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Sample records for curcumin inflammation ageing

  1. 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...

  2. Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?

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    Yan He

    2015-05-01

    Full Text Available It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

  3. Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies

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    S. Salvioli

    2007-01-01

    Full Text Available Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.

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

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    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.

  5. Curcumin-functionalized silk biomaterials for anti-aging utility.

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    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.

  6. TPGS-Stabilized Curcumin Nanoparticles Exhibit Superior Effect on Carrageenan-Induced Inflammation in Wistar Rat

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    Heni Rachmawati

    2016-08-01

    Full Text Available Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW. Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

  7. The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update.

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    Ghosh, Shatadal; Banerjee, Sharmistha; Sil, Parames C

    2015-09-01

    The concept of using phytochemicals has ushered in a new revolution in pharmaceuticals. Naturally occurring polyphenols (like curcumin, morin, resveratrol, etc.) have gained importance because of their minimal side effects, low cost and abundance. Curcumin (diferuloylmethane) is a component of turmeric isolated from the rhizome of Curcuma longa. Research for more than two decades has revealed the pleiotropic nature of the biological effects of this molecule. More than 7000 published articles have shed light on the various aspects of curcumin including its antioxidant, hypoglycemic, anti-inflammatory and anti-cancer activities. Apart from these well-known activities, this natural polyphenolic compound also exerts its beneficial effects by modulating different signalling molecules including transcription factors, chemokines, cytokines, tumour suppressor genes, adhesion molecules, microRNAs, etc. Oxidative stress and inflammation play a pivotal role in various diseases like diabetes, cancer, arthritis, Alzheimer's disease and cardiovascular diseases. Curcumin, therefore, could be a therapeutic option for the treatment of these diseases, provided limitations in its oral bioavailability can be overcome. The current review provides an updated overview of the metabolism and mechanism of action of curcumin in various organ pathophysiologies. The review also discusses the potential for multifunctional therapeutic application of curcumin and its recent progress in clinical biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Neuroprotective Effect of Curcumin Against Cerebral Ischemia-Reperfusion Via Mediating Autophagy and Inflammation.

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    Huang, Lifa; Chen, Chengwei; Zhang, Xin; Li, Xu; Chen, Zupeng; Yang, Chao; Liang, Xiaolong; Zhu, Guochong; Xu, Zhen

    2018-01-01

    Curcumin, a polyphenolic compound extracted from Curcuma longa, has drawn attention for its effective bioactivities against ischemia-induced injury. This study aimed to evaluate the neuroprotective effect of curcumin and investigate the underlying mechanism that mediates autophagy and inflammation in an animal model of middle cerebral artery occlusion (MCAO) in rats. Curcumin was delivered to Sprague Dawley male rats at a dose of 200 mg/kg curcumin by intraperitoneal injection 30 min after ischemia-reperfusion (I/R). LY294002, a specific inhibitor of the PI3K/Akt/mTOR pathway, as well as anisomycin, an activator of TLR4/p38/MAPK, was administered by ventricle injection 30 min before MCAO. The same volume of saline was given as a control. Brain infarction and neurological function were determined 24 h post-MCAO. Immunoblotting and immunofluorescence were used to detect alterations in autophagy-relevant proteins Akt, p-Akt, mTOR, p-mTOR, LC3-II, and LC3-I, and inflammation-related proteins TLR4, p-38, p-p38, and IL-1 in the ipsilateral hemisphere. Cerebral I/R injury resulted in significant alterations of LC3-II/LC3-I, IL-1, TLR4, and p-p38. Curcumin in MCAO rats significantly improved brain damage and neurological function by upregulating p-Akt and p-mTOR and downregulating LC3-II/LC3-I, IL-1, TLR4, p-38, and p-p38. However, these protective effects against ischemia could be suppressed when LY294002 or anisomycin was included. Curcumin exerts neuroprotective effects by attenuating autophagic activities through mediating the PI3K/Akt/mTOR pathway, while also suppressing an inflammatory reaction by regulating the TLR4/p38/MAPK pathway. Furthermore, this study indicates that curcumin could be an effective therapy for patients afflicted with ischemia.

  9. Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases

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    Sathish Sundar Dhilip Kumar

    2018-04-01

    Full Text Available Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

  10. Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases.

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    Sundar Dhilip Kumar, Sathish; Houreld, Nicolette Nadene; Abrahamse, Heidi

    2018-04-05

    Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric ( Curcuma longa ) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

  11. Anti-inflammation performance of curcumin-loaded mesoporous calcium silicate cement.

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    Chen, Yuan-Chien; Shie, Ming-You; Wu, Yuan-Haw Andrew; Lee, Kai-Xing Alvin; Wei, Li-Ju; Shen, Yu-Fang

    2017-09-01

    Calcium silicate (CS) cements have excellent bioactivity and can induce the bone-like apatite formation. They are good biomaterials for bone tissue engineering and bone regenerative medicine. However, they have degradability and the dissolved CS can cause the inflammatory response at the early post-implantation stage. The purpose of this study was to design and prepare the curcumin-loaded mesoporous CS (MesoCS/curcumin) cements as a strategy to reduce the inflammatory reaction after implantation. The MesoCS/curcumin cements were designed and prepared. The characteristics of MesoCS/curcumin specimens were examined by transmission electron microscopy (TEM), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Their physical properties, biocompatibility, and anti-inflammatory ability were also evaluated. The MesoCS/curcumin cements displayed excellent biocompatibility and physical properties. Their crystalline characterizations were very similar with MesoCS cements. After soaking in simulated body fluid, the bone-like apatite layer of the MesoCS/curcumin cements could be formed. In addition, it could inhibit the expression of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) after inflammation reaction induced by lipopolysaccharides and had good anti-inflammatory ability. Adding curcumin in MesoCS cements can reduce the inflammatory reaction, but does not affect the original biological activity and properties of MesoCS cements. It can provide a good strategy to inhibit the inflammatory reaction after implantation for bone tissue engineering and bone regenerative medicine. Copyright © 2017. Published by Elsevier B.V.

  12. Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

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    António M. Santos

    2015-01-01

    Full Text Available Helicobacter pylori (H. pylori infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT and quantitative real-time polymerase chain reaction (PCR. Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.

  13. Ageing: From inflammation to cancer

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    Leonardi, G.; Accardi, G.; Monastero, R.; Nicoletti, F.; Libra, M.

    2018-01-01

    Ageing is the major risk factor for cancer development. Hallmark of the ageing process is represented by inflammaging, which is a chronic and systemic low-grade inflammatory process. Inflammation is also a hallmark of cancer and is widely recognized to influence all cancer stages from cell transformation to metastasis. Therefore, inflammaging may represent the biological phenomena able to couple ageing process with cancer development. Here we review the molecular and cellular pathway involved...

  14. 4-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal Inflammation

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    Ying Gu

    2013-01-01

    Full Text Available Chronic inflammatory diseases such as periodontitis have been associated with increased risk for various medical conditions including diabetes and cardiovascular disease. Endotoxin (lipopolysaccharide, LPS, derived from gram-negative periodonto-pathogens, can induce the local accumulation of mononuclear cells in the inflammatory lesion, increasing proinflammatory cytokines and matrix metalloproteinases (MMPs. This ultimately results in the destruction of periodontal connective tissues including alveolar bone. Curcumin is the principal dyestuff in the popular Indian spice turmeric and has significant regulatory effects on inflammatory mediators but is characterized by poor solubility and low bioactivity. Recently, we developed a series of chemically modified curcumins (CMCs with increased solubility and zinc-binding activity, while retaining, or further enhancing, their therapeutic effects. In the current study, we demonstrate that a novel CMC (CMC 2.5: 4-methoxycarbonyl curcumin has significant inhibitory effects, better than the parent compound curcumin, on proinflammatory cytokines and MMPs in in vitro, in cell culture, and in an animal model of periodontal inflammation. The therapeutic potential of CMC 2.5 and its congeners may help to prevent tissue damage during various chronic inflammatory diseases including periodontitis and may reduce the risks of systemic diseases associated with this local disorder.

  15. Imiquimod-induced psoriasis-like inflammation in differentiated Human keratinocytes: Its evaluation using curcumin.

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    Varma, Sandeep R; Sivaprakasam, Thiyagarajan O; Mishra, Abheepsa; Prabhu, Sunil; M, Rafiq; P, Rangesh

    2017-10-15

    Psoriasis is considered to be a systemic disease of immune dysfunction. It is still unclear what triggers the inflammatory cascade associated with psoriasis but recent evidences suggest the vital role of IL-23/IL-17A cytokine axis in etiology of psoriasis. Several studies have been conducted in psoriatic-like animal models but ethical issues and complexity surrounding it halts the screening of new anti-psoriatic drug candidates. Hence, in this study, we developed a new in-vitro model for psoriasis using imiquimod (IMQ) induced differentiated HaCaT cells which could be used for screening of new anti-psoriatic drug candidates. The differentiated HaCaT cells were treated with IMQ (100μM) to induce psoriatic like inflammation and its effect was investigated using a natural anti-psoriatic compound, curcumin. The proliferation of psoriatic-like cells was inhibited by curcumin at 25 and 50µM concentrations. The psoriatic-like cells decreased in number with increase in apoptotic and dead cells upon curcumin treatment. Curcumin inhibited the proliferation of IMQ-induced differentiated HaCaT cells (Psoriatic-like cells) by down-regulation of pro-inflammatory cytokines, interleukin-17, tumor necrosis factor-α, interferon-γ, and interleukin-6. Apart from this, curcumin significantly enhanced the skin-barrier function by up-regulation of involucrin (iNV) and filaggrin (FLG), the regulators of epidermal skin barrier. The IMQ-induced differentiated HaCaT in vitro model recapitulated some aspects of the psoriasis pathogenesis similar to murine model. Henceforth, we conclude that this model may be used for rapid screening of anti-psoriatic drug candidates and warrant further mechanistic studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

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    Rashid, Kahkashan; Sil, Parames C.

