Yongxuan; Wei, Zhencheng; Tang, Xiaojun; Zhang, Mingwei

    2017-11-08

    Liver injury is the most common consequence of alcohol abuse, which is promoted by the inflammatory response triggered by gut-derived endotoxins produced as a consequence of intestinal microbiota dysbiosis and barrier dysfunction. The aim of this study was to investigate whether modulation of intestinal microbiota and barrier function, and liver inflammation contributes to the hepatoprotective effect of lychee pulp phenolic extract (LPPE) in alcohol-fed mice. Mice were treated with an ethanol-containing liquid diet alone or in combination with LPPE for 8 weeks. LPPE supplementation alleviated ethanol-induced liver injury and downregulated key markers of inflammation. Moreover, LPPE supplementation reversed the ethanol-induced alteration of intestinal microbiota composition and increased the expression of intestinal tight junction proteins, mucus protecting proteins, and antimicrobial proteins. Furthermore, in addition to decreasing serum endotoxin level, LPPE supplementation suppressed CD14 and toll-like receptor 4 expression, and repressed the activation of nuclear factor-κB p65 in the liver. These data suggest that intestinal microbiota dysbiosis, intestinal barrier dysfunction, and liver inflammation are improved by LPPE, and therefore, the intake of LPPE or Litchi pulp may be an effective strategy to alleviate the susceptibility to alcohol-induced hepatic diseases.

  7. Novel dipeptide nanoparticles for effective curcumin delivery

    Science.gov (United States)

    Alam, Shadab; Panda, Jiban J; Chauhan, Virander S

    2012-01-01

    Background: Curcumin, the principal curcuminoid of the popular Indian spice turmeric, has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin is a major challenge in its development as a useful drug. To enhance the aqueous solubility and bioavailability of curcumin, attempts have been made to encapsulate it in liposomes, polymeric nanoparticles (NPs), lipid-based NPs, biodegradable microspheres, cyclodextrin, and hydrogels. Methods: In this work, we attempted to entrap curcumin in novel self-assembled dipeptide NPs containing a nonprotein amino acid, α, β-dehydrophenylalanine, and investigated the biological activity of dipeptide-curcumin NPs in cancer models both in vitro and in vivo. Results: Of the several dehydrodipeptides tested, methionine-dehydrophenylalanine was the most suitable one for loading and release of curcumin. Loading of curcumin in the dipeptide NPs increased its solubility, improved cellular availability, enhanced its toxicity towards different cancerous cell lines, and enhanced curcumin’s efficacy towards inhibiting tumor growth in Balb/c mice bearing a B6F10 melanoma tumor. Conclusion: These novel, highly biocompatible, and easy to construct dipeptide NPs with a capacity to load and release curcumin in a sustained manner significantly improved curcumin’s cellular uptake without altering its anticancer or other therapeutic properties. Curcumin-dipeptide NPs also showed improved in vitro and in vivo chemotherapeutic efficacy compared to curcumin alone. Such dipeptide-NPs may also improve the delivery of other potent hydrophobic drug molecules that show poor cellular uptake, bioavailability, and efficacy. PMID:22915849

  8. The functional genomic studies of curcumin.

    Science.gov (United States)

    Huminiecki, Lukasz; Horbańczuk, Jarosław; Atanasov, Atanas G

    2017-10-01

    Curcumin is a natural plant-derived compound that has attracted a lot of attention for its anti-cancer activities. Curcumin can slow proliferation of and induce apoptosis in cancer cell lines, but the precise mechanisms of these effects are not fully understood. However, many lines of evidence suggested that curcumin has a potent impact on gene expression profiles; thus, functional genomics should be the key to understanding how curcumin exerts its anti-cancer activities. Here, we review the published functional genomic studies of curcumin focusing on cancer. Typically, a cancer cell line or a grafted tumor were exposed to curcumin and profiled with microarrays, methylation assays, or RNA-seq. Crucially, these studies are in agreement that curcumin has a powerful effect on gene expression. In the majority of the studies, among differentially expressed genes we found genes involved in cell signaling, apoptosis, and the control of cell cycle. Curcumin can also induce specific methylation changes, and is a powerful regulator of the expression of microRNAs which control oncogenesis. We also reflect on how the broader technological progress in transcriptomics has been reflected on the field of curcumin. We conclude by discussing the areas where more functional genomic studies are highly desirable. Integrated OMICS approaches will clearly be the key to understanding curcumin's anticancer and chemopreventive effects. Such strategies may become a template for elucidating the mode of action of other natural products; many natural products have pleiotropic effects that are well suited for a systems-level analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. A curcumin activated carboxymethyl cellulose-montmorillonite clay nanocomposite having enhanced curcumin release in aqueous media.

    Science.gov (United States)

    Madusanka, Nadeesh; de Silva, K M Nalin; Amaratunga, Gehan

    2015-12-10

    A novel curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is reported. A superabsorbent biopolymer; carboxymethyl cellulose (CMC) was used as an emulsifier for curcumin which is a turmeric derived water insoluble polyphenolic compound with antibacterial/anti-cancer properties. Montmorillonite (MMT) nanoclay was incorporated in the formulation as a matrix material which also plays a role in release kinetics. It was observed that water solubility of curcumin in the nanocomposite has significantly increased (60% release within 2h and 30 min in distilled water at pH 5.4) compared to pure curcumin. The prepared curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is suitable as a curcumin carrier having enhanced release and structural properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB.

    Science.gov (United States)

    Xu, Ying; Ku, Baoshan; Tie, Lu; Yao, Haiyan; Jiang, Wengao; Ma, Xing; Li, Xuejun

    2006-11-29

    Curcuma longa is a major constituent of the traditional Chinese medicine Xiaoyao-san, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and its antidepressant effects were described in our prior studies in mouse models of behavioral despair. We hypothesized that curcumin may also alleviate stress-induced depressive-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Thus in present study we assessed whether curcumin treatment (2.5, 5 and 10 mg/kg, p.o.) affects behavior in a chronic unpredictable stress model of depression in rats and examined what its molecular targets may be. We found that subjecting animals to the chronic stress protocol for 20days resulted in performance deficits in the shuttle-box task and several physiological effects, such as an abnormal adrenal gland weight to body weight (AG/B) ratio and increased thickness of the adrenal cortex as well as elevated serum corticosterone levels and reduced glucocorticoid receptor (GR) mRNA expression. These changes were reversed by chronic curcumin administration (5 or 10 mg/kg, p.o.). In addition, we also found that the chronic stress procedure induced a down-regulation of brain-derived neurotrophic factor (BDNF) protein levels and reduced the ratio of phosphorylated cAMP response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in the hippocampus and frontal cortex of stressed rats. Furthermore, these stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, may be related to their modulating effects on the HPA axis and neurotrophin factor expressions.

  11. Metabolic basis of ethanol-induced cytotoxicity in recombinant HepG2 cells: Role of nonoxidative metabolism

    International Nuclear Information System (INIS)

    Wu Hai; Cai Ping; Clemens, Dahn L.; Jerrells, Thomas R.; Ansari, G.A. Shakeel; Kaphalia, Bhupendra S.

    2006-01-01

    Chronic alcohol abuse, a major health problem, causes liver and pancreatic diseases and is known to impair hepatic alcohol dehydrogenase (ADH). Hepatic ADH-catalyzed oxidation of ethanol is a major pathway for the ethanol disposition in the body. Hepatic microsomal cytochrome P450 (CYP2E1), induced in chronic alcohol abuse, is also reported to oxidize ethanol. However, impaired hepatic ADH activity in a rat model is known to facilitate a nonoxidative metabolism resulting in formation of nonoxidative metabolites of ethanol such as fatty acid ethyl esters (FAEEs) via a nonoxidative pathway catalyzed by FAEE synthase. Therefore, the metabolic basis of ethanol-induced cytotoxicity was determined in HepG2 cells and recombinant HepG2 cells transfected with ADH (VA-13), CYP2E1 (E47) or ADH + CYP2E1 (VL-17A). Western blot analysis shows ADH deficiency in HepG2 and E47 cells, compared to ADH-overexpressed VA-13 and VL-17A cells. Attached HepG2 cells and the recombinant cells were incubated with ethanol, and nonoxidative metabolism of ethanol was determined by measuring the formation of FAEEs. Significantly higher levels of FAEEs were synthesized in HepG2 and E47 cells than in VA-13 and VL-17A cells at all concentrations of ethanol (100-800 mg%) incubated for 6 h (optimal time for the synthesis of FAEEs) in cell culture. These results suggest that ADH-catalyzed oxidative metabolism of ethanol is the major mechanism of its disposition, regardless of CYP2E1 overexpression. On the other hand, diminished ADH activity facilitates nonoxidative metabolism of ethanol to FAEEs as found in E47 cells, regardless of CYP2E1 overexpression. Therefore, CYP2E1-mediated oxidation of ethanol could be a minor mechanism of ethanol disposition. Further studies conducted only in HepG2 and VA-13 cells showed lower ethanol disposition and ATP concentration and higher accumulation of neutral lipids and cytotoxicity (apoptosis) in HepG2 cells than in VA-13 cells. The apoptosis observed in HepG2 vs

  12. Evaluation of cell proliferation, apoptosis, and dna-repair genes as potential biomarkers for ethanol-induced cns alterations

    Directory of Open Access Journals (Sweden)

    Hicks Steven D

    2012-10-01

    Full Text Available Abstract Background Alcohol use disorders (AUDs lead to alterations in central nervous system (CNS architecture along with impaired learning and memory. Previous work from our group and that of others suggests that one mechanism underlying these changes is alteration of cell proliferation, apoptosis, and DNA-repair in neural stem cells (NSCs produced as a consequence of ethanol-induced effects on the expression of genes related to p53-signaling. This study tests the hypothesis that changes in the expression of p53-signaling genes represent biomarkers of ethanol abuse which can be identified in the peripheral blood of rat drinking models and human AUD subjects and posits that specific changes may be correlated with differences in neuropsychological measures and CNS structure. Results Remarkably, microarray analysis of 350 genes related to p53-signaling in peripheral blood leukocytes (PBLs of binge-drinking rats revealed 190 genes that were significantly altered after correcting for multiple testing. Moreover, 40 of these genes overlapped with those that we had previously observed to be changed in ethanol-exposed mouse NSCs. Expression changes in nine of these genes were tested for independent confirmation by a custom QuantiGene Plex (QGP assay for a subset of p53-signaling genes, where a consistent trend for decreased expression of mitosis-related genes was observed. One mitosis-related gene (Pttg1 was also changed in human lymphoblasts cultured with ethanol. In PBLs of human AUD subjects seven p53-signaling genes were changed compared with non-drinking controls. Correlation and principal components analysis were then used to identify significant relationships between the expression of these seven genes and a set of medical, demographic, neuropsychological and neuroimaging measures that distinguished AUD and control subjects. Two genes (Ercc1 and Mcm5 showed a highly significant correlation with AUD-induced decreases in the volume of the left

  13. TLR4 response mediates ethanol-induced neurodevelopment alterations in a model of fetal alcohol spectrum disorders.

    Science.gov (United States)

    Pascual, María; Montesinos, Jorge; Montagud-Romero, Sandra; Forteza, Jerónimo; Rodríguez-Arias, Marta; Miñarro, José; Guerri, Consuelo

    2017-07-24

    ). These changes are associated with long-term behavioral impairments, in the 66-day-old alcohol-exposed pups. TLR4-deficient mice are protected against ethanol-induced cytokine/chemokine production in alcohol-treated dams and offspring, along with synaptic and myelin alterations, and the log-term behavioral dysfunction induced by ethanol in offspring. These results suggest that the immune system activation, through the TLR4 response, might play an important role in the neurodevelopmental defects in FASD.

  14. The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats.

    Science.gov (United States)

    Al-Wajeeh, Nahla Saeed; Hajerezaie, Maryam; Noor, Suzita Mohd; Halabi, Mohammed Farouq; Al-Henhena, Nawal; Azizan, Ainnul Hamidah Syahadah; Kamran, Sareh; Hassandarvish, Pouya; Shwter, Abdrabuh N; Karimian, Hamed; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

    2017-01-19

    Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups. After 60 min, the normal control group of rats was orally administered 10% Tween 20, while absolute ethanol was orally administered to the groups of ulcer control, omeprazole and experimental groups. Stomachs of the rats were examined macroscopically and histologically. Homogenates of stomachs were used to evaluate endogenous antioxidant enzyme activities. Rats pre-fed with plant extract presented a significant decrease in the sore area, increased pH of gastric contents and preserved stomach wall mucus compared to the ulcer group. Histologically, rats pre-fed with C. barometz hair extract showed mild to moderate disruptions of the surface epithelium while animals pre-fed with absolute ethanol showed severe disruptions of the stomach epithelium with edema and leucocyte penetration of the submucosal layer. A Periodic acid Schiff (PAS) staining revealed that each rat pre-treated with the plant extract displayed an intense uptake of stomach epithelial glycoprotein magenta color compared to the ulcer control group. Immunohistochemical analysis revealed that rats pre-fed with the plant extract showed an up-regulation of the heat shock protein 70 (HSP70) and down-regulation of Bax proteins compared to ulcer control rats. Homogenates of the stomach tissue demonstrated significant increases in the endogenous antioxidant enzymatic activity and decreased lipid peroxidation (MDA) in rats pre-treated with C. barometz hair extract compared with the ulcer control rats. In acute

  15. Total glucosides of peony attenuates 2,4,6-trinitrobenzene sulfonic acid/ethanol-induced colitis in rats through adjustment of TH1/TH2 cytokines polarization.

    Science.gov (United States)

    Zhang, Yabing; Zhou, Rui; Zhou, Feng; Cheng, Hong; Xia, Bing

    2014-01-01

    The present study is to investigate effects of total glucosides of peony (TGP) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol-induced colitis in rats and to explore potential clinical use of TGP for treatment of inflammatory bowel disease. Sixty Sprague-Dawley rats were randomly grouped into normal controls, model controls, sulfasalazine (SASP) controls (100 mg/kg/day), and low, medium, and high-dose TGP groups (25, 50, and 100 mg/kg/day, respectively). 24 h following colonic instillation of TNBS, TGP, and SASP were given by gastric gavage three times a day for 7 days. Disease activity index (DAI), colon macroscopic damage index (CMDI), histopathological score (HPS), and myeloperoxidase (MPO) activity were evaluated. Levels of serum TNF-α, IL-1β, and IL-10 were measured by ELISA, and expression of TNF-α, IL-1β, and IL-10 mRNA and protein in colonic tissues was detected by RT-PCR and western blot, respectively. Compared with rats in the model controls, TGP (50 or 100 mg/kg/day)-treated rats with TNBS/ethanol-induced colitis showed significant improvements of DAI, CMDI, HPS, and MPO activity. Moreover, administration of TGP (50 or 100 mg/kg/day) decreased the up-regulated levels of serum TNF-α and IL-1β, and expression of TNF-α and IL-1β mRNA and protein in colonic tissues, and increased the serum IL-10 and colonic IL-10 mRNA and protein level. And there was no significant difference compared with administration of SASP (P > 0.05). TGP attenuates TNBS/ethanol-induced colitis in rats and its efficacy is similar to SASP, the potential mechanism might be related to the adjustment of Th1/Th2 cytokines polarization by decreasing pro-inflammatory cytokine TNF-α and IL-1β, and increasing anti-inflammatory cytokine IL-10.

  16. Regulation of COX and LOX by curcumin.

    Science.gov (United States)

    Rao, Chinthalapally V

    2007-01-01

    Turmeric (Curcuma longa) is extensively used as a household remedy for various diseases. For the last few decades, work has been done to establish the biological activities and pharmacological actions of curcumin, the principle constituent of turmeric. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases due to its anti-inflammatory activity. Arachidonic acid-derived lipid mediators that are intimately involved in inflammation are biosynthesized by pathways dependent on cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. The role of LOX and COX isoforms, particularly COX-2, in the inflammation has been well established. At cellular and molecular levels, curcumin has been shown to regulate a number of signaling pathways, including the eicosanoid pathway involving COX and LOX. A number of studies have been conducted that support curcumin-mediated regulation of COX and LOX pathways, which is an important mechanism by which curcumin prevents a number of disease processes, including the cancer. The specific regulation of 5-LOX and COX-2 by curcumin is not fully established; however, existing evidence indicates that curcumin regulates LOX and COX-2 predominately at the transcriptional level and, to a certain extent, the posttranslational level. Thus, the curcumin-selective transcriptional regulatory action of COX-2, and dual COX/LOX inhibitory potential of this naturally occurring agent provides distinctive advantages over synthetic COX/LOX inhibitors, such as nonsteroidal anti-inflammatory drugs. In this review, we discuss evidence that supports the regulation of COX and LOX enzymes by curcumin as the key mechanism for its beneficial effects in preventing various inflammatory diseases.

  17. Neuroprotective effects of curcumin and highly bioavailable curcumin on oxidative stress induced by sodium nitroprusside in rat striatal cell culture.

    Science.gov (United States)

    Nazari, Qand Agha; Kume, Toshiaki; Izuo, Naotaka; Takada-Takatori, Yuki; Imaizumi, Atsushi; Hashimoto, Tadashi; Izumi, Yasuhiko; Akaike, Akinori

    2013-01-01

    Curcumin, a polyphenolic compound extracted from Curcuma longa, has several pharmacological activities such as anticancer, anti-inflammatory, and antioxidant effects. The purpose of this study was to investigate the protective effects of curcumin and THERACURMIN, a highly bioavailable curcumin, against sodium nitroprusside (SNP)-induced oxidative damage in primary striatal cell culture. THERACURMIN as well as curcumin significantly prevented SNP-induced cytotoxicity. To elucidate the cytoprotective effects of curcumin and THERACURMIN, we measured the intracellular glutathione level in striatal cells. Curcumin and THERACURMIN significantly elevated the glutathione level, which was decreased by treatment with SNP. Moreover, curcumin showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging ability. Finally, a ferrozine assay showed that curcumin (10-100 µg/mL) has potent Fe(2+)-chelating ability. These results suggest that curcumin and THERACURMIN exert potent protective effects against SNP-induced cytotoxicity by free radical-scavenging and iron-chelating activities.

  18. Ethanol activation of protein kinase A regulates GABA-A receptor subunit expression in the cerebral cortex and contributes to ethanol-induced hypnosis

    Directory of Open Access Journals (Sweden)

    Sandeep eKumar

    2012-04-01

    Full Text Available Protein kinases are implicated in neuronal cell functions such as modulation of ion channel function, trafficking and synaptic excitability. Both protein kinase C (PKC and A (PKA are involved in regulation of γ-aminobutyric acid type A (GABA-A receptors through phosphorylation. However, the role of PKA in regulating GABA-A receptors following acute ethanol exposure is not known. The present study investigated the role of PKA in ethanol effects on GABA-A receptor α1 subunit expression in the P2 synaptosomal fraction of the rat cerebral cortex. Additionally, GABA-related behaviors were also examined. Rats were administered ethanol (2.0 – 3.5 g/kg or saline and PKC, PKA and GABA-A receptor α1 subunit levels were measured by Western blot analysis. Ethanol (3.5 g/kg transiently increased GABA-A receptor α1 subunit expression and PKA RIIβ subunit expression at similar time points whereas PKA RIIα was increased at later time points. In contrast, PKC isoform expression remained unchanged. Notably, the moderate ethanol dose (2.0g/kg had no effect on GABA-A α1 subunit levels although PKA RIIα and RIIβ were increased at 10 and 60 minutes, when PKC isozymes are also known to be elevated. To determine if PKA activation was responsible for the ethanol-induced elevation of GABA-A α1 subunits, the PKA antagonist H89 was administered to rats prior to ethanol exposure. H89 administration prevented ethanol-induced increases in GABA-A receptor α1 subunit expression. Moreover, increasing PKA activity intracerebroventricularly with Sp-cAMP prior to a hypnotic dose of ethanol increased ethanol-induced loss of righting reflex duration. This effect appears to be mediated in part by GABA-A receptors as increasing PKA activity also increased the duration of muscimol-induced loss of righting reflex. Overall these data suggest that PKA mediates ethanol-induced GABA-A receptor expression and contributes to ethanol behavioral effects involving GABA-A receptors.

  19. Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy.

    Science.gov (United States)

    Karuppagounder, Vengadeshprabhu; Arumugam, Somasundaram; Giridharan, Vijayasree V; Sreedhar, Remya; Bose, Rajendran J C; Vanama, Jyothi; Palaniyandi, Suresh S; Konishi, Tetsuya; Watanabe, Kenichi; Thandavarayan, Rajarajan A

    2017-02-01

    Diabetic cardiomyopathy (DCM) is described as impaired cardiac diastolic and systolic functions. Diabetes mellitus (DM), a related cardiovascular disease, has become one of the major causes of death in DM patients. Mortality in these diseases is 2 to 3 times higher than in non-DM patients with cardiovascular disease. The progression of DCM and the cellular and molecular perturbations associated with the pathogenesis are complex and multifactorial. Although considerable progress has been achieved, the molecular etiologies of DCM remain poorly understood. There is an expanding need for natural antidiabetic medicines that do not cause the side effects of modern drugs. Curcumin, a pleiotropic molecule, from Curcuma longa, is known to possess numerous impacts such as scavenging free radical, antioxidant, antitumor, and antiinflammatory activities. The reports from preclinical and clinical findings revealed that curcumin can reverse insulin resistance, hyperglycemia, obesity, and obesity-related metabolic diseases. The current review provides an updated overview of the possible molecular mechanism of DCM and multitarget approach of curcumin in alleviating DCM and diabetic complication. Additionally, we mentioned the approaches that are currently being implemented to improve the bioavailability of this promising natural product in diabetes therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Inhibition of HIV-1 by curcumin A, a novel curcumin analog

    Science.gov (United States)

    Kumari, Namita; Kulkarni, Amol A; Lin, Xionghao; McLean, Charlee; Ammosova, Tatiana; Ivanov, Andrey; Hipolito, Maria; Nekhai, Sergei; Nwulia, Evaristus

    2015-01-01

    Despite the remarkable success of combination antiretroviral therapy at curtailing HIV progression, emergence of drug-resistant viruses, chronic low-grade inflammation, and adverse effects of combination antiretroviral therapy treatments, including metabolic disorders collectively present the impetus for development of newer and safer antiretroviral drugs. Curcumin, a phytochemical compound, was previously reported to have some in vitro anti-HIV and anti-inflammatory activities, but poor bioavailability has limited its clinical utility. To circumvent the bioavailability problem, we derivatized curcumin to sustain retro-aldol decomposition at physiological pH. The lead compound derived, curcumin A, showed increased stability, especially in murine serum where it was stable for up to 25 hours, as compared to curcumin that only had a half-life of 10 hours. Both curcumin and curcumin A showed similar inhibition of one round of HIV-1 infection in cultured lymphoblastoid (also called CEM) T cells (IC50=0.7 μM). But in primary peripheral blood mononuclear cells, curcumin A inhibited HIV-1 more potently (IC50=2 μM) compared to curcumin (IC50=12 μM). Analysis of specific steps of HIV-1 replication showed that curcumin A inhibited HIV-1 reverse transcription, but had no effect on HIV-1 long terminal repeat basal or Tat-induced transcription, or NF-κB-driven transcription at low concentrations that affected reverse transcription. Finally, we showed curcumin A induced expression of HO-1 and decreased cell cycle progression of T cells. Our findings thus indicate that altering the core structure of curcumin could yield more stable compounds with potent antiretroviral and anti-inflammatory activities. PMID:26366056

  1. Curcumin Implants, not Curcumin Diet Inhibits Estrogen-Induced Mammary Carcinogenesis in ACI Rats

    Science.gov (United States)

    Bansal, Shyam S.; kausar, Hina; Vadhanam, Manicka V.; Ravoori, Srivani; Pan, Jianmin; Rai, Shesh N.; Gupta, Ramesh C.

    2014-01-01

    Curcumin is widely known for its anti-oxidant, anti-inflammatory and anti-proliferative activities in cell culture studies. However, poor oral bioavailability limited its efficacy in animal and clinical studies. Recently, we developed polymeric curcumin implants that circumvents oral bioavailability issues, and tested their potential against 17β-estradiol (E2)-mediated mammary tumorigenesis. Female ACI rats were administered curcumin either via diet (1,000 ppm) or via polymeric curcumin implants (two 2-cm; 200 mg each; 20% drug load) 4 days prior to grafting a subcutaneous E2 silastic implant (1.2 cm, 9 mg E2). Implants were changed after 4½ months to provide higher curcumin dose at the appearance of palpable tumors. The animals were euthanized after 3 weeks, 3 months and after the tumor incidence reached >80% (~6 months) in control animals. The curcumin administered via implants resulted in significant reduction in both the tumor multiplicity (2±1 vs 5±3; p=0.001) and tumor volume (184±198 mm3 vs 280±141 mm3; p=0.0283); the dietary curcumin, however, was ineffective. Dietary curcumin increased hepatic CYP1A and CYP1B1 activities without any effect on CYP3A4 activity whereas curcumin implants increased both CYP1A and CYP3A4 activities but decreased CYP1B1 activity in presence of E2. Since CYP1A and 3A4 metabolize most of the E2 to its non-carcinogenic 2-OH metabolite and CYP1B1 produces potentially carcinogenic 4-OH metabolite, favorable modulation of these CYPs via systemically delivered curcumin could be one of the potential mechanisms. The analysis of plasma and liver by HPLC showed substantially higher curcumin levels via implants versus the dietary route despite substantially higher dose administered. PMID:24501322

  2. Protective Effects of Tetrahydrocurcumin and Curcumin against ...

    African Journals Online (AJOL)

    Curcumin (CUR) is a phenolic compound from. Curcuma longa. .... captured on a Nikon fluorescence microscope. The fluorescence data were ... The images shown were representative of experiments with similar results. Each bar represents ...

  3. Curcumin nanoformulations: a future nanomedicine for cancer

    Science.gov (United States)

    Yallapu, Murali M; Jaggi, Meena; Chauhan, Subhash C

    2011-01-01

    Curcumin, a natural diphenolic compound derived from turmeric Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion, apoptosis and cell death, revealing its anticancer potential. In this review, we focus on the design and development of nanoparticles, self-assemblies, nanogels, liposomes and complex fabrication for sustained and efficient curcumin delivery. We also discuss the anticancer applications and clinical benefits of nanocurcumin formulations. Only a few novel multifunctional and composite nanosystem strategies offer simultaneous therapy as well as imaging characteristics. We also summarize the challenges to developing curcumin delivery platforms and up-to-date solutions for improving curcumin bioavailability and anticancer potential for therapy. PMID:21959306

  4. Role of curcumin in health and disease.

    Science.gov (United States)

    Pari, Leelavinothan; Tewas, Daniel; Eckel, Juergen

    2008-04-01

    Curcumin (diferuloylmethane) is an orange-yellow component of turmeric (Curcuma longa), a spice often found in curry powder. In recent years, considerable interest has been focused on curcumin due to its use to treat a wide variety of disorders without any side effects. It is one of the major curcuminoids of turmeric, which impart its characteristic yellow colour. It was used in ancient times on the Indian subcontinent to treat various illnesses such as rheumatism, body ache, skin diseases, intestinal worms, diarrhoea, intermittent fevers, hepatic disorders, biliousness, urinary discharges, dyspepsia, inflammations, constipation, leukoderma, amenorrhea, and colic. Curcumin has the potential to treat a wide variety of inflammatory diseases including cancer, diabetes, cardiovascular diseases, arthritis, Alzheimer's disease, psoriasis, etc, through modulation of numerous molecular targets. This article reviews the use of curcumin for the chemoprevention and treatment of various diseases.

  5. The interplay between ventro striatal BDNF levels and the effects of valproic acid on the acquisition of ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Dos Santos, Manuel Alves; Escudeiro, Sarah Sousa; Vasconcelos, Germana Silva; Matos, Natália Castelo Branco; de Souza, Marcos Romário Matos; Patrocínio, Manoel Cláudio Azevedo; Dantas, Leonardo Pimentel; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2017-11-01

    Alcohol addiction is a chronic, relapsing and progressive brain disease with serious consequences for health. Compulsive use of alcohol is associated with the capacity to change brain structures involved with the reward pathway, such as ventral striatum. Recent evidence suggests a role of chromatin remodeling in the pathophysiology of alcohol dependence and addictive-like behaviors. In addition, neuroadaptive changes mediated by the brain-derived neurotrophic factor (BDNF) seems to be an interesting pharmacological target for alcoholism treatment. In the present study, we evaluated the effects of the deacetylase inhibitor valproic acid (VPA) (300mg/kg) on the conditioned rewarding effects of ethanol using conditioned place preference (CPP) (15% v/v; 2g/kg). Ethanol rewarding effect was investigated using a biased protocol of CPP. BDNF levels were measured in the ventral striatum. Ethanol administration induced CPP. VPA pretreatment did not reduce ethanol-CPP acquisition. VPA pretreatment increased BDNF levels when compared to ethanol induced-CPP. VPA pretreatment increased BDNF levels even in saline conditioned mice. Taken together, our results indicate a modulatory effect of VPA on the BDNF levels in the ventral striatum. Overall, this study brings initial insights into the involvement of neurotrophic mechanisms in the ventral striatum in ethanol-induced addictive-like behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

    Science.gov (United States)

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5’-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5’-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage. PMID:16865772

  7. Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on ethanol-induced fatty liver in rats.

    Science.gov (United States)

    Nwozo, Sarah Onyenibe; Osunmadewa, Damilola Adeola; Oyinloye, Babatunji Emmanuel

    2014-01-01

    The present study is aimed at evaluating the protective effects of oils from Zingiber officinale (ginger) and Curcuma longa (turmeric) on acute ethanol-induced fatty liver in male Wistar rats. Ferric reducing antioxidant power activity and oxygen radical absorbance capacity of the oils were evaluated ex vivo. Rats were pretreated for 28 d with standard drug (Livolin Forte) and oils from Z. officinale and C. longa before they were exposed to 45% ethanol (4.8 g/kg) to induce acute fatty liver. Histological changes were observed and the degree of protection was measured by using biochemical parameters such as alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities. Serum triglyceride (TG) level, total cholesterol (TC) level and the effects of both oils on reduced gluthatione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) levels were estimated. Oils from Z. officinale and C. longa at a dose of 200 mg/kg showed hepatoprotection by decreasing the activities of serum enzymes, serum TG, serum TC and hepatic MDA, while they significantly restored the level of GSH as well as GST and SOD activities. Histological examination of rats tissues was related to the obtained results. From the results it may be concluded that oils from Z. officinale and C. longa (200 mg/kg) exhibited hepatoprotective activity in acute ethanol-induced fatty liver and Z. officinale oil was identified to have better effects than C. longa oil.

  8. Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats.

    Science.gov (United States)

    Sherrill, Luke K; Berthold, Claire; Koss, Wendy A; Juraska, Janice M; Gulley, Joshua M

    2011-11-20

    Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Gastroprotective Effects of Lion’s Mane Mushroom Hericium erinaceus (Bull.:Fr. Pers. (Aphyllophoromycetideae Extract against Ethanol-Induced Ulcer in Rats

    Directory of Open Access Journals (Sweden)

    Jing-Yang Wong

    2013-01-01

    Full Text Available Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in Sprague Dawley rats were investigated. The possible involvements of lipid peroxidation, superoxide dismutase, and catalase were also investigated. Acute toxicity study was performed. The effects of aqueous extract of H. erinaceus on the ulcer areas, ulcer inhibition, gastric wall mucus, gross and histological gastric lesions, antioxidant levels, and malondialdehyde (MDA contents were evaluated in ethanol-induced ulcer in vivo. In acute toxicity study, a high dose of 5 g/kg did not manifest any toxicological signs in rats. The extract promoted ulcer protection as ascertained by a significant reduction of the ulcer area. Furthermore, it exhibited a significant protection activity against gastric mucosal injury by preventing the depletion of antioxidant enzymes. The level of MDA was also limited in rat stomach tissues when compared with the ulcer control group. Immunohistochemistry showed upregulation of HSP70 protein and downregulation of BAX protein in rats pretreated with the extract. The aqueous extract of H. erinaceus protected gastric mucosa in our in vivo model. It is speculated that the bioactive compounds present in the extract may play a major role in gastroprotective activity.

  10. Gastroprotective Effects of Lion's Mane Mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats

    Science.gov (United States)

    Wong, Jing-Yang; Raman, Jegadeesh; Kuppusamy, Umah Rani; Sabaratnam, Vikineswary

    2013-01-01

    Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in Sprague Dawley rats were investigated. The possible involvements of lipid peroxidation, superoxide dismutase, and catalase were also investigated. Acute toxicity study was performed. The effects of aqueous extract of H. erinaceus on the ulcer areas, ulcer inhibition, gastric wall mucus, gross and histological gastric lesions, antioxidant levels, and malondialdehyde (MDA) contents were evaluated in ethanol-induced ulcer in vivo. In acute toxicity study, a high dose of 5 g/kg did not manifest any toxicological signs in rats. The extract promoted ulcer protection as ascertained by a significant reduction of the ulcer area. Furthermore, it exhibited a significant protection activity against gastric mucosal injury by preventing the depletion of antioxidant enzymes. The level of MDA was also limited in rat stomach tissues when compared with the ulcer control group. Immunohistochemistry showed upregulation of HSP70 protein and downregulation of BAX protein in rats pretreated with the extract. The aqueous extract of H. erinaceus protected gastric mucosa in our in vivo model. It is speculated that the bioactive compounds present in the extract may play a major role in gastroprotective activity. PMID:24302966

  11. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage.

    Science.gov (United States)

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-07-21

    To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

  12. Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents

    Directory of Open Access Journals (Sweden)

    Opeyemi J. Olatunji

    2015-12-01

    Full Text Available The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH, superoxide dismutase (SOD, malondialdehyde (MDA, myeloperoxidase (MPO activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6 and interleukin-1β (IL-1β in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1β in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers.

  13. Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study

    Directory of Open Access Journals (Sweden)

    Taro Yamaguchi

    2017-08-01

    Full Text Available We sought to determine the preventive effects of curcumin and its highly bioavailable preparation on noise-induced hearing loss in a novel murine model of permanent hearing loss developed by repeated exposure to noise. Upon exposure to noise (8-kHz octave band noise, 90 dB sound pressure level, 1 h, hearing ability was impaired in a temporary and reversible manner. During repeated noise exposure (1-h exposure per day, 5 days, there was a progressive increase in the auditory threshold shift at 12 and 20 kHz. The threshold shift persisted for at least 6 days after noise exposure. Oral administration of curcumin for 3 days before and each day during noise exposure significantly alleviated the hearing loss induced by repeated noise exposure. Curcumin abolished intranuclear translocation of nuclear factor-κB-p65 and generation of 4-hydroxynonenal-adducted proteins found in the cochlea after noise exposure. Theracurmin®, a highly absorbable and bioavailable preparation of curcumin, had strong preventive effects on hearing loss induced by repeated noise exposure. Together, these data suggest that curcumin exerts a preventive effect on noise-induced hearing loss and is therefore a good therapeutic candidate for preventing sensorineural hearing loss.

  14. Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study.

    Science.gov (United States)

    Yamaguchi, Taro; Yoneyama, Masanori; Onaka, Yusuke; Imaizumi, Atsushi; Ogita, Kiyokazu

    2017-08-01

    We sought to determine the preventive effects of curcumin and its highly bioavailable preparation on noise-induced hearing loss in a novel murine model of permanent hearing loss developed by repeated exposure to noise. Upon exposure to noise (8-kHz octave band noise, 90 dB sound pressure level, 1 h), hearing ability was impaired in a temporary and reversible manner. During repeated noise exposure (1-h exposure per day, 5 days), there was a progressive increase in the auditory threshold shift at 12 and 20 kHz. The threshold shift persisted for at least 6 days after noise exposure. Oral administration of curcumin for 3 days before and each day during noise exposure significantly alleviated the hearing loss induced by repeated noise exposure. Curcumin abolished intranuclear translocation of nuclear factor-κB-p65 and generation of 4-hydroxynonenal-adducted proteins found in the cochlea after noise exposure. Theracurmin ® , a highly absorbable and bioavailable preparation of curcumin, had strong preventive effects on hearing loss induced by repeated noise exposure. Together, these data suggest that curcumin exerts a preventive effect on noise-induced hearing loss and is therefore a good therapeutic candidate for preventing sensorineural hearing loss. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  15. The Protective Effects of Curcumin on Obesity-Related Glomerulopathy Are Associated with Inhibition of Wnt/β-Catenin Signaling Activation in Podocytes

    Directory of Open Access Journals (Sweden)

    Bao-li Liu

    2015-01-01

    Full Text Available The present study investigated the effects of curcumin, one of the most important active ingredients of turmeric, on podocyte injury in vitro and obesity-related glomerulopathy (ORG in vivo. Cellular experiments in vitro showed that curcumin significantly antagonized leptin-induced downregulation of the mRNA and protein expression of podocyte-associated molecules including nephrin, podocin, podoplanin, and podocalyxin. Animal experiments in vivo showed that curcumin significantly reduced the body weight, Lee’s index, abdominal fat index, urinary protein excretion, and average glomerular diameter and significantly upregulated the mRNA and protein expressions of the above podocyte-associated molecules in ORG mice. Furthermore, the experiments in vitro and in vivo both displayed that curcumin could downregulate the mRNA and protein expressions of Wnt1, Wnt2b, Wnt6, and β-catenin and upregulate the phosphorylation level of β-catenin protein in podocytes and renal tissue. In conclusion, curcumin is able to alleviate the harmful reaction of leptin on podocytes and reduce the severity of ORG. The above protective effects are associated with the inhibition of Wnt/β-catenin signaling activation in podocytes.

  16. Epigenetic impact of curcumin on stroke prevention

    OpenAIRE

    Kalani, Anuradha; Kamat, Pradip K; Kalani, Komal; Tyagi, Neetu

    2014-01-01

    The epigenetic impact of curcumin in stroke and neurodegenerative disorders is curiosity-arousing. It is derived from Curcuma longa (spice), possesses anti-oxidative, anti-inflammatory, anti-lipidemic, neuro-protective and recently shown to exhibit epigenetic modulatory properties. Epigenetic studies include DNA methylation, histone modifications and RNA-based mechanisms which regulate gene expression without altering nucleotide sequences. Curcumin has been shown to affect cancer by altering ...

  17. Therapeutic potential of curcumin in gastrointestinal diseases

    OpenAIRE

    Rajasekaran, Sigrid A

    2011-01-01

    Curcumin, also known as diferuloylmethane, is derived from the plant Curcuma longa and is the active ingredient of the spice turmeric. The therapeutic activities of curcumin for a wide variety of diseases such as diabetes, allergies, arthritis and other chronic and inflammatory diseases have been known for a long time. More recently, curcumin’s therapeutic potential for preventing and treating various cancers is being recognized. As curcumin’s therapeutic promise is being explored more system...

  18. Flow Linear Dichroism Spectroscopic Studies of the Natural Product Curcumin and Double Stranded DNA

    DEFF Research Database (Denmark)

    Leth, Rasmus; Thulstrup, Peter Waaben

    2011-01-01

    Curcumin is a polyphenol found in the rhizomes of the plant Curcuma Longa, commonly known as turmeric. Curcumin has a bright yellow color, and in turmeric, curcumin exists along with two other curcuminoids: desmethoxy curcumin and bisdesmethoxy curcumin [1]. Curcumin has shown multiple biological...... effect, including antibacterial effects [2], antioxidant activities [1], antidepressant effects [3] and anticarcinogenic effects among others as reviewed by [4]. Importantly, it is known that curcumin can bind to and cross cellular membranes [5]....

  19. Topical Curcumin-Based Cream Is Equivalent to Dietary Curcumin in a Skin Cancer Model

    International Nuclear Information System (INIS)

    Sonavane, K.; Phillips, J.; Lakshmaiah, R. R.; Ekshyyan, O.; Moore-Medlin, T.; Rong, X.; Nathan, C. O.; Ekshyyan, O.; Moore-Medlin, T.; Rong, X.; Nathan, C.O.; Gill, J. R.; Clifford, J. L.; Abreo, F.; Boudreaux, D.; Nathan, C. O.

    2012-01-01

    Skin squamous cell carcinoma (SCC), the most common cancer in the USA, is a growing problem with the use of tanning booths causing sun-damaged skin. Antiproliferative effects of curcumin were demonstrated in an aggressive skin cancer cell line SRB12-p9 (ρ< 0.05 compared to control). Topical formulation was as effective as oral curcumin at suppressing tumor growth in a mouse skin cancer model. Curcumin at 15 mg administered by oral, topical, or combined formulation significantly reduced tumor growth compared to control (ρ=0.004). Inhibition of pAKT, pS6, p-4EBP1, pSTAT3, and pERK 1/2 was noted in SRB12-p9 cells post-curcumin treatment compared to control (ρ<0.05). Inhibition of pSTAT3 and pERK 1/2 was also noted in curcumin-treated groups in vivo. IHC analysis revealed human tumor specimens that expressed significantly more activated pERK ( ρ=0.006) and pS6 (ρ< 0.0001) than normal skin samples. This is the first study to compare topical curcumin to oral curcumin. Our data supports the use of curcumin as a chemo preventive for skin SCC where condemned skin is a significant problem. Prevention strategies offer the best hope of future health care costs in a disease that is increasing in incidence due to increased sun exposure.

  20. Antiproliferative effects of an analog of curcumin in Hep-2 cells: a comparative study with curcumin.

    Science.gov (United States)

    Kumaravel, Mohankumar; Sankar, Pajaniradje; Latha, Periyasamy; Benson, Chellakan S; Rukkumani, Rajagopalan

    2013-02-01

    Curcumin, the major active principle of Curcuma longa, is one of the promising, plant-derived, chemopreventive agents being studied for its anticarcinogenic and antioxidant properties. Hence, in our study, we aimed at testing the antiproliferative efficacy of an o-hydroxyl substituted analog of curcumin, bis demethoxy curcumin analog (BDMC-A), and comparing its efficacy with that of curcumin. BDMC-A was synthesised with a yield of 78% and 98% purity. Hep-2 cells and the MTT cell viability assay were used to examine cell proliferation. LDH assay and cell counts were performed to assess the cytotoxicity and anti-proliferative effects of the compound, respectively. Flow cytometry followed by Western blot were performed to investigate the cell cycle distribution. BDMC-A inhibited cell proliferation at a much lower concentration (IC50 20 microM) than curcumin (IC50 50 microM). Similar effects were observed in the LDH release and cell count assays. Flow cytometric studies using propidium iodide showed accumulation of cells in the G0/G1 phase and the arrest was further confirmed by immunoblotting of protein cyclin D1. BDMC-A was more potent in inhibiting the cells at a lower dose when compared with curcumin. Our results showed that the analog of curcumin is likely to possess more efficacy compared with curcumin in inhibiting cancer.

  1. Determination of process parameters for curcumin - dextrose cocrystallization

    Science.gov (United States)

    Katherine; Nugroho, Denny; Sugih, Asaf K.

    2018-01-01

    Curcumin is a polyphenol that could act as anti-oxidant and anti - inflammation agent. It is usually isolated from rhizome plants such as turmeric and temulawak. Despite its many favorable properties, curcumin is practically insoluble in water, thus limiting its application. In the present investigation, variables affecting preparation of curcumin-dextrose cocrystal were examined with the aim to increase the solubility of curcumin. The effect of different processing conditions, such as water to dextrose ratio, final heating temperature and water bath temperature to the formation of cocrystal, were studied and the yield and solubility of curcumin - dextrose cocrystal products were analyzed. The morphology of the cocrystals were also analyzed using SEM and fluorescence microscopy.. Curcumin - dextrose cocrystals showed a significant increase in solubility up to 25 mg curcumin per mL water compared to pure curcumin.

  2. Curcumin loaded in bovine serum albumin–chitosan derived ...

    Indian Academy of Sciences (India)

    study proved that BSA–chitosan based nanoparticles can be used as an efficient vehicle for effective curcumin ... tions in treating cerebral ischaemia by delivering Tanshinone. ∗ ... curcumin is its poor water solubility, which in turn reduces.

  3. Direct regulation of IL-2 by curcumin.

    Science.gov (United States)

    Oh, Jin-Gyo; Hwang, Da-Jeong; Heo, Tae-Hwe

    2018-01-01

    Interleukin-2 (IL-2) is a crucial growth factor for both regulatory and effector T cells. Thus, IL-2 plays a critical role in the stimulation and suppression of immune responses. Recently, anti-IL-2 antibodies (Abs) have been shown to possess strong IL-2 modulatory activities by affecting the interaction between IL-2 and IL-2 receptors. In this study, we screened an herbal library to identify a compound that regulates IL-2, which resulted in the identification of curcumin as a direct binder and inhibitor of IL-2. Curcumin is a phytochemical with well-known anti-cancer properties. In this study, curcumin mimicked or altered the binding pattern of anti-IL-2 Abs against IL-2 and remarkably inhibited the interaction of recombinant IL-2 with the IL-2 receptor α, CD25. Interestingly, curcumin neutralized the biological activities of IL-2 both in vitro and in vivo. In this report, we elucidated the unsolved mechanism of the anti-cancer effect of curcumin by identifying IL-2 as a direct molecular target. Curcumin, as a small molecule IL-2 modulator, has the potential to be used to treat IL-2 related pathologic conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Curcumin: the spicy modulator of breast carcinogenesis.

    Science.gov (United States)

    Banik, Urmila; Parasuraman, Subramani; Adhikary, Arun Kumar; Othman, Nor Hayati

    2017-07-19

    Worldwide breast cancer is the most common cancer in women. For many years clinicians and the researchers are examining and exploring various therapeutic modalities for breast cancer. Yet the disease has remained unconquered and the quest for cure is still going on. Present-day strategy of breast cancer therapy and prevention is either combination of a number of drugs or a drug that modulates multiple targets. In this regard natural products are now becoming significant options. Curcumin exemplifies a promising natural anticancer agent for this purpose. This review primarily underscores the modulatory effect of curcumin on the cancer hallmarks. The focus is its anticancer effect in the complex pathways of breast carcinogenesis. Curcumin modulates breast carcinogenesis through its effect on cell cycle and proliferation, apoptosis, senescence, cancer spread and angiogenesis. Largely the NFkB, PI3K/Akt/mTOR, MAPK and JAK/STAT are the key signaling pathways involved. The review also highlights the curcumin mediated modulation of tumor microenvironment, cancer immunity, breast cancer stem cells and cancer related miRNAs. Using curcumin as a therapeutic and preventive agent in breast cancer is perplexed by its diverse biological activity, much of which remains inexplicable. The information reviewed here should point toward potential scope of future curcumin research in breast cancer.

  5. Modulation of transcription factors by curcumin.

    Science.gov (United States)

    Shishodia, Shishir; Singh, Tulika; Chaturvedi, Madan M

    2007-01-01

    Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.

  6. Comparison between the efficacies of curcumin and puerarin in C57BL/6 mice with steatohepatitis induced by a methionine- and choline-deficient diet

    OpenAIRE

    WANG, YUNLIANG; LI, JIAN; ZHUGE, LI; SU, DONGMEI; YANG, MEIJUAN; TAO, SHIYING; LI, JUNXIANG

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease, which features an abnormal accumulation of lipids inside hepatocytes. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Curcumin and puerarin are herbal products widely used in Asia, which are believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. In this study, mice models of steatohepatitis induced by a methionine- and choline-deficient diet (MCD) w...

  7. Structural and Spectral Properties of Curcumin and Metal- Curcumin Complex Derived from Turmeric (Curcuma longa)

    Science.gov (United States)

    Bich, Vu Thi; Thuy, Nguyen Thi; Binh, Nguyen Thanh; Huong, Nguyen Thi Mai; Yen, Pham Nguyen Dong; Luong, Tran Thanh

    Structural and spectral properties of curcumin and metal- curcumin complex derived from turmeric (Curcuma longa) were studied by SEM and vibrational (FTIR and Raman) techniques. By comparison between curcumin commercial, fresh turmeric and a yellow powder obtained via extraction and purification of turmeric, we have found that this insoluble powder in water is curcumin. The yellow compound could complex with certain ion metal and this metal-curcumin coloring complex is water soluble and capable of producing varying hues of the same colors and having antimicrobial, cytotoxicity activities for use in foodstuffs and pharmacy. The result also demonstrates that Micro-Raman spec-troscopy is a valuable non-destructive tool and fast for investigation of a natural plant even when occurring in low concentrations.

  8. Antiangiogenic effects of synthetic analogs of curcumin in vivo ...

    African Journals Online (AJOL)

    The active compound curcumin is isolated from the spice turmeric. Curcumin, curcuminoids and their synthetic analogs have been shown to inhibit the progression of cancer in animal models. In colon and skin carcinogenesis the genetic changes engross different genes, but curcumin is effective in preventing ...

  9. β-Cyclodextrin-curcumin complex inhibit telomerase gene ...

    African Journals Online (AJOL)

    Yomi

    2011-12-21

    Dec 21, 2011 ... have various applications in cancer therapy. But, its low water solubility and bioavailability is possible for poor drug delivery of curcumin. In this study, we prepared β-cyclodextrin-curcumin complex to determine the inhibitory effect of this drug on telomerase gene expression. Curcumin was encapsulated.

  10. Curcumin inhibits amygdaloid kindled seizures in rats.

    Science.gov (United States)

    DU, Peng; Li, Xin; Lin, Hao-Jie; Peng, Wei-Feng; Liu, Jian-Ying; Ma, Yu; Fan, Wei; Wang, Xin

    2009-06-20

    Curcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats. With an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses. Curcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds). Our study suggests that curcumin has

  11. Comparison of Inhibitory Effect of Curcumin Nanoparticles and Free Curcumin in Human Telomerase Reverse Transcriptase Gene Expression in Breast Cancer

    OpenAIRE

    Nosratollah Zarghami; Abbas Rami; Fatemeh Kazemi-Lomedasht

    2013-01-01

    Purpose: Telomerase is expressed in most cancers, including breast cancer. Curcumin, a polyphenolic compound that obtained from the herb of Curcuma longa, has many anticancer effects. But, its effect is low due to poor water solubility. In order to improve its solubility and drug delivery, we have utilized a β-cyclodextrin-curcumin inclusion complex. Methods: To evaluate cytotoxic effects of cyclodextrin-curcumin and free curcumin, MTT assay was done. Cells were treated with equal concentrati...

  12. Comparison of Inhibitory Effect of Curcumin Nanoparticles and Free Curcumin in Human Telomerase Reverse Transcriptase Gene Expression in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Nosratollah Zarghami

    2013-02-01

    Full Text Available Purpose: Telomerase is expressed in most cancers, including breast cancer. Curcumin, a polyphenolic compound that obtained from the herb of Curcuma longa, has many anticancer effects. But, its effect is low due to poor water solubility. In order to improve its solubility and drug delivery, we have utilized a β-cyclodextrin-curcumin inclusion complex. Methods: To evaluate cytotoxic effects of cyclodextrin-curcumin and free curcumin, MTT assay was done. Cells were treated with equal concentration of cyclodextrin-curcumin and free curcumin. Telomerase gene expression level in two groups was compared by Real-time PCR. Results: MTT assay demonstrated that β-cyclodextrin-curcumin enhanced curcumin delivery in T47D breast cancer cells. The level of telomerase gene expression in cells treated with cyclodextrin-curcumin was lower than that of cells treated with free curcumin (P=0.001. Conclusion: Results are suggesting that cyclodextrin-curcumin complex can be more effective than free curcumin in inhibition of telomerase expression.

  13. Curcumin inhibits aggregation of alpha-synuclein.

    Science.gov (United States)

    Pandey, Neeraj; Strider, Jeffrey; Nolan, William C; Yan, Sherry X; Galvin, James E

    2008-04-01

    Aggregation of amyloid-beta protein (Abeta) is a key pathogenic event in Alzheimer's disease (AD). Curcumin, a constituent of the Indian spice Turmeric is structurally similar to Congo Red and has been demonstrated to bind Abeta amyloid and prevent further oligomerization of Abeta monomers onto growing amyloid beta-sheets. Reasoning that oligomerization kinetics and mechanism of amyloid formation are similar in Parkinson's disease (PD) and AD, we investigated the effect of curcumin on alpha-synuclein (AS) protein aggregation. In vitro model of AS aggregation was developed by treatment of purified AS protein (wild-type) with 1 mM Fe3+ (Fenton reaction). It was observed that the addition of curcumin inhibited aggregation in a dose-dependent manner and increased AS solubility. The aggregation-inhibiting effect of curcumin was next investigated in cell culture utilizing catecholaminergic SH-SY5Y cell line. A model system was developed in which the red fluorescent protein (DsRed2) was fused with A53T mutant of AS and its aggregation examined under different concentrations of curcumin. To estimate aggregation in an unbiased manner, a protocol was developed in which the images were captured automatically through a high-throughput cell-based screening microscope. The obtained images were processed automatically for aggregates within a defined dimension of 1-6 microm. Greater than 32% decrease in mutant alpha-synuclein aggregation was observed within 48 h subsequent to curcumin addition. Our data suggest that curcumin inhibits AS oligomerization into higher molecular weight aggregates and therefore should be further explored as a potential therapeutic compound for PD and related disorders.

  14. Curcumin: getting back to the roots.

    Science.gov (United States)

    Shishodia, Shishir; Sethi, Gautam; Aggarwal, Bharat B

    2005-11-01

    The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."

  15. Olive (Olea europaea) leaf methanolic extract prevents HCl/ethanol-induced gastritis in rats by attenuating inflammation and augmenting antioxidant enzyme activities.

    Science.gov (United States)

    Al-Quraishy, Saleh; Othman, Mohamed S; Dkhil, Mohamed A; Abdel Moneim, Ahmed Esmat

    2017-07-01

    Gastritis is preponderantly characterized by inflammation of the lining epithelial layer and the chronic gastritis is considered as a pre-cancer lesion. For many centuries olive (Olea europaea) leaf has been used for its putative health potential, nonetheless, to date, the gastroprotective effects of olive leaves have not been studied yet. Hence, in this study we investigated whether olive leaf extract (OLE) could protect gastric mucosa against HCl/ethanol-induced gastric mucosal damage in rats. Hcl/ethanol administration caused significant damage to the gastric mucosa, as confirmed by gastric ulcer index and histological evaluation. However, this damage was largely prevented by pre-administering 20mg/kg omeprazole or 100mg/kg OLE. Interestingly, the damage was completely prevented by pre-administering 200 and 300mg/kg OLE. Moreover, OLE attenuated the inflammatory response by decreasing nuclear factor-κB (NF-κB), cycloxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expressions, and down-regulating inducible nitric oxide synthase (iNOS) and interleukin-1β (IL-1β) in gastric mucosa. The gastroprotective mechanism of OLE involved the promotion of enzymatic and nonenzymatic molecules (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione reduced form), promoting nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression, halting lipid peroxidation and preventing the overproduction of nitric oxide. Together, our findings clearly demonstrated that OLE could prevent HCl/ethanol-induced gastritis by attenuating inflammation and oxidant/antioxidant imbalance. Indeed, OLE could potentially be useful as a natural therapy for gastritis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors

    Directory of Open Access Journals (Sweden)

    Tingling Joseph D

    2005-09-01

    Full Text Available Abstract Background The fetal cortical neuroepithelium is a mosaic of distinct progenitor populations that elaborate diverse cellular fates. Ethanol induces apoptosis and interferes with the survival of differentiating neurons. However, we know little about ethanol's effects on neuronal progenitors. We therefore exposed neurosphere cultures from fetal rat cerebral cortex, to varying ethanol concentrations, to examine the impact of ethanol on stem cell fate. Results Ethanol promoted cell cycle progression, increased neurosphere number and increased diversity in neurosphere size, without inducing apoptosis. Unlike controls, dissociated cortical progenitors exposed to ethanol exhibited morphological evidence for asymmetric cell division, and cells derived from ethanol pre-treated neurospheres exhibited decreased proliferation capacity. Ethanol significantly reduced the numbers of cells expressing the stem cell markers CD117, CD133, Sca-1 and ABCG2, without decreasing nestin expression. Furthermore, ethanol-induced neurosphere proliferation was not accompanied by a commensurate increase in telomerase activity. Finally, cells derived from ethanol-pretreated neurospheres exhibited decreased differentiation in response to retinoic acid. Conclusion The reduction in stem cell number along with a transient ethanol-driven increase in cell proliferation, suggests that ethanol promotes stem to blast cell maturation, ultimately depleting the reserve proliferation capacity of neuroepithelial cells. However, the lack of a concomitant change in telomerase activity suggests that neuroepithelial maturation is accompanied by an increased potential for genomic instability. Finally, the cellular phenotype that emerges from ethanol pre-treated, stem cell depleted neurospheres is refractory to additional differentiation stimuli, suggesting that ethanol exposure ablates or delays subsequent neuronal differentiation.

  17. Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-кB pathway.

    Science.gov (United States)

    Zhao, Zhongyan; Gong, Shilin; Wang, Shumin; Ma, Chunhua

    2015-09-01

    Evodiamine (EVD), a major alkaloid compound extracted from the dry unripened fruit Evodia fructus (Evodia rutaecarpa Benth., Rutaceae), has various pharmacological effects. The purpose of the present study was to investigate the possible anti-ulcerogenic potential of EVD and explore the underlying mechanism against ethanol-induced gastric ulcer in mice. Administration of EVD at the doses of 20, 40mg/kg body weight prior to the ethanol ingestion could effectively protect the stomach from ulceration. The gastric lesion was significantly ameliorated in the EVD group compared with that in the model group. Pre-treatment with EVD prevented the oxidative damage and decreased the levels of prostaglandin E2 (PGE2) content, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, EVD pretreatment markedly increased the serum levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), decreased malonaldehyde (MDA) content in serum and activity of myeloperoxidase (MPO) in stomach tissues compared with those in the model group. In the mechanistic study, significant elevation of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 expressions were observed in the gastric mucosa group, whereas EVD effectively suppressed the protein expressions of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 in mice. Moreover, EVD showed protective activity on ethanol-induced GES-1 cells, while the therapeutic effects were not due to its cytotoxity. Taken together, these results strongly indicated that EVD exerted a gastro-protective effect against gastric ulceration. The underlying mechanism might be associated with the improvement of antioxidant and anti-inflammatory status through Rho/NF-κB pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Determining whether curcumin degradation/condensation is actually bioactivation (Review).

    Science.gov (United States)

    Jankun, Jerzy; Wyganowska-Świątkowska, Marzena; Dettlaff, Katarzyna; Jelińska, Anna; Surdacka, Anna; Wątróbska-Świetlikowska, Dorota; Skrzypczak-Jankun, Ewa

    2016-05-01

    Curcumin has been shown to exert therapeutic or protective effects against a variety of diseases, such as cancer, pulmonary diseases, neurological, liver, metabolic, autoimmune, cardiovascular diseases and numerous other chronic ailments. Over 116 clinical studies on curcumin in humans were registered with the US National Institutes of Health in 2015. However, it is mystifying how curcumin can be so effective in the treatment of many diseases since it has very low water solubility and bioavailability. Furthermore, curcumin is not stable under various conditions; its degradation or condensation into different bioactive compounds may be responsible for its biological activities rather than curcumin itself. In this review, we provide evidence of curcumin degradation and condensation into different compounds which have or may have health benefits themselves. Literature reviews strongly suggest that these molecules contribute to the observed health benefits, rather than curcumin itself.

  19. Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

    Science.gov (United States)

    Wu, Xiang; Chen, Huixin; Huang, Chunhui; Gu, Xinmei; Wang, Jialing; Xu, Dilin; Yu, Xin; Shuai, Chu; Chen, Liping; Li, Shun; Xu, Yiguo; Gao, Tao; Ye, Mingrui; Su, Wei; Liu, Haixiong; Zhang, Jinrong; Wang, Chuang; Chen, Junping; Wang, Qinwen; Cui, Wei

    2017-06-01

    Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

  20. Alleviating energy poverty: Indian experience

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Garima

    2010-09-15

    Energy services play an important role in human welfare. India faces acute energy poverty indicating lack of access of clean energy fuels. Access to electricity is limited to 56% households in India and about 89% of rural households depend on polluting energy sources. Energy poverty impacts income poverty as poor find it difficult to acquire high priced cleaner fuels. It also adversely impacts the socio economic conditions of women. The paper highlights the linkage of energy poverty with income poverty and gender inequality. It analyses measures taken to alleviate energy poverty and recommends regulatory and policy measures as way forward.

  1. Protective effect and its mechanism of curcumin on ischemia-reperfusion injury of cerebral cortex in rats

    Directory of Open Access Journals (Sweden)

    Li LIU

    2013-03-01

    Full Text Available Objective  To investigate the effect of curcumin pretreatment on the expression of uncoupling protein 2 (UCP2 and mitochondrial transcription factor A (MTFA in rats' cerebral cortex against focal ischemia reperfusion injury. Methods  Eighty male SD rats weighed 220g–300g were randomly divided into 4 groups: sham-operated group, ischemia/reperfusion (I/R group, curcumine 50mg/kg+I/R (low dose group, and curcumine 100mg/kg+I/R (high dose group. The common carotid artery, external carotid artery and internal carotid artery on the right side were exposed in the sham-operated group. Animals of the other groups were subjected to a 2-hour period of right middle cerebral artery occlusion, followed by 24 hours of reperfusion, and then they were sacrificed. Curcumin was administered (ip in a dose of 50mg/kg (low dose group or 100mg/kg (high dose group for 5 days, respectively, prior to arterial occlusion. The pathological changes in neurons and their mitochondria in the cerebral cortex supplied by middle cerebral artery were observed with Nissl staining and electron microscope, respectively. The expressions of UCP2 and MTFA in corresponding cotex were assessed by immunohistochemistry and RT-PCR. Results  Compared with sham-operated group, animals in I/R group presented edema of neurons in the corresponding cortex, reduction in the number of Nissl bodies, and swelling of mitochondria with broken, even lysis of cristae. Low dose and high dose of curcumin pretreatment before brain ischemia significantly alleviated the loss of neurons and the damage of mitochondria, accompanied with an increase in the expression of UCP2 and TFAM (P<0.05, and the changes appeared a dose-dependent manner (P<0.05. Conclusions  Curcumin may prevent neurons from focal cerebral ischemia reperfusion injury by up-regulating UCP2 and MTFA. Regulation of mitochondrial biogenesis may probably be a potential target of curcumin as a neuroprotective drug.

  2. Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury

    Science.gov (United States)

    2014-01-01

    Background Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with potent anti-inflammatory properties that is extracted from the rhizome Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following TBI. Methods Neurological function, brain water content and cytokine levels were tested in TLR4-/- mice subjected to weight-drop contusion injury. Wild-type (WT) mice were injected intraperitoneally with different concentrations of curcumin or vehicle 15 minutes after TBI. At 24 hours post-injury, the activation of microglia/macrophages and TLR4 was detected by immunohistochemistry; neuronal apoptosis was measured by FJB and TUNEL staining; cytokines were assayed by ELISA; and TLR4, MyD88 and NF-κB levels were measured by Western blotting. In vitro, a co-culture system comprised of microglia and neurons was treated with curcumin following lipopolysaccharide (LPS) stimulation. TLR4 expression and morphological activation in microglia and morphological damage to neurons were detected by immunohistochemistry 24 hours post-stimulation. Results The protein expression of TLR4 in pericontusional tissue reached a maximum at 24 hours post-TBI. Compared with WT mice, TLR4-/- mice showed attenuated functional impairment, brain edema and cytokine release post-TBI. In addition to improvement in the above aspects, 100 mg/kg curcumin treatment post-TBI significantly reduced the number of TLR4-positive microglia/macrophages as well as inflammatory mediator release and neuronal apoptosis in WT mice. Furthermore, Western blot analysis indicated that the levels of TLR4 and its known downstream effectors (MyD88, and NF-κB) were also decreased after curcumin treatment. Similar outcomes were observed in the microglia and

  3. Iron-Mediated Lysosomal Membrane Permeabilization in Ethanol-Induced Hepatic Oxidative Damage and Apoptosis: Protective Effects of Quercetin

    Directory of Open Access Journals (Sweden)

    Yanyan Li

    2016-01-01

    Full Text Available Iron, in its free ferrous states, can catalyze Fenton reaction to produce OH∙, which is recognized as a crucial role in the pathogenesis of alcoholic liver diseases (ALD. As a result of continuous decomposition of iron-containing compounds, lysosomes contain a pool of redox-active iron. To investigate the important role of intralysosomal iron in alcoholic liver injury and the potential protection of quercetin, male C57BL/6J mice fed by Lieber De Carli diets containing ethanol (30% of total calories were cotreated by quercetin or deferoxamine (DFO for 15 weeks and ethanol-incubated mice primary hepatocytes were pretreated with FeCl3, DFO, and bafilomycin A1 at their optimal concentrations and exposure times. Chronic ethanol consumption caused an evident increase in lysosomal redox-active iron accompanying sustained oxidative damage. Iron-mediated ROS could trigger lysosomal membrane permeabilization (LMP and subsequent mitochondria apoptosis. The hepatotoxicity was attenuated by reducing lysosomal iron while being exacerbated by escalating lysosomal iron. Quercetin substantially alleviated the alcoholic liver oxidative damage and apoptosis by decreasing lysosome iron and ameliorating iron-mediated LMP, which provided a new prospective of the use of quercetin against ALD.

  4. Curcumin and diabetes: a systematic review.

    Science.gov (United States)

    Zhang, Dong-Wei; Fu, Min; Gao, Si-Hua; Liu, Jun-Li

    2013-01-01

    Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant of the ginger family, has been used for the treatment of diabetes in Ayurvedic and traditional Chinese medicine. The active component of turmeric, curcumin, has caught attention as a potential treatment for diabetes and its complications primarily because it is a relatively safe and inexpensive drug that reduces glycemia and hyperlipidemia in rodent models of diabetes. Here, we review the recent literature on the applications of curcumin for glycemia and diabetes-related liver disorders, adipocyte dysfunction, neuropathy, nephropathy, vascular diseases, pancreatic disorders, and other complications, and we also discuss its antioxidant and anti-inflammatory properties. The applications of additional curcuminoid compounds for diabetes prevention and treatment are also included in this paper. Finally, we mention the approaches that are currently being sought to generate a "super curcumin" through improvement of the bioavailability to bring this promising natural product to the forefront of diabetes therapeutics.

  5. Detoxification and antioxidant effects of garlic and curcumin in Oreochromis niloticus injected with aflatoxin B₁ with reference to gene expression of glutathione peroxidase (GPx) by RT-PCR.

    Science.gov (United States)

    El-Barbary, Manal I

    2016-04-01

    The present study aims to investigate the effects of both garlic and curcumin through evaluating their therapeutic properties as antioxidants on liver and kidney functions, hepatic antioxidants and GPx gene expression against aflatoxicosis of O. niloticus. In total, 180 of tilapia were divided into ten groups; T1 represented the negative control fed on a basal diet, and T2 was injected with a single intraperitoneal (i.p.) dose of AFB1 (6 mg/kg b.w.). Fish in T3-T6 were fed on a basal diet supplemented with both garlic (T3 and T4) and curcumin (T5 and T6) at the two concentrations of 10 and 20 g/kg diet, respectively. Fish in T7-T10 groups were injected with AFB1 and fed on the garlic (T7 and T8) and curcumin (T9 and T10) dietaries. The results showed that AFB1 has significant potency for increasing the activity of plasma AST, ALT, creatinine and uric acid values, and hepatic MDA as well as for reducing the concentrations of plasma TP, AL, GL and hepatic activity of TAC, while AFB1 led to up-regulated GPx gene expression when compared to the control (T1). These harmful effects of AFB1 were alleviated due to the garlic and curcumin dietaries in some studied parameters. Garlic reflected the highest induction of gene expression (T7); however, curcumin showed significant down-regulated (T9). These results concluded that the effects of garlic were better than curcumin at the two concentrations and the low concentration of them is more beneficial than the high concentration when it used against AFB1 in O. niloticus.

  6. Absorption and fluorescence studies of curcumin bound to liposomes and lymphocytes: effect of {gamma}- irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kunwar, Amit; Barik, A; Indira Priyadarsini, K [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai (India); Pandey, R [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai (India)

    2006-01-15

    Absorption and fluorescence spectral changes in curcumin were employed to follow its binding to liposomes and lymphocytes. The association constants indicated high affinity of curcumin to liposomes. Tumor lymphocytes show mere intense fluorescence of curcumin over the normal lymphocytes. The loss of curcumin in cells after {gamma}-irradiation could be followed by reduction in curcumin fluorescence. The studies indicate that such fluorescence changes can be used as markers to understand the preferential loading of curcumin to cells. (author)

  7. Absorption and fluorescence studies of curcumin bound to liposomes and lymphocytes: effect of γ- irradiation

    International Nuclear Information System (INIS)

    Kunwar, Amit; Barik, A.; Indira Priyadarsini, K.; Pandey, R.