    2015-01-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  17. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

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    Rashid, Kahkashan; Sil, Parames C., E-mail: parames@jcbose.ac.in

    2015-02-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  18. Curcumin and salsalate suppresses colonic inflammation and procarcinogenic signaling in high-fat-fed, azoxymethane-treated mice

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    High-fat diets (HFDs) and excess adiposity increase proinflammatory cytokines in the colon, altering gene expression in a manner that promotes the development of colorectal cancer (CRC). Thus, compounds that reduce this biochemical inflammation are potential chemopreventive agents. Curcumin (CUR), a...

  19. Ameliorating Amyloid-β Fibrils Triggered Inflammation via Curcumin-Loaded Polymeric Nanoconstructs

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    Andrea Ameruoso

    2017-10-01

    Full Text Available Inflammation is a common hallmark in several diseases, including atherosclerosis, cancer, obesity, and neurodegeneration. In Alzheimer’s disease (AD, growing evidence directly correlates neuronal damage with inflammation of myeloid brain cells, such as microglia. Here, polymeric nanoparticles were engineered and characterized for the delivery of anti-inflammatory molecules to macrophages stimulated via direct incubation with amyloid-β fibers. 200 nm spherical polymeric nanoconstructs (SPNs and 1,000 nm discoidal polymeric nanoconstructs (DPNs were synthesized using poly(lactic-co-glycolic acid (PLGA, polyethylene glycol (PEG, and lipid chains as building blocks. First, the internalization propensity in macrophages of both nanoparticles was assessed via cytofluorimetric and confocal microscopy analyses, demonstrating that SPNs are by far more rapidly taken up as compared to DPNs (99.6 ± 0.11 vs 14.4 ± 0.06%, within 24 h. Then, Curcumin-loaded SPNs (Curc-SPNs were realized by encapsulating Curcumin, a natural anti-inflammatory molecule, within the PLGA core of SPNs. Finally, Curc-SPNs were shown to diminish up to 6.5-fold the production of pro-inflammatory cytokines—IL-1β; IL-6, and TNF-α—in macrophages stimulated via amyloid-β fibers. Although more sophisticated in vitro models and systematic analyses on the blood–brain barrier permeability are critically needed, these findings hold potential in the development of nanoparticles for modulating inflammation in AD.

  20. Preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed obese rats.

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    Maithilikarpagaselvi, Nachimuthu; Sridhar, Magadi Gopalakrishna; Swaminathan, Rathinam Palamalai; Sripradha, Ramalingam

    2016-06-01

    The present study investigated the beneficial effects of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed male Wistar rats. Five-month-old male Wistar rats (n=20) were divided into two groups (10 rats in each group). Among the two groups, one group received 30 % high-fat diet (HFD) and another group received 30 % HFD with curcumin (200 mg/kg body weight). Food intake, body weight and biochemical parameters were measured at the beginning and at the end of the study. After 10 weeks, oxidative stress parameters in skeletal muscle and hepatic triacylglycerol (TAG) content were estimated. Histological examinations of the liver samples were performed at the end of the experiment. High-fat feeding caused increase in body weight, liver and adipose tissue mass. Rats fed with HFD showed increased levels of fasting plasma glucose, insulin, Homeostasis Model Assessment for Insulin resistance (HOMA-IR), total cholesterol (TC), TAG, very low density lipoprotein cholesterol (VLDL-c) and decreased high-density lipoprotein cholesterol (HDL-c). There was also increase in the plasma inflammatory markers [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP)] and skeletal muscle oxidative stress parameters [malondialdehyde (MDA), total oxidant status (TOS)] in these rats. In addition, high-fat feeding increased liver TAG content and caused fat accumulation in the liver. Treatment with curcumin significantly reduced body weight, relative organ weights (liver, adipose tissue), glucose, insulin and HOMA-IR. Curcumin supplementation decreased plasma levels of TC, TAG, VLDL-c, TNF-α and increased HDL-c. Administration of curcumin also reduced MDA, TOS in skeletal muscle, hepatic TAG content and liver fat deposition. Curcumin supplementation improved HFD-induced dyslipidemia, oxidative stress, inflammation and insulin resistance.

  1. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

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    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...

  2. Curcumin protects dopaminergic neurons against inflammation-mediated damage and improves motor dysfunction induced by single intranigral lipopolysaccharide injection.

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    Sharma, Neha; Sharma, Sheetal; Nehru, Bimla

    2017-06-01

    model is by inhibiting glial activation. Therefore, curcumin could be a potential therapeutic agent for inflammation-driven neurodegenerative disorders like PD, and its neuroprotective role should be explored further.

  3. Evaluation of the Effects of Curcumin on Palm Inflammation and Level of Acute Phase Proteins in Arthritic Rats

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    F. Aghaei Borashan

    2008-10-01

    Full Text Available Background and ObjectivesRheumatoid arthritis (RA is a chronic inflammatory disease which is characterized by joint swelling, and synovial inflammation. C reactive protein (CRP and ceruloplasmin (CP are identified as important biomarkers of RA and various inflammatory diseases. Curcumin, a widely used yellow color spice is the most active component of Curcuma longa L (Turmeric. Curcumin contains potent anti-inflammatory and antioxidant properties. The goal of this study is evaluation of the anti-inflammatory effect of curcumin on arthritic palm of rats and levels of the CRP and CP in the blood samples of arthritis induced male albino Wistar rats.Methods Arthritis was induced by subcutaneous injection of Freund’s Complete Adjuvant (FCA into the palm of right rear foot of 8 different male albino Wistar rats. The rats were randomly divided into five groups after the injection. These groups were as follow: Group Ι, control normal rats Group II, carrier arthritic rats Group III, arthritic rats which were given 30mg/ kg of curcumin orally seven days prior to FCA injectionGroup IV, arthritic rats treated with 30mg/kg of curcumin Group V, arthritic rats treated with 3 mg/kg of indomethacin.All the groups except group III received oral treatment with curcumin seven days after FCA injection and the treatment was continued fourteen days thereafter. The rear foot thicknesses of all the rats were measured on days 1, 5, 10, 15, 20 after FCA injection. The rats were destroyed after 20th day and their blood samples were collected.ResultsThe results of this study indicate that curcumin significantly decreases swelling of the rats rear foot (p<0.05, and levels of the CRP and CP as compared to carrier arthritic rats (p<0.05. One-way variance analysis by ANOVA program and post test analysis by Tukey were used for analysis of the collected data. ConclusionEvaluation of the results of this experiment supports the anti-inflammatory, and possibly anti

  4. Evaluation of the Effects of Curcumin on Palm Inflammation and Level of Acute Phase Proteins in Arthritic Rats

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    F Aghaei Borashan

    2012-05-01

    Full Text Available

    Background and Objectives

    Rheumatoid arthritis (RA is a chronic inflammatory disease which is characterized by joint swelling, and synovial inflammation. C reactive protein (CRP and ceruloplasmin (CP are identified as important biomarkers of RA and various inflammatory diseases. Curcumin, a widely used yellow color spice is the most active component of Curcuma longa L (Turmeric. Curcumin contains potent anti-inflammatory and antioxidant properties. The goal of this study is evaluation of the anti-inflammatory effect of curcumin on arthritic palm of rats and levels of the CRP and CP in the blood samples of arthritis induced male albino Wistar rats.

     

    Methods

    Arthritis was induced by subcutaneous injection of Freund’s Complete Adjuvant (FCA into the palm of right rear foot of 8 different male albino Wistar rats. The rats were randomly divided into five groups after the injection. These groups were as follow:

    Group Ι, control normal rats

    Group II, carrier arthritic rats

    Group III, arthritic rats which were given 30mg/ kg of curcumin orally seven days prior to FCA injection

    Group IV, arthritic rats treated with 30mg/kg of curcumin

    Group V, arthritic rats treated with 3 mg/kg of indomethacin.

    All the groups except group III received oral treatment with curcumin seven days after FCA injection and the treatment was continued fourteen days thereafter. The rear foot thicknesses of all the rats were measured on days 1, 5, 10, 15, 20 after FCA injection. The rats were destroyed after 20th day and their blood samples were collected.

     

    Results

    The results of this study indicate that curcumin significantly decreases swelling of the rats rear foot (p<0.05, and levels of the CRP and CP as compared to carrier arthritic rats (p<0.05.

    One-way variance analysis

  5. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress.

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    Santos-Parker, Jessica R; Strahler, Talia R; Bassett, Candace J; Bispham, Nina Z; Chonchol, Michel B; Seals, Douglas R

    2017-01-03

    We hypothesized that curcumin would improve resistance and conduit artery endothelial function and large elastic artery stiffness in healthy middle-aged and older adults. Thirty-nine healthy men and postmenopausal women (45-74 yrs) were randomized to 12 weeks of curcumin (2000 mg/day Longvida®; n=20) or placebo (n=19) supplementation. Forearm blood flow response to acetylcholine infusions (FBF ACh ; resistance artery endothelial function) increased 37% following curcumin supplementation (107±13 vs. 84±11 AUC at baseline, P=0.03), but not placebo (P=0.2). Curcumin treatment augmented the acute reduction in FBF ACh induced by the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA; P=0.03), and reduced the acute increase in FBF ACh to the antioxidant vitamin C (P=0.02), whereas placebo had no effect (both P>0.6). Similarly, brachial artery flow-mediated dilation (conduit artery endothelial function) increased 36% in the curcumin group (5.7±0.4 vs. 4.4±0.4% at baseline, P=0.001), with no change in placebo (P=0.1). Neither curcumin nor placebo influenced large elastic artery stiffness (aortic pulse wave velocity or carotid artery compliance) or circulating biomarkers of oxidative stress and inflammation (all P>0.1). In healthy middle-aged and older adults, 12 weeks of curcumin supplementation improves resistance artery endothelial function by increasing vascular nitric oxide bioavailability and reducing oxidative stress, while also improving conduit artery endothelial function.

  6. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people

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    DiSilvestro Robert A

    2012-09-01

    Full Text Available Abstract Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old with a low dose of curcumin (80 mg/day in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19 or placebo (N = 19 for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.

  7. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

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    Zun-Jing Liu

    2013-01-01

    Full Text Available 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 PPARγ agonist in that it upregulated PPARγ expression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγ interacted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγ induced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

  8. Role of inflammation in the aging bones.

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    Abdelmagid, Samir M; Barbe, Mary F; Safadi, Fayez F

    2015-02-15

    Chronic inflammation in aging is characterized by increased inflammatory cytokines, bone loss, decreased adaptation, and defective tissue repair in response to injury. Aging leads to inherent changes in mesenchymal stem cell (MSC) differentiation, resulting in impaired osteoblastogenesis. Also, the pro-inflammatory cytokines increase with aging, leading to enhanced myelopoiesis and osteoclastogenesis. Bone marrow macrophages (BMMs) play pivotal roles in osteoblast differentiation, the maintenance of hematopoietic stem cells (HSCs), and subsequent bone repair. However, during aging, little is known about the role of macrophages in the differentiation and function of MSC and HSC. Aged mammals have higher circulating pro-inflammatory cytokines than young adults, supporting the hypothesis of increased inflammation with aging. This review will aid in the understanding of the potential role(s) of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in differentiation and function of osteoblasts and osteoclasts in relation to aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Dietary Curcumin Ameliorates Aging-Related Cerebrovascular Dysfunction through the AMPK/Uncoupling Protein 2 Pathway

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    Yunfei Pu

    2013-11-01

    Full Text Available Background/Aims: Age-related cerebrovascular dysfunction contributes to stroke, cerebral amyloid angiopathy, cognitive decline and neurodegenerative diseases. One pathogenic mechanism underlying this effect is increased oxidative stress. Up-regulation of mitochondrial uncoupling protein 2 (UCP2 plays a crucial role in regulating reactive oxygen species (ROS production. Dietary patterns are widely recognized as contributors to cardiovascular and cerebrovascular disease. In this study, we tested the hypothesis that dietary curcumin, which has an antioxidant effect, can improve aging-related cerebrovascular dysfunction via UCP2 up-regulation. Methods: The 24-month-old male rodents used in this study, including male Sprague Dawley (SD rats and UCP2 knockout (UCP2-/- and matched wild type mice, were given dietary curcumin (0.2%. The young control rodents were 6-month-old. Rodent cerebral artery vasorelaxation was detected by wire myograph. The AMPK/UCP2 pathway and p-eNOS in cerebrovascular and endothelial cells were observed by immunoblotting. Results: Dietary curcumin administration for one month remarkably restored the impaired cerebrovascular endothelium-dependent vasorelaxation in aging SD rats. In cerebral arteries from aging SD rats and cultured endothelial cells, curcumin promoted eNOS and AMPK phosphorylation, up-regulated UCP2 and reduced ROS production. These effects of curcumin were abolished by either AMPK or UCP2 inhibition. Chronic dietary curcumin significantly reduced ROS production and improved cerebrovascular endothelium-dependent relaxation in aging wild type mice but not in aging UCP2-/- mice. Conclusions: Curcumin improves aging-related cerebrovascular dysfunction via the AMPK/UCP2 pathway.

  10. Effect of curcumin on aged Drosophila melanogaster: a pathway prediction analysis.

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    Zhang, Zhi-guo; Niu, Xu-yan; Lu, Ai-ping; Xiao, Gary Guishan

    2015-02-01

    To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis. A total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Genes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

  11. Curcumin attenuates oxidative stress induced NFκB mediated inflammation and endoplasmic reticulum dependent apoptosis of splenocytes in diabetes.

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    Rashid, Kahkashan; Chowdhury, Sayantani; Ghosh, Sumit; Sil, Parames C

    2017-11-01

    The present study was aimed to determine the curative role of curcumin against diabetes induced oxidative stress and its associated splenic complications. Diabetes was induced in the experimental rats via the intraperitoneal administration of a single dose of STZ (65mgkg -1 body weight). Increased blood glucose and intracellular ROS levels along with decreased body weight, the activity of cellular antioxidant enzymes and GSH/GSSG ratio were observed in the diabetic animals. Histological assessment showed white pulp depletion and damaged spleen anatomy in these animals. Oral administration of curcumin at a dose of 100mgkg -1 body weight daily for 8weeks, however, restored these alterations. Investigation of the mechanism of hyperglycemia induced oxidative stress mediated inflammation showed upregulation of inflammatory cytokines, chemokines, adhesion molecules and increased translocation of NFκB into the nucleus. Moreover, ER stress dependent cell death showed induction of eIF2α and CHOP mediated signalling pathways as well as increment in the expression of GRP78, Caspase-12, Calpain-1, phospho JNK, phospho p38 and phospho p53 in the diabetic group. Alteration of Bax/Bcl-2 ratio; disruption of mitochondrial membrane potential, release of cytochrome-C from mitochondria and upregulation of caspase 3 along with the formation of characteristic DNA ladder in the diabetic animals suggest the involvement of mitochondria dependent apoptotic pathway in the splenic cells. Treatment with curcumin could, however, protect cells from inflammatory damage and ER as well as mitochondrial apoptotic death by restoring the alterations of these parameters. Our results suggest that curcumin has the potential to act as an anti-diabetic, anti-oxidant, anti-inflammatory and anti-apoptotic therapeutic against diabetes mediated splenic damage. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity.

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    Suzhen Dong

    Full Text Available BACKGROUND: Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. METHODOLOGY: We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. CONCLUSIONS: The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment in aged rats, which may be due to its diverse effects on genes related to growth and plasticity.

  13. Curcumin Enhances Neurogenesis and Cognition in Aged Rats: Implications for Transcriptional Interactions Related to Growth and Synaptic Plasticity

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    Mitchell, E. Siobhan; Xiu, Jin; Tiwari, Jyoti K.; Hu, Yinghe; Cao, Xiaohua; Zhao, Zheng

    2012-01-01

    Background Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. Methodology We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. Conclusions The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment in aged rats, which may be due to its diverse effects on genes related to growth and plasticity. PMID:22359574

  14. Aging, not age-associated inflammation, determines blood pressure and endothelial responses to acute inflammation.

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    Lane-Cordova, Abbi D; Ranadive, Sushant M; Kappus, Rebecca M; Cook, Marc D; Phillips, Shane A; Woods, Jeffrey A; Wilund, Kenneth R; Baynard, Tracy; Fernhall, Bo

    2016-12-01

    Aging is characterized by a state of chronic, low-grade inflammation that impairs vascular function. Acute inflammation causes additional decrements in vascular function, but these responses are not uniform in older compared with younger adults. We sought to determine if older adults with low levels of baseline inflammation respond to acute inflammation in a manner similar to younger adults. We hypothesized age-related differences in the vascular responses to acute inflammation, but that older adults with low baseline inflammation would respond similarly to younger adults. Inflammation was induced with an influenza vaccine in 96 participants [older = 67 total, 38 with baseline C-reactive protein (CRP) > 1.5 mg/l and 29 with CRP < 1.5 mg/l; younger = 29]; serum inflammatory markers IL-6 and CRP, blood pressure and flow-mediated dilation (FMD) were measured 24 and 48 h later. Younger adults increased IL-6 and CRP more than the collective older adult group and increased pulse pressure, whereas older adults decreased SBP and reduced pulse pressure. The entire cohort decreased FMD from 11.3 ± 0.8 to 8.3 ± 0.7 to 8.7 ± 0.7% in younger and from 5.8 ± 0.3 to 5.0 ± 0.4 to 4.7 ± 0.4% in older adults, P less than 0.05 for main effect. Older adult groups with differing baseline CRP had the same IL-6, blood pressure, and FMD response to acute inflammation, P less than 0.05 for all interactions, but the low-CRP group increased CRP at 24 and 48 h (from 0.5 ± 0.1 to 1.4 ± 0.2 to 1.7 ± 0.3 mg/l), whereas the high-CRP group did not (from 4.8 ± 0.5 to 5.4 ± 0.5 to 5.4 ± 0.6 mg/l), P less than 0.001 for interaction. Aging, not age-related chronic, low-grade inflammation, determines the vascular responses to acute inflammation.

  15. Targeting Inflammation-Induced Obesity and Metabolic Diseases by Curcumin and Other Nutraceuticals

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    Aggarwal, Bharat B.

    2011-01-01

    Extensive research within the past two decades has revealed that obesity, a major risk factor for type 2 diabetes, atherosclerosis, cancer, and other chronic diseases, is a proinflammatory disease. Several spices have been shown to exhibit activity against obesity through antioxidant and anti-inflammatory mechanisms. Among them, curcumin, a yellow pigment derived from the spice turmeric (an essential component of curry powder), has been investigated most extensively as a treatment for obesity and obesity-related metabolic diseases. Curcumin directly interacts with adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells. There, it suppresses the proinflammatory transcription factors nuclear factor-kappa B, signal transducer and activators of transcription-3, and Wnt/β-catenin, and it activates peroxisome proliferator-activated receptor-γ and Nrf2 cell-signaling pathways, thus leading to the downregulation of adipokines, including tumor necrosis factor, interleukin-6, resistin, leptin, and monocyte chemotactic protein-1, and the upregulation of adiponectin and other gene products. These curcumin-induced alterations reverse insulin resistance, hyperglycemia, hyperlipidemia, and other symptoms linked to obesity. Other structurally homologous nutraceuticals, derived from red chili, cinnamon, cloves, black pepper, and ginger, also exhibit effects against obesity and insulin resistance. PMID:20420526

  16. Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis.