    2006-01-01

    Absorption and fluorescence spectral changes in curcumin were employed to follow its binding to liposomes and lymphocytes. The association constants indicated high affinity of curcumin to liposomes. Tumor lymphocytes show mere intense fluorescence of curcumin over the normal lymphocytes. The loss of curcumin in cells after γ-irradiation could be followed by reduction in curcumin fluorescence. The studies indicate that such fluorescence changes can be used as markers to understand the preferential loading of curcumin to cells. (author)

  8. Transdermal delivery of curcumin via microemulsion.

    Science.gov (United States)

    Sintov, Amnon C

    2015-03-15

    The objective of this study was to evaluate the transdermal delivery potential of a new curcumin-containing microemulsion system. Three series of experiments were carried out to comprehend the system characteristics: (a) examining the influence of water content on curcumin permeation, (b) studying the effect of curcumin loading on its permeability, and (c) assessing the contribution of the vesicular nature of the microemulsion on permeability. The skin permeability of curcumin from microemulsions, which contained 5%, 10%, and 20% of water content (1% curcumin), was measured in vitro using excised rat skin. It has been shown that the permeability coefficient of CUR in a formulation containing 10% aqueous phase (ME-10) was twofold higher than the values obtained for formulations with 5% and 20% water (Papp=0.116 × 10(-3)± 0.052 × 10(-3)vs. 0.043 × 10(-3)± 0.022 × 10(-3) and 0.047 × 10(-3)± 0.025 × 10(-3)cm/h, respectively. A reasonable explanation for this phenomenon may be the reduction of both droplet size and droplets' concentration in the microemulsion as the aqueous phase decreased from 20% to 5%. It has also been shown that a linear correlation exists between the decrease in droplet size and the increase of curcumin loading in the microemulsion. In addition, it has been demonstrated that a micellar system, S/O-mix, and a plain solution of curcumin resulted in a significantly lower curcumin permeation relative to that presented by the microemulsion, Papp=0.018 × 10(-3)± 0.011 × 10(-3), 0.005 × 10(-3)± 0.002 × 10(-3), and 0.002 × 10(-3)± 0.000 × 10(-3)cm/h, respectively, vs. 0.110 × 10(-3)± 0.021 × 10(-3)cm/h for the microemulsion. The enhancement ratio (ER=Jss-ME/Jss-solution) of CUR permeated via 1% loaded microemulsion was 55. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Curcumin as potential therapeutic natural product: a nanobiotechnological perspective.

    Science.gov (United States)

    Shome, Soumitra; Talukdar, Anupam Das; Choudhury, Manabendra Dutta; Bhattacharya, Mrinal Kanti; Upadhyaya, Hrishikesh

    2016-12-01

    Nanotechnology-based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite preparation of curcumin with metal oxide nanoparticles, poly lactic-co-glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue. Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti-inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress-induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination. Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness. © 2016 Royal Pharmaceutical Society.

  10. Curcumin as a potential protective compound against cardiac diseases.

    Science.gov (United States)

    Jiang, Shuai; Han, Jing; Li, Tian; Xin, Zhenlong; Ma, Zhiqiang; Di, Wencheng; Hu, Wei; Gong, Bing; Di, Shouyin; Wang, Dongjin; Yang, Yang

    2017-05-01

    Curcumin, which was first used 3000 years ago as an anti-inflammatory agent, is a well-known bioactive compound derived from the active ingredient of turmeric (Curcuma longa). Previous research has demonstrated that curcumin has immense therapeutic potential in a variety of diseases via anti-oxidative, anti-apoptotic, and anti-inflammatory pathways. Cardiac diseases are the leading cause of mortality worldwide and cause considerable harm to human beings. Numerous studies have suggested that curcumin exerts a protective role in the human body whereas its actions in cardiac diseases remain elusive and poorly understood. On the basis of the current evidence, we first give a brief introduction of cardiac diseases and curcumin, especially regarding the effects of curcumin in embryonic heart development. Secondly, we analyze the basic roles of curcumin in pathways that are dysregulated in cardiac diseases, including oxidative stress, apoptosis, and inflammation. Thirdly, actions of curcumin in different cardiac diseases will be discussed, as will relevant clinical trials. Eventually, we would like to discuss the existing controversial opinions and provide a detailed analysis followed by the remaining obstacles, advancement, and further prospects of the clinical application of curcumin. The information compiled here may serve as a comprehensive reference of the protective effects of curcumin in the heart, which is significant to the further research and design of curcumin analogs as therapeutic options for cardiac diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Recent developments in curcumin and curcumin based polymeric materials for biomedical applications: A review.

    Science.gov (United States)

    Mahmood, Kashif; Zia, Khalid Mahmood; Zuber, Mohammad; Salman, Mahwish; Anjum, Muhammad Naveed

    2015-11-01

    Turmeric (Curcuma longa) is a popular Indian spice that has been used for centuries in herbal medicines for the treatment of a variety of ailments such as rheumatism, diabetic ulcers, anorexia, cough and sinusitis. Curcumin (diferuloylmethane) is the main curcuminoid present in turmeric and responsible for its yellow color. Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anticoagulant and anti-infective effects. This review summarizes and discusses recently published papers on the key biomedical applications of curcumin based materials. The highlighted studies in the review provide evidence of the ability of curcumin to show the significant vitro antioxidant, diabetic complication, antimicrobial, neuroprotective, anti-cancer activities and detection of hypochlorous acid, wound healing, treatment of major depression, healing of paracentesis, and treatment of carcinoma and optical detection of pyrrole properties. Hydrophobic nature of this polyphenolic compound along with its rapid metabolism, physicochemical and biological instability contribute to its poor bioavailability. To redress these problems several approaches have been proposed like encapsulation of curcumin in liposomes and polymeric micelles, inclusion complex formation with cyclodextrin, formation of polymer-curcumin conjugates, etc. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Preparation of curcumin nanoparticle by using reinforcement ionic gelation technique

    Science.gov (United States)

    Suryani, Halid, Nur Hatidjah Awaliyah; Akib, Nur Illiyyin; Rahmanpiu, Mutmainnah, Nina

    2017-05-01

    Curcumin, a polyphenolic compound present in curcuma longa has a wide range of activities including anti-inflammatory properties. The potency of curcumin is limited by its poor oral bioavailability because of its poor solubility in aqueous. Various methods have been tried to solve the problem including its encapsulation into nanoparticle. The aim of this study is to develop curcumin nanoparticle by using reinforcement ionic gelation technique and to evaluate the stability of curcumin nanoparticles in gastrointestinal fluid. Curcumin nanoparticles were prepared by using reinforcement ionic gelation technique with different concentrations of chitosan, trypolyphosphate, natrium alginate and calcium chloride. Curcumin nanoparticles were then characterized including particle size and zeta potential by using particle size analyzer and morphology using a transmission electron microscope, entrapment efficiency using UV-Vis Spectrophotometer and chemical structure analysis by Infra Red Spectrophotometer (FTIR). Furthermore, the stability of curcumin nanoparticles were evaluated on artificial gastric fluid and artificial intestinal fluids by measuring the amount of curcumin released in the medium at a time interval. The result revealed that curcumin nanoparticles can be prepared by reinforcement ionic gelation technique, the entrapment efficiency of curcumin nanoparticles were from 86.08 to 91.41%. The average of particle size was 272.9 nm and zeta potential was 12.05 mV. The morphology examination showed that the curcumin nanoparticles have spherical shape. The stability evaluation of curcumin nanoparticles showed that the nanoparticles were stable on artificial gastric fluid and artificial intestinal fluid. This result indicates that curcumin nanoparticles have the potential to be developed for oral delivery.

  13. Molecular mechanisms of anti-angiogenic effect of curcumin.

    Science.gov (United States)

    Gururaj, Anupama E; Belakavadi, Madesh; Venkatesh, Deepak A; Marmé, Dieter; Salimath, Bharathi P

    2002-10-04

    Modulation of pathological angiogenesis by curcumin (diferuloylmethane), the active principle of turmeric, seems to be an important possibility meriting mechanistic investigations. In this report, we have studied the effect of curcumin on the growth of Ehrlich ascites tumor cells and endothelial cells in vitro. Further, regulation of tumor angiogenesis by modulation of angiogenic ligands and their receptor gene expression in tumor and endothelial cells, respectively, by curcumin was investigated. Curcumin, when injected intraperitoneally (i.p) into mice, effectively decreased the formation of ascites fluid by 66% in EAT bearing mice in vivo. Reduction in the number of EAT cells and human umbelical vein endothelial cells (HUVECs) in vitro by curcumin, without being cytotoxic to these cells, is attributed to induction of apoptosis by curcumin, as is evident by an increase in cells with fractional DNA content seen in our results on FACS analysis. However, curcumin had no effect on the growth of NIH3T3 cells. Curcumin proved to be a potent angioinhibitory compound, as demonstrated by inhibition of angiogenesis in two in vivo angiogenesis assay systems, viz. peritoneal angiogenesis and chorioallantoic membrane assay. The angioinhibitory effect of curcumin in vivo was corroborated by the results on down-regulation of the expression of proangiogenic genes, in EAT, NIH3T3, and endothelial cells by curcumin. Our results on Northern blot analysis clearly indicated a time-dependent (0-24h) inhibition by curcumin of VEGF, angiopoietin 1 and 2 gene expression in EAT cells, VEGF and angiopoietin 1 gene expression in NIH3T3 cells, and KDR gene expression in HUVECs. Further, decreased VEGF levels in conditioned media from cells treated with various doses of curcumin (1 microM-1mM) for various time periods (0-24h) confirm its angioinhibitory action at the level of gene expression. Because of its non-toxic nature, curcumin could be further developed to treat chronic diseases that

  14. Physiological barriers to the oral delivery of curcumin.

    Science.gov (United States)

    Berginc, K; Trontelj, J; Basnet, N Skalko; Kristl, A

    2012-06-01

    Curcumin, a principal component from Curcuma longa, with antioxidant and anti-inflammatory activities was proposed as a potential candidate for the preventation and/or treatment of cancer and chronic diseases. However, curcumin could not achieve its expected therapeutic outcome in clinical trials due to its low solubility and poor bioavailability. The actual intestinal physiological barriers limiting curcumin absorption after oral administration have not been fully investigated. To identify the main barriers curtailing its absorption, in vitro permeability of curcumin and flux of its glucuronide were monitored in rat jejunum and Transwell grown Caco-2 cells. Curcumin was more permeable under acidic conditions, but the permeability was substantially below the permeability of highly permeable standards. Its efflux could not be inhibited by specific Pgp and MRP inhibitors. BCRP was found to participate in curcumin transport, but the Organic Anion Transporting Polypeptide (OATP) did not. The permeability of curcumin significantly increased when the structure of mucus was compromised. The inhibitor of curcumin metabolism, piperin, failed to act as a permeability enhancer. Piperin inhibited Pgp and MRP transporters and decreased the amount of glucuronide transported back into the intestine. Inclusion of piperin in curcumin-containing formulations is highly recommended as to inhibit curcumin glucuronidation and to increase the transport of formed glucuronides into the plasma, therefore increasing the probability of glucuronide distribution into target tissue and inter-convertion to curcumin. It would also be beneficial, if curcumin delivery systems could reversibly compromise the mucous integrity to minimize the non-specific binding of curcumin to its constituents.

  15. Supramolecular curcumin-barium prodrugs for formulating with ceramic particles.

    Science.gov (United States)

    Kamalasanan, Kaladhar; Anupriya; Deepa, M K; Sharma, Chandra P

    2014-10-01

    A simple and stable curcumin-ceramic combined formulation was developed with an aim to improve curcumin stability and release profile in the presence of reactive ceramic particles for potential dental and orthopedic applications. For that, curcumin was complexed with barium (Ba(2+)) to prepare curcumin-barium (BaCur) complex. Upon removal of the unbound curcumin and Ba(2+) by dialysis, a water-soluble BaCur complex was obtained. The complex was showing [M+1](+) peak at 10,000-20,000 with multiple fractionation peaks of MALDI-TOF-MS studies, showed that the complex was a supramolecular multimer. The (1)H NMR and FTIR studies revealed that, divalent Ba(2+) interacted predominantly through di-phenolic groups of curcumin to form an end-to-end complex resulted in supramolecular multimer. The overall crystallinity of the BaCur was lower than curcumin as per XRD analysis. The complexation of Ba(2+) to curcumin did not degrade curcumin as per HPLC studies. The fluorescence spectrum was blue shifted upon Ba(2+) complexation with curcumin. Monodisperse nanoparticles with size less than 200dnm was formed, out of the supramolecular complex upon dialysis, as per DLS, and upon loading into pluronic micelles the size was remaining in similar order of magnitude as per DLS and AFM studies. Stability of the curcumin was improved greater than 50% after complexation with Ba(2+) as per UV/Vis spectroscopy. Loading of the supramloecular nanoparticles into pluronic micelles had further improved the stability of curcumin to approx. 70% in water. These BaCur supramolecule nanoparticles can be considered as a new class of prodrugs with improved solubility and stability. Subsequently, ceramic nanoparticles with varying chemical composition were prepared for changing the material surface reactivity in terms of the increase in, degradability, surface pH and protein adsorption. Further, these ceramic particles were combined with curcumin prodrug formulations and optimized the curcumin release

  16. PROSPECTS OF CURCUMIN USE IN NANOBIOTECHNOLOGY

    Directory of Open Access Journals (Sweden)

    M. I. Kaniuk

    2016-06-01

    Full Text Available The aim of the work was a generalization of literature data on the prospects for curcumin usage in biotechnology as a component for biologically active nanocomplexes with anti-inflammatory and antioxidant activity creation. It is emphasized that their effectiveness depends on the solubility in aqueous medium and on the metabolism rate decreasing in the body. Current trend is the development of creation methods of hydrophilic curcumin-based nanostructures to increase the time of its biological action. Its nanostructures with silicium, polylysine, copolymers of lactic and glycolic acids and metal ions are the most promising in this respect. For multicomponent hybrid nanoparticles effective usage the substantiation of their component combined use features is necessary. The practical task is to create and to study the functional properties of such combined nanocomplexes. Curcumin complex with metal ions creation contributes to its water solubility and to increase the efficiency of biological action. These complexes have specific characteristics depending on the nature of metal ion. The creation of curcumin-based biocompatible nanocomposites with amplifiers of its action that are known pharmaceuticals is perspective. Such multifunctional nanocomplexes will facilitate the targeted medicines delivery to the places of pathological processes localization and the reduction of their side effects.

  17. Protective Effects of Tetrahydrocurcumin and Curcumin against ...

    African Journals Online (AJOL)

    Purpose: To investigate the cytoprotective effect of tetrahydrocurcumin, (THC) and curcumin (CUR) on cytotoxicity induced by doxorubicin and cadmium in Chang liver cells. Methods: Cytotoxicity was determined by sulforhodamine B assay. The expression of nuclear factorerythroid- 2-related factor 2 (Nrf2) Nrf2 regulated ...

  18. A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin

    Science.gov (United States)

    Zorofchian Moghadamtousi, Soheil; Abdul Kadir, Habsah; Hassandarvish, Pouya; Tajik, Hassan; Abubakar, Sazaly; Zandi, Keivan

    2014-01-01

    Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent. PMID:24877064

  19. A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin

    Directory of Open Access Journals (Sweden)

    Soheil Zorofchian Moghadamtousi

    2014-01-01

    Full Text Available Curcuma longa L. (Zingiberaceae family and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent.

  20. Enzymatic Synthesis and Anti-Allergic Activities of Curcumin Oligosaccharides

    Directory of Open Access Journals (Sweden)

    Kei Shimoda

    2010-01-01

    Full Text Available Curcumin 4‘- O -glucooligosaccharides were synthesized by a two step-enzymatic method using almond β-glucosidase and cyclodextrin glucanotransferase (CGTase. Curcumin was glucosylated to curcumin 4‘- O -β-D-glucopyranoside by almond β-glucosidase in 19% yield. Curcumin 4‘- O -β-D-glucopyranoside was converted into curcumin 4‘- O -β-glucooligosaccharides, i.e. 4‘- O -β-maltoside (51% and 4‘- O -β-maltotrioside (25%, by further CGTase-catalyzed glycosylation. Curcumin 4‘- O -β-glycosides showed suppressive action on IgE antibody formation and inhibitory effects on histamine release from rat peritoneal mast cells.

  1. Curcumin prevents human dendritic cell response to immune stimulants

    International Nuclear Information System (INIS)

    Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

    2008-01-01

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14 + monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4 + T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant

  2. Biological and therapeutic activities, and anticancer properties of curcumin.

    Science.gov (United States)

    Perrone, Donatella; Ardito, Fatima; Giannatempo, Giovanni; Dioguardi, Mario; Troiano, Giuseppe; Lo Russo, Lucio; DE Lillo, Alfredo; Laino, Luigi; Lo Muzio, Lorenzo

    2015-11-01

    Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Curcumin has been used extensively in Ayurvedic medicine, as it is nontoxic and exhibits a variety of therapeutic properties, including antioxidant, analgesic, anti-inflammatory and antiseptic activities. Recently, certain studies have indicated that curcumin may exert anticancer effects in a variety of biological pathways involved in mutagenesis, apoptosis, tumorigenesis, cell cycle regulation and metastasis. The present study reviewed previous studies in the literature, which support the therapeutic activity of curcumin in cancer. In addition, the present study elucidated a number of the challenges concerning the use of curcumin as an adjuvant chemotherapeutic agent. All the studies reviewed herein suggest that curcumin is able to exert anti-inflammatory, antiplatelet, antioxidative, hepatoprotective and antitumor activities, particularly against cancers of the liver, skin, pancreas, prostate, ovary, lung and head neck, as well as having a positive effect in the treatment of arthritis.

  3. Curcumin in chemoprevention of breast cancer

    Directory of Open Access Journals (Sweden)

    Katarzyna Terlikowska

    2014-01-01

    Full Text Available Breast cancer is the most common malignant cancer among women, both in Poland and worldwide. Due to the constantly increasing number of breast cancer cases, it is vital to develop effective activities in primary and secondary prevention. One of the promising methods of best value, connecting both types of cancer prevention, appears to be chemoprevention. Chemoprevention uses natural or synthetic compounds to inhibit, delay or reverse the process of carcinogenesis. Among ingredients of natural origin, great attention is paid to curcumin – a broad-spectrum anti-cancer polyphenol derivative, extracted from the rhizome of Curcuma longa L. Curcumin has a number of chemopreventive properties such as anti-inflammatory activity, induction of apoptosis, inhibition of angiogenesis as well as tumor metastasis. Numerous in vitro and in vivo studies have demonstrated the mentioned anti-cancer effect in the epithelial breast cell line MCF-10A and in the epithelial breast cell lines MCF-7, BT-474, SK-BR-3-hr and MDA-MB-231. The main problem associated with the use of curcumin as a chemopreventive agent in humans is its low absorption from the gastrointestinal tract, poor solubility in body fluids and low bioavailability. Current studies are underway to increase the bioavailability and effectiveness of curcumin in vivo. Good results in the prevention and the treatment of breast cancer could be ensured by curcumin nanoparticles coated with albumin, known as nanocurcumin. The studies using nanocurcumin, however, are still in the preclinical stage, which is why there is a need to conduct extensive long-term randomized clinical trials to determine its effectiveness.

  4. Curcumin Nanomedicine: A Road to Cancer Therapeutics

    Science.gov (United States)

    Yallapu, Murali M.; Jaggi, Meena; Chauhan, Subhash C.

    2013-01-01

    Cancer is the second leading cause of death in the United States. Conventional therapies cause widespread systemic toxicity and lead to serious side effects which prohibit their long term use. Additionally, in many circumstances tumor resistance and recurrence is commonly observed. Therefore, there is an urgent need to identify suitable anticancer therapies that are highly precise with minimal side effects. Curcumin is a natural polyphenol molecule derived from the Curcuma longa plant which exhibits anticancer, chemo-preventive, chemo- and radio-sensitization properties. Curcumin’s widespread availability, safety, low cost and multiple cancer fighting functions justify its development as a drug for cancer treatment. However, various basic and clinical studies elucidate curcumin’s limited efficacy due to its low solubility, high rate of metabolism, poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s) using first line therapeutic drugs have been approved or are under consideration by the Food and Drug Administration (FDA) to improve human health. These nanotechnology strategies may help to overcome challenges and ease the translation of curcumin from bench to clinical application. Prominent research is reviewed which shows that advanced drug delivery of curcumin (curcumin nanoformulations or curcumin nanomedicine) is able to leverage therapeutic benefits by improving bioavailability and pharmacokinetics which in turn improves binding, internalization and targeting of tumor(s). Outcomes using these novel drug delivery systems have been discussed in detail. This review also describes the tumor-specific drug delivery system(s) that can be highly effective in destroying tumors. Such new approaches are expected to lead to clinical trials and to improve cancer therapeutics. PMID:23116309

  5. Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth

    Directory of Open Access Journals (Sweden)

    Yallapu Murali M

    2010-04-01

    Full Text Available Abstract Background Chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells. Methods Cisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and β-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on β-catenin transcription activity. The poly(lactic acid-co-glycolic acid (PLGA nanoparticle formulation of curcumin (Nano-CUR was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods. Results Curcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-XL and Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre

  6. Facile Synthesis of Curcumin-Loaded Starch-Maleate Nanoparticles

    OpenAIRE

    Suh Cem Pang; Soon Hiang Tay; Suk Fun Chin

    2014-01-01

    We have demonstrated the loading of curcumin onto starch maleate (SM) under mild conditions by mixing dissolved curcumin and SM nanoparticles separately in absolute ethanol and ethanol/aqueous (40 : 60 v/v), respectively. Curcumin-loaded starch-maleate (CurSM) nanoparticles were subsequently precipitated from a homogeneous mixture of these solutions in absolute ethanol based on the solvent exchange method. TEM analysis indicated that the diameters of CurSM nanoparticles were ranged between 30...

  7. A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin

    OpenAIRE

    Zorofchian Moghadamtousi, Soheil; Abdul Kadir, Habsah; Hassandarvish, Pouya; Tajik, Hassan; Abubakar, Sazaly; Zandi, Keivan

    2014-01-01

    Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agen...

  8. Curcumin: a novel therapeutic for burn pain and wound healing

    Science.gov (United States)

    2013-08-01

    given as an adjuvant with the nonsteroidal antiinflammatory drug (NSAID) diclofenac, reduces spontaneous pain behaviors in a formalin-induced orofacial ...R, Hota D, Chakrabarti A. Evaluation of antihyperalgesic effect of curcumin on formalin-induced orofacial pain in rat. Phytother Res 2009;23:507-12...bioavailability 5. Curcumin delivery vehicles 6. Conclusion 7. Expert opinion Review Curcumin: a novel therapeutic for burn pain and wound healing Bopaiah

  9. Novel delivery system for natural products: Nano-curcumin formulations

    OpenAIRE

    Hamid Reza Rahimi; Reza Nedaeinia; Alireza Sepehri Shamloo; Shima Nikdoust; Reza Kazemi Oskuee

    2016-01-01

    Objective: Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rh...

  10. Poverty Alleviation Programmes in Nigeria: Reflections on ...

    African Journals Online (AJOL)

    In it, we have argued that past poverty alleviation policies and programmes have been elitist and non-participatory, especially by the target population. In most cases the designs for poverty alleviations are characterized by improper conceptualization, grandiosity and lack of social justice even in implementation. Based on ...

  11. Production, solubility and antioxidant activity of curcumin nanosuspension

    Directory of Open Access Journals (Sweden)

    Deivis de Moraes Carvalho

    2015-03-01

    Full Text Available Curcumin is a powerful bioactive agent and natural antioxidant, but it is practically water-insoluble and has low bioavailability; a possible solution to this obstacle would be formulations of curcumin nanoparticles. Surfactants such as tween 80 can be used to stabilize low-solubility molecules preventing particle aggregation. The objectives of this study were the preparation of a suspension with curcumin nanoparticles in tween 80, the testing of pure curcumin solubility and of a simple mixture of curcumin with tween 80 and nanosuspension in water and ethanol as solvents, and finally the assessment of the antioxidant activity. We prepared the nanosuspension by injecting a curcumin solution in dichloromethane at low flow in water with tween 80 under heating and ultrasound. The analysis of particles size was conducted through dynamic light scattering; the non-degradation of curcumin was verified through thin-layer chromatography. The analyses of antioxidant activity were carried out according to the DPPH method. The method applied to reduce the particles size was efficient. Both the curcumin suspension and nanosuspension in tween 80 increased its solubility. Curcumin and the formulations presented antioxidant activity.

  12. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies.

    Science.gov (United States)

    Mirzaei, Hamed; Shakeri, Abolfazl; Rashidi, Bahman; Jalili, Amin; Banikazemi, Zarrin; Sahebkar, Amirhossein

    2017-01-01

    Curcumin, a hydrophobic polyphenol, is the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric). Curcumin is known as a strong anti-oxidant and anti-inflammatory agent that has different pharmacological effects. In addition, several studies have demonstrated that curcumin is safe even at dosages as high as 8g per day; however, instability at physiological pH, low solubility in water and rapid metabolism results in a low oral bioavailability of curcumin. The phytosomal formulation of curcumin (a complex of curcumin with phosphatidylcholine) has been shown to improve curcumin bioavailability. Existence of phospholipids in phytosomes leads to specific physicochemical properties such as amphiphilic nature that allows dispersion in both hydrophilic and lipophilic media. The efficacy and safety of curcumin phytosomes have been shown against several human diseases including cancer, osteoarthritis, diabetic microangiopathy and retinopathy, and inflammatory diseases. This review focuses on the pharmacokinetics as well as pharmacological and clinical effects of phytosomal curcumin. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Anti-ischemic effect of curcumin in rat brain.

    Science.gov (United States)

    Shukla, Pradeep K; Khanna, Vinay K; Ali, Mohd M; Khan, Mohd Y; Srimal, Rikhab C

    2008-06-01

    Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.

  14. Curcumin enhances human macrophage control of Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Bai, Xiyuan; Oberley-Deegan, Rebecca E; Bai, An; Ovrutsky, Alida R; Kinney, William H; Weaver, Michael; Zhang, Gong; Honda, Jennifer R; Chan, Edward D

    2016-07-01

    With the worldwide emergence of highly drug-resistant tuberculosis (TB), novel agents that have direct antimycobacterial effects or that enhance host immunity are urgently needed. Curcumin is a polyphenol responsible for the bright yellow-orange colour of turmeric, a spice derived from the root of the perennial herb Curcuma longa. Curcumin is a potent inducer of apoptosis-an effector mechanism used by macrophages to kill intracellular Mycobacterium tuberculosis (MTB). An in vitro human macrophage infection model was used to determine the effects of curcumin on MTB survival. We found that curcumin enhanced the clearance of MTB in differentiated THP-1 human monocytes and in primary human alveolar macrophages. We also found that curcumin was an inducer of caspase-3-dependent apoptosis and autophagy. Curcumin mediated these anti-MTB cellular functions, in part, via inhibition of nuclear factor-kappa B (NFκB) activation. Curcumin protects against MTB infection in human macrophages. The host-protective role of curcumin against MTB in macrophages needs confirmation in an animal model; if validated, the immunomodulatory anti-TB effects of curcumin would be less prone to drug resistance development. © 2016 Asian Pacific Society of Respirology.

  15. Novel delivery system for natural products: Nano-curcumin formulations.

    Science.gov (United States)

    Rahimi, Hamid Reza; Nedaeinia, Reza; Sepehri Shamloo, Alireza; Nikdoust, Shima; Kazemi Oskuee, Reza

    2016-01-01

    Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer's, inflammatory bowel disease (IBD), and even it has wound healing. Oral bioavailability of curcumin is rather poor, which would certainly put some boundaries in the employment of this drug. Bibliographical searches were performed using MEDLINE/ScienceDirect/OVID up to February 2015 using the following keywords (all fields): ("Curcumin" OR "Curcuma longa") AND [(nanoparticles) OR (Nanomicelles) OR (micro emulsions) OR (liposome) OR (phospholipid). Consequently, for any developments of curcumin in the future, analogues of curcumin that have better bioavailability or substitute formulations are needed crucially. These studies indicated that nanotechnology can formulate curcumin effectively, and this nano-formulated curcumin with a potent ability against various cancer cells, were represented to have better efficacy and bioavailability under in vivo conditions.

  16. Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury.

    Science.gov (United States)

    Kalani, Anuradha; Chaturvedi, Pankaj; Kamat, Pradip K; Maldonado, Claudio; Bauer, Philip; Joshua, Irving G; Tyagi, Suresh C; Tyagi, Neetu

    2016-10-01

    We tested whether the combined nano-formulation, prepared with curcumin (anti-inflammatory and neuroprotective molecule) and embryonic stem cell exosomes (MESC-exo cur ), restored neurovascular loss following an ischemia reperfusion (IR) injury in mice. IR-injury was created in 8-10 weeks old mice and divided into two groups. Out of two IR-injured groups, one group received intranasal administration of MESC-exo cur for 7days. Similarly, two sham groups were made and one group received MESC-exo cur treatment. The study determined that MESC-exo cur treatment reduced neurological score, infarct volume and edema following IR-injury. As compared to untreated IR group, MESC-exo cur treated-IR group showed reduced inflammation and N-methyl-d-aspartate receptor expression. Treatment of MESC-exo cur also reduced astrocytic GFAP expression and alleviated the expression of NeuN positive neurons in IR-injured mice. In addition, MESC-exo cur treatment restored vascular endothelial tight (claudin-5 and occludin) and adherent (VE-cadherin) junction proteins in IR-injured mice as compared to untreated IR-injured mice. These results suggest that combining the potentials of embryonic stem cell exosomes and curcumin can help neurovascular restoration following ischemia-reperfusion injury in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Harnessing motivation to alleviate neglect

    Directory of Open Access Journals (Sweden)

    Charlotte eRussell

    2013-06-01

    Full Text Available The syndrome of spatial neglect results from the combination of a number of deficits in attention, with patients demonstrating both spatially lateralised and non-lateralised impairments. Previous reports have hinted that there may be a motivational component to neglect and that modulating this might alleviate some of the debilitating symptoms. Additionally, recent work on the effects of reward on attention in healthy participants has revealed improvements across a number of paradigms. As the primary deficit in neglect has been associated with attention, this evidence for reward’s effects is potentially important. However, until very recently there have been few empirical studies addressing this potential therapeutic avenue. Here we review the growing body of evidence that attentional impairments in neglect can be reduced by motivation, for example in the form of preferred music or anticipated monetary reward, and discuss the implications of this for treatments for these patients. Crucially these effects of positive motivation are not observed in all patients with neglect, suggesting that the consequences of motivation may relate to individual lesion anatomy. Given the key role of dopaminergic systems in motivational processes, we suggest that motivational stimulation might act as a surrogate for dopaminergic stimulation. In addition, we consider the relationship between clinical post stroke apathy and lack of response to motivation.

  18. Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weixin [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wu, Mingchai [Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzou, Zhejiang (China); Tang, Longguang; Pan, Yong; Liu, Zhiguo [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zeng, Chunlai [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Wang, Jingying [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wei, Tiemin, E-mail: lswtm@sina.com [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2015-01-15

    Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia

  19. Gastroprotection of Suaveolol, Isolated from Hyptis suaveolens, against Ethanol-Induced Gastric Lesions in Wistar Rats: Role of Prostaglandins, Nitric Oxide and Sulfhydryls

    Directory of Open Access Journals (Sweden)

    María Elena Sánchez-Mendoza

    2012-07-01

    Full Text Available Hyptis suaveolens is a medicinal plant that is, according to traditional medicine, considered useful in the treatment of gastric ulcers. Although its gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim of the present study was to identify at least one active compound potentially responsible for the gastroprotective activity of H. suaveolens by using a bioassay guided study with an ethanol-induced gastric ulcer experimental model in rats. The results show that the hexane extract had protective activity (close to 70% when using doses between 10 and 100 mg/kg, and that the compound suaveolol, isolated from this extract, was one of the active gastroprotective agents. This is the first report about the gastroprotective activity of suaveolol. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 12.6, 21.3, 39.6 and 70.2% gastroprotection respectively. The effect elicited by suaveolol (at 100 mg/kg was attenuated by pretreatment with either NG-nitro-L-arginine methyl ester (70 mg/kg, i.p., a nitric oxide (NO synthase inhibitor, indomethacin (10 mg/kg, s.c., a blocker of prostaglandin synthesis, or N-ethylmaleimide (10 mg/kg, s.c., a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of this compound involves NO, prostaglandins and sulfhydryl groups.

  20. Gastroprotective activity of polysaccharide from Hericium erinaceus against ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer, and its antioxidant activities.

    Science.gov (United States)

    Wang, Xiao-Yin; Yin, Jun-Yi; Zhao, Ming-Ming; Liu, Shi-Yu; Nie, Shao-Ping; Xie, Ming-Yong

    2018-04-15

    The gastroprotective activity of Hericium erinaceus polysaccharide was investigated in rats. The antioxidant activities were also evaluated. Pre-treatment of polysaccharide could reduce ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer. The polysaccharide exhibited scavenging activities of 1, 1-diphenyl-2-picryl-hydrozyl and hydroxyl radicals, and ferrous ion-chelating ability. In the pylorus ligation-induced model, gastric secretions (volume of gastric juice, gastric acid, pepsin and mucus) of ulcer rats administrated with polysaccharide were regulated. Levels of tumor necrosis factor-α and interleukins-1β in serum, and myeloperoxidase activity of gastric tissue were reduced, while antioxidant status of gastric tissue was improved. Defensive factors (nitric oxide, prostaglandin E2, epidermal growth factor) in gastric tissue were increased. These results indicate that Hericium erinaceus polysaccharide possess gastroprotective activity, and the possible mechanisms are related to its regulations of gastric secretions, improvements of anti-inflammatory and antioxidant status, as well as increments of defensive factors releases. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Neuroprotective effect of geraniol and curcumin in an acrylamide model of neurotoxicity in Drosophila melanogaster: relevance to neuropathy.

    Science.gov (United States)

    Prasad, Sathya N; Muralidhara

    2014-01-01

    Chronic exposure of acrylamide (ACR) leads to neuronal damage in both experimental animals and humans. The primary focus of this study was to assess the ameliorative effect of geraniol, (a natural monoterpene) against ACR-induced oxidative stress, mitochondrial dysfunction and neurotoxicity in a Drosophila model and compare its efficacy to that of curcumin, a spice active principle with pleiotropic biological activity. Adult male flies (8-10 days) were exposed (7 days) to ACR (5 mM) with or without geraniol and curcumin (5-10 μM) in the medium. Both phytoconstituents significantly reduced the incidence of ACR-induced mortality, rescued the locomotor phenotype and alleviated the enhanced levels of oxidative stress markers in head/body regions. The levels of reduced glutathione (GSH) and total thiols (TSH) resulting from ACR exposure was also restored with concomitant elevation in the activities of detoxifying enzymes. Interestingly, ACR induced mitochondrial dysfunctions (MTT reduction, activities of SDH and citrate synthase enzymes) were alleviated by both phytoconstituents. While ACR elevated the activity of acetylcholinesterase in head/body regions, marked diminution in enzyme activity ensued with co-exposure to phytoconstituents suggesting their potency to mitigate cholinergic function. Furthermore, phytoconstituents also restored the dopamine levels in head/body regions. The neuroprotective effect of geraniol was comparable to curcumin in terms of phenotypic and biochemical markers. Based on our evidences in fly model we hypothesise that geraniol possess significant neuromodulatory propensity and may be exploited for therapeutic application in human pathophysiology associated with neuropathy. However, the precise mechanism/s by which geraniol offers neuroprotection needs to be investigated in appropriate neuronal cell models. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Conjugation of curcumin onto alginate enhances aqueous solubility and stability of curcumin.

    Science.gov (United States)

    Dey, Soma; Sreenivasan, K

    2014-01-01

    Curcumin is a potential drug for various diseases including cancer. Prime limitations associated with curcumin are low water solubility, rapid hydrolytic degradation and poor bioavailability. In order to redress these issues we developed Alginate-Curcumin (Alg-Ccm) conjugate which was characterized by FTIR and (1)H NMR spectroscopy. The conjugate self-assembled in aqueous solution forming micelles with an average hydrodynamic diameter of 459 ± 0.32 nm and negative zeta potential. The spherical micelles were visualized by TEM. The critical micelle concentration (CMC) of Alg-Ccm conjugate was determined. A significant enhancement in the aqueous solubility of curcumin was observed upon conjugation with alginate. Formation of micelles improved the stability of curcumin in water at physiological pH. The cytotoxic activity of Alg-Ccm was quantified by MTT assay using L-929 fibroblast cells and it was found to be potentially cytotoxic. Hence, Alg-Ccm could be a promising drug conjugate as well as a nanosized delivery vehicle. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Recent progress on curcumin-based therapeutics: a patent review (2012-2016). Part I: Curcumin.

    Science.gov (United States)

    Di Martino, Rita Maria Concetta; Luppi, Barbara; Bisi, Alessandra; Gobbi, Silvia; Rampa, Angela; Abruzzo, Angela; Belluti, Federica

    2017-05-01

    curcumin is the main bioactive component contained in Curcuma Longa, largely employed in traditional medicine. Recently, beneficial properties, useful for prevention and treatment of several disorders, have been discovered for this compound. Peculiar structural feature is an α,β-unsaturated carbonyl system essential for establishing contacts with critical cysteine residues of several targets. This distinctive mechanism of action imparts to the molecule the ability to affect a large number of targets, accounting for its pleiotropic behaviour and definition of "privileged structure". Areas covered: The objective of the review is an examination of the recent developments in the field of the anti-cancer applications of curcumin, together with formulation issues, considering the patent literature in the years 2012-2016. Expert opinion: The wide therapeutic efficacy of curcumin is related to synergistic interactions with several biological targets, along with the modulation of several signaling pathways. This peculiar behaviour could be useful in the treatment of multifactorial diseases such as cancer. Combination of curcumin with a first line antineoplastic drug proved to be a valuable strategy to obtain an amplified response with minimized side effects. Innovative curcumin formulations based on the nanotechnology approach allowed improving both bioavailability and therapeutic efficacy.

  4. Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress.

    Science.gov (United States)

    Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Rajasekaran, Kallikat Narayanan; Menon, Venugopal Padmanabhan

    2004-08-20

    Alcoholic liver disease is a major medical complication of alcohol abuse and a common liver disease in western countries. Increasing evidence demonstrates that oxidative stress plays an important etiologic role in the development of alcoholic liver disease. Alcohol alone or in combination with high fat is known to cause oxidative injury. The present study therefore aims at evaluating the protective role of curcumin, an active principle of turmeric and a synthetic analog of curcumin (CA) on alcohol and thermally oxidised sunflower oil (DeltaPUFA) induced oxidative stress. Male albino Wistar rats were used for the experimental study. The liver marker enzymes: gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), the lipid peroxidative indices: thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP) and antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were used as biomarkers for testing the antioxidant potential of the drugs. The liver marker enzymes and lipid peroxidative indices were increased significantly in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups. Administration of curcumin and CA abrograted this effect. The antioxidant status which was decreased in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups was effectively modulated by both curcumin and CA treatment. However, the reduction in oxidative stress was more pronounced in CA treatment groups compared to curcumin. In conclusion, these observations show that CA exerts its protective effect by decreasing the lipid peroxidation and improving antioxidant status, thus proving itself as an effective antioxidant.

  5. Curcumin-Eudragit® E PO solid dispersion: A simple and potent method to solve the problems of curcumin.

    Science.gov (United States)

    Li, Jinglei; Lee, Il Woo; Shin, Gye Hwa; Chen, Xiguang; Park, Hyun Jin

    2015-08-01

    Using a simple solution mixing method, curcumin was dispersed in the matrix of Eudragit® E PO polymer. Water solubility of curcumin in curcumin-Eudragit® E PO solid dispersion (Cur@EPO) was greatly increased. Based on the results of several tests, curcumin was demonstrated to exist in the polymer matrix in amorphous state. The interaction between curcumin and the polymer was investigated through Fourier transform infrared spectroscopy and (1)H NMR which implied that OH group of curcumin and carbonyl group of the polymer involved in the H bonding formation. Cur@EPO also provided protection function for curcumin as verified by the pH challenge and UV irradiation test. The pH value influenced curcumin release profile in which sustained release pattern was revealed. Additionally, in vitro transdermal test was conducted to assess the potential of Cur@EPO as a vehicle to deliver curcumin through this alternative administration route. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Fluorescence enhancement effect for the determination of curcumin with yttrium(III)-curcumin-sodium dodecyl benzene sulfonate system

    International Nuclear Information System (INIS)

    Wang Feng; Huang Wei; Wang Yanwei

    2008-01-01

    It is found that the fluorescence of curcumin is greatly enhanced by yttrium(III) (Y 3+ ) in the presence of sodium dodecyl benzene sulfonate. Based on this, a sensitive fluorimetric method for the determination of curcumin in aqueous solution is proposed. In the potassium hydrogen phthalate (KHP) buffer, the fluorescence intensity of curcumin is proportional to the concentration of curcumin in the range of 7.37x10 -4 -0.18, 0.18-2.95 μg mL -1 and the detection limit is 0.1583 ng mL -1 . The actual samples are satisfactorily determined. In addition, the interaction mechanism is also studied

  7. Effects of curcumin on cytochrome P450 and glutathione S-transferase activities in rat liver.

    NARCIS (Netherlands)

    Oetari, S.; Sudibyo, M.; Commandeur, J.N.M.; Samhoedi, R.; Vermeulen, N.P.E.

    1996-01-01

    The stability of curcumin, as well as the interactions between curcumin and cytochrome P450s (P450s) and glutathione S-transferases (GSTs) in rat liver, were studied. Curcumin is relatively unstable in phosphate buffer at pH 7.4. The stability of curcumin was strongly improved by lowering the pH or

  8. Enhanced solubility and targeted delivery of curcumin by lipopeptide micelles.

    Science.gov (United States)

    Liang, Ju; Wu, Wenlan; Lai, Danyu; Li, Junbo; Fang, Cailin

    2015-01-01

    A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid (C12) as the hydrophobic tails has been designed and prepared by standard solid-phase peptide synthesis technique. LP can self-assemble into spherical micelles with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin-loaded LP micelles were prepared in order to increase the water solubility, sustain the releasing rate, and improve the tumor targeted delivery of curcumin. Water solubility, cytotoxicity, in vitro release behavior, and intracellular uptake of curcumin-loaded LP micelles were investigated. The results showed that LP micelles can increase the water solubility of curcumin 1.1 × 10(3) times and sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa) and HepG2 cells. When incubating these curcumin-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD (functionalized peptide sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better efficiency of the self-assembled LP micelles for curcumin delivery than crude curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays. Combined with the enhanced solubility and higher cell inhibition, LP micelles reported in this study may be promising in clinical application for targeted curcumin delivery.

  9. Polydatin Protects Rat Liver against Ethanol-Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF-κB p65 Pathway

    Directory of Open Access Journals (Sweden)

    Qiong-Hui Huang

    2017-01-01

    Full Text Available Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH in the serum, suppressed the malonaldehyde (MDA and triglyceride (TG content and the production of reactive oxygen species (ROS, and enhanced the activities of superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, catalase (CAT, andalcohol dehydrogenase (ADH, and aldehyde dehydrogenase (ALDH, paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1 and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2 and its target gene haem oxygenase-1 (HO-1. Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6 via downregulating toll-like receptor 4 (TLR4 and nuclear factor kappa B (NF-κB p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

  10. Photodecomposition Profile of Curcumin in the Existence of Tungsten Trioxide Particles

    Science.gov (United States)

    Nandiyanto, A. B. D.; Zaen, R.; Oktiani, R.; Abdullah, A. G.

    2018-02-01

    The purpose of this study was to investigate the stability of curcumin solution in the existence of tungsten trioxide (WO3) particles under light illumination. In the experimental method, curcumin extracted from Indonesian local turmeric was added with WO3 microparticles and put into the photoreactor system. The photostability performance of curcumin was conducted for 22 hours using 100 W of Neon Lamp. The results showed that the curcumin solution was relatively stable. When curcumin without existence of WO3 was irradiated, no change in the curcumin concentration was found. However, when curcumin solution was mixed with WO3 particles, decreases in the concentration of curcumin was found. The concentration of curcumin with WO3 after light irradiation was about 73.58%. Based on the results, we concluded that the curcumin is relatively stable against light. However, its lightirradiation stability decreases with additional inorganic material.

  11. Oxidative stress induced by zearalenone in porcine granulosa cells and its rescue by curcumin in vitro.

    Directory of Open Access Journals (Sweden)

    Xunsi Qin

    Full Text Available Oxidative stress (OS, as a signal of aberrant intracellular mechanisms, plays key roles in maintaining homeostasis for organisms. The occurrence of OS due to the disorder of normal cellular redox balance indicates the overproduction of reactive oxygen species (ROS and/or deficiency of antioxidants. Once the balance is broken down, repression of oxidative stress is one of the most effective ways to alleviate it. Ongoing studies provide remarkable evidence that oxidative stress is involved in reproductive toxicity induced by various stimuli, such as environmental toxicants and food toxicity. Zearalenone (ZEA, as a toxic compound existing in contaminated food products, is found to induce mycotoxicosis that has a significant impact on the reproduction of domestic animals, especially pigs. However, there is no information about how ROS and oxidative stress is involved in the influence of ZEA on porcine granulosa cells, or whether the stress can be rescued by curcumin. In this study, ZEA-induced effect on porcine granulosa cells was investigated at low concentrations (15 μM, 30 μM and 60 μM. In vitro ROS levels, the mRNA level and activity of superoxide dismutase, glutathione peroxidase and catalase were obtained. The results showed that in comparison with negative control, ZEA increased oxidative stress with higher ROS levels, reduced the expression and activity of antioxidative enzymes, increased the intensity of fluorogenic probes 2', 7'-Dichlorodihydrofluorescin diacetate and dihydroethidium in flow cytometry assay and fluorescence microscopy. Meanwhile, the activity of glutathione (GSH did not change obviously following 60 μM ZEA treatment. Furthermore, the underlying protective mechanisms of curcumin on the ZEA-treated porcine granulosa cells were investigated. The data revealed that curcumin pre-treatment significantly suppressed ZEA-induced oxidative stress. Collectively, porcine granulosa cells were sensitive to ZEA, which may induce

  12. Curcumin and Diabetes: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Dong-wei Zhang

    2013-01-01

    Full Text Available Turmeric (Curcuma longa, a rhizomatous herbaceous perennial plant of the ginger family, has been used for the treatment of diabetes in Ayurvedic and traditional Chinese medicine. The active component of turmeric, curcumin, has caught attention as a potential treatment for diabetes and its complications primarily because it is a relatively safe and inexpensive drug that reduces glycemia and hyperlipidemia in rodent models of diabetes. Here, we review the recent literature on the applications of curcumin for glycemia and diabetes-related liver disorders, adipocyte dysfunction, neuropathy, nephropathy, vascular diseases, pancreatic disorders, and other complications, and we also discuss its antioxidant and anti-inflammatory properties. The applications of additional curcuminoid compounds for diabetes prevention and treatment are also included in this paper. Finally, we mention the approaches that are currently being sought to generate a “super curcumin” through improvement of the bioavailability to bring this promising natural product to the forefront of diabetes therapeutics.

  13. Kinetic Study of Curcumin on Modal Fabric

    Directory of Open Access Journals (Sweden)

    Abu Naser Md. Ahsanul Haque

    2018-03-01

    Full Text Available A kinetic study of curcumin on modal fabric was carried out using an initial dye concentration of 1 g/L at three different temperatures, 70 °C, 85 °C and 100 °C, at pH 7 and an material to liquor ratio of 1:20. Pseudo first-order and pseudo second-order kinetics were applied, and it was found that the adsorption kinetics of curcumin on modal fabric matched the pseudo second-order kinetic model. The activation energy was found to be equal to 71.14 kJ/mol, while the enthalpy and entropy of activation were 68.16 kJ/mol and –66.02 J/molK respectively.

  14. Curcumin and Diabetes: A Systematic Review

    OpenAIRE

    Dong-wei Zhang; Min Fu; Si-Hua Gao; Jun-Li Liu

    2013-01-01

    Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant of the ginger family, has been used for the treatment of diabetes in Ayurvedic and traditional Chinese medicine. The active component of turmeric, curcumin, has caught attention as a potential treatment for diabetes and its complications primarily because it is a relatively safe and inexpensive drug that reduces glycemia and hyperlipidemia in rodent models of diabetes. Here, we review the recent literature on the applications ...

  15. Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: the Golden Pigment from Golden Spice

    OpenAIRE

    Prasad, Sahdeo; Tyagi, Amit K.; Aggarwal, Bharat B.

    2014-01-01

    Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa) that has been associated with antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial activities as indicated by over 6,000 citations. In addition, over one hundred clinical studies have been carried out with curcumin. One of the major problems with curcumin is perceived to be the bioavailability. How curcumin should be delivered in vivo, how bioavailable is it, how well curcumin is...

  16. Drug-Drug/Drug-Excipient Compatibility Studies on Curcumin using Non-Thermal Methods

    OpenAIRE

    Moorthi Chidambaram; Kathiresan Krishnasamy

    2014-01-01

    Purpose: Curcumin is a hydrophobic polyphenol isolated from dried rhizome of turmeric. Clinical usefulness of curcumin in the treatment of cancer is limited due to poor aqueous solubility, hydrolytic degradation, metabolism, and poor oral bioavailability. To overcome these limitations, we proposed to fabricate curcumin-piperine, curcumin-quercetin and curcumin-silibinin loaded polymeric nanoformulation. However, unfavourable combinations of drug-drug and drug-excipient may result in interacti...

  17. Curcumin Inhibits Growth of Saccharomyces cerevisiae through Iron Chelation ▿ ††

    OpenAIRE

    Minear, Steven; O'Donnell, Allyson F.; Ballew, Anna; Giaever, Guri; Nislow, Corey; Stearns, Tim; Cyert, Martha S.

    2011-01-01

    Curcumin, a polyphenol derived from turmeric, is an ancient therapeutic used in India for centuries to treat a wide array of ailments. Interest in curcumin has increased recently, with ongoing clinical trials exploring curcumin as an anticancer therapy and as a protectant against neurodegenerative diseases. In vitro, curcumin chelates metal ions. However, although diverse physiological effects have been documented for this compound, curcumin's mechanism of action on mammalian cells remains un...

  18. Effect of curcumin on Helicobacter pylori biofilm formation ...

    African Journals Online (AJOL)

    Three-dimensional structure of biofilm was imaged by scanning electron microscopy. The effect of curcumin on H. pylori adherence to HEp-2 cells was also investigated. Subinhibitory concentrations of curcumin inhibited the biofilm in dose dependent manner. However, H.pylori could restore ability to form biofilm during ...

  19. Facile Synthesis of Curcumin-Loaded Starch-Maleate Nanoparticles

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    Suh Cem Pang

    2014-01-01

    Full Text Available We have demonstrated the loading of curcumin onto starch maleate (SM under mild conditions by mixing dissolved curcumin and SM nanoparticles separately in absolute ethanol and ethanol/aqueous (40 : 60 v/v, respectively. Curcumin-loaded starch-maleate (CurSM nanoparticles were subsequently precipitated from a homogeneous mixture of these solutions in absolute ethanol based on the solvent exchange method. TEM analysis indicated that the diameters of CurSM nanoparticles were ranged between 30 nm and 110 nm with a mean diameter of 50 nm. The curcumin loading capacity of SM as a function of loading duration was investigated using the UV-visible spectrophotometer. The loading of curcumin onto SM increased rapidly initially with loading duration, and the curcumin loading capacity of 15 mg/g was reached within 12 hours. CurSM nanoparticles exhibited substantially higher water solubility of 6.0 × 10−2 mg/mL which is about 300 times higher than that of pure curcumin. With enhanced water solubility and bioaccessibility of curcumin, the potential utility of CurSM nanoparticles in various biomedical applications is therefore envisaged.

  20. Curcumin Attenuates Staurosporine-Mediated Death of Retinal Ganglion Cells

    OpenAIRE

    Burugula, Balabharathi; Ganesh, Bhagyalaxmi S.; Chintala, Shravan K.

    2011-01-01

    The functional effect of curcumin, a free radical scavenger and an herbal medicine from Indian yellow curry spice, Curcuma longa, on protease-mediated retinal ganglion cell death was investigated. These results show, for the first time, that curcumin indeed prevents the protease-mediated death of RGCs, both in vitro and in vivo.

  1. Effects of curcumin on sperm parameters abnormalities induced by ...

    African Journals Online (AJOL)

    Morphine, which is commonly used for the treatment of severe pain, gastrointestinal tract and kidneys. Curcumin petals consist of, glycosides, flavonoids, and anthocyanin. The study aims at evaluating curcumin effect and morphine on sperm parameters, testis tissue and serum testosterone level in rat. In this experimental ...

  2. Antibacterial activity of indium curcumin and indium diacetylcurcumin

    African Journals Online (AJOL)

    Studies on curcumin, the principal element of turmeric powder, have demonstrated several biological actions such as antibacterial activity. Evaluation of new analogs or new compounds of curcumin for their antibacterial effect is interesting for researchers. In this in vitro study, we attempted to test the antibacterial activity of ...

  3. Curcumin Modulates α-Synuclein Aggregation and Toxicity

    Science.gov (United States)

    2012-01-01

    In human beings, Parkinson’s disease (PD) is associated with the oligomerization and amyloid formation of α-synuclein (α-Syn). The polyphenolic Asian food ingredient curcumin has proven to be effective against a wide range of human diseases including cancers and neurological disorders. While curcumin has been shown to significantly reduce cell toxicity of α-Syn aggregates, its mechanism of action remains unexplored. Here, using a series of biophysical techniques, we demonstrate that curcumin reduces toxicity by binding to preformed oligomers and fibrils and altering their hydrophobic surface exposure. Further, our fluorescence and two-dimensional nuclear magnetic resonance (2D-NMR) data indicate that curcumin does not bind to monomeric α-Syn but binds specifically to oligomeric intermediates. The degree of curcumin binding correlates with the extent of α-Syn oligomerization, suggesting that the ordered structure of protein is required for effective curcumin binding. The acceleration of aggregation by curcumin may decrease the population of toxic oligomeric intermediates of α-Syn. Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases. PMID:23509976

  4. Full Length Research Paper Curcumin induces cleavage of -catenin ...

    African Journals Online (AJOL)

    β-Catenin/Tcf-4 signaling pathway plays important roles in colorectal tumorigenesis. RT-PCR, western blotting and immunoprecipitation were used to study the effects of curcumin on β-catenin/Tcf-4 signaling pathway in HT-29 cells. Treatment of curcumin could induce cleavage of β-catenin and the cleavage could be ...

  5. Antioxidant Effect of Curcumin Against Microcystin- LR-Induced ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of curcumin on microcystin-LR (MC-LR)- induced renal oxidative damage in Balb/c mice. Methods: 40 male Balb/c mice were assigned randomly to 4 groups each having 10 mice. One group served as normal (saline treated) while another group was used as curcumin control. The third ...

  6. Novel delivery system for natural products: Nano-curcumin formulations

    Directory of Open Access Journals (Sweden)

    Hamid Reza Rahimi

    2016-06-01

    Full Text Available Objective: Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA and messengers (RNA. A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer’s, inflammatory bowel disease (IBD, and even it has wound healing. Oral bioavailability of curcumin is rather poor, which would certainly put some boundaries in the employment of this drug. Materials and Methods: Bibliographical searches were performed using MEDLINE/ScienceDirect/OVID up to February 2015 using the following keywords (all fields: (“Curcumin” OR “Curcuma longa” AND [(nanoparticles OR (Nanomicelles OR (micro emulsions OR (liposome OR (phospholipid. Results: Consequently, for any developments of curcumin in the future, analogues of curcumin that have better bioavailability or substitute formulations are needed crucially. Conclusion: These studies indicated that nanotechnology can formulate curcumin effectively, and this nano-formulated curcumin with a potent ability against various cancer cells, were represented to have better efficacy and bioavailability under in vivo conditions.

  7. Oxidative Metabolites of Curcumin Poison Human Type II Topoisomerases†

    Science.gov (United States)

    Ketron, Adam C.; Gordon, Odaine N.; Schneider, Claus; Osheroff, Neil

    2013-01-01

    The polyphenol curcumin is the principal flavor and color component of the spice turmeric. Beyond its culinary uses, curcumin is believed to positively impact human health and displays antioxidant, anti-inflammatory, antibacterial, and chemopreventive properties. It also is in clinical trials as an anticancer agent. In aqueous solution at physiological pH, curcumin undergoes spontaneous autoxidation that is enhanced by oxidizing agents. The reaction proceeds through a series of quinone methide and other reactive intermediates to form a final dioxygenated bicyclopentadione product. Several naturally occurring polyphenols that can form quinones have been shown to act as topoisomerase II poisons (i.e., increase levels of topoisomerase II-mediated DNA cleavage). Because several of these compounds have chemopreventive properties, we determined the effects of curcumin, its oxidative metabolites, and structurally related degradation products (vanillin, ferulic acid, and feruloylmethane), on the DNA cleavage activities of human topoisomerase IIα and IIβ. Intermediates in the curcumin oxidation pathway increased DNA scission mediated by both enzymes ~4-5–fold. In contrast, curcumin and the bicyclopentadione, as well as vanillin, ferulic acid, and feruloylmethane, had no effect on DNA cleavage. As found for other quinone-based compounds, curcumin oxidation intermediates acted as redox-dependent (as opposed to interfacial) topoisomerase II poisons. Finally, under conditions that promote oxidation, the dietary spice turmeric enhanced topoisomerase II-mediated DNA cleavage. Thus, even within the more complex spice formulation, oxidized curcumin intermediates appear to function as topoisomerase II poisons. PMID:23253398

  8. Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult.

    Science.gov (United States)

    Qi, Zhangyang; Wu, Meihao; Fu, Yun; Huang, Tengfei; Wang, Tingting; Sun, Yanjie; Feng, Zhibo; Li, Changzheng

    2017-01-01

    The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer's disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ. P-curcumin was prepared through chemical synthesis. Its structure was determined via nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). An MTT assay was used to assess Aβ cytotoxicity and the protective effect of P-curcumin on SH-SY5Y cells. The effect of P-curcumin on Aβ-induced ROS production in vitro and in vivo were assessed based on changes in dichlorofluorescein (DCF) fluorescence. A spectrophotometric method was employed to detect lipid peroxidation. To mimic the interaction of P-curcumin on cell membranes with Aβ, liposomes were prepared by thin film method. Finally, the interactions between free P-curcumin and P-curcumin cultivated on liposomes and Aβ were determined via spectrophotometry. A novel derivative, palmitic acid curcumin ester was prepared and characterized. This curcumin, cultivated on the membranes of neurocytes, may prevent Aβ-mediated ROS production and may inhibit the direct interaction between Aβ and the cellular membrane. Furthermore, P-curcumin could scavenge Aβ-mediated ROS as curcumin in vitro and in vivo, and had the potential to prevent lipid peroxidation. Morphological analyses showed that P-curcumin was better than curcumin at protecting cell shape. To examine P-curcumin's ability to attenuate direct interaction between Aβ and cell membranes, the binding affinity of Aβ to curcumin and P-curcumin was determined. The association

  9. Poverty Alleviation Programmes and Economic Development in ...

    African Journals Online (AJOL)

    Poverty Alleviation Programmes and Economic Development in Nigeria: A Comparative Assessment of Asa and Ilorin West Local ... Journal Home > Vol 3, No 4 (2009) > ... and worst hit income inequality group with about 84percent of total

  10. Exercise alleviates depression related systemic inflammation in ...

    African Journals Online (AJOL)

    Exercise alleviates depression related systemic inflammation in chronic obstructive pulmonary disease patients. ... African Health Sciences ... Currently, physical activity is an important lifestyle factor that has the potential to modify inflammatory ...

  11. Curcumin and its topical formulations for wound healing applications.

    Science.gov (United States)

    Mohanty, Chandana; Sahoo, Sanjeeb K

    2017-10-01

    Oxidative damage and inflammation have been identified, through clinical and preclinical studies, as the main causes of nonhealing chronic wounds. Reduction of persistent chronic inflammation by application of antioxidant and anti-inflammatory agents such as curcumin has been well studied. However, low aqueous solubility, poor tissue absorption, rapid metabolism and short plasma half-life have made curcumin unsuitable for systemic administration for better wound healing. Recently, various topical formulations of curcumin such as films, fibers, emulsion, hydrogels and different nanoformulations have been developed for targeted delivery of curcumin at wounded sites. In this review, we summarize and discuss different topical formulations of curcumin with emphasis on their wound-healing properties in animal models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. The Chemistry of Curcumin: From Extraction to Therapeutic Agent

    Directory of Open Access Journals (Sweden)

    Kavirayani Indira Priyadarsini

    2014-12-01

    Full Text Available Curcumin, a pigment from turmeric, is one of the very few promising natural products that has been extensively investigated by researchers from both the biological and chemical point of view. While there are several reviews on the biological and pharmacological effects of curcumin, chemistry reviews are comparatively scarcer. In this article, an overview of different aspects of the unique chemistry research on curcumin will be discussed. These include methods for the extraction from turmeric, laboratory synthesis methods, chemical and photochemical degradation and the chemistry behind its metabolism. Additionally other chemical reactions that have biological relevance like nucleophilic addition reactions, and metal chelation will be discussed. Recent advances in the preparation of new curcumin nanoconjugates with metal and metal oxide nanoparticles will also be mentioned. Directions for future investigations to be undertaken in the chemistry of curcumin have also been suggested.

  13. Curcumin, a potential therapeutic candidate for retinal diseases.

    Science.gov (United States)

    Wang, Lei-Lei; Sun, Yue; Huang, Kun; Zheng, Ling

    2013-09-01

    Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Stabilisation of Laryngeal AL Amyloidosis with Long Term Curcumin Therapy

    Directory of Open Access Journals (Sweden)

    Terry Golombick

    2015-01-01

    Full Text Available Multiple myeloma (MM, smoldering myeloma (SMM, and monoclonal gammopathy of undetermined significance (MGUS represent a spectrum of plasma cell dyscrasias (PCDs. Immunoglobulin light chain amyloidosis (AL falls within the spectrum of these diseases and has a mortality rate of more than 80% within 2 years of diagnosis. Curcumin, derived from turmeric, has been shown to have a clinical benefit in some patients with PCDs. In addition to a clinical benefit in these patients, curcumin has been found to have a strong affinity for fibrillar amyloid proteins. We thus administered curcumin to a patient with laryngeal amyloidosis and smoldering myeloma and found that the patient has shown a lack of progression of his disease for a period of five years. This is in keeping with our previous findings of clinical benefits of curcumin in patients with plasma cell dyscrasias. We recommend further evaluation of curcumin in patients with primary AL amyloidosis.

  15. Facile synthesis of water-soluble curcumin nanocrystals

    Directory of Open Access Journals (Sweden)

    Marković Zoran M.

    2015-01-01

    Full Text Available In this paper, facile synthesis of water soluble curcumin nanocrystals is reported. Solvent exchange method was applied to synthesize curcumin nanocrystals. Different techniques were used to characterize the structural and photophysical properties of curcumin nanocrystals. We found that nanocurcumin prepared by this method had good chemical and physical stability, could be stored in the powder form at room temperature, and was freely dispersible in water. It was established that the size of curcumin nanocrystals was varied in the range of 20-500 nm. Fourier transform infrared spectroscopy and UV-Vis analyses showed the presence of tetrahydrofuran inside the curcumin nanocrystals. Also, it was found that nanocurcumin emitted photoluminescencewith yellow-green colour. [Projekat Ministarstva nauke Republike Srbije, br. 172003

  16. The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Bahi, Amine; Sadek, Bassem; Nurulain, Syed M; Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

    2015-11-01

    It has become clear that histamine H3 receptors (H3R) have been implicated in modulating ethanol intake and preference in laboratory animals. The novel non-imidazole H3R antagonist DL77 with excellent selectivity profile shows high in-vivo potency as well as in-vitro antagonist affinity with ED50 of 2.1 ± 0.2 mg/kg and pKi=8.08, respectively. In the present study, and applying an unlimited access two-bottle choice procedure, the anti-alcohol effects of the H3R antagonist, DL77 (0, 3, 10 and 30 mg/kg; i.p.), were investigated in adult mice. In this C57BL/6 line, effects of DL77 on voluntary alcohol intake and preference, as well as on total fluid intake were evaluated. Results have shown that DL77, dose-dependently, reduced both ethanol intake and preference. These effects were very selective as both saccharin and quinine, used to control for taste sensitivity, and intakes were not affected following DL77 pre-application. More importantly, systemic administration of DL77 (10 mg/kg) during acquisition inhibited ethanol-induced conditioned-place preference (EtOH-CPP) as measured using an unbiased protocol. The anti-alcohol activity observed for DL77 was abrogated when mice were pretreated with the selective H3R agonist R-(α)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist pyrilamine (PYR) (10mg/kg). These results suggest that DL77 has a predominant role in two in vivo effects of ethanol. Therefore, signaling via H3R is essential for ethanol-related consumption and conditioned reward and may represent a novel therapeutic pharmacological target to tackle ethanol abuse and alcoholism. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice.

    Science.gov (United States)

    Al Mansouri, Shamma; Ojha, Shreesh; Al Maamari, Elyazia; Al Ameri, Mouza; Nurulain, Syed M; Bahi, Amine

    2014-09-01

    Several recent studies have suggested that brain CB2 cannabinoid receptors play a major role in alcohol reward. In fact, the implication of cannabinoid neurotransmission in the reinforcing effects of ethanol (EtOH) is becoming increasingly evident. The CB2 receptor agonist, β-caryophyllene (BCP) was used to investigate the role of the CB2 receptors in mediating alcohol intake and ethanol-induced conditioned place preference (EtOH-CPP) and sensitivity in mice. The effect of BCP on alcohol intake was evaluated using the standard two-bottle choice drinking method. The mice were presented with increasing EtOH concentrations and its consumption was measured daily. Consumption of saccharin and quinine solutions was measured following the EtOH preference tests. Finally, the effect of BCP on alcohol reward and sensitivity was tested using an unbiased EtOH-CPP and loss of righting-reflex (LORR) procedures, respectively. BCP dose-dependently decreased alcohol consumption and preference. Additionally, BCP-injected mice did not show any difference from vehicle mice in total fluid intake in a 24-hour paradigm nor in their intake of graded concentrations of saccharin or quinine, suggesting that the CB2 receptor activation did not alter taste function. More importantly, BCP inhibited EtOH-CPP acquisition and exacerbated LORR duration. Interestingly, these effects were abrogated when mice were pre-injected with a selective CB2 receptor antagonist, AM630. Overall, the CB2 receptor system appears to be involved in alcohol dependence and sensitivity and may represent a potential pharmacological target for the treatment of alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Molecular complexation of curcumin with pH sensitive cationic copolymer enhances the aqueous solubility, stability and bioavailability of curcumin.

    Science.gov (United States)

    Kumar, Sunny; Kesharwani, Siddharth S; Mathur, Himanshi; Tyagi, Mohit; Bhat, G Jayarama; Tummala, Hemachand

    2016-01-20

    Curcumin is a natural dietary compound with demonstrated potential in preventing/treating several chronic diseases in animal models. However, this success is yet to be translated to humans mainly because of its poor oral bioavailability caused by extremely low water solubility. This manuscript demonstrates that water insoluble curcumin (~1μg/ml) forms highly aqueous soluble complexes (>2mg/ml) with a safe pH sensitive polymer, poly(butyl-methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl-methacrylate) when precipitated together in water. The complexation process was optimized to enhance curcumin loading by varying several formulation factors. Acetone as a solvent and polyvinyl alcohol as a stabilizer with 1:2 ratio of drug to polymer yielded complexes with relatively high loading (~280μg/ml) and enhanced solubility (>2mg/ml). The complexes were amorphous in solid and were soluble only in buffers with pHs less than 5.0. Hydrogen bond formation and hydrophobic interactions between curcumin and the polymer were recorded by infrared spectroscopy and nuclear magnetic resonance spectroscopy, respectively. Molecular complexes of curcumin were more stable at various pHs compared to unformulated curcumin. In mice, these complexes increased peak plasma concentration of curcumin by 6 times and oral bioavailability by ~20 times. This is a simple, economic and safer strategy of enhancing the oral bioavailability of curcumin. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in Aβ1-42 insult in vitro.

    Directory of Open Access Journals (Sweden)

    Zijian Xiao

    Full Text Available This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aβ1-42 (10 µg/ml to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aβ1-42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aβ1-42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1.