    Science.gov (United States)

    Csaki, Constanze; Mobasheri, Ali; Shakibaei, Mehdi

    2009-01-01

    Currently available treatments for osteoarthritis (OA) are restricted to nonsteroidal anti-inflammatory drugs, which exhibit numerous side effects and are only temporarily effective. Thus novel, safe and more efficacious anti-inflammatory agents are needed for OA. Naturally occurring polyphenolic compounds, such as curcumin and resveratrol, are potent agents for modulating inflammation. Both compounds mediate their effects by targeting the NF-kappaB signalling pathway. We have recently demonstrated that in chondrocytes resveratrol modulates the NF-kappaB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-kappaB by inhibiting upstream kinases (Akt). However, the combinational effects of these compounds in chondrocytes has not been studied and/or compared with their individual effects. The aim of this study was to investigate the potential synergistic effects of curcumin and resveratrol on IL-1beta-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy. Treatment with curcumin and resveratrol suppressed NF-kappaB-regulated gene products involved in inflammation (cyclooxygenase-2, matrix metalloproteinase (MMP)-3, MMP-9, vascular endothelial growth factor), inhibited apoptosis (Bcl-2, Bcl-xL, and TNF-alpha receptor-associated factor 1) and prevented activation of caspase-3. IL-1beta-induced NF-kappaB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Ikappakappa and proteasome activation, inhibition of IkappaBalpha phosphorylation and degradation, and inhibition of nuclear translocation of NF-kappaB. The modulatory effects of curcumin and resveratrol on IL-1beta-induced expression of cartilage specific matrix and proinflammatory enzymes were mediated in part by the cartilage-specific transcription factor Sox-9. We propose that combining these natural compounds may be a useful strategy in OA therapy as compared with separate treatment with each individual

  17. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

    NARCIS (Netherlands)

    Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas

    Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced

  18. Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging

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    Daniela Frasca

    2017-08-01

    Full Text Available Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation. We also report data in the literature showing adipose tissue infiltration with immune cells and how these cells are recruited and contribute to local and systemic inflammation. We show that several types of immune cells infiltrate the adipose tissue and these include macrophages, neutrophils, NK cells, innate lymphoid cells, eosinophils, T cells, B1, and B2 cells. Our main focus is how the adipose tissue affects immune responses, in particular B cell responses and antibody production. The role of leptin in generating inflammation and decreased B cell responses is also discussed. We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies.

  19. A Neutraceutical by Design: The Clinical Application of Curcumin in Colonic Inflammation and Cancer

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    D. Soni

    2012-01-01

    Full Text Available Unquestionably, the natural food additive curcumin, derived from the colorful spice turmeric used in many Asian cuisines, possesses a diverse array of biological activities. These range from its anti-inflammatory, antineoplastic, and metabolic modifying properties to surprising roles in disorders ranging from Alzheimer's disease to cystic fibrosis. Its effects on growth factor receptors, signaling molecules, and transcription factors, together with its epigenetic effects are widely considered to be extraordinary. These pleiotropic attributes, coupled with its safety even when used orally at well over 10 g/day, are unparalleled amongst pharmacological agents. However, there is one drawback; apart from the luminal gastrointestinal tract where its pharmacology predicts that reasonable drug levels can be attained, its broader use is hampered by its poor solubility and hence near undetectable plasma levels. Medicinal chemistry and nanotechnology have resulted in the generation of compounds where the modified drug or its delivery system has improved matters such that this shortcoming has been addressed to some extent, with the surprising finding that it remains safe to use. It is predicted that either the parental compound or its derivatives may eventually find a place in the therapeutic management protocols of several conditions.

  20. Parainflammation, chronic inflammation and age-related macular degeneration

    Science.gov (United States)

    Chen, Mei; Xu, Heping

    2016-01-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune privileged tissue due to its unique anatomical and physiological properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate immune system, particularly microglia and the complement system, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), resulting in the breach of retinal immune privilege leading to the development of retinal lesions. This review discusses the basic principles of retinal innate immune responses to endogenous chronic insults in normal aging and in AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

  1. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress

    OpenAIRE

    Santos-Parker, Jessica R.; Strahler, Talia R.; Bassett, Candace J.; Bispham, Nina Z.; Chonchol, Michel B.; Seals, Douglas R.

    2017-01-01

    We hypothesized that curcumin would improve resistance and conduit artery endothelial function and large elastic artery stiffness in healthy middle-aged and older adults. Thirty-nine healthy men and postmenopausal women (45-74 yrs) were randomized to 12 weeks of curcumin (2000 mg/day Longvida?; n=20) or placebo (n=19) supplementation. Forearm blood flow response to acetylcholine infusions (FBFACh; resistance artery endothelial function) increased 37% following curcumin supplementation (107?13...

  2. 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.

  3. Curcumin ameliorates doxorubicin-induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats.

    Science.gov (United States)

    Benzer, Fulya; Kandemir, Fatih Mehmet; Ozkaraca, Mustafa; Kucukler, Sefa; Caglayan, Cuneyt

    2018-02-01

    Doxorubicin (DXR) is a highly effective drug for chemotherapy. However, cardiotoxicity reduces its clinical utility in humans. The present study aimed to assess the ameliorative effect of curcumin against DXR-induced cardiotoxicity in rats. Rats were subjected to oral treatment of curcumin (100 and 200 mg/kg body weight) for 7 days. Cardiotoxicity was induced by single intraperitoneal injection of DXR (40 mg/kg body weight) on the 5th day and the rats sacrificed on 8th day. Curcumin ameliorated DXR-induced lipid peroxidation, glutathione depletion, decrease in antioxidant (superoxide dismutase, catalase, and glutathione peroxidase) enzyme activities, and cardiac toxicity markers (CK-MB, LDH, and cTn-I). Curcumin also attenuated activities of Caspase-3, cyclooxygenase-2, inducible nitric oxide synthase, and levels of nuclear factor kappa-B, tumor necrosis factor-α, and interleukin-1β, and cardiac tissue damages that were induced by DXR. Moreover, curcumin decreased the expression of 8-OHdG and 3,3'-dityrosine. This study demonstrated that curcumin has a multi-cardioprotective effect due to its antioxidant, anti-inflammatory, and antiapoptotic properties. © 2018 Wiley Periodicals, Inc.

  4. Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis.

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    Luyan Guo

    Full Text Available Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9 and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS, tumor necrosis factor-α (TNF-α and monocyte chemoattractant protein-1 (MCP-1. HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K(+ current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K(+ channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K(+ channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K(+ current.

  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. Inflammation and premature aging in advanced chronic kidney disease.

    Science.gov (United States)

    Kooman, Jeroen P; Dekker, Marijke J; Usvyat, Len A; Kotanko, Peter; van der Sande, Frank M; Schalkwijk, Casper G; Shiels, Paul G; Stenvinkel, Peter

    2017-10-01

    Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed. Copyright © 2017 the American Physiological Society.

  7. Retinal Protection and Distribution of Curcumin in Vitro and in Vivo

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    Chiara B. M. Platania

    2018-06-01

    Full Text Available Diabetic retinopathy (DR, a secondary complication of diabetes, is a leading cause of irreversible blindness accounting for 5% of world blindness cases in working age. Oxidative stress and inflammation are considered causes of DR. Curcumin, a product with anti-oxidant and anti-inflammatory properties, is currently proposed as oral supplementation therapy for retinal degenerative diseases, including DR. In this study we predicted the pharmacodynamic profile of curcumin through an in silico approach. Furthermore, we tested the anti-oxidant and anti-inflammatory activity of curcumin on human retinal pigmented epithelial cells exposed to oxidative stress, human retinal endothelial and human retinal pericytes (HRPCs cultured with high glucose. Because currently marketed curcumin nutraceutical products have not been so far evaluated for their ocular bioavailability; we assessed retinal distribution of curcumin, following oral administration, in rabbit eye. Curcumin (10 μM decreased significantly (p < 0.01 ROS concentration and TNF-α release in retinal pigmented epithelial cells and retinal endothelial cells, respectively. The same curcumin concentration significantly (p < 0.01 protected retinal pericytes from high glucose damage as assessed by cell viability and LDH release. Among the tested formulations, only that containing a hydrophilic carrier provided therapeutic levels of curcumin in rabbit retina. In conclusion, our data suggest that curcumin, when properly formulated, may be of value in clinical practice to manage retinal diseases.

  8. Ghrelin receptor regulates adipose tissue inflammation in aging.

    Science.gov (United States)

    Lin, Ligen; Lee, Jong Han; Buras, Eric D; Yu, Kaijiang; Wang, Ruitao; Smith, C Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance.

  9. Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer.

    Directory of Open Access Journals (Sweden)

    Laxmidhar Das

    Full Text Available Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators. Previously we have delineated significant role of curcumin during its long term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes. Present study was designed to investigate long term effect of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals. Curcumin potentiated significant increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin modulated inflammation via upregulation of TGF-β and reciprocal regulation of iNOS and COX2. The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice.

  10. Aging, inflammation and depressive behavior: a review

    Directory of Open Access Journals (Sweden)

    Adriana Uzoni

    2015-04-01

    Full Text Available One of the most common co-morbidities of cerebrovascular disorders is neuroinflammation, a hallmark and decisive contributor to many central nervous system (CNS diseases. Although neuropathological conditions differ in etiology and in the way in which the inflammatory response is mounted, cellular and molecular mechanisms of neuroinflammation are probably similar in aging, hypertension, depression and cognitive impairment or after cerebral insult such as stroke. Moreover, a number of highly prevalent risk factors such as hypertension, diabetes and atherosclerosis are increasingly understood to act as “silent contributors” to neuroinflammation – not only establishing the condition as a central pathophysiological mechanism, but also constantly fuelling it. Mild, but continuous neuroinflammation can provide the ground for disorders such as cerebral small vessel disease (cSVD and subsequent dementia. Acute neuroinflammation, often in the context of traumatic or ischemic CNS lesions, aggravates the acute damage and can lead to depression, post-stroke dementia and neurodegeneration. All of these sequelae impair recovery and provide the ground for further cerebrovascular events. http://dx.doi.org/10.7175/rhc.v6i2.1170

  11. Low birth weight, adult BMI and inflammation in middle age

    DEFF Research Database (Denmark)

    Pedersen, Jolene Lee Masters; Rod, Naja Hulvej; Avlund, Kirsten

    2013-01-01

    This study examines the association between birthweight and adult BMI with inflammation in middle age measured by interleukin 6 (IL- 6), interleukin 10 (IL-10), interleukin 18 (IL-18), high sensitivity Creactive protein (hsCRP) and tumor necrosis factor alpha (tnf-α). The study is based on partic...

  12. Ghrelin receptor regulates adipose tissue inflammation in aging

    Science.gov (United States)

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth ho...

  13. Ageing and the telomere connection: An intimate relationship with inflammation.

    Science.gov (United States)

    Zhang, Jingwen; Rane, Grishma; Dai, Xiaoyun; Shanmugam, Muthu K; Arfuso, Frank; Samy, Ramar Perumal; Lai, Mitchell Kim Peng; Kappei, Dennis; Kumar, Alan Prem; Sethi, Gautam

    2016-01-01

    Telomeres are the heterochromatic repeat regions at the ends of eukaryotic chromosomes, whose length is considered to be a determinant of biological ageing. Normal ageing itself is associated with telomere shortening. Here, critically short telomeres trigger senescence and eventually cell death. This shortening rate may be further increased by inflammation and oxidative stress and thus affect the ageing process. Apart from shortened or dysfunctional telomeres, cells undergoing senescence are also associated with hyperactivity of the transcription factor NF-κB and overexpression of inflammatory cytokines such as TNF-α, IL-6, and IFN-γ in circulating macrophages. Interestingly, telomerase, a reverse transcriptase that elongates telomeres, is involved in modulating NF-κB activity. Furthermore, inflammation and oxidative stress are implicated as pre-disease mechanisms for chronic diseases of ageing such as neurodegenerative diseases, cardiovascular disease, and cancer. To date, inflammation and telomere shortening have mostly been studied individually in terms of ageing and the associated disease phenotype. However, the interdependent nature of the two demands a more synergistic approach in understanding the ageing process itself and for developing new therapeutic approaches. In this review, we aim to summarize the intricate association between the various inflammatory molecules and telomeres that together contribute to the ageing process and related diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Early-life inflammation, immune response and ageing.

    Science.gov (United States)

    Khan, Imroze; Agashe, Deepa; Rolff, Jens

    2017-03-15

    Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

  15. 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®.

  16. 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

  17. Curcumin and Boswellia serrata Modulate the Glyco-Oxidative Status and Lipo-Oxidation in Master Athletes

    Directory of Open Access Journals (Sweden)

    Nino Cristiano Chilelli

    2016-11-01

    Full Text Available Background: Chronic intensive exercise is associated with a greater induction of oxidative stress and with an excess of endogenous advanced glycation end-products (AGEs. Curcumin can reduce the accumulation of AGEs in vitro and in animal models. We examined whether supplementation with curcumin and Boswellia serrata (BSE gum resin for 3 months could affect plasma levels of markers of oxidative stress, inflammation, and glycation in healthy master cyclists. Methods. Forty-seven healthy male athletes were randomly assigned to Group 1, consisting of 22 subjects given a Mediterranean diet (MD alone (MD group, and Group 2 consisted of 25 subjects given a MD plus curcumin and BSE (curcumin/BSE group. Interleukin-6 (IL-6, tumor necrosis factor-α (TNFα, high-sensitivity c-reactive protein (hs-CRP, total AGE, soluble receptor for AGE (sRAGE, malondialdehyde (MDA, plasma phospholipid fatty acid (PPFA composition, and non-esterified fatty acids (NEFA were tested at baseline and after 12 weeks. Results: sRAGE, NEFA, and MDA decreased significantly in both groups, while only the curcumin/BSE group showed a significant decline in total AGE. Only the changes in total AGE and MDA differed significantly between the curcumin/BSE and MD groups. Conclusions. Our data suggest a positive effect of supplementation with curcumin and BSE on glycoxidation and lipid peroxidation in chronically exercising master athletes.

  18. Curcumin: An age-old anti-inflammatory and anti-neoplastic agent

    Directory of Open Access Journals (Sweden)

    Matthew C. Fadus

    2017-07-01

    Full Text Available Curcumin is a natural anti-inflammatory agent that has been used for treating medical conditions for many years. Several experimental and pharmacologic trials have demonstrated its efficacy in the role as an anti-inflammatory agent. Curcumin has been shown to be effective in treating chronic conditions like rheumatoid arthritis, inflammatory bowel disease, Alzheimer's and common malignancies like colon, stomach, lung, breast, and skin cancers. As treatments in medicine become more and more complex, the answer may be something simpler. This is a review article written with the objective to systematically analyze the wealth of information regarding the medical use of curcumin, the “curry spice”, and to understand the existent gaps which have prevented its widespread application in the medical community.

  19. A novel chemically modified curcumin reduces inflammation-mediated connective tissue breakdown in a rat model of diabetes: periodontal and systemic effects.

    Science.gov (United States)

    Elburki, M S; Moore, D D; Terezakis, N G; Zhang, Y; Lee, H-M; Johnson, F; Golub, L M

    2017-04-01

    Periodontal disease is the most common chronic inflammatory disease known to mankind (and the major cause of tooth loss in the adult population) and has also been linked to various systemic diseases, particularly diabetes mellitus. Based on the literature linking periodontal disease with diabetes in a "bidirectional manner", the objectives of the current study were to determine: (i) the effect of a model of periodontitis, complicated by diabetes, on mechanisms of tissue breakdown including bone loss; and (ii) the response of the combination of this local and systemic phenotype to a novel pleiotropic matrix metalloproteinase inhibitor, chemically modified curcumin (CMC) 2.24. Diabetes was induced in adult male rats by intravenous injection of streptozotocin (nondiabetic rats served as controls), and Escherichia coli endotoxin (lipopolysaccharide) was repeatedly injected into the gingiva to induce periodontitis. CMC 2.24 was administered by oral gavage (30 mg/kg) daily; untreated diabetic rats received vehicle alone. After 3 wk of treatment, the rats were killed, and gingiva, jaws, tibia and skin were collected. The maxillary jaws and tibia were dissected and radiographed. The gingival tissues of each experimental group (n = 6 rats/group) were pooled, extracted, partially purified and, together with individual skin samples, analyzed for matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography; MMP-8 was analyzed in gingival and skin tissue extracts, and in serum, by western blotting. The levels of three bone-resorptive cytokines [interleukin (IL)-1β, IL-6 and tumor necrosis factor-α], were measured in gingival tissue extracts and serum by ELISA. Systemic administration of CMC 2.24 to diabetic rats with endotoxin-induced periodontitis significantly inhibited alveolar bone loss and attenuated the severity of local and systemic inflammation. Moreover, this novel tri-ketonic phenylaminocarbonyl curcumin (CMC 2.24) appeared to reduce the pathologically excessive

  20. Mechanism of Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2012-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

  1. Mechanism of Inflammation in Age-Related Macular Degeneration

    Science.gov (United States)

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  2. Human T cell immunosenescence and inflammation in aging.

    Science.gov (United States)

    Bektas, Arsun; Schurman, Shepherd H; Sen, Ranjan; Ferrucci, Luigi

    2017-10-01

    The aging process is driven by a finite number of inter-related mechanisms that ultimately lead to the emergence of characteristic phenotypes, including increased susceptibility to multiple chronic diseases, disability, and death. New assays and analytical tools have become available that start to unravel some of these mechanisms. A prevailing view is that aging leads to an imbalance between stressors and stress-buffering mechanisms that causes loss of compensatory reserve and accumulation of unrepaired damage. Central to this paradigm are changes in the immune system and the chronic low-grade proinflammatory state that affect many older individuals, even when they are apparently healthy and free of risk factors. Independent of chronological age, high circulating levels of proinflammatory markers are associated with a high risk of multiple adverse health outcomes in older persons. In this review, we discuss current theories about causes and consequences of the proinflammatory state of aging, with a focus on changes in T cell function. We examine the role of NF-κB activation and its dysregulation and how NF-κB activity differs among subgroups of T cells. We explore emerging hypotheses about immunosenescence and changes in T cell behavior with age, including consideration of the T cell antigen receptor and regulatory T cells (T regs ). We conclude by illustrating how research using advanced technology is uncovering clues at the core of inflammation and aging. Some of the preliminary work in this field is already improving our understanding of the complex mechanisms by which immunosenescence of T cells is intertwined during human aging. © Society for Leukocyte Biology.

  3. Early age exposure to moisture damage and systemic inflammation at the age of 6 years.

    Science.gov (United States)

    Karvonen, A M; Tischer, C; Kirjavainen, P V; Roponen, M; Hyvärinen, A; Illi, S; Mustonen, K; Pfefferle, P I; Renz, H; Remes, S; Schaub, B; von Mutius, E; Pekkanen, J

    2018-05-01

    Cross-sectional studies have shown that exposure to indoor moisture damage and mold may be associated with subclinical inflammation. Our aim was to determine whether early age exposure to moisture damage or mold is prospectively associated with subclinical systemic inflammation or with immune responsiveness in later childhood. Home inspections were performed in children's homes in the first year of life. At age 6 years, subclinical systemic inflammation was measured by serum C-reactive protein (CRP) and blood leukocytes and immune responsiveness by ex vivo production of interleukin 1-beta (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) in whole blood cultures without stimulation or after 24 hours stimulation with phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG) in 251-270 children. Moisture damage in child's main living areas in infancy was not significantly associated with elevated levels of CRP or leukocytes at 6 years. In contrast, there was some suggestion for an effect on immune responsiveness, as moisture damage with visible mold was positively associated with LPS-stimulated production of TNF-α and minor moisture damage was inversely associated with PI-stimulated IL-1β. While early life exposure to mold damage may have some influence on later immune responsiveness, it does not seem to increase subclinical systemic inflammation in later life. © 2018 National Institute for Health and Welfare, Finland Indoor Air published by John Wiley & Sons Ltd.

  4. Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells.