  20. A comparative study of the spectral, fluorometric properties and photostability of natural curcumin, iron- and boron- complexed curcumin

    Science.gov (United States)

    Mohammed, Fatima; Rashid-Doubell, Fiza; Cassidy, Seamas; Henari, Fryad

    2017-08-01

    Curcumin is a yellow phenolic compound with a wide range of reported biological effects. However, two main obstacles hinder the use of curcumin therapeutically, namely its poor bioavailability and photostability. We have synthesized two curcumin complexes, the first a boron curcumin complex (B-Cur2) and the second an iron (Fe-Cur3) complex of curcumin. Both derivatives showed high fluorescence efficiency (quantum yield) and greater photostability in solution. The improved photostability could be attributed to the coordination structures and the removal of β-diketone group from curcumin. The fluorescence and ultra violet/visible absorption spectra of curcumin, B-Cur2 and Fe-Cur3 all have a similar spectral pattern when dissolved in the same organic solvent. However, a shift towards a lower wavelength was observed when moving from polar to non-polar solvents, possibly due to differences in solvent polarity. A plot of Stokes' shift vs the orientation polarity parameter (Δf) or vs the solvent polarity parameter (ET 30) showed an improved correlation between the solvent polarity parameter than with the orientation polarity parameter and indicating that the red shift observed could be due to hydrogen-bonding between the solvent molecules. A similar association was obtained when Stokes' shift was replaced by maximum synchronous fluorescence. Both B-Cur2 and Fe-Cur3 had larger quantum yields than curcumin, suggesting they may be good candidates for medical imaging and in vitro studies.

  1. Structure-Activity Relationship of Curcumin: Role of the Methoxy Group in Anti-inflammatory and Anticolitis Effects of Curcumin.

    Science.gov (United States)

    Yang, Haixia; Du, Zheyuan; Wang, Weicang; Song, Mingyue; Sanidad, Katherine; Sukamtoh, Elvira; Zheng, Jennifer; Tian, Li; Xiao, Hang; Liu, Zhenhua; Zhang, Guodong

    2017-06-07

    Curcumin, a dietary compound from turmeric, has beneficial effects on inflammatory diseases such as inflammatory bowel disease. Most previous studies have focused on the structure-activity relationship of the thiol-reactive α,β-unsaturated carbonyl groups of curcumin, so little is known about the roles of methoxy groups in biological activities of curcumin. Here we synthesized a series of curcumin analogues with different substitution groups (R = H-, Br-, Cl-, F-, NO 2 -, CH 3 -, and OH-) to replace the methoxy group and evaluated their biological effects in vitro and in vivo. Curcumin, Cur-OH, and Cur-Br (25 μM) suppressed 74.91 ± 0.88, 77.75 ± 0.89, and 71.75 ± 0.90% of LPS-induced NO production, respectively (P 0.05). In the dextran sulfate sodium (DSS)-induced colitis mouse model, the Cur-Br analogue also showed a beneficial effect the same as curcumin (P 0.05). Together, the analogues have dramatically different effects on inflammation, supporting that the substitution group on the methoxy position plays an important role in the anti-inflammatory effects of curcumin. The methoxy group is a potential structural candidate for modification to design curcumin-based drugs for inflammatory diseases.

  2. Telomerase: A Target for Therapeutic Effects of Curcumin and a Curcumin Derivative in Aβ1-42 Insult In Vitro

    Science.gov (United States)

    Lin, Jianwen; Zheng, Zhenyang; Shi, Xiaolei; Di, Wei; Qi, Weiwei; Zhu, Yingting; Zhou, Guijuan; Fang, Yannan

    2014-01-01

    This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aβ1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aβ1–42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1. PMID:24983737

  3. Curcumin-functionalized silk biomaterials for anti-aging utility.

    Science.gov (United States)

    Yang, Lei; Zheng, Zhaozhu; Qian, Cheng; Wu, Jianbing; Liu, Yawen; Guo, Shaozhe; Li, Gang; Liu, Meng; Wang, Xiaoqin; Kaplan, David L

    2017-06-15

    Curcumin is a natural antioxidant that is isolated from turmeric (Curcuma longa) and exhibits strong free radical scavenging activity, thus functional for anti-aging. However, poor stability and low solubility of curcumin in aqueous conditions limit its biomedical applications. Previous studies have shown that the anti-oxidation activity of curcumin embedded in silk fibroin films could be well preserved, resulting in the promoted adipogenesis from human mesenchymal stem cells (hMSCs) cultured on the surface of the films. In the present study, curcumin was encapsulated in both silk fibroin films (silk/cur films) and nanoparticles (silk/cur NPs), and their anti-aging effects were compared with free curcumin in solution, with an aim to elucidate the mechanism of anti-aging of silk-associated curcumin and to better serve biomedical applications in the future. The morphology and structure of silk/cur film and silk/cur NP were characterized using SEM, FTIR and DSC, indicating characteristic stable beta-sheet structure formation in the materials. Strong binding of curcumin molecules to the beta-sheet domains of silk fibroin resulted in the slow release of curcumin with well-preserved activity from the materials. For cell aging studies, rat bone marrow mesenchymal stem cells (rBMSCs) were cultured in the presence of free curcumin (FC), silk/cur film and silk/cur NP, and cell proliferation and markers of aging (P53, P16, HSP70 gene expression and β-Galactosidase activity) were examined. The results indicated that cell aging was retarded in all FC, silk/cur NP and silk/cur film samples, with the silk-associated curcumin superior to the FC. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

    Directory of Open Access Journals (Sweden)

    Ghosh A

    2014-11-01

    Full Text Available Aparajita Ghosh,1 Tanushree Banerjee,2 Suman Bhandary,1 Avadhesha Surolia31Division of Molecular Medicine, Bose Institute, Centenary Campus, Kolkata, West Bengal, India; 2Department of Biotechnology, University of Pune, Pune, India; 3Molecular Biophysics Unit, Indian Institute of Science, Bangalore, IndiaAim: The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria. Materials and methods: Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo. Results: The nanopreparation was found to be non-toxic and had a particle size distribution of 20–50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration [IC50]: 0.5 µM was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC50: 5 µM. Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei-infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only. Conclusion: Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria

  5. Curcumin exerts its antitumor effects in a context dependent fashion.

    Science.gov (United States)

    Kreutz, Dominique; Sinthuvanich, Chomdao; Bileck, Andrea; Janker, Lukas; Muqaku, Besnik; Slany, Astrid; Gerner, Christopher

    2018-06-30

    Proteome profiling profoundly contributes to the understanding of cell response mechanisms to drug actions. Such knowledge may become a key to improve personalized medicine. In the present study, the effects of the natural remedy curcumin on breast cancer model systems were investigated. MCF-7, ZR-75-1 and TGF-β1 pretreated fibroblasts, mimicking cancer-associated fibroblasts (CAFs), were treated independently as well as in tumor cell/CAF co-cultures. Remarkably, co-culturing with CAF-like cells (CLCs) induced different proteome alterations in MCF-7 and ZR-75-1 cells, respectively. Curcumin significantly induced HMOX1 in single cell type models and co-cultures. However, other curcumin effects differed. In the MCF-7/CLC co-culture, curcumin significantly down-regulated RC3H1, a repressor of inflammatory signaling. In the ZR-75-1/CLC co-culture, curcumin significantly down-regulated PEG10, an anti-apoptotic protein, and induced RRAGA, a pro-apoptotic protein involved in TNF-alpha signaling. Furthermore, curcumin induced AKR1C2, an important enzyme for progesterone metabolism. None of these specific curcumin effects were observed in single cell type cultures. All high-resolution mass spectrometry data are available via ProteomeXchange with the identifier PXD008719. The present data demonstrate that curcumin induces proteome alterations, potentially accounting for its known antitumor effects, in a strongly context-dependent fashion. Better means to understand and potentially predict individual variations of drug effects are urgently required. The present proteome profiling study of curcumin effects demonstrates the massive impact of the cell microenvironment on cell responses to drug action. Co-culture models apparently provide more biologically relevant information regarding curcumin effects than single cell type cultures. Copyright © 2018. Published by Elsevier B.V.

  6. Curcumin as a natural regulator of monocyte chemoattractant protein-1.

    Science.gov (United States)

    Karimian, Maryam Saberi; Pirro, Matteo; Majeed, Muhammed; Sahebkar, Amirhossein

    2017-02-01

    Monocyte chemoattractant/chemotactic protein-1 (MCP-1), a member of the CC chemokine family, is one of the key chemokines that regulate migration and tissue infiltration of monocytes/macrophages. Its role in the pathophysiology of several inflammatory diseases has been widely recognized, thus making MCP-1 a possible target for anti-inflammatory treatments. Curcumin (diferuloylmethane) is a natural polyphenol derived from the rhizomes of Curcuma Longa L. (turmeric). Anti-inflammatory action underlies numerous pharmacological effects of curcumin in the control and prevention of several diseases. The purpose of this review is to evaluate the effects of curcumin on the regulation of MCP-1 as a key mediator of chemotaxis and inflammation, and the biological consequences thereof. In vitro studies have shown that curcumin can decrease MCP-1 production in various cell lines. Animal studies have also revealed that curcumin can attenuate MCP-1 expression and improve a range of inflammatory diseases through multiple molecular targets and mechanisms of action. There is limited data from human clinical trials showing the decreasing effect of curcumin on MCP-1 concentrations and improvement of the course of inflammatory diseases. Most of the in vitro and animal studies confirm that curcumin exert its MCP-1-lowering and anti-inflammatory effects by down-regulating the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway. As yet, there is limited data from human clinical trials showing the effect of curcumin on MCP-1 levels and improvement of the course of inflammatory diseases. More evidence, especially from human studies, is needed to better assess the effects of curcumin on circulating MCP-1 in different human diseases and the role of this modulatory effect in the putative anti-inflammatory properties of curcumin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. (Cationic + nonionic) mixed surfactant aggregates for solubilisation of curcumin

    International Nuclear Information System (INIS)

    Kumar, Arun; Kaur, Gurpreet; Kansal, S.K.; Chaudhary, G.R.; Mehta, S.K.

    2016-01-01

    Highlights: • Critical micelle concentration of mixed surfactant has been measured. • Aqueous solubility and alkaline stability of curcumin has been significantly improved. • Location of curcumin within micelles has been evaluated. • Scavenging activity of curcumin has been improved. • Non-intercalative binding with ct-DNA has been observed. - Abstract: Curcumin is a potential drug for variety of diseases. Major limitations of curcumin are low water solubility, rapid hydrolytic degradation in alkaline medium and poor bioavailability. To overcome these limitations, highly potential mixed micellar system has been prepared. In order to reduce inter ionic repulsion and precipitation of surfactants, (cationic + non-ionic) mixed system have been chosen that directly influence its applicability. Hydrophobic chain of non-ionic surfactant significantly influences the cmc of mixed surfactant system as indicated by fluorescence and conductivity data. UV–visible spectroscopy analyses show that solubility, stability and antioxidant property of the curcumin is remarkably improved depending on cmc and aggregation number (N_a_g_g) of mixed surfactants, where N_a_g_g plays crucial role. Generally, curcumin undergoes complete degradation in slight basic medium, but stability has been maintained up to 8 h at pH-13 using formulated mixed micelles (only (20 to 25)% degraded). Location of curcumin which is monitored using emission spectroscopy, fluorescence quenching and "1H NMR spectroscopy techniques play the most important role. Observed results show that the major population of curcumin is located at the polar region and some are in hydrophobic region of the mixed micelles. To ensure the effect of mixed surfactants and curcumin loaded mixed surfactants on DNA, the interaction parameter indicates non-interclative interactions.

  8. Curcumin administration suppress acetylcholinesterase gene expression in cadmium treated rats.

    Science.gov (United States)

    Akinyemi, Ayodele Jacob; Oboh, Ganiyu; Fadaka, Adewale Oluwaseun; Olatunji, Babawale Peter; Akomolafe, Seun

    2017-09-01

    Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes have been reported to exert anticholinesterase potential with limited information on how they regulate acetylcholinesterase (AChE) gene expression. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) activity and their mRNA gene expression level in cadmium (Cd)-treated rats. Furthermore, in vitro effect of different concentrations of curcumin (1-5μg/mL) on rat cerebral cortex AChE activity was assessed. Animals were divided into six groups (n=6): group 1 serve as control (without Cd) and receive saline/vehicle, group 2 receive saline plus curcumin at 25mg/kg, group 3 receive saline plus curcumin 50mg/kg, group 4 receive Cd plus vehicle, group 5 receive Cd plus curcumin at 25mg/kg and group 6 receive Cd plus curcumin at 50mg/kg. Rats received Cd (2.5mg/kg) and curcumin (25 and 50mg/kg, respectively) by oral gavage for 7days. Acetylcholinesterase activity was measured by Ellman's method and AChE expression was carried out by a quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assay. We observed that acute administration of Cd increased acetylcholinesterase activity and in addition caused a significant (Pcurcumin inhibited AChE activity and alters AChE mRNA levels when compared to Cd-treated group. In addition, curcumin inhibits rat cerebral cortex AChE activity in vitro. In conclusion, curcumin exhibit anti-acetylcholinesterase activity and suppressed AChE mRNA gene expression level in Cd exposed rats, thus providing some biochemical and molecular evidence on the therapeutic effect of this turmeric-derived compound in treating neurological disorders including Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult

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    Zhangyang Qi

    2017-11-01

    Full Text Available Background/Aims: The generation of reactive oxygen species (ROS caused by amyloid-β (Aβ is considered to be one of mechanisms underlying the development of Alzheimer’s disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ. Methods: P-curcumin was prepared through chemical synthesis. Its structure was determined via nuclear magnetic resonance (NMR and high-resolution mass spectrometry (HRMS. An MTT assay was used to assess Aβ cytotoxicity and the protective effect of P-curcumin on SH-SY5Y cells. The effect of P-curcumin on Aβ-induced ROS production in vitro and in vivo were assessed based on changes in dichlorofluorescein (DCF fluorescence. A spectrophotometric method was employed to detect lipid peroxidation. To mimic the interaction of P-curcumin on cell membranes with Aβ, liposomes were prepared by thin film method. Finally, the interactions between free P-curcumin and P-curcumin cultivated on liposomes and Aβ were determined via spectrophotometry. Results: A novel derivative, palmitic acid curcumin ester was prepared and characterized. This curcumin, cultivated on the membranes of neurocytes, may prevent Aβ-mediated ROS production and may inhibit the direct interaction between Aβ and the cellular membrane. Furthermore, P-curcumin could scavenge Aβ-mediated ROS as curcumin in vitro and in vivo, and had the potential to prevent lipid peroxidation. Morphological analyses showed that P-curcumin was better than curcumin at protecting cell shape. To examine P-curcumin’s ability to attenuate direct interaction between Aβ and cell membranes, the binding affinity of Aβ to curcumin

  10. Eliminating the Heart from the Curcumin Molecule: Monocarbonyl Curcumin Mimics (MACs)

    Science.gov (United States)

    Shetty, Dinesh; Kim, Yong Joon; Shim, Hyunsuk; Snyder, James P.

    2015-01-01

    Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin’s Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ~ 7.4. Researchers have sought to unlock curcumin’s assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs). A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10–20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK) profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer’s disease and malaria. PMID:25547726

  11. Eliminating the Heart from the Curcumin Molecule: Monocarbonyl Curcumin Mimics (MACs

    Directory of Open Access Journals (Sweden)

    Dinesh Shetty

    2014-12-01

    Full Text Available Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin’s Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ~ 7.4. Researchers have sought to unlock curcumin’s assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs. A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10–20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer’s disease and malaria.

  12. Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Wenxuan; Lu, Chunfeng; Yao, Lu; Zhang, Feng; Shao, Jiangjuan [Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province (China); Zheng, Shizhong, E-mail: nytws@163.com [Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province (China); Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province (China)

    2017-01-15

    Alcoholic liver disease (ALD) is a common etiology of liver diseases, characterized by hepatic steatosis. We previously identified farnesoid X receptor (FXR) as a potential therapeutic target for ALD. Dihydroartemisinin (DHA) has been recently identified to possess potent pharmacological activities on liver diseases. This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies. Results demonstrated that DHA rescued FXR expression and activity in alcoholic rat livers. DHA also reduced serodiagnostic markers of liver injury, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. DHA improved alcohol-induced liver histological lesions, expression of inflammation genes, and inflammatory cell infiltration. In addition, DHA not only attenuated hyperlipidemia but also reduced hepatic steatosis through regulating lipogenesis and lipolysis genes. In vitro experiments further consolidated the concept that DHA ameliorated ethanol-caused hepatocyte injury and steatosis. Noteworthily, DHA effects were reinforced by FXR agonist obeticholic acid or FXR expression plasmids but abrogated by FXR antagonist Z-guggulsterone or FXR siRNA. In summary, DHA significantly improved alcoholic liver injury by inhibiting hepatic steatosis, which was dependent on its activation of FXR in hepatocytes. - Highlights: • DHA rescues FXR expression in alcoholic livers. • DHA improves alcoholic liver inflammation and steatosis in a FXR-dependent way. • DHA alleviates ethanol-induced hepatocyte steatosis by activation of FXR.

  13. Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner

    International Nuclear Information System (INIS)

    Xu, Wenxuan; Lu, Chunfeng; Yao, Lu; Zhang, Feng; Shao, Jiangjuan; Zheng, Shizhong

    2017-01-01

    Alcoholic liver disease (ALD) is a common etiology of liver diseases, characterized by hepatic steatosis. We previously identified farnesoid X receptor (FXR) as a potential therapeutic target for ALD. Dihydroartemisinin (DHA) has been recently identified to possess potent pharmacological activities on liver diseases. This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies. Results demonstrated that DHA rescued FXR expression and activity in alcoholic rat livers. DHA also reduced serodiagnostic markers of liver injury, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. DHA improved alcohol-induced liver histological lesions, expression of inflammation genes, and inflammatory cell infiltration. In addition, DHA not only attenuated hyperlipidemia but also reduced hepatic steatosis through regulating lipogenesis and lipolysis genes. In vitro experiments further consolidated the concept that DHA ameliorated ethanol-caused hepatocyte injury and steatosis. Noteworthily, DHA effects were reinforced by FXR agonist obeticholic acid or FXR expression plasmids but abrogated by FXR antagonist Z-guggulsterone or FXR siRNA. In summary, DHA significantly improved alcoholic liver injury by inhibiting hepatic steatosis, which was dependent on its activation of FXR in hepatocytes. - Highlights: • DHA rescues FXR expression in alcoholic livers. • DHA improves alcoholic liver inflammation and steatosis in a FXR-dependent way. • DHA alleviates ethanol-induced hepatocyte steatosis by activation of FXR.

  14. Niosome Encapsulation of Curcumin: Characterization and Cytotoxic Effect on Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ying-Qi Xu

    2016-01-01

    Full Text Available Curcumin, a natural chemical compound found in Curcuma longa, has been applied in multiple medicinal areas from antibiotic to antitumor treatment. However, the chemical structure of curcumin results in poor stability, low solubility, and rapid degradation in vivo, hindering its clinical utilization. To address these issues, we have developed a novel niosome system composed of nonionic surfactants: Span 80, Tween 80, and Poloxamer 188. Curcumin was encapsulated in the niosomes with a high entrapment efficiency of 92.3±0.4%. This system provided controlled release of curcumin, thereby improving its therapeutic capability. Dynamic dialysis was conducted to evaluate the in vitro drug release of curcumin-niosomes. Curcumin-niosomes exhibited enhanced cytotoxic activity and apoptotic rate against ovarian cancer A2780 cells compared with freely dispersed curcumin. These results demonstrate that the curcumin-niosome system is a promising strategy for the delivery of curcumin and ovarian cancer therapy.

  15. The Stability, Sustained Release and Cellular Antioxidant Activity of Curcumin Nanoliposomes

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    Xing Chen

    2015-08-01

    Full Text Available Curcumin is a multifunctional and natural agent considered to be pharmacologically safe. However, its application in the food and medical industry is greatly limited by its poor water solubility, physicochemical instability and inadequate bioavailability. Nanoliposome encapsulation could significantly enhance the solubility and stability of curcumin. Curcumin nanoliposomes exhibited good physicochemical properties (entrapment efficiency = 57.1, particle size = 68.1 nm, polydispersity index = 0.246, and zeta potential = −3.16 mV. Compared with free curcumin, curcumin nanoliposomes exhibited good stability against alkaline pH and metal ions as well as good storage stability at 4 °C. Curcumin nanoliposomes also showed good sustained release properties. Compared with free curcumin, curcumin nanoliposomes presented an equal cellular antioxidant activity, which is mainly attributed to its lower cellular uptake as detected by fluorescence microscopy and flow cytometry. This study provide theoretical and practical guides for the further application of curcumin nanoliposomes.

  16. Curcumin phytosomal softgel formulation: Development, optimization and physicochemical characterization.

    Science.gov (United States)

    Allam, Ahmed N; Komeil, Ibrahim A; Abdallah, Ossama Y

    2015-09-01

    Curcumin, a naturally occurring lipophilic molecule can exert multiple and diverse bioactivities. However, its limited aqueous solubility and extensive presystemic metabolism restrict its bioavailability. Curcumin phytosomes were prepared by a simple solvent evaporation method where free flowing powder was obtained in addition to a newly developed semisolid formulation to increase curcumin content in softgels. Phytosomal powder was characterized in terms of drug content and zeta potential. Thirteen different softgel formulations were developed using oils such as Miglyol 812, castor oil and oleic acid, a hydrophilic vehicle such as PEG 400 and bioactive surfactants such as Cremophor EL and KLS P 124. Selected formulations were characterized in terms of curcumin in vitro dissolution. TEM analysis revealed good stability and a spherical, self-closed structure of curcumin phytosomes in complex formulations. Stability studies of chosen formulations prepared using the hydrophilic vehicle revealed a stable curcumin dissolution pattern. In contrast, a dramatic decrease in curcumin dissolution was observed in case of phytosomes formulated in oily vehicles.

  17. Polymeric Nanoparticles for Increasing Oral Bioavailability of Curcumin

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    Anita Umerska

    2018-03-01

    Full Text Available Despite the promising biological and antioxidant properties of curcumin, its medical applications are limited due to poor solubility in water and low bioavailability. Polymeric nanoparticles (NPs adapted to oral delivery may overcome these drawbacks. Properties such as particle size, zeta potential, morphology and encapsulation efficiency were assessed. Then, the possibility of storing these NPs in a solid-state form obtained by freeze-drying, in vitro curcumin dissolution and cytocompatibility towards intestinal cells were evaluated. Curcumin-loaded Eudragit® RLPO (ERL NPs showed smaller particle diameters (245 ± 2 nm and better redispersibility after freeze-drying than either poly(lactic-co-glycolic acid (PLGA or polycaprolactone (PCL NPs. The former NPs showed lower curcumin encapsulation efficiency (62% than either PLGA or PCL NPs (90% and 99%, respectively. Nevertheless, ERL NPs showed rapid curcumin release with 91 ± 5% released over 1 h. The three curcumin-loaded NPs proposed in this work were also compatible with intestinal cells. Overall, ERL NPs are the most promising vehicles for increasing the oral bioavailability of curcumin.

  18. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

    Science.gov (United States)

    Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Harsha, Choudhary; Banik, Kishore; Gupta, Subash C; Aggarwal, Bharat B

    2017-08-01

    Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  19. Antibacterial Action of Curcumin against Staphylococcus aureus: A Brief Review

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    Sin-Yeang Teow

    2016-01-01

    Full Text Available Curcumin, the major constituent of Curcuma longa L. (Zingiberaceae family or turmeric, commonly used for cooking in Asian cuisine, is known to possess a broad range of pharmacological properties at relatively nontoxic doses. Curcumin is found to be effective against Staphylococcus aureus (S. aureus. As demonstrated by in vitro experiment, curcumin exerts even more potent effects when used in combination with various other antibacterial agents. Hence, curcumin which is a natural product derived from plant is believed to have profound medicinal benefits and could be potentially developed into a naturally derived antibiotic in the future. However, there are several noteworthy challenges in the development of curcumin as a medicine. S. aureus infections, particularly those caused by the multidrug-resistant strains, have emerged as a global health issue and urgent action is needed. This review focuses on the antibacterial activities of curcumin against both methicillin-sensitive S. aureus (MSSA and methicillin-resistant S. aureus (MRSA. We also attempt to highlight the potential challenges in the effort of developing curcumin into a therapeutic antibacterial agent.

  20. Targeted delivery of curcumin for treating type 2 diabetes.

    Science.gov (United States)

    Maradana, Muralidhara Rao; Thomas, Ranjeny; O'Sullivan, Brendan J

    2013-09-01

    Type 2 diabetes is a chronic condition in which cells have reduced insulin signalling, leading to hyperglycemia and long-term complications, including heart, kidney and liver disease. Macrophages activated by dying or stressed cells, induce the transcription factor nuclear factor kappa-B leading to the production of pro-inflammatory cytokines including TNF and IL-6. These inflammatory macrophages in liver and adipose tissue promote insulin resistance, and medications which reduce inflammation and enhance insulin signalling improve glucose control. Curcumin is an anti-oxidant and nuclear factor kappa-B inhibitor derived from turmeric. A number of studies have shown that dietary curcumin reduces inflammation and delays or prevents obesity-induced insulin resistance and associated complications, including atherosclerosis and immune mediate liver disease. Unfortunately dietary curcumin is poorly absorbed by the digestive system and undergoes glucuronidation and excretion rather than being released into the serum and systemically distributed. This confounds understanding of how dietary curcumin exerts its beneficial effects in type 2 diabetes and associated diseases. New improved methods of delivering curcumin are being developed including nanoparticles and lipid/liposome formulations that increase absorption and bioavailability of curcumin. Development and refinement of these technologies will enable cell-directed targeting of curcumin and improved therapeutic outcome. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Modulation of Erythrocyte Plasma Membrane Redox System Activity by Curcumin

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    Prabhakar Singh

    2016-01-01

    Full Text Available Plasma membrane redox system (PMRS is an electron transport chain system ubiquitously present throughout all cell types. It transfers electron from intracellular substrates to extracellular acceptors for regulation of redox status. Curcumin, isolated from Curcuma longa, has modulatory effects on cellular physiology due to its membrane interaction ability and antioxidant potential. The present study investigates the effect of curcumin on PMRS activity of erythrocytes isolated from Wistar rats in vitro and in vivo and validated through an in silico docking simulation study using Molegro Virtual Docker (MVD. Effects of curcumin were also evaluated on level of glutathione (GSH and the oxidant potential of plasma measured in terms of plasma ferric equivalent oxidative potentials (PFEOP. Results show that curcumin significantly (p<0.01 downregulated the PMRS activity in a dose-dependent manner. Molecular docking results suggest that curcumin interacts with amino acids at the active site cavity of cytochrome b5 reductase, a key constituent of PMRS. Curcumin also increased the GSH level in erythrocytes and plasma while simultaneously decreasing the oxidant potential (PFEOP of plasma. Altered PMRS activity and redox status are associated with the pathophysiology of several health complications including aging and diabetes; hence, the above finding may explain part of the role of curcumin in health beneficial effects.

  2. Identification of proteins regulated by curcumin in cerebral ischemia.

    Science.gov (United States)

    Shah, Fawad-Ali; Gim, Sang-Ah; Sung, Jin-Hee; Jeon, Seong-Jun; Kim, Myeong-Ok; Koh, Phil-Ok

    2016-03-01

    Curcumin is known to have a neuroprotective effect against cerebral ischemia. The objective of this study was to identify various proteins that are differentially expressed by curcumin treatment in focal cerebral ischemia using a proteomic approach. Adult male rats were treated with vehicle or curcumin 1 h after middle cerebral artery occlusion. Brain tissues were collected 24 h after the onset of middle cerebral artery occlusion, and cerebral cortices proteins were identified by two-dimensional gel electrophoresis and mass spectrometry. We detected several proteins with altered expression levels between vehicle- and curcumin-treated animals. Among these proteins, ubiquitin carboxy-terminal hydrolase L1, isocitrate dehydrogenase, adenosylhomocysteinase, and eukaryotic initiation factor 4A were decreased in the vehicle-treated animal, and curcumin treatment attenuated the injury-induced decreases of these proteins. Conversely, pyridoxal phosphate phosphatase was increased in the vehicle-treated animal, and curcumin treatment prevented decreases in this protein. The identified altered proteins are associated with cellular metabolism and differentiation. The results of this study suggest that curcumin exerts a neuroprotective effect by regulating the expression of various proteins in focal cerebral ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Curcumin phytosomal softgel formulation: Development, optimization and physicochemical characterization

    Directory of Open Access Journals (Sweden)

    Allam Ahmed N.

    2015-09-01

    Full Text Available Curcumin, a naturally occurring lipophilic molecule can exert multiple and diverse bioactivities. However, its limited aqueous solubility and extensive presystemic metabolism restrict its bioavailability. Curcumin phytosomes were prepared by a simple solvent evaporation method where free flowing powder was obtained in addition to a newly developed semisolid formulation to increase curcumin content in softgels. Phytosomal powder was characterized in terms of drug content and zeta potential. Thirteen different softgel formulations were developed using oils such as Miglyol 812, castor oil and oleic acid, a hydrophilic vehicle such as PEG 400 and bioactive surfactants such as Cremophor EL and KLS P 124. Selected formulations were characterized in terms of curcumin in vitro dissolution. TEM analysis revealed good stability and a spherical, self-closed structure of curcumin phytosomes in complex formulations. Stability studies of chosen formulations prepared using the hydrophilic vehicle revealed a stable curcumin dissolution pattern. In contrast, a dramatic decrease in curcumin dissolution was observed in case of phytosomes formulated in oily vehicles.

  4. Renoprotective effect of the antioxidant curcumin: Recent findings☆

    Science.gov (United States)

    Trujillo, Joyce; Chirino, Yolanda Irasema; Molina-Jijón, Eduardo; Andérica-Romero, Ana Cristina; Tapia, Edilia; Pedraza-Chaverrí, José

    2013-01-01

    For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2), inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury. PMID:24191240

  5. Novel water-soluble curcumin derivative mediating erectile signaling.

    Science.gov (United States)

    Abdel Aziz, Mohamed Talaat; El Asmer, Mohammed F; Rezq, Ameen; Kumosani, Taha Abdullah; Mostafa, Samya; Mostafa, Taymour; Atta, Hazem; Abdel Aziz Wassef, Mohamed; Fouad, Hanan H; Rashed, Laila; Sabry, Dina; Hassouna, Amira A; Senbel, Amira; Abdel Aziz, Ahmed

    2010-08-01

    Curcumin is an inducer of heme oxygenase enzyme-1 (HO-1) that is involved in erectile signaling via elevating cyclic guanosine monophosphate (cGMP)levels. To assess the effect of oral administration of a water-soluble long-acting curcumin derivative on erectile signaling. Two hundred and thirty six male white albino rats were divided into four groups; group 1 (N = 20) includes control. Group 2 (N = 72) was equally divided into four subgroups; subgroup 1 received pure curcumin (10 mg/kg), subgroup 2 received the long-acting curcumin derivative (2 mg/kg), subgroup 3 received the long-acting curcumin derivative (10 mg/kg), and subgroup 4 received sildenafil (4 mg/kg). Subgroups were sacrificed after the first, second, and third hour. Group 3 (N = 72) was equally divided into the same four subgroups already mentioned and were sacrificed after 24 hours, 48 hours, and 1 week. Group 4 (N = 72) was subjected to intracavernosal pressure (ICP) measurements 1 hour following oral administration of the same previous doses in the same rat subgroups. Cavernous tissue HO enzyme activity, cGMP, and ICP. In group 2, there was a significant progressive maintained elevation of HO activity and cGMP tissue levels starting from the first hour in subgroups 3 and 4, whereas, the rise in HO activity and cGMP started from second hour regarding the other rat subgroups. Sildenafil effect decreased after 3 hours. In group 3, there was a significant maintained elevation of HO activity and cGMP tissue levels extended to 1 week as compared to controls for all rat subgroups that received both forms of curcumin. In group 4, long-acting curcumin derivative exhibited more significant potentiation of intracavernosal pressure as compared to control and to the pure curcumin. Water-soluble long-acting curcumin derivative could mediate erectile function via upregulating cavernous tissue cGMP. © 2009 International Society for Sexual Medicine.

  6. Antidepressant activity of curcumin: involvement of serotonin and dopamine system.

    Science.gov (United States)

    Kulkarni, Shrinivas K; Bhutani, Mohit Kumar; Bishnoi, Mahendra

    2008-12-01

    Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions. The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin. Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10-80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities. The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.

  7. The effects of Curcuma longa and curcumin on reproductive systems.

    Science.gov (United States)

    Mohebbati, R; Anaeigoudari, A; Khazdair, M R

    2017-10-26

    Curcuma longa (C. longa) was used in some countries such as China and India for various medicinal purposes. Curcumin, the active component of C. longa, is commonly used as a coloring agent in foods, drugs, and cosmetics. C. longa and curcumin have been known to act as antioxidant, anti-inflammatory, anti-mutagen, and anti-carcinogenic agents. Th e attempt of the present review was to give an effort on a detailed literature survey concentrated on the protective effects of C. longa and curcumin on the reproductive organs activity. The databases such as, PubMed, Web of Science, Google Scholar, Scopus, and Iran- Medex, were considered. The search terms were "testis" or "ovary" and "Curcuma longa", "curcumin", "antioxidant effect", "anti-inflammatory effect" and "anti-cancer effect". C. longa and curcumin inhibited the production of the tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) and increased the caspases (3, 8 and 9) activities in HL-60 prostate cancer. Furthermore, C. longa and curcumin suppressed the vascular endothelial growth factor (VEGF), phosphorylated signal transducers and activators of the transcription 3 (STAT) and matrix metalloproteinase-9 (MMP-9) in ovarian cancer cell line. C. longa and curcumin might decrease the risk of cancer and other malignant diseases in the reproductive system. C. longa and curcumin have a protective effect on the reproductive organs activity such as, anti-inflammatory, anti-apoptotic, and antioxidant effects in normal cells but showed pro-apoptotic effects in the malignant cells. Therefore, different effects of C. longa and curcumin are dependent on the doses and the type of cells used in various models studied.

  8. Renoprotective effect of the antioxidant curcumin: Recent findings

    Directory of Open Access Journals (Sweden)

    Joyce Trujillo

    2013-01-01

    Full Text Available For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2, inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury.

  9. Curcumin-Free Turmeric Exhibits Activity against Human HCT-116 Colon Tumor Xenograft: Comparison with Curcumin and Whole Turmeric

    Science.gov (United States)

    Prasad, Sahdeo; Tyagi, Amit K.; Siddik, Zahid H.; Aggarwal, Bharat B.