    Science.gov (United States)

    Dai, Chongshan; Li, Bin; Zhou, Yan; Li, Daowen; Zhang, Shen; Li, Hui; Xiao, Xilong; Tang, Shusheng

    2016-09-01

    The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor -kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Curcumin, an active constiuent of the ancient medicinal herb Curcuma longa L.: some uses and the establishment and biological basis of medical efficacy.

    Science.gov (United States)

    Witkin, Jeffrey M; Li, Xia

    2013-06-01

    The root extract, curcumin (diferuloylmethane), is a constituent of the ancient herbal medicine Jiawei-Xiaoyaosan that has been used for dyspepsia, stress, and mood disorders. Curcumin engenders a diverse profile of biological actions that result in changes in oxidative stress, inflammation, and cell-death pathways. Combined with its historical use in medical practice and its safety profile, curcumin has been studied for its potential therapeutic applications in cancer, aging, endocrine, immunological, gastrointestinal, and cardiac diseases. In addition, data in animal models and in humans have also begun to be collected in stroke, Alzheimer's disease, and Parkinson's disease. A compelling new body of literature is also mounting to support the efficacy of curcumin in stress and mood disorders. Current understanding of the biological basis for antidepressant-relevant biochemical and behavioral changes shows convergence with some mechanisms known for standard antidepressants. In addition, the mechanisms of the antidepressant-like pharmacology of curcumin also appear to overlap with those of other disease states. Thus, ancient wisdom might be built into this interesting and newly-appreciated natural molecule. Although curcumin is a primary ingredient in anti-aging pills, cosmetic creams, eye treatments, diet products, etc, a key hurdle to the development of curcumin for disease treatment and prevention is overcoming its low oral bioavailability. Although multiple approaches to this problem are being examined, a solution to the bioavailability issue will be needed to ensure appropriate tissue exposures of curcumin in clinical investigation. Progress in this regard is underway.

  6. PPARgamma agonist curcumin reduces the amyloid-beta-stimulated inflammatory responses in primary astrocytes.

    Science.gov (United States)

    Wang, Hong-Mei; Zhao, Yan-Xin; Zhang, Shi; Liu, Gui-Dong; Kang, Wen-Yan; Tang, Hui-Dong; Ding, Jian-Qing; Chen, Sheng-Di

    2010-01-01

    Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Accumulating data indicate that astrocytes play an important role in the neuroinflammation related to the pathogenesis of AD. It has been shown that microglia and astrocytes are activated in AD brain and amyloid-beta (Abeta) can increase the expression of cyclooxygenase 2 (COX-2), interleukin-1, and interleukin-6. Suppressing the inflammatory response caused by activated astrocytes may help to inhibit the development of AD. Curcumin is a major constituent of the yellow curry spice turmeric and proved to be a potential anti-inflammatory drug in arthritis and colitis. There is a low age-adjusted prevalence of AD in India, a country where turmeric powder is commonly used as a culinary compound. Curcumin has been shown to suppress activated astroglia in amyloid-beta protein precursor transgenic mice. The real mechanism by which curcumin inhibits activated astroglia is poorly understood. Here we report that the expression of COX-2 and glial fibrillary acidic protein were enhanced and that of peroxisome proliferator-activated receptor gamma (PPARgamma) was decreased in Abeta(25-35)-treated astrocytes. In line with these results, nuclear factor-kappaB translocation was increased in the presence of Abeta. All these can be reversed by the pretreatment of curcumin. Furthermore, GW9662, a PPARgamma antagonist, can abolish the anti-inflammatory effect of curcumin. These results show that curcumin might act as a PPARgamma agonist to inhibit the inflammation in Abeta-treated astrocytes.

  7. Obesity and Age-Related Changes in Markers of Oxidative Stress and Inflammation Across Four Generations

    NARCIS (Netherlands)

    Hulsegge, Gerben; Herber-Gast, Gerrie-Cor M; Spijkerman, Annemieke M W; Picavet, H. Susan J; van der Schouw, Yvonne T; Bakker, Stephan J L; Gansevoort, Ron T; Dollé, Martijn E T; Smit, Henriette A; Monique Verschuren, W M

    OBJECTIVE: The prevalence of obesity increases with age and is higher in each younger generation (unfavorable generation shift). This may influence patterns of oxidative stress and inflammation. Age-related changes and generation shifts in markers of oxidative stress and inflammation were

  8. Obesity and Age-Related Changes in Markers of Oxidative Stress and Inflammation Across Four Generations

    NARCIS (Netherlands)

    Hulsegge, Gerben; Herber-Gast, Gerrie-Cor M; Spijkerman, Annemieke M W; Susan, H; Picavet, J; van der Schouw, Yvonne T; Bakker, Stephan J L; Gansevoort, Ron T; Dollé, Martijn E T; Smit, Henriette A; Monique Verschuren, W M

    ObjectiveThe prevalence of obesity increases with age and is higher in each younger generation (unfavorable generation shift). This may influence patterns of oxidative stress and inflammation. Age-related changes and generation shifts in markers of oxidative stress and inflammation were

  9. 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.

  10. Effectiveness of Topical Curcumin for Treatment of Mastitis in Breastfeeding Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Raha Afshariani

    2014-09-01

    Full Text Available Objective: To determine the efficacy of topical curcumin in reducing breast inflammation in women suffering from lactational mastitis. Methods: A randomized double-blind, placebo-controlled study including 63 breastfeeding women with lactational mastitis were randomly assigned to receive curcumin topical cream, one pump every 8 hours for 3 days (n=32 or topical moisturizer as placebo (n=31. Using an index for severity of breast inflammation, all of the patients had moderate breast inflammation before entering the study. The outcome of treatment was evaluated using the same index at 24, 48 and 72 hours of starting the treatment. Results: There was no significant difference between two study groups regarding the baseline characteristics such as age (p=0.361 and duration of lactation (p=0.551. After 72-hour of therapy, patients in curcumin groups had significantly lower rate of moderate (p=0.019 and mild (p=0.002 mastitis. Patients in curcumin group had significantly lower scores for tension (p<0.001, erythema (p<0.001 and pain (p<0.001, after 72-hour of treatment. Conclusion: The results of the current study indicate that topical preparation of curcumin successfully decrease the markers of lactational mastitis such as pain, breast tension and erythema within 72 hours of administration without side effects. Thus, topical preparation of curcumin could be safely administered for those suffering from lactational mastitis after excluding infectious etiologies.

  11. 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.

  12. The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

    Directory of Open Access Journals (Sweden)

    Omoigui Sota

    2007-03-01

    Full Text Available Abstract We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation.

  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. 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.

  15. Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

    Science.gov (United States)

    Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

    2009-12-01

    Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

  16. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs.

    Science.gov (United States)

    McCubrey, James A; Lertpiriyapong, Kvin; Steelman, Linda S; Abrams, Steve L; Yang, Li V; Murata, Ramiro M; Rosalen, Pedro L; Scalisi, Aurora; Neri, Luca M; Cocco, Lucio; Ratti, Stefano; Martelli, Alberto M; Laidler, Piotr; Dulińska-Litewka, Joanna; Rakus, Dariusz; Gizak, Agnieszka; Lombardi, Paolo; Nicoletti, Ferdinando; Candido, Saverio; Libra, Massimo; Montalto, Giuseppe; Cervello, Melchiorre

    2017-06-12

    Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric ( Curcuma longa ). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants ( e.g., Coptis chinensis ) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health.

  17. Curcumin ameliorates hepatic fibrosis in type 2 diabetes mellitus – insights into its mechanisms of action

    Science.gov (United States)

    Stefanska, B

    2012-01-01

    A wide variety of beneficial effects have been attributed to curcumin, a major polyphenol from the golden spice Curcuma longa known as turmeric, including amelioration of severe complications of type 2 diabetes such as hepatic fibrosis, retinopathy, neuropathy and nephropathy. In the present issue of BJP, Lin and colleagues reveal new mechanisms by which curcumin inhibits the activation of hepatic stellate cells in vitro, a hallmark of non-alcoholic steatohepatitis and hepatic fibrogenesis associated with type 2 diabetes mellitus. They demonstrated that curcumin suppresses the advanced glycation end-products (AGEs)-mediated induction of the receptor for AGEs (RAGE) gene expression by increasing PPARγ activity and stimulating de novo synthesis of glutathione. As a result, downstream elements of RAGE-activated pathways are inhibited, which prevents oxidative stress, inflammation and hepatic stellate cell activation. This report suggests that curcumin may have potential as an anti-fibrotic agent in type 2 diabetes and opens the door to the evaluation of curcumin therapeutic effects in liver conditions of different aetiology and in other disorders linked to the impairment of PPARγ activity, such as obesity and atherosclerosis. LINKED ARTICLE This article is a commentary on Lin et al., pp. 2212–2227 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.01910.x PMID:22452372

  18. Curcumin ameliorates hepatic fibrosis in type 2 diabetes mellitus - insights into its mechanisms of action.

    Science.gov (United States)

    Stefanska, B

    2012-08-01

    A wide variety of beneficial effects have been attributed to curcumin, a major polyphenol from the golden spice Curcuma longa known as turmeric, including amelioration of severe complications of type 2 diabetes such as hepatic fibrosis, retinopathy, neuropathy and nephropathy. In the present issue of BJP, Lin and colleagues reveal new mechanisms by which curcumin inhibits the activation of hepatic stellate cells in vitro, a hallmark of non-alcoholic steatohepatitis and hepatic fibrogenesis associated with type 2 diabetes mellitus. They demonstrated that curcumin suppresses the advanced glycation end-products (AGEs)-mediated induction of the receptor for AGEs (RAGE) gene expression by increasing PPARγ activity and stimulating de novo synthesis of glutathione. As a result, downstream elements of RAGE-activated pathways are inhibited, which prevents oxidative stress, inflammation and hepatic stellate cell activation. This report suggests that curcumin may have potential as an anti-fibrotic agent in type 2 diabetes and opens the door to the evaluation of curcumin therapeutic effects in liver conditions of different aetiology and in other disorders linked to the impairment of PPARγ activity, such as obesity and atherosclerosis. This article is a commentary on Lin et al., pp. 2212-2227 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.01910.x. © 2012 The Author. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  19. Age-related ventricular-vascular coupling during acute inflammation in humans: Effect of physical activity.