    2017-01-01

    Extensive research within last two decades has indicated that curcumin extracted from turmeric (Curcuma longa), exhibits anticancer potential, in part through the modulation of inflammatory pathways. However, the residual antitumor activity of curcumin-free turmeric (CFT) relative to curcumin or turmeric is not well-understood. In the present study, therefore, we determined activities of these agents in both in vitro and in vivo models of human HCT-116 colorectal cancer (CRC). When examined in an in vitro antiproliferative, clonogenic or anti-inflammatory assay system, we found that curcumin was highly active whereas turmeric and CFT had relatively poor activity against CRC cells. However, when examined in vivo at an oral dose of either 100 or 500 mg/kg given to nude mice bearing CRC xenografts, all three preparations of curcumin, turmeric, and CFT similarly suppressed the growth of the xenograft. The effect of CFT on suppression of tumor growth was dose-dependent, with 500 mg/kg tending to be more effective than 100 mg/kg. Interestingly, 100 mg/kg curcumin or turmeric was found to be more effective than 500 mg/kg. When examined in vivo for the expression of biomarkers associated with cell survival (cIAP-1, Bcl-2, and survivin), proliferation (Ki-67 and cyclin D1) and metastasis (ICAM-1 and VEGF), all were down-modulated. These agents also suppressed inflammatory transcription factors (NF-κB and STAT3) in tumor cells. Overall, our results with CFT provide evidence that turmeric must contain additional bioactive compounds other than curcumin that, in contrast to curcumin, exhibit greater anticancer potential in vivo than in vitro against human CRC. Moreover, our study highlights the fact that the beneficial effects of turmeric and curcumin in humans may be more effectively realized at lower doses, whereas CFT could be given at higher doses without loss in favorable activity. PMID:29311914

  10. Curcumin-Free Turmeric Exhibits Activity against Human HCT-116 Colon Tumor Xenograft: Comparison with Curcumin and Whole Turmeric

    Directory of Open Access Journals (Sweden)

    Sahdeo Prasad

    2017-12-01

    Full Text Available Extensive research within last two decades has indicated that curcumin extracted from turmeric (Curcuma longa, exhibits anticancer potential, in part through the modulation of inflammatory pathways. However, the residual antitumor activity of curcumin-free turmeric (CFT relative to curcumin or turmeric is not well-understood. In the present study, therefore, we determined activities of these agents in both in vitro and in vivo models of human HCT-116 colorectal cancer (CRC. When examined in an in vitro antiproliferative, clonogenic or anti-inflammatory assay system, we found that curcumin was highly active whereas turmeric and CFT had relatively poor activity against CRC cells. However, when examined in vivo at an oral dose of either 100 or 500 mg/kg given to nude mice bearing CRC xenografts, all three preparations of curcumin, turmeric, and CFT similarly suppressed the growth of the xenograft. The effect of CFT on suppression of tumor growth was dose-dependent, with 500 mg/kg tending to be more effective than 100 mg/kg. Interestingly, 100 mg/kg curcumin or turmeric was found to be more effective than 500 mg/kg. When examined in vivo for the expression of biomarkers associated with cell survival (cIAP-1, Bcl-2, and survivin, proliferation (Ki-67 and cyclin D1 and metastasis (ICAM-1 and VEGF, all were down-modulated. These agents also suppressed inflammatory transcription factors (NF-κB and STAT3 in tumor cells. Overall, our results with CFT provide evidence that turmeric must contain additional bioactive compounds other than curcumin that, in contrast to curcumin, exhibit greater anticancer potential in vivo than in vitro against human CRC. Moreover, our study highlights the fact that the beneficial effects of turmeric and curcumin in humans may be more effectively realized at lower doses, whereas CFT could be given at higher doses without loss in favorable activity.

  11. Curcuma longa Linn. extract and curcumin protect CYP 2E1 enzymatic activity against mercuric chloride-induced hepatotoxicity and oxidative stress: A protective approach.

    Science.gov (United States)

    Joshi, Deepmala; Mittal, Deepak Kumar; Shukla, Sangeeta; Srivastav, Sunil Kumar; Dixit, Vaibhav A

    2017-07-05

    The present investigation has been conducted to evaluate the therapeutic potential of Curcuma longa (200mgkg -1 , po) and curcumin (80mgkg -1 , po) for their hepatoprotective efficacy against mercuric chloride (HgCl 2 : 12μmolkg -1 , ip; once only) hepatotoxicity. The HgCl 2 administration altered various biochemical parameters, including transaminases, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transferase, triglycerides and cholesterol contents with a concomitant decline in protein and albumin concentration in serum which were restored towards control by therapy of Curcuma longa or curcumin. On the other hand, both treatments showed a protective effect on drug metabolizing enzymes viz. aniline hydroxylase (AH) and amidopyrine-N-demethylase (AND), hexobarbitone induced sleep time and BSP retention. Choleretic, 1,1-diphenyl-2-picryl-hydrazil (DPPH)-free radical scavenging activities and histological studies also supported the biochemical findings. The present study concludes that Curcuma longa extract or curcumin has the ability to alleviate the hepatotoxic effects caused by HgCl 2 in rats. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. Alleviating gizzard erosion with Hepasan ® - Provisional ...

    African Journals Online (AJOL)

    Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. DOWNLOAD FULL TEXT Open Access DOWNLOAD FULL TEXT Subscription or Fee Access. Alleviating gizzard erosion with Hepasan® - Provisional Communication. K Boa-Amponsem, A Osei-Somuah. Full Text:.

  13. Alleviating Poverty Through Vocational Education: The Nigerian ...

    African Journals Online (AJOL)

    The paper concludes that well-articulated vocational education policy and programmes will assist in employment generations and poverty reduction in Nigeria. Keywords: Alleviating Poverty, Vocational Education, Nigerian Experience Journal of Technology and Education in Nigeria Vol. 10 (2) 2005: pp. 10-14 ...

  14. Chinese herbal medicine alleviating hyperandrogenism of PCOS ...

    African Journals Online (AJOL)

    Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women hence Chinese herbal medicine (CHM) has been chosen by many clinicians and patients as alternative treatment for PCOS. The present study was to explore the effects of CHM in alleviating hyperandrogenism of PCOS ...

  15. GLP-1 nanomedicine alleviates gut inflammation.

    Science.gov (United States)

    Anbazhagan, Arivarasu N; Thaqi, Mentor; Priyamvada, Shubha; Jayawardena, Dulari; Kumar, Anoop; Gujral, Tarunmeet; Chatterjee, Ishita; Mugarza, Edurne; Saksena, Seema; Onyuksel, Hayat; Dudeja, Pradeep K

    2017-02-01

    The gut hormone, glucagon like peptide-1 (GLP-1) exerts anti-inflammatory effects. However, its clinical use is limited by its short half-life. Previously, we have shown that GLP-1 as a nanomedicine (GLP-1 in sterically stabilized phospholipid micelles, GLP-1-SSM) has increased in vivo stability. The current study was aimed at testing the efficacy of this GLP-1 nanomedicine in alleviating colonic inflammation and associated diarrhea in dextran sodium sulfate (DSS) induced mouse colitis model. Our results show that GLP-1-SSM treatment markedly alleviated the colitis phenotype by reducing the expression of pro-inflammatory cytokine IL-1β, increasing goblet cells and preserving intestinal epithelial architecture in colitis model. Further, GLP-1-SSM alleviated diarrhea (as assessed by luminal fluid) by increasing protein expression of intestinal chloride transporter DRA (down regulated in adenoma). Our results indicate that GLP-1 nanomedicine may act as a novel therapeutic tool in alleviating gut inflammation and associated diarrhea in inflammatory bowel disease (IBD). Published by Elsevier Inc.

  16. Tau hyperphosphorylation and P-CREB reduction are involved in acrylamide-induced spatial memory impairment: Suppression by curcumin.

    Science.gov (United States)

    Yan, Dandan; Yao, Jianling; Liu, Ying; Zhang, Xing; Wang, Yiqi; Chen, Xiaoyi; Liu, Liegang; Shi, Nian; Yan, Hong

    2018-04-26

    Acrylamide (ACR) is an axonal toxicant that produces peripheral neuropathy in laboratory animals and humans. Epidemiological study found that diet ACR exposure was associated with a mild cognitive decline in men. However, limited information is available as regards its potential and underlying mechanism to cause memory alterations. Curcumin is a polyphenol with neuroprotective and cognitive-enhancing properties. In this study, we aimed to investigate the mechanism of ACR-induced spatial memory impairment and the beneficial effect of curcumin. ACR exposure at 10 mg/kg/d for 7 weeks caused slight gait abnormality and spatial memory deficits, which was associated with an activation of glial cells, a reduction of phosphorylated cAMP response elements binding protein (P-CREB) and an aggregation of hyperphosphorylated tau including p-tau (Ser 262 ), AT8 (p-tau Ser 202 /Thr 205 ) and PHF1 (p-tau Ser 396/404 ) in the hippocampus and cortex. ACR markedly regulate the expression of glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase-5 (cdk5) to accelerate tau hyperphosphorylation. ACR inhibited the protein phosphatase 2A (PP2A) and lysosomal protease cathepsin D to decrease the p-tau dephosphorylation and degradation. The P-CREB and brain derived neurotrophic factor (BDNF) were significantly decreased by ACR. The upstream signalings of P-CREB, extracellular signal-related kinase (ERK) and Akt were markedly inhibited. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) -eukaryotic initiation factor-2α (eIF2α) - activating transcription factor 4 (ATF4) signaling which negatively regulate memory processes by suppressing CREB was activated by ACR. Curcumin alleviated ACR-induced spatial memory impairment through reversing tau abnormalities and P-CREB reduction in the hippocampus. These results offered deeper insight into the mechanisms of and presented a potential new treatment for ACR-induced neurotoxicity. Copyright © 2018 Elsevier Inc. All

  17. Use of Novel Polyurethane Microspheres in a Curcumin Delivery System

    Directory of Open Access Journals (Sweden)

    Yongmei Hu

    2014-01-01

    Full Text Available Despite having a wide range of beneficial pharmacological effects, curcumin is characterized by poor water solubility and absorption. In this study, novel polyurethane microspheres containing curcumin (Cur-PUMs were prepared using carboxymethyl cellulose sodium to improve the bioavailability and prolong the retention time of curcumin. The prepared Cur-PUMs were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, and ultraviolet spectrophotometer. The sustained-release effects of Cur-PUMs were demonstrated using stability tests in vitro and in vivo pharmacokinetic studies following oral administration. We found that the stability of Cur-PUMs was strongly affected by pH variation. Further, compared with free curcumin, Cur-PUMs showed significantly improved maximum concentration and half-life.

  18. How curcumin affords effective protection against amyloid fibrillation in insulin?

    DEFF Research Database (Denmark)

    Rabiee, Atefeh; Ebrahim Habibi, Azadeh; Ghasemi, Atiyeh Ghasemi

    2013-01-01

    Since the formation of amyloid structures from proteins was recognized in numerous diseases, many efforts have been devoted to the task of finding effective anti-amyloidogenic compounds. In a number of these investigations, the existence of “generic” compounds is implicitly acknowledged. Curcumin...... been shown effectively influenced by micro molar concentrations of curcumin. Under amyloidogenic conditions (pH 2.5 and 37°C), the compound was observed to inhibit fibril formation of insulin in a dose-dependent manner. Moreover, addition of curcumin to the protein incubated in such conditions...... at different time points resulted in reduced amounts of final fibrils. Disaggregation of pre-formed fibrils was also observed upon addition of curcumin, as well as reduction in final fibril amounts after seeding. Overall, this compound appears to be able to interact with native, intermediate and fibrillar...

  19. Beneficial effect of Curcumin in Letrozole induced polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    P. Sushma Reddy

    2016-04-01

    Conclusion: Curcumin showed beneficial effects in Letrozole induced PCOS in female Wistar rats. Its effect was comparable to that of Clomiphene citrate, most widely used treatment for ovulation induction in PCOS condition.

  20. Curcumin and turmeric attenuate arsenic-induced angiogenesis in ovo.

    Science.gov (United States)

    Pantazis, Panayotis; Varman, Aarthi; Simpson-Durand, Cindy; Thorpe, Jessica; Ramalingam, Satish; Subramaniam, Dharmalingam; Houchen, Courtney; Ihnat, Michael; Anant, Shrikant; Ramanujam, Rama P

    2010-01-01

    Trivalent arsenic [As(III)] is currently approved by the FDA for the treatment of chronic and acute leukemias. However, As(III) has also demonstrated damaging effects on human health, including development of cardiovascular disease, diabetes, and cancer. Further, As(III) is a potent angiogenic agent. In this context, curcumin, an active ingredient in the dietary agent turmeric, has demonstrated potent antiproliferative, antiinflammatory, and antiangiogenic properties. In this report, we have shown that both curcumin and turmeric inhibit expression of vascular endothelial growth factor in HCT-116 human colon cancer cells exposed to As(III). Further, in the chicken chorioallantoic membrane assay model, treatment with low As(III) concentrations results in extensive increase in blood vessel density, which, however, is reduced in the presence of curcumin or turmeric. Collectively, the findings reported here strongly suggest that turmeric and curcumin can dramatically attenuate the process of angiogenesis induced by low As(III) concentrations.

  1. Augmentation of therapeutic potential of curcumin using nanotechnology: current perspectives.

    Science.gov (United States)

    Sivasami, Pulavendran; Hemalatha, Thiagarajan

    2018-02-28

    Curcumin, an active principle of Curcuma longa, is extracted from the rhizome. Its therapeutic efficiency has been proved using various in vitro and in vivo models. Inflammatory, neoplastic and preneoplastic diseases are the major targets using curcumin as therapeutic agent. Feasible clinical formulations could not be obtained because of its lack of solubility, stability and higher degradation rate. Recently, many techniques have been evolved to improve the physicochemical properties of pharmacological compounds, thereby increasing their biological activity. Curcumin has been developed using various techniques, particularly micro and nanotechnology to improve its stability and bioavailability. This review focuses on the studies pertaining to the delivery of curcumin in the form of micro and nanosize formulations for the treatment of a variety of diseases.

  2. Metabolic intervention of aflatoxin B1 toxicity by curcumin.

    Science.gov (United States)

    Nayak, Sujatha; Sashidhar, R B

    2010-02-17

    Curcumin, bioactive principle of turmeric (Curcuma longa Linn) is an important constituent of Indian traditional medicine. Turmeric has been known to possess several therapeutic properties. The modulatory effect of dietary curcumin (0.05%, w/w) on drug metabolizing and general marker enzymes of liver and formation of AFB(1)-adducts (DNA and protein) due to dietary AFB(1) exposure for a period of 6 weeks in a rodent model, have been evaluated. Drug metabolizing enzymes CYP1A1, GSHT, UGT1A and general marker enzymes (LDH, ALT, AST, ALP and gamma-GT) of liver were estimated by standardized methods. Aflatoxin adducts (DNA and protein) were quantitated by indirect competitive ELISA. Dietary curcumin enhanced GSHT (pcurcumin in the diet normalized the altered activities of LDH and ALT. At molecular level, curcumin significantly reduced AFB(1)-N(7)-guanine adduct (pcurcumin intervention ameliorates the AFB(1) induced toxicity. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  3. Modulation of radioresponse of DT-diaphorase by Curcumin

    International Nuclear Information System (INIS)

    Chandra, D.; Choudhary, D.; Kale, R.K.

    1998-01-01

    In the present work, Curcumin (diferuloyl methane), a phytochemical present in the rhizome of Curcuma longa Linn. has been examined for its radioprotective property using the DT-diaphorase (DTD) system

  4. Amelioration of Cisplatin-Induced Nephrotoxicity in Rats by Curcumin

    African Journals Online (AJOL)

    Keywords: Cisplatin, Oxidative stress, Curcumin, α-Tocopherol, Nephrotoxicity. Tropical ... exerts various side effects in several organs particularly in ... Previous study provides evidence which ..... chemotherapy by cisplatin but further in vivo.

  5. Cardioactive effects of diphenhydramine and curcumin in Daphnia magna

    Directory of Open Access Journals (Sweden)

    Noelle Erin Romero

    2009-01-01

    Full Text Available Although used as a model for examining the cardioactive effects of various compounds, the neuromuscular regulation of the heart of the crustacean Daphnia magna (D. magna is not well understood. In the present study, we sought to determine how the heart rate of D. magna was affected by two previously untested compounds: curcumin and diphenhydramine (DPHM. DPHM produces a number of cardiotoxic side effects in vertebrates, particularly sinus tachycardia. Curcumin acts as a monoamine oxidase inhibitor (MAOI and was expected toincrease the heart rate of D. magna. DPHM was found unexpectedly to lower the heart rate of D. magna with time. Curcumin increased heart rate when administered in higher concentrations. However, co-administration of curcumin with DPHM negated this effect. These findings may be explained by the potential role of histamine as a sympathetic cardiac neurotransmitter in D. magna.

  6. Collagen–curcumin interaction – A physico-chemical study

    Indian Academy of Sciences (India)

    Administrator

    years due to its wide spectrum of biological and pharmacological ... pancreatitis and arthritis. Curcumin is capable of ... inflammation, in heart diseases and in cancer. Cur- .... tion between adjacent molecules, expressed in force per unit width ...

  7. The Effects of Curcumin and Curcumin-Phospholipid Complex on the Serum Pro-oxidant-Antioxidant Balance in Subjects with Metabolic Syndrome.

    Science.gov (United States)

    Ghazimoradi, Maryam; Saberi-Karimian, Maryam; Mohammadi, Farzane; Sahebkar, Amirhossein; Tavallaie, Shima; Safarian, Hamideh; Ferns, Gordon A; Ghayour-Mobarhan, Majid; Moohebati, Mohsen; Esmaeili, Habibollah; Ahmadinejad, Malihe

    2017-11-01

    Metabolic syndrome (MetS) is defined by a clustering of metabolic and anthropometric abnormalities and is associated by an increased risk of cardiovascular disease. We have investigated the effect of curcumin supplementation on the serum pro-oxidant-antioxidant balance (PAB) in patients with MetS. This double-blind, randomized, placebo-controlled trial was conducted over 6 weeks. Subjects (n = 120) were randomly allocated to one of three groups (curcumin, phospholipidated curcumin, and placebo). The curcumin group received 1 g/day of simple curcumin, the phospholipidated curcumin group received 1 g/day of phospholipidated curcumin (containing 200 mg of pure curcumin), and the control group received 1 g/day of placebo. Serum PAB was measured before and after the intervention (at baseline and at 6 weeks). Data analyses were performed using spss software (version 16.0). Serum PAB increased significantly in the curcumin group (p curcumin group, elevation of PAB level was not significant (p = 0.053). The results of our study did not suggest any improvement of PAB following supplementation with curcumin in MetS subjects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Construction and characterization of curcumin nanoparticles system

    Science.gov (United States)

    Sun, Weitong; Zou, Yu; Guo, Yaping; Wang, Lu; Xiao, Xue; Sun, Rui; Zhao, Kun

    2014-03-01

    This study was aimed at developing a nanoparticles system for curcumin, a widely used traditional Chinese medicine, but with the disadvantage of poor aqueous solubility. The objective was intended to improve in vitro release characteristics, enhance blood and gastrointestinal stability, increase bioavailability and pharmacological activities. Curcumin nanoparticles system (Cur-NS) was prepared by ionotropic gelation technique. Cur-NS was characterized by particle size, zeta potential, drug entrapment efficiency, drug loading, and physical stability, respectively. Cur-NS presented controlled release properties, and the release properties of Cur from NS were fit non-Fickian mechanism, controlled by the expected diffusional release and the erosion or solubilization from the crosslink layer of polymer carrier. In addition, the pharmacokinetic study in rats revealed a notable improved oral bioavailability of Cur, and the anti-tumor activity in vivo of Cur-NS on tumor growth was investigated. Cur-NS significantly inhibited tumor effect compared with non-vehicle group, thus making it a potential candidate for cancer therapy.

  9. Liposomal curcumin and its application in cancer

    Directory of Open Access Journals (Sweden)

    Feng T

    2017-08-01

    Full Text Available Ting Feng,1,* Yumeng Wei,1,* Robert J Lee,2 Ling Zhao1 1Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA *These authors contributed equally to this work Abstract: Curcumin (CUR is a yellow polyphenolic compound derived from the plant turmeric. It is widely used to treat many types of diseases, including cancers such as those of lung, cervices, prostate, breast, bone and liver. However, its effectiveness has been limited due to poor aqueous solubility, low bioavailability and rapid metabolism and systemic elimination. To solve these problems, researchers have tried to explore novel drug delivery systems such as liposomes, solid dispersion, microemulsion, micelles, nanogels and dendrimers. Among these, liposomes have been the most extensively studied. Liposomal CUR formulation has greater growth inhibitory and pro-apoptotic effects on cancer cells. This review mainly focuses on the preparation of liposomes containing CUR and its use in cancer therapy. Keywords: curcumin, liposomes, drug delivery, bioavailability, cancer 

  10. Curcumin Quantum Dots Mediated Degradation of Bacterial Biofilms

    Directory of Open Access Journals (Sweden)

    Ashish K. Singh

    2017-08-01

    Full Text Available Bacterial biofilm has been reported to be associated with more than 80% of bacterial infections. Curcumin, a hydrophobic polyphenol compound, has anti-quorum sensing activity apart from having antimicrobial action. However, its use is limited by its poor aqueous solubility and rapid degradation. In this study, we attempted to prepare quantum dots of the drug curcumin in order to achieve enhanced solubility and stability and investigated for its antimicrobial and antibiofilm activity. We utilized a newer two-step bottom up wet milling approach to prepare Curcumin Quantum Dots (CurQDs using acetone as a primary solvent. Minimum inhibitory concentration against select Gram-positive and Gram-negative bacteria was performed. The antibiofilm assay was performed at first using 96-well tissue culture plate and subsequently validated by Confocal Laser Scanning Microscopy. Further, biofilm matrix protein was isolated using formaldehyde sludge and TCA/Acetone precipitation method. Protein extracted was incubated with varying concentration of CurQDs for 4 h and was subjected to SDS–PAGE. Molecular docking study was performed to observe interaction between curcumin and phenol soluble modulins as well as curli proteins. The biophysical evidences obtained from TEM, SEM, UV-VIS, fluorescence, Raman spectroscopy, and zeta potential analysis confirmed the formation of curcumin quantum dots with increased stability and solubility. The MICs of curcumin quantum dots, as observed against both select gram positive and negative bacterial isolates, was observed to be significantly lower than native curcumin particles. On TCP assay, Curcumin observed to be having antibiofilm as well as biofilm degrading activity. Results of SDS–PAGE and molecular docking have shown interaction between biofilm matrix proteins and curcumin. The results indicate that aqueous solubility and stability of Curcumin can be achieved by preparing its quantum dots. The study also demonstrates

  11. The circadian clock modulates anti-cancer properties of curcumin

    International Nuclear Information System (INIS)

    Sarma, Ashapurna; Sharma, Vishal P.; Sarkar, Arindam B.; Sekar, M. Chandra; Samuel, Karunakar; Geusz, Michael E.

    2016-01-01

    Curcuminoids of the spice turmeric and their enhanced derivatives have much potential as cancer treatments. They act on a wide variety of biological pathways, including those regulating cell division and circadian rhythms. It is known that circadian clocks can modify cancer therapy effectiveness, according to studies aimed at optimizing treatments based on the circadian cycle. It is therefore important to determine whether treatments with curcumin or similar chemotherapeutic agents are regulated by circadian timing. Similarly, it is important to characterize any effects of curcumin on timing abilities of the circadian clocks within cancer cells. We examined the circadian clock’s impact on the timing of cell death and cell division in curcumin-treated C6 rat glioma cells through continuous video microscopy for several days. To evaluate its persistence and distribution in cancer cells, curcumin was localized within cell compartments by imaging its autofluorescence. Finally, HPLC and spectroscopy were used to determine the relative stabilities of the curcumin congeners demethoxycurcumin and bisdemethoxycurcumin that are present in turmeric. Circadian rhythms in cell death were observed in response to low (5 μM) curcumin, reaching a peak several hours before the peak in rhythmic expression of mPER2 protein, a major circadian clock component. These results revealed a sensitive phase of the circadian cycle that could be effectively targeted in patient therapies based on curcumin or its analogs. Curcumin fluorescence was observed in cell compartments at least 24 h after treatment, and the two congeners displayed greater stability than curcumin in cell culture medium. We propose a mechanism whereby curcuminoids act in a sustained manner, over several days, despite their tendency to degrade rapidly in blood and other aqueous media. During cancer therapy, curcumin or its analogs should be delivered to tumor cells at the optimal phase for highest efficacy after identifying

  12. Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

    Science.gov (United States)

    Ghosh, Aparajita; Banerjee, Tanushree; Bhandary, Suman; Surolia, Avadhesha

    2014-01-01

    Aim The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria. Materials and methods Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo. Results The nanopreparation was found to be non-toxic and had a particle size distribution of 20–50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration [IC50]: 0.5 μM) was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC50: 5 μM). Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei-infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only. Conclusion Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria as a test system. PMID:25484584

  13. Curcumin Modulates Pancreatic Adenocarcinoma Cell-Derived Exosomal Function

    Science.gov (United States)

    Osterman, Carlos J. Diaz; Lynch, James C.; Leaf, Patrick; Gonda, Amber; Ferguson Bennit, Heather R.; Griffiths, Duncan; Wall, Nathan R.

    2015-01-01

    Pancreatic cancer has the highest mortality rates of all cancer types. One potential explanation for the aggressiveness of this disease is that cancer cells have been found to communicate with one another using membrane-bound vesicles known as exosomes. These exosomes carry pro-survival molecules and increase the proliferation, survival, and metastatic potential of recipient cells, suggesting that tumor-derived exosomes are powerful drivers of tumor progression. Thus, to successfully address and eradicate pancreatic cancer, it is imperative to develop therapeutic strategies that neutralize cancer cells and exosomes simultaneously. Curcumin, a turmeric root derivative, has been shown to have potent anti-cancer and anti-inflammatory effects in vitro and in vivo. Recent studies have suggested that exosomal curcumin exerts anti-inflammatory properties on recipient cells. However, curcumin’s effects on exosomal pro-tumor function have yet to be determined. We hypothesize that curcumin will alter the pro-survival role of exosomes from pancreatic cancer cells toward a pro-death role, resulting in reduced cell viability of recipient pancreatic cancer cells. The main objective of this study was to determine the functional alterations of exosomes released by pancreatic cancer cells exposed to curcumin compared to exosomes from untreated pancreatic cancer cells. We demonstrate, using an in vitro cell culture model involving pancreatic adenocarcinoma cell lines PANC-1 and MIA PaCa-2, that curcumin is incorporated into exosomes isolated from curcumin-treated pancreatic cancer cells as observed by spectral studies and fluorescence microscopy. Furthermore, curcumin is delivered to recipient pancreatic cancer cells via exosomes, promoting cytotoxicity as demonstrated by Hoffman modulation contrast microscopy as well as AlamarBlue and Trypan blue exclusion assays. Collectively, these data suggest that the efficacy of curcumin may be enhanced in pancreatic cancer cells through

  14. CURCUMIN FOR ALZHEIMER’S DISEASE (AD) POTENTIAL TREATMENT

    OpenAIRE

    Sutiono, Dias Rima; Iasmartua, Steven

    2017-01-01

    Various studies had been conducted regarding the effect of curcumin on AD patients, thus, many of the studies had suggested that curcumin had the potential to prevent and treat AD through several molecular mechanisms including act as anti-inflammatory, anti-oxidant, binding the Aβ plaques, metal chelation, and lowering cholesterol level. One of the prominent characteristics of this neurodegenerative disease is shown by the presence of beta amyloids plaques (Aβ) and inflammation inside the pat...

  15. CURCUMIN DECREASES SPECIFICITY PROTEIN (Sp) EXPRESSION IN BLADDER CANCER CELLS

    OpenAIRE

    Chadalapaka, Gayathri; Jutooru, Indira; Chintharlapalli, Sudhakar; Papineni, Sabitha; Smith, Roger; Li, Xiangrong; Safe, Stephen

    2008-01-01

    Curcumin is the active component of tumeric, and this polyphenolic compound has been extensively investigated as an anticancer drug that modulates multiple pathways and genes. In this study, 10 – 25 µM curcumin inhibited 253JB-V and KU7 bladder cancer cell growth, and this was accompanied by induction of apoptosis and decreased expression of the proapoptotic protein survivin and the angiogenic proteins vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR1). Since expression of...

  16. PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα.

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    Xiaoyu Hu

    Full Text Available Opioid-induced hyperalgesia (OIH is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin's mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling.

  17. Phosphoproteomic Analysis Identifies Signaling Pathways Regulated by Curcumin in Human Colon Cancer Cells.

    Science.gov (United States)

    Sato, Tatsuhiro; Higuchi, Yutaka; Shibagaki, Yoshio; Hattori, Seisuke

    2017-09-01

    Curcumin, a major polyphenol of the spice turmeric, acts as a potent chemopreventive and chemotherapeutic agent in several cancer types, including colon cancer. Although various proteins have been shown to be affected by curcumin, how curcumin exerts its anticancer activity is not fully understood. Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways. Curcumin inhibited the growth of the two cell lines in a dose-dependent manner. Thirty-nine curcumin-regulated phosphoproteins were identified, five of which are involved in cancer signaling pathways. Detailed analyses revealed that the mTORC1 and p53 signaling pathways are main targets of curcumin. Our results provide insight into the molecular mechanisms of the anticancer activities of curcumin and future molecular targets for its clinical application. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Curcumin AntiCancer Studies in Pancreatic Cancer

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    Sabrina Bimonte

    2016-07-01

    Full Text Available Pancreatic cancer (PC is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

  19. New Dendrimer-Based Nanoparticles Enhance Curcumin Solubility.

    Science.gov (United States)

    Falconieri, Maria Cristina; Adamo, Mauro; Monasterolo, Claudio; Bergonzi, Maria Camilla; Coronnello, Marcella; Bilia, Anna Rita

    2017-03-01

    Curcumin, the main curcuminoid of the popular Indian spice turmeric, is a potent chemopreventive agent and useful in many different diseases. A major limitation of applicability of curcumin as a health promoting and medicinal agent is its extremely low bioavailability due to efficient first pass metabolism, poor gastrointestinal absorption, rapid elimination, and poor aqueous solubility. In the present study, nanotechnology was selected as a choice approach to enhance the bioavailability of the curcuminis. A new polyamidoamine dendrimer (G0.5) was synthesized, characterized, and tested for cytotoxicity in human breast cancer cells (MCF-7). No cytotoxicity of G0.5 was found in the range between 10 -3 and 3 × 10 -8  M. Consequently, G0.5 was used to prepare spherical nanoparticles of ca. 150 nm, which were loaded with curcumin [molar ratio G0.5/curcumin 1 : 1 (formulation 1) and 1 : 0.5 (formulation 2)]. Remarkably, the occurrence of a single population of nanoparticles having an excellent polydispersity index (solubility of curcumin was increased ca. 415 and 150 times with respect to the unformulated drug, respectively, for formulation 1 and formulation 2. The release of curcumin from the nanoparticles showed an interesting prolonged and sustained release profile. Georg Thieme Verlag KG Stuttgart · New York.

  20. Enhanced solubilization of curcumin in mixed surfactant vesicles.

    Science.gov (United States)

    Kumar, Arun; Kaur, Gurpreet; Kansal, S K; Chaudhary, Ganga Ram; Mehta, S K

    2016-05-15

    Self-assemblies of equimolar double and single chain mixed ionic surfactants, with increasing numbers of carbon atoms of double chain surfactant, were analyzed on the basis of fluorescence and conductivity results. Attempts were also made to enhance the solubilization of curcumin in aqueous equimolar mixed surfactant systems. Mixed surfactant assembly was successful in retarding the degradation of curcumin in alkaline media (only 25-28 40% degraded in 10h at pH 13). Fluorescence spectroscopy and fluorescence quenching methods were employed to predict the binding position and mechanism of curcumin with self-assemblies. Results indicate that the interactions take place according to both dynamic and static quenching mechanisms and curcumin was distributed in a palisade layer of mixed aggregates. Antioxidant activity (using DPPH radical) and biocompatibility (using calf-thymus DNA) of curcumin-loaded mixed surfactant formulations were also evaluated. The prepared systems improved the stability, solubility and antioxidant activity of curcumin and additionally are biocompatible. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Hybrid Curcumin Compounds: A New Strategy for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Marie-Hélène Teiten

    2014-12-01

    Full Text Available Cancer is a multifactorial disease that requires treatments able to target multiple intracellular components and signaling pathways. The natural compound, curcumin, was already described as a promising anticancer agent due to its multipotent properties and huge amount of molecular targets in vitro. Its translation to the clinic is, however, limited by its reduced solubility and bioavailability in patients. In order to overcome these pharmacokinetic deficits of curcumin, several strategies, such as the design of synthetic analogs, the combination with specific adjuvants or nano-formulations, have been developed. By taking into account the risk-benefit profile of drug combinations, as well as the knowledge about curcumin’s structure-activity relationship, a new concept for the combination of curcumin with scaffolds from different natural products or components has emerged. The concept of a hybrid curcumin molecule is based on the incorporation or combination of curcumin with specific antibodies, adjuvants or other natural products already used or not in conventional chemotherapy, in one single molecule. The high diversity of such conjugations enhances the selectivity and inherent biological activities and properties, as well as the efficacy of the parental compound, with particular emphasis on improving the efficacy of curcumin for future clinical treatments.

  2. Anti-inflammatory Effects of Curcumin in Microglial Cells

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    Yangyang Yu

    2018-04-01

    Full Text Available Lipoteichoic acid (LTA induces neuroinflammatory molecules, contributing to the pathogenesis of neurodegenerative diseases. Therefore, suppression of neuroinflammatory molecules could be developed as a therapeutic method. Although previous data supports an immune-modulating effect of curcumin, the underlying signaling pathways are largely unidentified. Here, we investigated curcumin’s anti-neuroinflammatory properties in LTA-stimulated BV-2 microglial cells. Inflammatory cytokine tumor necrosis factor-α [TNF-α, prostaglandin E2 (PGE2, and Nitric Oxide (NO] secretion in LTA-induced microglial cells were inhibited by curcumin. Curcumin also inhibited LTA-induced inducible NO synthases (iNOS and cyclooxygenase-2 (COX-2 expression. Subsequently, our mechanistic studies revealed that curcumin inhibited LTA-induced phosphorylation of mitogen-activated protein kinase (MAPK including ERK, p38, Akt and translocation of NF-κB. Furthermore, curcumin induced hemeoxygenase (HO-1HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf-2 expression in microglial cells. Inhibition of HO-1 reversed the inhibition effect of HO-1 on inflammatory mediators release in LTA-stimulated microglial cells. Taken together, our results suggest that curcumin could be a potential therapeutic agent for the treatment of neurodegenerative disorders via suppressing neuroinflammatory responses.