    Science.gov (United States)

    Lane, Abbi D; Kappus, Rebecca M; Bunsawat, Kanokwan; Ranadive, Sushant M; Yan, Huimin; Phillips, Shane; Baynard, Tracy; Woods, Jeffrey A; Motl, Robert; Fernhall, Bo

    2015-07-01

    Aging is commonly accompanied by increased arterial and ventricular stiffness (determined by arterial elastance (Ea) and ventricular elastance (Elv)), augmented ventricular-vascular coupling ratios (Ea/Elv) and systemic inflammation. Acute inflammation may impact ventricular-vascular coupling and predispose older adults to cardiovascular events. However, physically active older adults have more compliant large arteries and left ventricles and lower inflammation than sedentary older adults. We hypothesized that acute inflammation would alter Ea, Elv, and Ea/Elv more in older versus younger adults but that higher levels of physical activity would attenuate inflammation-induced changes. End-systolic and central blood pressures were obtained using applanation tonometry before and at 24 and 48 h post-influenza vaccination in 24 older and 38 younger adults. Ultrasonography was used to measure ventricular volumes and other indices of cardiac performance. Physical activity was measured with accelerometry. Ea and Ea/Elv were maintained (p > 0.05), but Elv was reduced (p  0.05) except in the most active group of seniors (p < 0.05). Aging did not affect the elastance responses but did affect central blood pressure and other ventricular systolic responses to acute inflammation. Aging, not physical activity, appears to modulate cardiovascular responses to acute inflammation, except in the most active older adults. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  20. 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...

  1. Curcumin for maintenance of remission in ulcerative colitis.

    Science.gov (United States)

    Kumar, Sushil; Ahuja, Vineet; Sankar, Mari Jeeva; Kumar, Atul; Moss, Alan C

    2012-10-17

    Ulcerative colitis (UC) is a chronic inflammatory condition of the colon characterized by episodes of disease activity and symptom-free remission.There is paucity of evidence regarding the efficacy and safety of complementary or alternative medicines for the management of UC. Curcumin, an anti-inflammatory agent, has been used in many chronic inflammatory conditions such as rheumatoid arthritis, esophagitis and post-surgical inflammation. The efficacy of this agent for maintenance of remission in patients with UC has not been systematically evaluated. The primary objective was to systematically review the efficacy and safety of curcumin for maintenance of remission in UC. A computer-assisted literature search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Inflammatory Bowel Disease Specialized Trial Register was performed on July 11, 2012 to identify relevant publications. Proceedings from major gastroenterology meetings and references from published articles were also searched to identify additional studies. Randomized placebo-controlled trials (RCT) of curcumin for maintenance of remission in UC were included. Studies included patients (of any age) who were in remission at the time of recruitment. Co-interventions were allowed. Two authors independently extracted data and assessed the methodological quality of the included studies using the Cochrane risk of bias tool. Data were analyzed using Review Manager (RevMan 5.1). We calculated the relative risk (RR) and 95% confidence interval (95% CI) for each dichotomous outcome. For continuous outcomes we calculated the mean difference (MD) and 95% CI. Only one trial (89 patients) fulfilled the inclusion criteria. This trial randomized 45 patients to curcumin and 44 patients to placebo. All patients received treatment with sulfasalazine or mesalamine. The study was rated as low risk of bias. Curcumin was administered orally in a dose of 2 g/day for six months. Fewer patients

  2. Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways in Treating Age-Related Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Panchanan Maiti

    2018-05-01

    Full Text Available Progressive accumulation of misfolded amyloid proteins in intracellular and extracellular spaces is one of the principal reasons for synaptic damage and impairment of neuronal communication in several neurodegenerative diseases. Effective treatments for these diseases are still lacking but remain the focus of much active investigation. Despite testing several synthesized compounds, small molecules, and drugs over the past few decades, very few of them can inhibit aggregation of amyloid proteins and lessen their neurotoxic effects. Recently, the natural polyphenol curcumin (Cur has been shown to be a promising anti-amyloid, anti-inflammatory and neuroprotective agent for several neurodegenerative diseases. Because of its pleotropic actions on the central nervous system, including preferential binding to amyloid proteins, Cur is being touted as a promising treatment for age-related brain diseases. Here, we focus on molecular targeting of Cur to reduce amyloid burden, rescue neuronal damage, and restore normal cognitive and sensory motor functions in different animal models of neurodegenerative diseases. We specifically highlight Cur as a potential treatment for Alzheimer’s, Parkinson’s, Huntington’s, and prion diseases. In addition, we discuss the major issues and limitations of using Cur for treating these diseases, along with ways of circumventing those shortcomings. Finally, we provide specific recommendations for optimal dosing with Cur for treating neurological diseases.

  3. Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors.

    Science.gov (United States)

    Henry, Curtis J; Casás-Selves, Matias; Kim, Jihye; Zaberezhnyy, Vadym; Aghili, Leila; Daniel, Ashley E; Jimenez, Linda; Azam, Tania; McNamee, Eoin N; Clambey, Eric T; Klawitter, Jelena; Serkova, Natalie J; Tan, Aik Choon; Dinarello, Charles A; DeGregori, James

    2015-12-01

    The incidence of cancer is higher in the elderly; however, many of the underlying mechanisms for this association remain unexplored. Here, we have shown that B cell progenitors in old mice exhibit marked signaling, gene expression, and metabolic defects. Moreover, B cell progenitors that developed from hematopoietic stem cells (HSCs) transferred from young mice into aged animals exhibited similar fitness defects. We further demonstrated that ectopic expression of the oncogenes BCR-ABL, NRAS(V12), or Myc restored B cell progenitor fitness, leading to selection for oncogenically initiated cells and leukemogenesis specifically in the context of an aged hematopoietic system. Aging was associated with increased inflammation in the BM microenvironment, and induction of inflammation in young mice phenocopied aging-associated B lymphopoiesis. Conversely, a reduction of inflammation in aged mice via transgenic expression of α-1-antitrypsin or IL-37 preserved the function of B cell progenitors and prevented NRAS(V12)-mediated oncogenesis. We conclude that chronic inflammatory microenvironments in old age lead to reductions in the fitness of B cell progenitor populations. This reduced progenitor pool fitness engenders selection for cells harboring oncogenic mutations, in part due to their ability to correct aging-associated functional defects. Thus, modulation of inflammation--a common feature of aging--has the potential to limit aging-associated oncogenesis.

  4. Energy metabolism and inflammation in brain aging and Alzheimer's disease.

    Science.gov (United States)

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-11-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. The role of vitamin K in chronic aging diseases: inflammation, cardiovascular disease and osteoarthritis

    Science.gov (United States)

    Vitamin K is an enzyme cofactor required for the carboxylation of vitamin K dependent proteins, several of which have been implicated in diseases of aging. Inflammation is recognized as a crucial component of many chronic aging diseases, and evidence suggests vitamin K has an anti-inflammatory actio...

  6. Short-term Treatment of Daumone Improves Hepatic Inflammation in Aged Mice

    OpenAIRE

    Park, Jong Hee; Ha, Hunjoo

    2015-01-01

    Chronic inflammation has been proposed as one of the main molecular mechanisms of aging and age-related diseases. Although evidence in humans is limited, short-term calorie restriction (CR) has been shown to have anti-inflammatory effects in aged experimental animals. We reported on the long-term treatment of daumone, a synthetic pheromone secreted by Caenorhabditis elegans in an energy deficient environment, extends the life-span and attenuates liver injury in aged mice. The present study ex...

  7. 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.

  8. 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 ...

  9. The effect of aging on atherosclerotic plaque inflammation and molecular calcification: A PET CT imaging study

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Simonsen, Jane Angel

    Aim: Aging is an important independent risk factor for the inception and maturation of atherosclerotic plaques. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and molecular calcification. Methods: Thirteen healthy volunteers without traditional......SUV) [Mean SUVAORTA - Mean SUVBLOOD POOL]. Furthermore, the average maximum 18F-NaF cSUV was determined in the coronary arteries. Calculating regression and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18F-FDG avidity. A second order...... polynomial regression established that aging is a strong predictor of the degree of aortic plaque inflammation (R2 = 0.71, F statistic = 11.98, P = 0.002). A linear relationship was observed between aging and molecular calcification. Linear regression established that aging is a predictor of both the degree...

  10. Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation.

    Science.gov (United States)

    Ramasamy, Ravichandran; Vannucci, Susan J; Yan, Shirley Shi Du; Herold, Kevan; Yan, Shi Fang; Schmidt, Ann Marie

    2005-07-01

    The products of nonenzymatic glycation and oxidation of proteins and lipids, the advanced glycation end products (AGEs), accumulate in a wide variety of environments. AGEs may be generated rapidly or over long times stimulated by a range of distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. A critical property of AGEs is their ability to activate receptor for advanced glycation end products (RAGE), a signal transduction receptor of the immunoglobulin superfamily. It is our hypothesis that due to such interaction, AGEs impart a potent impact in tissues, stimulating processes linked to inflammation and its consequences. We hypothesize that AGEs cause perturbation in a diverse group of diseases, such as diabetes, inflammation, neurodegeneration, and aging. Thus, we propose that targeting this pathway may represent a logical step in the prevention/treatment of the sequelae of these disorders.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging.