  3. Understanding curcumin-induced modulation of protein aggregation.

    Science.gov (United States)

    Ahmad, Basir; Borana, Mohanish S; Chaudhary, Ankur P

    2017-07-01

    Curcumin, a diarylheptanoid compound, found in spice turmeric is known to alter the aggregation of proteins and reduce the toxicity of the aggregates. This review looks at the molecular basis of modulating protein aggregation and toxicity of the aggregates. Foremost, we identify the interaction of curcumin and its derivatives with proteins/peptides and the effect of their interaction on the conformational stability and unfolding/folding pathway(s). The unfolding/folding processes generate partially folded/unfolded intermediate, which serve as aggregation precursor state. Secondly, we discuss the effect of curcumin binding on the kinetics parameters of the aggregation process, which give information about the mechanism of the aggregation inhibition. We describe, in addition, that curcumin can accelerate/promote fibril formation by binding to oligomeric intermediate(s) accumulated in the aggregation pathway. Finally, we discuss the correlation of curcumin-induced monomeric and/or oligomeric precursor states with aggregate structure and toxicity. On the basis of these discussions, we propose a model describing curcumin-induced inhibition/promotion of formation of amyloid-like fibrils. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Immune response modulation by curcumin in a latex allergy model

    Directory of Open Access Journals (Sweden)

    Raju Raghavan

    2007-01-01

    Full Text Available Abstract Background There has been a worldwide increase in allergy and asthma over the last few decades, particularly in industrially developed nations. This resulted in a renewed interest to understand the pathogenesis of allergy in recent years. The progress made in the pathogenesis of allergic disease has led to the exploration of novel alternative therapies, which include herbal medicines as well. Curcumin, present in turmeric, a frequently used spice in Asia has been shown to have anti-allergic and inflammatory potential. Methods We used a murine model of latex allergy to investigate the role of curcumin as an immunomodulator. BALB/c mice were exposed to latex allergens and developed latex allergy with a Th2 type of immune response. These animals were treated with curcumin and the immunological and inflammatory responses were evaluated. Results Animals exposed to latex showed enhanced serum IgE, latex specific IgG1, IL-4, IL-5, IL-13, eosinophils and inflammation in the lungs. Intragastric treatment of latex-sensitized mice with curcumin demonstrated a diminished Th2 response with a concurrent reduction in lung inflammation. Eosinophilia in curcumin-treated mice was markedly reduced, co-stimulatory molecule expression (CD80, CD86, and OX40L on antigen-presenting cells was decreased, and expression of MMP-9, OAT, and TSLP genes was also attenuated. Conclusion These results suggest that curcumin has potential therapeutic value for controlling allergic responses resulting from exposure to allergens.

  5. Effects of curcumin on the gastric emptying of albino rats.

    Science.gov (United States)

    Purwar, Brijesh; Shrivastava, Abha; Arora, Neetu; Kumar, Anil; Saxena, Yogesh

    2012-01-01

    Curcumin (diferuloylmethane), a polyphenol, is an active principle of the perennial herb Curcuma longa commonly known as turmeric. Turmeric (CURCUMA LONGA L.) is a medicinal plant extensively used in Ayurveda, Unani, and Siddha medicine as a home remedy for various diseases including biliary diseases, cough, hepatic diseases, wound healing. However studies on the effect of curcumin on the gastric emptying are nearly nonexistent. It is hypothesized that curcumin may have an effect on gastric emptying. For this reason the present study was aimed to study the effect of curcumin on gastric emptying. Rats were divided into 5 groups (Group I - Group V), based on the time interval between administration of curcumin/vehicular fluid to administration of barium sulphate (Group I - 1 hr, Group II - 8 hrs, Group III - 16 hrs, Group IV - 24 hrs, Group V - 48 hrs). Each group was further divided into two subgroups, Group A (control) and Group B (experimental), containing 6 rats each. Rats in experimental group were administered curcumin intragastrically, in the dose of 1 gm/kg body weight, suspended in normal saline (0.9% NaCl). The controls were given vehicular fluid intragastrically, in volume equal to the experimental animals. It was observed that there was a decrease in the gastric emptying in all the experimental groups.

  6. Lesions of the lateral habenula increase voluntary ethanol consumption and operant self-administration, block yohimbine-induced reinstatement of ethanol seeking, and attenuate ethanol-induced conditioned taste aversion.

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    Andrew K Haack

    Full Text Available The lateral habenula (LHb plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.

  7. Mechanistic Studies of the Anti-Ulcerogenic Activity and Acute Toxicity Evaluation of Dichlorido-Copper(II-4-(2-5-Bromo-benzylideneaminoethyl Piperazin-1-ium Phenolate Complex against Ethanol-Induced Gastric Injury in Rats

    Directory of Open Access Journals (Sweden)

    A. Hamid A. Hadi

    2011-10-01

    Full Text Available The compound dichlorido-copper(II-4-(2-5-bromobenzylideneaminoethyl piperazin-1-ium phenolate (CuLBS was synthesized, characterized and screened for acute toxicity and protective activity against ethanol-induced gastric mucosal injury in rats. Gross microscopic lesions, biochemical and immunological parameters and histochemcial staining of glycogen storage were taken into consideration. Oral administration of CuLBS (30 and 60 mg/Kg for two weeks dose-dependently flattened gastric mucosa, significantly increased gastric mucus and total acidity, compared with control group (P < 0.01. Serum levels of liver enzymes aspartate (AST and alanine transaminases (ALT, pro-inflammatory (IL-6 and TNF-α and anti-inflammatory (IL-10 cytokines in the rats exposed to ethanol induced ulceration have been altered. Administration of CuLBS showed considerable (P < 0.05 protection against ulceration by modulating the acute alterations of cytokines AST, ALT and stomach glycogen. Interestingly, CuLBS did not interfere with the natural release of nitric oxide. CuLBS alone (60 mg/Kg did not exhibit any ulcerogenic effect as assessed using Adami’s scoring scale. An acute toxicity study showed that rats treated with CuLBS (1,000 and 2,000 mg/Kg manifested no abnormal signs. These findings therefore, suggested that the gastroprotective activity of CuLBS might contribute in modulating the inflammatory cytokine-mediated oxidative damage to gastric mucosa.

  8. Biocompatible Lipid Nanoparticles as Carriers To Improve Curcumin Efficacy in Ovarian Cancer Treatment.

    Science.gov (United States)

    Bondì, Maria Luisa; Emma, Maria Rita; Botto, Chiara; Augello, Giuseppa; Azzolina, Antonina; Di Gaudio, Francesca; Craparo, Emanuela Fabiola; Cavallaro, Gennara; Bachvarov, Dimcho; Cervello, Melchiorre

    2017-02-22

    Curcumin is a natural molecule with proved anticancer efficacy on several human cancer cell lines. However, its clinical application has been limited due to its poor bioavailability. Nanocarrier-based drug delivery approaches could make curcumin dispersible in aqueous media, thus overtaking the limits of its low solubility. The aim of this study was to increase the bioavailability and the antitumoral activity of curcumin, by entrapping it into nanostructured lipid carriers (NLCs). For this purpose here we describe the preparation and characterization of three kinds of curcumin-loaded NLCs. The nanosystems allowed the achievement of a controlled release of curcumin, the amounts of curcumin released after 24 h from Compritol-Captex, Compritol-Miglyol, and Compritol NLCs being, respectively, equal to 33, 28, and 18% w/w on the total entrapped curcumin. Considering the slower curcumin release profile, Compritol NLCs were chosen to perform successive in vitro studies on ovarian cancer cell lines. The results show that curcumin-loaded NLCs maintain anticancer activity, and reduce cell colony survival more effectively than free curcumin. As an example, the ability of A2780S cells to form colonies was decreased after treatment with 5 μM free curcumin by 50% ± 6, whereas, at the same concentration, the delivery of curcumin with NLC significantly (p < 0.05) inhibited colony formation to approximately 88% ± 1, therefore potentiating the activity of curcumin to inhibit A2780S cell growth. The obtained results clearly suggest that the entrapment of curcumin into NLCs increases curcumin efficacy in vitro, indicating the potential use of NLCs as curcumin delivery systems.

  9. Evaluation of curcumin acetates and amino acid conjugates as proteasome inhibitors

    OpenAIRE

    Wan, Sheng Biao; Yang, Huanjie; Zhou, Zhongyuan; Cui, Qiuzhi Cindy; Chen, Di; Kanwar, Jyoti; Mohammad, Imthiyaz; Dou, Q. Ping; Chan, Tak Hang

    2010-01-01

    Curcumin (diferuloylmethane) is the main active ingredient of turmeric, a traditional herbal medicine and food of south Asia. Curcumin has been found to have a wide range of biological activities, including antioxidant, anti-inflammatory, chemopreventive and chemotherapeutic activities. Curcumin is currently being tested in clinical trials for treatment of various types of cancers, including multiple myeloma, pancreatic cancer and colon cancer. Although no toxicity associated with curcumin (e...

  10. ANALYTICAL STUDY OF CURCUMIN CONTENT IN DIFFERENT DOSAGE FORMS CONTAINING TURMERIC EXTRACT POWDER AND TURMERIC OLEORESIN

    OpenAIRE

    Rane Rajashree; Gangolli Divya; Patil Sushma; Ingawale Kanchan; Kundalwal Sachin

    2013-01-01

    Different dosage forms namely tablets, capsules, creams and syrups were analysed for curcumin content, by the well-known spectrophotometric method. Turmeric extract powder was used as a source of curcumin in capsule and tablet formulations. Turmeric oleoresin was used as a source of curcumin in cream formulation. Additionally, syrup formulations containing turmeric extract powder as well as turmeric oleoresin, separately, were also tested for their curcumin contents. Analytical results for cu...

  11. Synthesis of [diene-"1"4C] curcumin at high specific activity

    International Nuclear Information System (INIS)

    Filer, Crist N.; Lacy, James M.; Wright, Christopher

    2016-01-01

    An efficient method is described to label curcumin with "1"4C at high specific activity. - Highlights: • This paper describes the synthesis of ["1"4C] Curcumin at the highest specific activity and total activity amount yet reported. • The "1"4C label was installed in the diene framework of Curcumin. • This paper also describes the characterization of ["1"4C] Curcumin by HPLC and mass spectrometry.

  12. Efficacy of Biodegradable Curcumin Nanoparticles in Delaying Cataract in Diabetic Rat Model

    OpenAIRE

    Grama, Charitra N.; Suryanarayana, Palla; Patil, Madhoosudan A.; Raghu, Ganugula; Balakrishna, Nagalla; Kumar, M. N. V. Ravi; Reddy, Geereddy Bhanuprakash

    2013-01-01

    Curcumin, the active principle present in the yellow spice turmeric, has been shown to exhibit various pharmacological actions such as antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Previously we have reported that dietary curcumin delays diabetes-induced cataract in rats. However, low peroral bioavailability is a major limiting factor for the success of clinical utilization of curcumin. In this study, we have administered curcumin encapsulated nanoparticles ...

  13. Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult

    OpenAIRE

    Zhangyang Qi; Meihao Wu; Yun Fu; Tengfei Huang; Tingting Wang; Yanjie Sun; Zhibo Feng; Changzheng Li

    2017-01-01

    Background/Aims: The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer’s disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane...

  14. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

    OpenAIRE

    Zun-Jing Liu; Wei Liu; Lei Liu; Cheng Xiao; Yu Wang; Jing-Song Jiao

    2013-01-01

    Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPAR ? agonist in that it upregulated PPAR ? expression and PPAR ? -PPRE binding activity. Administration of curcumin markedly dec...

  15. The Stability, Sustained Release and Cellular Antioxidant Activity of Curcumin Nanoliposomes

    OpenAIRE

    Chen, Xing; Zou, Li-Qiang; Niu, Jing; Liu, Wei; Peng, Sheng-Feng; Liu, Cheng-Mei

    2015-01-01

    Curcumin is a multifunctional and natural agent considered to be pharmacologically safe. However, its application in the food and medical industry is greatly limited by its poor water solubility, physicochemical instability and inadequate bioavailability. Nanoliposome encapsulation could significantly enhance the solubility and stability of curcumin. Curcumin nanoliposomes exhibited good physicochemical properties (entrapment efficiency = 57.1, particle size = 68.1 nm, polydispersity index = ...

  16. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, M.J. van; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, P.J. van; Aarts, J.M.M.J.G.; Ommen, B. van

    2004-01-01

    Background. Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  17. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, van M.J.; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, van P.J.; Aarts, J.M.M.J.G.; Ommen, van B.

    2004-01-01

    Background: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  18. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Van Erk, Marjan J; Teuling, Eva; Staal, Yvonne C. M.; Huybers, Sylvie; Van Bladeren, Peter J; Aarts, Jac MMJG; Van Ommen, Ben

    2004-01-01

    BACKGROUND: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  19. Curcumin as a clinically-promising anti-cancer agent: pharmacokinetics and drug interactions.

    Science.gov (United States)

    Adiwidjaja, Jeffry; McLachlan, Andrew J; Boddy, Alan V

    2017-09-01

    Curcumin has been extensively studied for its anti-cancer properties. While a diverse array of in vitro and preclinical research support the prospect of curcumin use as an anti-cancer therapeutic, most human studies have failed to meet the intended clinical expectation. Poor systemic availability of orally-administered curcumin may account for this disparity. Areas covered: This descriptive review aims to concisely summarise available clinical studies investigating curcumin pharmacokinetics when administered in different formulations. A critical analysis of pharmacokinetic- and pharmacodynamic-based interactions of curcumin with concomitantly administered drugs is also provided. Expert opinion: The encouraging clinical results of curcumin administration are currently limited to people with colorectal cancer, given that sufficient curcumin concentrations persist in colonic mucosa. Higher parent curcumin systemic exposure, which can be achieved by several newer formulations, has important implications for optimal treatment of cancers other than those in gastrointestinal tract. Curcumin-drug pharmacokinetic interactions are also almost exclusively in the enterocytes, owing to extensive first pass metabolism and poor curcumin bioavailability. Greater scope of these interactions, i.e. modulation of the systemic elimination of co-administered drugs, may be expected from more-bioavailable curcumin formulations. Further studies are still warranted, especially with newer formulations to support the inclusion of curcumin in cancer therapy regimens.

  20. Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila

    Science.gov (United States)

    Curcumin is an antioxidant extracted from the root of the turmeric plant. We examined the antioxidant effect and lifespan extension of curcumin in Drosophila. To ascertain the antioxidant effects of curcumin with regard to lifespan extension and the response to reactive oxygen species, female and ma...

  1. Curcumin Inhibits Tau Aggregation and Disintegrates Preformed Tau Filaments in vitro.

    Science.gov (United States)

    Rane, Jitendra Subhash; Bhaumik, Prasenjit; Panda, Dulal

    2017-01-01

    The pathological aggregation of tau is a common feature of most of the neuronal disorders including frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. The inhibition of tau aggregation is considered to be one of the important strategies for treating these neurodegenerative diseases. Curcumin, a natural polyphenolic molecule, has been reported to have neuroprotective ability. In this work, curcumin was found to bind to adult tau and fetal tau with a dissociation constant of 3.3±0.4 and 8±1 μM, respectively. Molecular docking studies indicated a putative binding site of curcumin in the microtubule-binding region of tau. Using several complementary techniques, including dynamic light scattering, thioflavin S fluorescence, 90° light scattering, electron microscopy, and atomic force microscopy, curcumin was found to inhibit the aggregation of tau. The dynamic light scattering analysis and atomic force microscopic images revealed that curcumin inhibits the oligomerization of tau. Curcumin also disintegrated preformed tau oligomers. Using Far-UV circular dichroism, curcumin was found to inhibit the β-sheets formation in tau indicating that curcumin inhibits an initial step of tau aggregation. In addition, curcumin inhibited tau fibril formation. Furthermore, the effect of curcumin on the preformed tau filaments was analyzed by atomic force microscopy, transmission electron microscopy, and 90° light scattering. Curcumin treatment disintegrated preformed tau filaments. The results indicated that curcumin inhibited the oligomerization of tau and could disaggregate tau filaments.

  2. In vitro evaluation of antioxidant and neuroprotective effects of curcumin loaded in Pluronic micelles

    Directory of Open Access Journals (Sweden)

    Cvetelina Gorinova

    2016-09-01

    Full Text Available Curcumin is a polyphenolic substance with attractive pharmacological activities (e.g. antioxidant, anti-inflammatory, anticancer. Incorporation of curcumin in polymeric micelles could overcome the problems associated with its instability and low aqueous solubility. The aim of this study was to load curcumin in polymeric micelles based on Pluronic® P 123 or Pluronic® F 127 triblock copolymers and evaluate the antioxidant and neuroprotective effects after micellization. The micelles were prepared and loaded with curcumin by applying the dissolution method. Higher encapsulation efficiency was observed in the micelles formulated with Pluronic® P 123. These micelles were characterized with small size and narrow size distribution. The effects of micellar curcumin were investigated in two in vitro models. First, the capacity of micellar curcumin to inhibit iron/ascorbic acid-induced lipid peroxidation in rat liver microsomes was evaluated. Micellar curcumin and free drug showed similar inhibition of lipid peroxidation. Second, micellar curcumin and free curcumin showed protective potential in a model of 6-hydroxydopamine induced neurotoxicity in rat brain synaptosomes. The results from both methods indicated preservation of antioxidant and neuroprotective activity of curcumin in micelles. The small micellar size, high loading capacity and preservation of antioxidant activity of curcumin into Pluronic micelles, suggested their further evaluation as a curcumin delivery system.

  3. Curcumin homing to the nucleolus: mechanism for initiation of an apoptotic program.

    Science.gov (United States)

    Ghosh, Mistuni; Ryan, Robert O

    2014-11-01

    Curcumin is a plant-derived polyphenol that displays antitumor properties. Incubation of cultured SF-767 glioma cells with curcumin gave rise to intense intranuclear foci of curcumin fluorescence. In vitro studies revealed that nuclear homing by curcumin is not a result of DNA/chromatin binding. On the other hand, curcumin fluorescence colocalized with nucleophosmin, a nucleolus marker protein. To determine the temporal relationship between curcumin-induced apoptosis and nucleolar homing, confocal live cell imaging was performed. The data show that curcumin localization to the nucleolus occurs prior to cell surface exposure of phosphatidylserine. In studies of the mechanism of curcumin-induced apoptosis in SF-767 cells, its effect on the subcellular location of p14(ARF) was determined. Whereas p14(ARF) was confined to the nucleolus in untreated cells, 2 h following incubation with curcumin, it displayed a diffuse nuclear distribution. Given the role of nuclear p14(ARF) in binding the E3 ubiquitin ligase, mouse double minute 2 homolog (MDM2), the effect of curcumin treatment on cellular levels of the tumor suppressor protein, p53, was examined. Between 2 and 4 h following curcumin treatment, p53 levels increased with maximum levels reached by 8 h. Thus, curcumin homing to the nucleolus induces redistribution of p14(ARF) to the nucleoplasm where interaction with MDM2 leads to stabilization of p53, with subsequent initiation of apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

    International Nuclear Information System (INIS)

    Yu, Teng; Ji, Jiang; Guo, Yong-li

    2013-01-01

    Highlights: •Curcumin activates MST1 in melanoma cells. •MST1 mediates curcumin-induced apoptosis of melanoma cells. •ROS production is involved in curcumin-induced MST1 activation. •MST1 mediates curcumin-induced JNK activation in melanoma cells. •MST1 mediates curcumin-induced Foxo3a nuclear translocation and Bim expression. -- Abstract: Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen species (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

  5. MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Teng, E-mail: tengyu33@yahoo.com [Department of Dermatology, Shandong Ji-ning No. 1 People’s Hospital, Shandong Province 272011 (China); Ji, Jiang [Department of Dermatology, The Second Hospital Affiliated of Soochow University, SuZhou, Jiangsu Province 215000 (China); Guo, Yong-li [Department of Oncology, Shandong Ji-ning No. 1 People’s Hospital, Shandong Province 272011 (China)

    2013-11-08

    Highlights: •Curcumin activates MST1 in melanoma cells. •MST1 mediates curcumin-induced apoptosis of melanoma cells. •ROS production is involved in curcumin-induced MST1 activation. •MST1 mediates curcumin-induced JNK activation in melanoma cells. •MST1 mediates curcumin-induced Foxo3a nuclear translocation and Bim expression. -- Abstract: Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen species (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells.

  6. Effect of curcumin on galactose-induced cataractogenesis in rats.

    Science.gov (United States)

    Suryanarayana, Palla; Krishnaswamy, Kamala; Reddy, Geereddy Bhanuprakash

    2003-06-09

    Curcumin, the active principle of turmeric, has been shown to have both antioxidant and hypoglycemic activity in vitro and in vivo. The purpose of this study was to investigate the effect of curcumin on the onset and maturation of galactose induced cataract. Sprague-Dawley rats (21 days old) were divided into 5 groups. The control group (A) received an AIN-93 diet, the galactose group (B) received 30% galactose in the diet, the test groups (C and D) received the B group diet plus 0.002% and 0.01% curcumin respectively, and group (E) received the control diet plus 0.01% curcumin, all for a period of 4 weeks. Cataract progression due to galactose feeding was monitored by slit lamp microscope and classified into 4 stages. At the end of the experiment biochemical parameters such as lipid peroxidation, aldose reductase (AR), sorbitol dehydrogenase (SDH), reduced glutathione, protein content, and protein carbonyls were measured in the lens. Advanced glycated end products (AGE) and protein oxidation were measured by AGE and tryptophon fluorescence respectively. Crystallin profile was analyzed by size exclusion chromatography (HPLC). Slit lamp microscope observations indicated that curcumin at 0.002% (group C) delayed the onset and maturation of cataract. In contrast even though there was a slight delay in the onset of cataract at the 0.01% level (group D), maturation of cataract was faster when compared to group B. Biochemical analysis showed that curcumin at the 0.002% level appeared to exert antioxidant and antiglycating effects, as it inhibited lipid peroxidation, AGE-fluorescence, and protein aggregation. Though the reasons for faster onset and maturation of cataract in group D rats was not clear, the data suggested that under hyperglycemic conditions higher levels of curcumin (0.01%) in the diet may increase oxidative stress, AGE formation, and protein aggregation. However, feeding of curcumin to normal rats up to a 0.01% level did not result in any changes in lens

  7. Integration of family planning with poverty alleviation.

    Science.gov (United States)

    Peng, P

    1996-12-01

    The Chinese Communist Central Committee and the State Council aim to solve food and clothing problems among impoverished rural people by the year 2000. This goal was a priority on the agenda of the recent October 1996 National Conference on Poverty Alleviation and Development and the 1996 National Conference of the State Family Planning Commission. Poverty is attributed to rapid population growth and underdevelopment. Poverty is concentrated in parts of 18 large provinces. These provinces are characterized by Family Planning Minister Peng as having high birth rates, early marriage and childbearing, unplanned births, and multiple births. Overpopulation is tied to overconsumption, depletion of resources, deforestation, soil erosion, pollution, shortages of water, decreases in shares of cultivated land, degraded grasslands, and general destruction of the environment. Illiteracy in poor areas is over 20%, compared to the national average of 15%. Mortality and morbidity are higher. Family planning is harder to enforce in poor areas. Pilot programs in Sichuan and Guizhou provinces are promoting integration of family planning with poverty alleviation. Several conferences have addressed the integrated program strategies. Experience has shown that poverty alleviation occurs by controlled population growth and improved quality of life. Departments should "consolidate" their development efforts under Communist Party leadership at all levels. Approaches should emphasize self-reliance and public mobilization. The emphasis should be on women's participation in development. Women's income should be increased. Family planning networks at the grassroots level need to be strengthened simultaneously with increased poverty alleviation and development. The government strategy is to strengthen leadership, mobilize the public, and implement integrated programs.

  8. Curcumin β-D-Glucuronide Plays an Important Role to Keep High Levels of Free-Form Curcumin in the Blood.

    Science.gov (United States)

    Ozawa, Hitomi; Imaizumi, Atsushi; Sumi, Yoshihiko; Hashimoto, Tadashi; Kanai, Masashi; Makino, Yuji; Tsuda, Takanori; Takahashi, Nobuaki; Kakeya, Hideaki

    2017-01-01

    Curcumin, a polyphenol derived from the rhizome of the naturally occurring plant Curcuma longa, has various pharmacological actions such as antioxidant and anti-inflammatory effects. In this paper, we evaluated the role of its internal metabolite, curcumin β-D-glucuronide (curcumin monoglucuronide, CMG), by investigating curcumin kinetics and metabolism in the blood. Firstly, we orally administered highly bioavailable curcumin to rats to elucidate its kinetics, and observed not only the free-form of curcumin, but also, curcumin in a conjugated form, within the portal vein. We confirmed that curcumin is conjugated when it passes through the intestinal wall. CMG, one of the metabolites, was then orally administered to rats. Despite its high aqueous solubility compared to free-form curcumin, it was not well absorbed. In addition, CMG was injected intravenously into rats in order to assess its metabolic behavior in the blood. Interestingly, high levels of free-form curcumin, thought to be sufficiently high to be pharmacologically active, were observed. The in vivo antitumor effects of CMG following intravenous injection were then evaluated in tumor-bearing mice with the HCT116 human colon cancer cell line. The tumor volume within the CMG group was significantly less than that of the control group. Moreover, there was no significant loss of body weight in the CMG group compared to the control group. These results suggest that CMG could be used as an anticancer agent without the serious side effects that most anticancer agents have.

  9. Liposomal curcumin and its application in cancer.

    Science.gov (United States)

    Feng, Ting; Wei, Yumeng; Lee, Robert J; Zhao, Ling

    2017-01-01

    Curcumin (CUR) is a yellow polyphenolic compound derived from the plant turmeric. It is widely used to treat many types of diseases, including cancers such as those of lung, cervices, prostate, breast, bone and liver. However, its effectiveness has been limited due to poor aqueous solubility, low bioavailability and rapid metabolism and systemic elimination. To solve these problems, researchers have tried to explore novel drug delivery systems such as liposomes, solid dispersion, microemulsion, micelles, nanogels and dendrimers. Among these, liposomes have been the most extensively studied. Liposomal CUR formulation has greater growth inhibitory and pro-apoptotic effects on cancer cells. This review mainly focuses on the preparation of liposomes containing CUR and its use in cancer therapy.

  10. Synchronous fluorescence spectroscopic study of solvatochromic curcumin dye

    Science.gov (United States)

    Patra, Digambara; Barakat, Christelle

    2011-09-01

    Curcumin, the main yellow bioactive component of turmeric, has recently acquired attention by chemists due its wide range of potential biological applications as an antioxidant, an anti-inflammatory, and an anti-carcinogenic agent. This molecule fluoresces weakly and poorly soluble in water. In this detailed study of curcumin in thirteen different solvents, both the absorption and fluorescence spectra of curcumin was found to be broad, however, a narrower and simple synchronous fluorescence spectrum of curcumin was obtained at Δ λ = 10-20 nm. Lippert-Mataga plot of curcumin in different solvents illustrated two sets of linearity which is consistent with the plot of Stokes' shift vs. the ET30. When Stokes's shift in wavenumber scale was replaced by synchronous fluorescence maximum in nanometer scale, the solvent polarity dependency measured by λSFSmax vs. Lippert-Mataga plot or ET30 values offered similar trends as measured via Stokes' shift for protic and aprotic solvents for curcumin. Better linear correlation of λSFSmax vs. π* scale of solvent polarity was found compared to λabsmax or λemmax or Stokes' shift measurements. In Stokes' shift measurement both absorption/excitation as well as emission (fluorescence) spectra are required to compute the Stokes' shift in wavenumber scale, but measurement could be done in a very fast and simple way by taking a single scan of SFS avoiding calculation and obtain information about polarity of the solvent. Curcumin decay properties in all the solvents could be fitted well to a double-exponential decay function.

  11. Inhibition of EV71 by curcumin in intestinal epithelial cells.

    Science.gov (United States)

    Huang, Hsing-I; Chio, Chi-Chong; Lin, Jhao-Yin

    2018-01-01

    EV71 is a positive-sense single-stranded RNA virus that belongs to the Picornaviridae family. EV71 infection may cause various symptoms ranging from hand-foot-and-mouth disease to neurological pathological conditions such as aseptic meningitis, ataxia, and acute transverse myelitis. There is currently no effective treatment or vaccine available. Various compounds have been examined for their ability to restrict EV71 replication. However, most experiments have been performed in rhabdomyosarcoma or Vero cells. Since the gastrointestinal tract is the entry site for this pathogen, we anticipated that orally ingested agents may exert beneficial effects by decreasing virus replication in intestinal epithelial cells. In this study, curcumin (diferuloylmethane, C21H20O6), an active ingredient of turmeric (Curcuma longa Linn) with anti-cancer properties, was investigated for its anti-enterovirus activity. We demonstrate that curcumin treatment inhibits viral translation and increases host cell viability. Curcumin does not exert its anti-EV71 effects by modulating virus attachment or virus internal ribosome entry site (IRES) activity. Furthermore, curcumin-mediated regulation of mitogen-activated protein kinase (MAPK) signaling pathways is not involved. We found that protein kinase C delta (PKCδ) plays a role in virus translation in EV71-infected intestinal epithelial cells and that curcumin treatment decreases the phosphorylation of this enzyme. In addition, we show evidence that curcumin also limits viral translation in differentiated human intestinal epithelial cells. In summary, our data demonstrate the anti-EV71 properties of curcumin, suggesting that ingestion of this phytochemical may protect against enteroviral infections.

  12. Inhibition of EV71 by curcumin in intestinal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Hsing-I Huang

    Full Text Available EV71 is a positive-sense single-stranded RNA virus that belongs to the Picornaviridae family. EV71 infection may cause various symptoms ranging from hand-foot-and-mouth disease to neurological pathological conditions such as aseptic meningitis, ataxia, and acute transverse myelitis. There is currently no effective treatment or vaccine available. Various compounds have been examined for their ability to restrict EV71 replication. However, most experiments have been performed in rhabdomyosarcoma or Vero cells. Since the gastrointestinal tract is the entry site for this pathogen, we anticipated that orally ingested agents may exert beneficial effects by decreasing virus replication in intestinal epithelial cells. In this study, curcumin (diferuloylmethane, C21H20O6, an active ingredient of turmeric (Curcuma longa Linn with anti-cancer properties, was investigated for its anti-enterovirus activity. We demonstrate that curcumin treatment inhibits viral translation and increases host cell viability. Curcumin does not exert its anti-EV71 effects by modulating virus attachment or virus internal ribosome entry site (IRES activity. Furthermore, curcumin-mediated regulation of mitogen-activated protein kinase (MAPK signaling pathways is not involved. We found that protein kinase C delta (PKCδ plays a role in virus translation in EV71-infected intestinal epithelial cells and that curcumin treatment decreases the phosphorylation of this enzyme. In addition, we show evidence that curcumin also limits viral translation in differentiated human intestinal epithelial cells. In summary, our data demonstrate the anti-EV71 properties of curcumin, suggesting that ingestion of this phytochemical may protect against enteroviral infections.

  13. Curcumin induces autophagic cell death in Spodoptera frugiperda cells.

    Science.gov (United States)

    Veeran, Sethuraman; Shu, Benshui; Cui, Gaofeng; Fu, Shengjiao; Zhong, Guohua

    2017-06-01

    The increasing interest in the role of autophagy (type II cell death) in the regulation of insect toxicology has propelled study of investigating autophagic cell death pathways. Turmeric, the rhizome of the herb Curcuma longa (Mañjaḷ in Tamil, India and Jiānghuáng in Chinese) have been traditionally used for the pest control either alone or combination with other botanical pesticides. However, the mechanisms by which Curcuma longa or curcumin exerts cytotoxicity in pests are not well understood. In this study, we investigated the potency of Curcuma longa (curcumin) as a natural pesticide employing Sf9 insect line. Autophagy induction effect of curcumin on Spodoptera frugiperda (Sf9) cells was investigated using various techniques including cell proliferation assay, morphology analysis with inverted phase contrast microscope and Transmission Electron Microscope (TEM) analysis. Autophagy was evaluated using the fluorescent dye monodansylcadaverine (MDC). Cell death measurement was examined using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) within the concentrations of 5-15μg/mL. Curcumin inhibited the growth of the Sf9 cells and induced autophagic cell death in a time and dose dependent manner. Staining the cells with MDC showed the presence of autophagic vacuoles while increased in a dose and time dependent manner. At the ultrastructural level transmission electron microscopy, cells revealed massive autophagy vacuole accumulation and absence of chromatin condensation. Protein expression levels of ATG8-I and ATG8-II, well-established markers of autophagy related protein were elevated in a time dependent manner after curcumin treatment. The present study proves that curcumin induces autophagic cell death in Sf9 insect cell line and this is the first report of cytotoxic effect of curcumin in insect cells and that will be utilized as natural pesticides in future. Copyright © 2017. Published by Elsevier Inc.

  14. Inhibition of EV71 by curcumin in intestinal epithelial cells

    Science.gov (United States)

    Chio, Chi-Chong; Lin, Jhao-Yin

    2018-01-01

    EV71 is a positive-sense single-stranded RNA virus that belongs to the Picornaviridae family. EV71 infection may cause various symptoms ranging from hand-foot-and-mouth disease to neurological pathological conditions such as aseptic meningitis, ataxia, and acute transverse myelitis. There is currently no effective treatment or vaccine available. Various compounds have been examined for their ability to restrict EV71 replication. However, most experiments have been performed in rhabdomyosarcoma or Vero cells. Since the gastrointestinal tract is the entry site for this pathogen, we anticipated that orally ingested agents may exert beneficial effects by decreasing virus replication in intestinal epithelial cells. In this study, curcumin (diferuloylmethane, C21H20O6), an active ingredient of turmeric (Curcuma longa Linn) with anti-cancer properties, was investigated for its anti-enterovirus activity. We demonstrate that curcumin treatment inhibits viral translation and increases host cell viability. Curcumin does not exert its anti-EV71 effects by modulating virus attachment or virus internal ribosome entry site (IRES) activity. Furthermore, curcumin-mediated regulation of mitogen-activated protein kinase (MAPK) signaling pathways is not involved. We found that protein kinase C delta (PKCδ) plays a role in virus translation in EV71-infected intestinal epithelial cells and that curcumin treatment decreases the phosphorylation of this enzyme. In addition, we show evidence that curcumin also limits viral translation in differentiated human intestinal epithelial cells. In summary, our data demonstrate the anti-EV71 properties of curcumin, suggesting that ingestion of this phytochemical may protect against enteroviral infections. PMID:29370243

  15. Curcumin and insulin resistance-Molecular targets and clinical evidences.

    Science.gov (United States)

    Jiménez-Osorio, Angélica Saraí; Monroy, Adriana; Alavez, Silvestre

    2016-11-12

    Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), the main component of the Indian spice turmeric, has been used in traditional medicine to improve diabetes and its comorbidities. Since the last two decades, scientific research has shown that in addition to its antioxidant properties, curcumin could also work as protein homeostasis regulator and it is able to modulate other intracellular pathways. Curcumin supplementation has been proposed to improve insulin resistance (IR) through the activation of the insulin receptor and its downstream pathways in several experimental models, pointing out that its clinical use may be a good and innocuous strategy to improve IR-related diseases. IR is associated with many diseases and syndromes like carbohydrate intolerance, diabetes, metabolic syndrome, and cardiovascular disease. Therefore, it is imperative to identify safe therapeutic interventions aimed to reduce side effects that could lead the patient to leave the treatment. To date, many clinical trials have been carried out using turmeric and curcumin to improve metabolic syndrome, carbohydrate intolerance, diabetes, and obesity in individuals with IR. Results so far are inconclusive because dose, time of treatment, and type of curcumin can change the study outcome significantly. However, there is some clinical evidence suggesting a beneficial effect of curcumin on IR. In this review, we discuss the factors that could influence curcumin effects in clinical trials aimed to improve IR and related diseases, and the conclusions that can be drawn from results obtained so far. © 2016 BioFactors, 42(6):561-580, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  16. Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

    Science.gov (United States)

    Szczepanowicz, Krzysztof; Jantas, Danuta; Piotrowski, Marek; Staroń, Jakub; Leśkiewicz, Monika; Regulska, Magdalena; Lasoń, Władysław; Warszyński, Piotr

    2016-09-01

    Poor water solubility and low bioavailability of lipophilic drugs can be potentially improved with the use of delivery systems. In this study, encapsulation of nanoemulsion droplets was utilized to prepare curcumin nanocarriers. Nanosize droplets containing the drug were encapsulated in polyelectrolyte shells formed by the layer-by-layer (LbL) adsorption of biocompatible polyelectrolytes: poly-L-lysine (PLL) and poly-L-glutamic acid (PGA). The size of synthesized nanocapsules was around 100 nm. Their biocompatibility and neuroprotective effects were evaluated on the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). Statistically significant toxic effect was clearly observed for PLL coated nanocapsules (reduction in cell viability about 20%-60%), while nanocapsules with PLL/PGA coating did not evoke any detrimental effects on SH-SY5Y cells. Curcumin encapsulated in PLL/PGA showed similar neuroprotective activity against hydrogen peroxide (H2O2)-induced cell damage, as did 5 μM curcumin pre-dissolved in DMSO (about 16% of protection). Determination of concentration of curcumin in cell lysate confirmed that curcumin in nanocapsules has cell protective effect in lower concentrations (at least 20 times) than when given alone. Intracellular mechanisms of encapsulated curcumin-mediated protection engaged the prevention of the H2O2-induced decrease in mitochondrial membrane potential (MMP) but did not attenuate Reactive Oxygen Species (ROS) formation. The obtained results indicate the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity.

  17. Therapeutic roles of curcumin: lessons learned from clinical trials.

    Science.gov (United States)

    Gupta, Subash C; Patchva, Sridevi; Aggarwal, Bharat B

    2013-01-01

    Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn's disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin's pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF-κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E(2), prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the

  18. Poverty alleviation in Uganda: the case for a viable optimum ...

    African Journals Online (AJOL)

    Poverty alleviation is a long and painstaking process. It involves knowing what poverty is, its causes and means of alleviating it. Poverty is one of the scourges including disease and ignorance a combination of which deprives humanity of the basic needs for living. Among the strategies to alleviate poverty is effective ...

  19. Rural tourism development: a viable formula for poverty alleviation ...

    African Journals Online (AJOL)

    The case of rural tourism and community development has been made in general terms with less focus on poverty alleviation and more emphasis on economic modernisation. Recently, a link between rural tourism and poverty alleviation has been emphasised in the contemporary tourism and poverty alleviation literature.

  20. Curcumin-Loaded Chitosan/Gelatin Composite Sponge for Wound Healing Application

    Directory of Open Access Journals (Sweden)

    Van Cuong Nguyen

    2013-01-01

    Full Text Available Three composite sponges were made with 10% of curcumin and by using polymers, namely, chitosan and gelatin with various ratios. The chemical structure and morphology were evaluated by FTIR and SEM. These sponges were evaluated for water absorption capacity, antibacterial activity, in vitro drug release, and in vivo wound healing studies by excision wound model using rabbits. The in vivo study presented a greater wound closure in wounds treated with curcumin-composite sponge than those with composite sponge without curcumin and untreated group. These obtained results showed that combination of curcumin, chitosan and gelatin could improve the wound healing activity in comparison to chitosan, and gelatin without curcumin.

  1. Protective effects of alginate–chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. (Zuojin Pill against ethanol-induced acute gastric mucosal injury in rats

    Directory of Open Access Journals (Sweden)

    Wang QS

    2015-11-01

    Full Text Available Qiang-Song Wang,1,2,* Xiao-Ning Zhu,1,* Heng-Li Jiang,1,* Gui-Fang Wang,3 Yuan-Lu Cui1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, 3Pharmacy Department, Baokang Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Zuojin Pill (ZJP, a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. in a ratio of 6:1 (w/w and was first recorded in “Danxi’s experiential therapy” for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss. Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the

  2. Preparation of Lipid Nano emulsions Incorporating Curcumin for Cancer Therapy

    International Nuclear Information System (INIS)

    Anuchapreeda, S.; Anuchapreeda, S.; Fukumori, Y.; Ichikawa, H.; Okonogi, S.

    2012-01-01

    The aim of this study was to develop a new formulation of a curcumin lipid nano emulsion having the smallest particle size, the highest loading, and a good physical stability for cancer chemotherapy. Curcumin lipid nano emulsions were prepared by a modified thin-film hydration method followed by sonication. Soybean oil, hydrogenated L-α-phosphatidylcholine from egg yolk, and co surfactants were used to formulate the emulsions. The resultant nano emulsions showed mean particle diameter of 47-55 nm, could incorporate 23-28 mg curcumin per 30 mL, and were stable in particle size for 60 days at 4 degree C. The cytotoxicity studies of curucumin solution and curcumin-loaded nano emulsion using B16F10 and leukemic cell lines showed IC 50 values ranging from 3.5 to 30.1 and 22.2 to 53.7μM, respectively. These results demonstrated the successful incorporation of curcumin into lipid nano emulsion particles with small particle size, high loading capacity, good physical stability, and preserved cytotoxicity

  3. Curcumin (Extracted from Tumeric and its Therapeutic Effects

    Directory of Open Access Journals (Sweden)

    Arezou khosrojerdi

    2017-01-01

    Full Text Available Background and Objectives:  The application of herbal medicine has been rising in recent years. Therefore, it is logical to revise and revive these traditional drugs while identifying their mechanisms of action can result in developing new treatments for many diseases. Curcumin is the most important component of Turmeric with numerous therapeutic properties. We aimed to review the anti-inflammatory and anti-microbial properties of Curcumin and introduce it as a therapeutic molecule in the present article. Methods: In this review, 121 articles were selected from authenticated electronic resources and scientific library databases such as Pubmed, Medline, Sciencedirect, WOS, DOAJ, SID, Iranmedex, Magiran and Google Scholar search engine in which Curcumin (Turmeric had been evaluated as a therapeutic molecule from differeny aspects. Results: Our findings from the literature revealed that immune responses against infectious and inflammatory factors could be fascilitated by Curcumin. However, the low solubility in water and minimal bioavailability which may lead to poor absorbance from gastrointestinal tract, quick metabolization and elimination from blood circulation are the most important problems during oral consumption. Conclusion: According to the results of the present review article, Curcumin possesses efficient anti-inflammatory, anti-microbial, anti-viral and anti-parasitic properties. However, the low bioavailability of this substance has limited its treatment properties. Nowadays, several mechanisms have been proposed to increase the bioavailability which can improve its absorption.

  4. Assessment in vitro of radioprotective efficacy of curcumin and resveratrol

    Energy Technology Data Exchange (ETDEWEB)

    Sebastia, Natividad, E-mail: natividad.sebastia@uv.es [Area de Nutricion y Bromatologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot (Spain); Montoro, Alegria [Servicio de Proteccion Radiologica, Hospital Universitario La Fe, 46009, Valencia (Spain); Montoro, Amparo [Area de Nutricion y Bromatologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot (Spain); Almonacid, Miguel; Villaescusa, Juan Ignacio [Servicio de Proteccion Radiologica, Hospital Universitario La Fe, 46009, Valencia (Spain); Cervera, Jose; Such, Esperanza; Silla, Ma Angeles [Servicio de Hematologia, Hospital Universitario La Fe, 46009, Valencia (Spain); Soriano, Jose Miguel [Area de Nutricion y Bromatologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot (Spain)

    2011-09-15

    Many natural substances have been studied in recent past to be used as radioprotectors to mitigate ionizing radiation-induced damage in mammalian systems due to its effectiveness given both pre- and post-irradiation and for long time with out drug-related toxicity. Curcumin and trans-resveratrol are both natural occurring polyphenols, obtained from the root of Curcuma longa and from grapes and other berries, respectively. These compounds have shown antioxidant, anti-inflammatory, immunostimulant and anti-carcinogenic properties. Our aim was to evaluate the radioprotective efficacy, in vitro, of curcumin and trans-resveratrol separately against radiation-induced chromosomal aberrations. The study was carried out by the pre-treatment of human blood lymphocytes at concentrations from 0 to 500 {mu}g mL{sup -1} and from 0 to 50 {mu}g mL{sup -1} for curcumin and trans-resveratrol, respectively. The results showed that all concentrations tested reduced radiation-induced chromosomal damage. Maximum damage protection was observed at the concentration of 5 {mu}g mL{sup -1} for curcumin and 0.5 {mu}g mL{sup -1} for trans-resveratrol. Thus, our results show that curcumin and trans-resveratrol pre-treatment significantly protect normal lymphocytes against {gamma}-radiation-induced cellular damage.

  5. Anti cancer effects of curcumin: cycle of life and death

    Directory of Open Access Journals (Sweden)

    Das Tanya

    2008-10-01

    Full Text Available Abstract Increasing knowledge on the cell cycle deregulations in cancers has promoted the introduction of phytochemicals, which can either modulate signaling pathways leading to cell cycle regulation or directly alter cell cycle regulatory molecules, in cancer therapy. Most human malignancies are driven by chromosomal translocations or other genetic alterations that directly affect the function of critical cell cycle proteins such as cyclins as well as tumor suppressors, e.g., p53. In this respect, cell cycle regulation and its modulation by curcumin are gaining widespread attention in recent years. Extensive research has addressed the chemotherapeutic potential of curcumin (diferuloylmethane, a relatively non-toxic plant derived polyphenol. The mechanisms implicated are diverse and appear to involve a combination of cell signaling pathways at multiple levels. In the present review we discuss how alterations in the cell cycle control contribute to the malignant transformation and provide an overview of how curcumin targets cell cycle regulatory molecules to assert anti-proliferative and/or apoptotic effects in cancer cells. The purpose of the current article is to present an appraisal of the current level of knowledge regarding the potential of curcumin as an agent for the chemoprevention of cancer via an understanding of its mechanism of action at the level of cell cycle regulation. Taken together, this review seeks to summarize the unique properties of curcumin that may be exploited for successful clinical cancer prevention.

  6. Porous silica nanoparticles as carrier for curcumin delivery

    Science.gov (United States)

    Hartono, Sandy Budi; Hadisoewignyo, Lannie; Irawaty, Wenny; Trisna, Luciana; Wijaya, Robby

    2018-04-01

    Mesoporous silica nanoparticles (MSN) with large surface areas and pore volumes show great potential as drug and gene carriers. However, there are still some challenging issues hinders their clinical application. Many types of research in the use of mesoporous silica material for drug and gene delivery involving complex and rigorous procedures. A facile and reproducible procedure to prepare combined drug carrier is required. We investigated the effect of physiochemical parameters of mesoporous silica, including structural symmetry (cubic and hexagonal), particles size (micro size: 1-2 µm and nano size: 100 -300 nm), on the solubility and release profile of curcumin. Transmission Electron Microscopy, X-Ray Powder Diffraction, and Nitrogen sorption were used to confirm the synthesis of the mesoporous silica materials. Mesoporous silica materials with different mesostructures and size have been synthesized successfully. Curcumin has anti-oxidant, anti-inflammation and anti-virus properties which are beneficial to fight various diseases such as diabetic, cancer, allergic, arthritis and Alzheimer. Curcumin has low solubility which minimizes its therapeutic effect. The use of nanoporous material to carry and release the loaded molecules is expected to enhance curcumin solubility. Mesoporous silica materials with a cubic mesostructure had a higher release profile and curcumin solubility, while mesoporous silica materials with a particle size in the range of nano meter (100-300) nm also show better release profile and solubility.

  7. Curcumin ameliorates gastrointestinal dysfunction and oxidative damage in diabetic rats

    Directory of Open Access Journals (Sweden)

    Nitin Indarchandji Kochar

    2014-05-01

    Full Text Available Diabetes is known to be associated with gastrointestinal complications characterized by nausea, vomiting, early satiety, bloating, and abdominal discomfort or pain commonly occurring in the advanced stages of the disease. Curcumin is the lipid-soluble antioxidant obtained from the rhizomes of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and oxidative stress pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, literature lacks conclusive evidence supporting its use as a therapeutic agent for the treatment of diabetes induced gastrointestinal complications. Hence, Curcumin was given in different doses to SD rats after 4 weeks of diabetic GI complication induction. At the end of 4 weeks, significant GI dysfunction characterized by weight loss, delayed gastric emptying and intestinal transit associated with reduction in antioxidant enzyme levels and increased lipid peroxidation was observed.  Upon treatment with Curcumin for further 4 weeks, reversal of GI dysfunction evidenced by restoration of body weight, GI emptying, intestinal transit, and restoration of antioxidant enzyme level and lipid peroxidation proves the beneficial role of Curcumin in diabetes induced GI complications due to its antioxidant potential.     

  8. Assessment in vitro of radioprotective efficacy of curcumin and resveratrol

    International Nuclear Information System (INIS)

    Sebastia, Natividad; Montoro, Alegria; Montoro, Amparo; Almonacid, Miguel; Villaescusa, Juan Ignacio; Cervera, Jose; Such, Esperanza; Silla, Ma Angeles; Soriano, Jose Miguel

    2011-01-01

    Many natural substances have been studied in recent past to be used as radioprotectors to mitigate ionizing radiation-induced damage in mammalian systems due to its effectiveness given both pre- and post-irradiation and for long time with out drug-related toxicity. Curcumin and trans-resveratrol are both natural occurring polyphenols, obtained from the root of Curcuma longa and from grapes and other berries, respectively. These compounds have shown antioxidant, anti-inflammatory, immunostimulant and anti-carcinogenic properties. Our aim was to evaluate the radioprotective efficacy, in vitro, of curcumin and trans-resveratrol separately against radiation-induced chromosomal aberrations. The study was carried out by the pre-treatment of human blood lymphocytes at concentrations from 0 to 500 μg mL -1 and from 0 to 50 μg mL -1 for curcumin and trans-resveratrol, respectively. The results showed that all concentrations tested reduced radiation-induced chromosomal damage. Maximum damage protection was observed at the concentration of 5 μg mL -1 for curcumin and 0.5 μg mL -1 for trans-resveratrol. Thus, our results show that curcumin and trans-resveratrol pre-treatment significantly protect normal lymphocytes against γ-radiation-induced cellular damage.

  9. Lipid Based Nanosystems for Curcumin: Past, Present and Future.

    Science.gov (United States)

    Nayak, Aditya P; Mills, Tom; Norton, Ian

    2016-01-01

    Curcumin is one of the principle bioactive compounds used in the ayurvedic medicine system that has the history of over 5000 years for human use. Curcumin an "Indian Gold" is used to treat simple ailments like the common cold to severe life threatening diseases like cancer, and HIV. Though its contribution is immense for the health protection and disease prevention, its clinical use is limited due to its susceptible nature to alkaline pH, high temperature, presence of oxygen and light. Hence it becomes extremely difficult to maintain its bioactivity during processing, storage and consumption. Recent advancements in the application of nanotechnology to curcumin offer an opportunity to enhance its stability, bioactivity and to overcome its pharmacokinetic mismatch. This in turn helps to bridge the gaps that exist between its bench top research data to its clinical findings. Among the various types of nano/micro delivery systems, lipid based delivery systems are well studied and are the best suited delivery systems to enhance the stability and pharmacokinetic profile of curcumin both for pharma and the food application. In the current review, effort will be made to recapitulate the work done in the past to use lipid based delivery systems (liposomes, solid lipid nanoparticles, and emulsions) to enhance the application of curcumin for health promotion and disease prevention. Further, future prospects for the utilization of these lipid-based delivery systems will be discussed in detail.

  10. Curcumin synergizes with resveratrol to inhibit colon cancer.

    Science.gov (United States)

    Majumdar, Adhip P N; Banerjee, Sanjeev; Nautiyal, Jyoti; Patel, Bhaumik B; Patel, Vaishali; Du, Jianhua; Yu, Yingjie; Elliott, Althea A; Levi, Edi; Sarkar, Fazlul H

    2009-01-01

    Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.

  11. Curcumin – A Potent Inhibitor of Galectin-3 Expression

    Directory of Open Access Journals (Sweden)

    Jerka Dumić

    2002-01-01

    Full Text Available The expression of galectin-3, a b-galactoside binding lectin, was found to be affected by different kinds of stressors, and is strongly modified in numerous physiological and pathophysiological conditions. Although no precise regulatory mechanisms of galectin-3 expression are unraveled, transcription factors AP-1 (activator protein 1 and NF-kB (nuclear factor kappa B play an important role in these processes. Activities of both transcription factors are affected by curcumin, a biologically active compound extracted from rhizomes of Curcuma species. We have analyzed the impact of curcumin on the expression of galectin-3 in glioblastoma cells under basal conditions and under stress invoked by the cell exposure to alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG and ultraviolet C (UV-C light. Galectin-3 level was measured by western-blot technique using M3/38 monoclonal antibody. Curcumin has decreased the basal level of galectin-3, while the pretreatment of cells with curcumin has considerably reduced the inducible effect of UV-C radiation and abolished the inducible effect of alkylating agent. Thus, curcumin has been identified as a potent inhibitor of galectin-3 expression.

  12. Curcumin protects against acoustic trauma in the rat cochlea.

    Science.gov (United States)

    Soyalıç, Harun; Gevrek, Fikret; Karaman, Serhat

    2017-08-01

    In this study we evaluated the therapeutic utility of curcumin in a rodent model of acoustic trauma using histopathology, immunohistochemical, and distortion product otoacoustic emission (DPOAEs) measurements. 28 Wistar albino rats were included in the study and randomly assigned to 4 treatment groups. The first group (group 1) served as the control and was exposed to acoustic trauma alone. Group 2 was the curcumin group. Group 3 was the curcumin plus acoustic trauma group. Group 4 was the saline plus acoustic trauma group. Otoacoustic emission measurements were collected at the end of the experiment and all animals were sacrificed. Cochlea were collected and prepared for TUNEL (TdT-mediated deoxyuridinetriphosphate nick end-labelling) staining assay. Group 3 maintained baseline DPOAEs values at 3000 Hz, 4000 Hz and 8000 Hz on the 3rd and 5th day of the experiment. DPOAEs results were correlated with the immunohistochemical and histopathological findings in all groups. In comparison to the histopathologic control group, Group 1 exhibited a statistically significant increase in apoptotic indices in the organ of Corti, inner hair cell, and outer hair cell areas (p curcumin may protect the cochlear tissues from acoustic trauma in rats. Curcumin injection prior to or after an acoustic trauma reduces cochlear hair cell damage and may protect against hearing loss. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Curcumin: A Review of Its’ Effects on Human Health

    Directory of Open Access Journals (Sweden)

    Susan J. Hewlings

    2017-10-01

    Full Text Available Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.

  14. Nanoformulations of curcumin: an emerging paradigm for improved remedial application.

    Science.gov (United States)

    Gera, Meeta; Sharma, Neelesh; Ghosh, Mrinmoy; Huynh, Do Luong; Lee, Sung Jin; Min, Taesun; Kwon, Taeho; Jeong, Dong Kee

    2017-09-12

    Curcumin is a natural polyphenol and essential curcuminoid derived from the rhizome of the medicinal plant Curcuma longa ( L .) is universally acknowledged as " Wonder drug of life ". It is a vital consumable and restorative herb, commonly keened for several ailments such as cancer, arthritis, pain, bruises, gastrointestinal quandaries, swelling and much more. Despite its enormous curative potential, the poor aqueous solubility and consequently, minimal systemic bioavailability with rapid degradation are some of the major factors which restrict the utilization of curcumin at medical perspective. However, to improve its clinically relevant parameters, nanoformulation of curcumin is emerging as a novel substitute for their superior therapeutic modality. It enhances its aqueous solubility and targeted delivery to the tissue of interest that prompts to enhance the bioavailability, better drug conveyance, and more expeditious treatment. Subsequent investigations are endeavored to enhance the bio-distribution of native curcumin by modifying with felicitous nano-carriers for encapsulation. In this review, we specifically focus on the recent nanotechnology based implementations applied for overcoming the innate constraints of native curcumin and additionally the associated challenges which restrict its potential therapeutic applications both in vivo and in-vitro studies, as well as their detailed mechanism of action, have additionally been discussed.

  15. Curcumin: a potential candidate for matrix metalloproteinase inhibitors.

    Science.gov (United States)

    Kumar, Dileep; Kumar, Manish; Saravanan, Chinnadurai; Singh, Sushil Kumar

    2012-10-01

    Curcumin, a natural yellow pigment of turmeric, has become focus of interest with regard to its role in regulation of matrix metalloproteinases (MMPs). MMPs are metal-dependent endopeptidases capable of degrading components of the extracellular matrix. MMPs are involved in chronic diseases such as arthritis, Alzheimer's disease, psoriasis, chronic obstructive pulmonary disease, asthma, cancer, neuropathic pain, and atherosclerosis. Curcumin regulates the expression and secretion of various MMPs. This review documents the matrix metalloproteinase inhibitory activity of curcumin on various diseases viz., cancer, arthritis, and ulcer. Finally, the steps to be taken for getting potent curcuminoids have also been discussed in the structure-activity relationship (SAR) section. From this review, readers can get answer to the question: Is curcumin a potential MMPI candidate? Numerous approaches have been taken to beget a molecule with specificity restricted to a particular MMP as well as good oral bioavailability; however, nearly all the molecules lack these criteria. Using quantitative structure-activity relationship (QSAR) modeling and virtual screening, new analogs of curcumin can be designed which will be selectively inhibiting different MMPs.

  16. Curcumin: A Review of Its' Effects on Human Health.

    Science.gov (United States)

    Hewlings, Susan J; Kalman, Douglas S

    2017-10-22

    Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.

  17. Enhancement of Curcumin Bioavailability Via the Prodrug Approach: Challenges and Prospects.

    Science.gov (United States)

    Ratnatilaka Na Bhuket, Pahweenvaj; El-Magboub, Asma; Haworth, Ian S; Rojsitthisak, Pornchai

    2017-06-01

    Curcumin is a natural product with many interesting pharmacological properties. However, these are offset by the particularly poor biopharmaceutical properties. The oral bioavailability of curcumin in humans is very low, mainly due to low solubility, poor stability, and extensive metabolism. This has led to multiple approaches to improve bioavailability, including administration of curcumin with metabolism inhibitors, formulation into nanoparticles, modification of the curcumin structure, and development of curcumin prodrugs. In this paper, we focus on the pharmacokinetic outcomes of these approaches. Pharmacokinetic parameters of curcumin after release from prodrugs are dependent on the linker between curcumin and the promoiety, and the release itself may depend on the physiological and enzymatic environment at the site of cleavage. This is an area in which more data are required for rational design of improved linkers. Cytotoxicity of curcumin prodrugs seems to correlate well with cellular uptake in vitro, but the in vivo relevance is uncertain. We conclude that improved experimental and theoretical models of absorption of curcumin prodrugs, development of accurate analytical methods for simultaneous measurement of plasma levels of prodrug and released curcumin, and acquisition of more pharmacokinetic data in animal models for dose prediction in humans are required to facilitate movement of curcumin prodrugs into clinical trials.

  18. Physico-chemical state influences in vitro release profile of curcumin from pectin beads.

    Science.gov (United States)

    Nguyen, An Thi-Binh; Winckler, Pascale; Loison, Pauline; Wache, Yves; Chambin, Odile

    2014-09-01

    Curcumin is a polyphenolic compound with diverse effects interesting to develop health benefit products but its formulation in functional foods or in food supplement is hampered by its poor water solubility and susceptibility to alkaline conditions, light, oxidation and heat. Encapsulation of curcumin could be a mean to overcome these difficulties. In this paper, curcumin was encapsulated by ionotropic gelation method in low methoxyl pectin beads associated with different surfactants: Solutol(®), Transcutol(®) and sodium caseinate. After encapsulation, physico-chemical properties of encapsulated curcumin such as its solubility, physical state, tautomeric forms and encapsulation efficiency as well as encapsulation yield were characterized. In vitro dissolution of curcumin from beads displayed different kinetic profiles according to bead composition due to different matrix network. As Solutol(®) was a good solvent for curcumin, the drug was present into amorphous form in these beads inducing a rapid release of curcumin in the simulated digestive fluids. In contrast, drug release was slower from sodium caseinate beads since curcumin was not totally dissolved during the manufacturing process. Moreover, the FLIM studies showed that a part of curcumin was encapsulated in caseinate micelles and that 34% of this drug was in keto form which may delay the curcumin release. The Transcutol beads showed also a slow drug release because of the low curcumin solubility and the high density of the matrix. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Drug-Drug/Drug-Excipient Compatibility Studies on Curcumin using Non-Thermal Methods

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    Moorthi Chidambaram

    2014-05-01

    Full Text Available Purpose: Curcumin is a hydrophobic polyphenol isolated from dried rhizome of turmeric. Clinical usefulness of curcumin in the treatment of cancer is limited due to poor aqueous solubility, hydrolytic degradation, metabolism, and poor oral bioavailability. To overcome these limitations, we proposed to fabricate curcumin-piperine, curcumin-quercetin and curcumin-silibinin loaded polymeric nanoformulation. However, unfavourable combinations of drug-drug and drug-excipient may result in interaction and rises the safety concern. Hence, the present study was aimed to assess the interaction of curcumin with excipients used in nanoformulations. Methods: Isothermal stress testing method was used to assess the compatibility of drug-drug/drug-excipient. Results: The combination of curcumin-piperine, curcumin-quercetin, curcumin-silibinin and the combination of other excipients with curcumin, piperine, quercetin and silibinin have not shown any significant physical and chemical instability. Conclusion: The study concludes that the curcumin, piperine, quercetin and silibinin is compatible with each other and with other excipients.

  20. Preparation, characterization and biological evaluation of curcumin loaded alginate aldehyde–gelatin nanogels

    Energy Technology Data Exchange (ETDEWEB)

    Sarika, P.R., E-mail: sarikapaithal@gmail.com [Department of Chemistry, Indian Institute of Space Science and Technology (IIST), Valiamala, Thiruvananthapuram, Kerala 695 547 (India); James, Nirmala Rachel, E-mail: nirmala@iist.ac.in [Department of Chemistry, Indian Institute of Space Science and Technology (IIST), Valiamala, Thiruvananthapuram, Kerala 695 547 (India); Anil Kumar, P.R., E-mail: anilkumarpr@sctimst.ac.in [Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Thiruvananthapuram, Kerala 695 012 (India); Raj, Deepa K., E-mail: kdeeps3@gmail.com [Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Thiruvananthapuram, Kerala 695 012 (India)

    2016-11-01

    Curcumin, a natural polyphenol exhibits chemopreventive and chemotherapeutic activities towards cancer. In order to improve the bioavailability and therapeutic efficacy, curcumin is encapsulated in alginate aldehyde–gelatin (Alg Ald-Gel) nanogels. Alginate aldehyde–gelatin nanogels are prepared by inverse miniemulsion technique. Physicochemical properties of the curcumin loaded nanogels are evaluated by, Dynamic light scattering (DLS), NMR spectroscopy and Scanning electron microscopy (SEM). Curcumin loaded nanogels show hydrodynamic diameter of 431 ± 8 nm and a zeta potential of − 36 ± 4 mV. The prepared nanogels exhibit an encapsulation efficiency of 72 ± 2%. In vitro drug release studies show a controlled release of curcumin from nanogels over a period of 48 h. Hemocompatibility and cytocompatibility of the nanogels are evaluated. Bare nanogels are cytocompatible and curcumin loaded nanogels induce anticancer activity towards MCF-7 cells. In vitro cellular uptake of the curcumin loaded nanogels using confocal laser scanning microscopy (CLSM) confirms the uptake of nanogels in MCF-7 cells. Hence, the developed nanogel system can be a suitable candidate for curcumin delivery to cancer cells. - Highlights: • Curcumin loaded alginate aldehyde–gelatin nanogels are prepared. • Alg Ald-Gel nanogels maintained spherical morphology after curcumin loading. • Curcumin release is higher at acidic pH compared to neutral pH. • Cytotoxicity analysis proved the toxicity of the nanogels in MCF-7 cells. • Green fluorescence in MCF-7 cells confirmed the intra cellular uptake.

  1. Protective Effects of Curcumin on Manganese-Induced BV-2 Microglial Cell Death.

    Science.gov (United States)

    Park, Euteum; Chun, Hong Sung

    2017-08-01

    Curcumin, a bioactive component in tumeric, has been shown to exert antioxidant, anti-inflammatory, anticarcinogenic, hepatoprotective, and neuroprotective effects, but the effects of curcumin against manganese (Mn)-mediated neurotoxicity have not been studied. This study examined the protective effects of curcumin on Mn-induced cytotoxicity in BV-2 microglial cells. Curcumin (0.1-10 µM) dose-dependently prevented Mn (250 µM)-induced cell death. Mn-induced mitochondria-related apoptotic characteristics, such as caspase-3 and -9 activation, cytochrome c release, Bax increase, and Bcl-2 decrease, were significantly suppressed by curcumin. In addition, curcumin significantly increased intracellular glutathione (GSH) and moderately potentiated superoxide dismutase (SOD), both which were diminished by Mn treatment. Curcumin pretreatment effectively suppressed Mn-induced upregulation of malondialdehyde (MDA), total reactive oxygen species (ROS). Moreover, curcumin markedly inhibited the Mn-induced mitochondrial membrane potential (MMP) loss. Furthermore, curcumin was able to induce heme oxygenase (HO)-1 expression. Curcumin-mediated inhibition of ROS, down-regulation of caspases, restoration of MMP, and recovery of cell viability were partially reversed by HO-1 inhibitor (SnPP). These results suggest the first evidence that curcumin can prevent Mn-induced microglial cell death through the induction of HO-1 and regulation of oxidative stress, mitochondrial dysfunction, and apoptotic events.

  2. Solubility enhancement and delivery systems of curcumin a herbal medicine: a review.

    Science.gov (United States)

    Hani, Umme; Shivakumar, H G

    2014-01-01

    Curcumin diferuloylmethane is a main yellow bioactive component of turmeric, possess wide spectrum of biological actions. It was found to have anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. However, the benefits are curtailed by its extremely poor aqueous solubility, which subsequently limits the bioavailability and therapeutic effects of curcumin. Nanotechnology is the available approach in solving these issues. Therapeutic efficacy of curcumin can be utilized effectively by doing improvement in formulation properties or delivery systems. Numerous attempts have been made to design a delivery system of curcumin. Currently, nanosuspensions, micelles, nanoparticles, nano-emulsions, etc. are used to improve the in vitro dissolution velocity and in vivo efficiency of curcumin. This review focuses on the methods to increase solubility of curcumin and various nanotechnologies based delivery systems and other delivery systems of curcumin.

  3. Strategies to enhance the bioavailability of curcumin: a potential antitumor drug

    Science.gov (United States)

    Kumar, Abhishek; Chittigori, Joshna; Li, Lian; Samuelson, Lynne; Sandman, Daniel; Kumar, Jayant

    2012-02-01

    Curcumin is a polyphenol which has elicited considerable interest for its antioxidant and anti tumor properties. Although curcumin may be used as potential therapeutic drug, it is very sparingly soluble in water which makes it less bioavailable under physiological conditions. We report two approaches to make curcumin more bioavailable. The first approach involves fabricating colloidal dispersions of curcumin in the range of tens of nanometers. The second approach involves functionalization of curcumin with polyethylene glycol (PEG) to render it water dispersible or soluble. Since curcumin is a fluorescent molecule as well as a potential drug, its interactions with cells have been investigated using one and two photon confocal fluorescence imaging. We have also observed strong interaction between curcumin and metal ions, which may have physiological implications.

  4. Curcumin Encapsulated in Milk Exosomes Resists Human Digestion and Possesses Enhanced Intestinal Permeability in Vitro.

    Science.gov (United States)

    Vashisht, Monika; Rani, Payal; Onteru, Suneel Kumar; Singh, Dheer

    2017-11-01

    Exosomes, the extracellular secretary nano-vesicles, act as carriers of biomolecules to the target cells. They exhibit several attributes of an efficient drug delivery system. Curcumin, despite having numerous bioactive and therapeutic properties, has limited pharmaceutical use due to its poor water solubility, stability, and low systemic bioavailability. Hence, this study aims to enhance the therapeutic potential of curcumin, a model hydrophobic drug, by its encapsulation into milk exosomes. In the present study, we investigated the stability of free curcumin and exosomal curcumin in PBS and in vitro digestive processes. Additionally, their uptake and trans-epithelial transport were studied on Caco-2 cells. Curcumin in milk exosomes had higher stability in PBS, sustained harsh digestive processes, and crossed the intestinal barrier than free curcumin. In conclusion, the encapsulation of curcumin into the exosomes enhances its stability, solubility, and bioavailability. Therefore, the present study demonstrated that milk exosomes act as stable oral drug delivery vehicles.

  5. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency

    Science.gov (United States)

    Nagahama, Koji; Utsumi, Tomoya; Kumano, Takayuki; Maekawa, Saeko; Oyama, Naho; Kawakami, Junji

    2016-08-01

    Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.

  6. PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα

    Science.gov (United States)

    Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena; Tian, Xuebi; Liu, Ying; Wang, Zaijie Jim

    2016-01-01

    Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin’s mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling. PMID:26744842

  7. Preparation and Char