    Science.gov (United States)

    Ghosh, Amiya K; O'Brien, Martin; Mau, Theresa; Yung, Raymond

    2017-09-07

    Adipose tissue (AT) inflammation is a central mechanism for metabolic dysfunction in both diet-induced obesity and age-associated obesity. Studies in diet-induced obesity have characterized the role of Fetuin A (Fet A) in Free Fatty Acids (FFA)-mediated TLR4 activation and adipose tissue inflammation. However, the role of Fet A & TLR4 in aging-related adipose tissue inflammation is unknown. In the current study, analysis of epidymymal fat pads of C57/Bl6 male mice, we found that, in contrast to data from diet-induced obesity models, adipose tissue from aged mice have normal Fet A and TLR4 expression. Interestingly, aged TLR4-deficient mice have diminished adipose tissue inflammation compared to normal controls. We further demonstrated that reduced AT inflammation in old TLR4-deficient mice is linked to impaired ER stress, augmented autophagy activity, and diminished senescence phenomenon. Importantly, old TLR4-deficient mice have improved glucose tolerance compared to age-matched wild type mice, suggesting that the observed reduced AT inflammation in aged TLR4-deficient mice has important physiological consequences. Taken together, our present study establishes novel aspect of aging-associated AT inflammation that is distinct from diet-induced AT inflammation. Our results also provide strong evidence that TLR4 plays a significant role in promoting aging adipose tissue inflammation.

  17. Tart cherry supplementation improves working memory, hippocampal inflammation and autophagy in aged rats

    Science.gov (United States)

    High consumption of fruits and vegetables has been associated with reduced risk of debilitating diseases and improved cognition in aged populations. These beneficial effects have been attributed to the antioxidant/anti-inflammation properties of phytochemicals found in fruits and vegetables. Tart ch...

  18. Anti-aging drugs reduce hypothalamic inflammation in a sex-specific manner.

    Science.gov (United States)

    Sadagurski, Marianna; Cady, Gillian; Miller, Richard A

    2017-08-01

    Aging leads to hypothalamic inflammation, but does so more slowly in mice whose lifespan has been extended by mutations that affect GH/IGF-1 signals. Early-life exposure to GH by injection, or to nutrient restriction in the first 3 weeks of life, also modulate both lifespan and the pace of hypothalamic inflammation. Three drugs extend lifespan of UM-HET3 mice in a sex-specific way: acarbose (ACA), 17-α-estradiol (17αE2), and nordihydroguaiaretic acid (NDGA), with more dramatic longevity increases in males in each case. In this study, we examined the effect of these anti-aging drugs on neuro-inflammation in hypothalamus and hippocampus. We found that age-associated hypothalamic inflammation is reduced in males but not in females at 12 months of age by ACA and 17αE2 and at 22 months of age in NDGA-treated mice. The three drugs blocked indices of hypothalamic reactive gliosis associated with aging, such as Iba-1-positive microglia and GFAP-positive astrocytes, as well as age-associated overproduction of TNF-α. This effect was not observed in drug-treated female mice or in the hippocampus of the drug-treated animals. On the other hand, caloric restriction (CR; an intervention that extends the lifespan in both sexes) significantly reduced hypothalamic microglia and TNF-α in both sexes at 12 months of age. Together, these results suggest that the extent of drug-induced changes in hypothalamic inflammatory processes is sexually dimorphic in a pattern that parallels the effects of these agents on mouse longevity and that mimics the changes seen, in both sexes, of long-lived nutrient restricted or mutant mice. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  19. Inflammation and infection do not promote arterial aging and cardiovascular disease risk factors among lean horticulturalists.

    Directory of Open Access Journals (Sweden)

    Michael Gurven

    2009-08-01

    Full Text Available Arterial aging is well characterized in industrial populations, but scantly described in populations with little access to modern medicine. Here we characterize health and aging among the Tsimane, Amazonian forager-horticulturalists with short life expectancy, high infectious loads and inflammation, but low adiposity and robust physical fitness. Inflammation has been implicated in all stages of arterial aging, atherogenesis and hypertension, and so we test whether greater inflammation associates with atherosclerosis and CVD risk. In contrast, moderate to vigorous daily activity, minimal obesity, and low fat intake predict minimal CVD risk among older Tsimane.Peripheral arterial disease (PAD, based on the Ankle-Brachial Index (ABI, and hypertension were measured in Tsimane adults, and compared with rates from industrialized populations. No cases of PAD were found among Tsimane and hypertension was comparatively low (prevalence: 3.5%, 40+; 23%, 70+. Markers of infection and inflammation were much higher among Tsimane than among U.S. adults, whereas HDL was substantially lower. Regression models examine associations of ABI and BP with biomarkers of energy balance and metabolism and of inflammation and infection. Among Tsimane, obesity, blood lipids, and disease history were not significantly associated with ABI. Unlike the Tsimane case, higher cholesterol, C-reactive protein, leukocytes, cigarette smoking and systolic pressure among North Americans are all significantly associated with lower ABI.Inflammation may not always be a risk factor for arterial degeneration and CVD, but instead may be offset by other factors: healthy metabolism, active lifestyle, favorable body mass, lean diet, low blood lipids and cardiorespiratory health. Other possibilities, including genetic susceptibility and the role of helminth infections, are discussed. The absence of PAD and CVD among Tsimane parallels anecdotal reports from other small-scale subsistence

  20. Biomarkers of oxidative stress and inflammation after wood smoke exposure in a reconstructed Viking Age house

    DEFF Research Database (Denmark)

    Jensen, Annie; Karottki, Dorina Gabriela; Christensen, Jannie Marie

    2014-01-01

    Exposure to particles from combustion of wood is associated with respiratory symptoms, whereas there is limited knowledge about systemic effects. We investigated effects on systemic inflammation, oxidative stress and DNA damage in humans who lived in a reconstructed Viking Age house, with indoor...... expression levels of CD11b, CD49d, and CD62L on monocytes after the stay in the house. In conclusion, even a high inhalation exposure to wood smoke was associated with limited systemic effects on markers of oxidative stress, DNA damage, inflammation, and monocyte activation....

  1. Induction of hyperandrogenism in lean reproductive-age women stimulates proatherogenic inflammation.

    Science.gov (United States)

    González, F; Sreekumaran Nair, K; Basal, E; Bearson, D M; Schimke, J M; Blair, H E

    2015-06-01

    We determined the effect of hyperandrogenemia as observed in polycystic ovary syndrome (PCOS) on fasting and glucose-stimulated proatherogenic inflammation markers in lean healthy reproductive-age women. Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n=8 each) for 5 days. Interleukin-6 (IL-6) mRNA and IL-6 release from mononuclear cells (MNC), plasma IL-6 and C-reactive protein (CRP), and MNC-derived (matrix metalloproteinase-2) MMP-2 protein were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment. Before treatment, subjects receiving dehydroepinadrosterone (DHEA) or placebo exhibited no differences in androgens, or any proatherogenic inflammation markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate (DHEA-S), and increased the percent change from baseline in fasting IL-6 mRNA, IL-6 release, plasma IL-6, and CRP and MMP-2 protein. However, there were no differences in any of the proatherogenic inflammation markers following glucose ingestion after DHEA administration. We conclude that in lean reproductive-age women, proatherogenic inflammation in the fasting state increases after raising circulating androgens to levels observed in PCOS. However, this hyperandrogenemia-induced MNC activation does not provoke a similar response to subsequent glucose ingestion. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice.

    Science.gov (United States)

    Kim, In Hee; Xu, Jun; Liu, Xiao; Koyama, Yukinori; Ma, Hsiao-Yen; Diggle, Karin; You, Young-Hyun; Schilling, Jan M; Jeste, Dilip; Sharma, Kumar; Brenner, David A; Kisseleva, Tatiana

    2016-08-01

    We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between old-aged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or

  3. 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.

  4. Ageing-Associated Oxidative Stress and Inflammation Are Alleviated by Products from Grapes

    Directory of Open Access Journals (Sweden)

    K. S. Petersen

    2016-01-01

    Full Text Available Advanced age is associated with increased incidence of a variety of chronic disease states which share oxidative stress and inflammation as causative role players. Furthermore, data point to a role for both cumulative oxidative stress and low grade inflammation in the normal ageing process, independently of disease. Therefore, arguably the best route with which to address premature ageing, as well as age-associated diseases such as diabetes, cardiovascular disease, and dementia, is preventative medicine aimed at modulation of these two responses, which are intricately interlinked. In this review, we provide a detailed account of the literature on the communication of these systems in the context of ageing, but with inclusion of relevant data obtained in other models. In doing so, we attempted to more clearly elucidate or identify the most probable cellular or molecular targets for preventative intervention. In addition, given the absence of a clear pharmaceutical solution in this context, together with the ever-increasing consumer bias for natural medicine, we provide an overview of the literature on grape (Vitis vinifera derived products, for which beneficial effects are consistently reported in the context of both oxidative stress and inflammation.

  5. Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

    Science.gov (United States)

    Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2013-07-01

    Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

  6. Plasma Proteome Biomarkers of Inflammation in School Aged Children in Nepal.

    Directory of Open Access Journals (Sweden)

    Sun Eun Lee

    Full Text Available Inflammation is a condition stemming from complex host defense and tissue repair mechanisms, often simply characterized by plasma levels of a single acute reactant. We attempted to identify candidate biomarkers of systemic inflammation within the plasma proteome. We applied quantitative proteomics using isobaric mass tags (iTRAQ tandem mass spectrometry to quantify proteins in plasma of 500 Nepalese children 6-8 years of age. We evaluated those that co-vary with inflammation, indexed by α-1-acid glycoprotein (AGP, a conventional biomarker of inflammation in population studies. Among 982 proteins quantified in >10% of samples, 99 were strongly associated with AGP at a family-wise error rate of 0.1%. Magnitude and significance of association varied more among proteins positively (n = 41 than negatively associated (n = 58 with AGP. The former included known positive acute phase proteins including C-reactive protein, serum amyloid A, complement components, protease inhibitors, transport proteins with anti-oxidative activity, and numerous unexpected intracellular signaling molecules. Negatively associated proteins exhibited distinct differences in abundance between secretory hepatic proteins involved in transporting or binding lipids, micronutrients (vitamin A and calcium, growth factors and sex hormones, and proteins of largely extra-hepatic origin involved in the formation and metabolic regulation of extracellular matrix. With the same analytical approach and the significance threshold, seventy-two out of the 99 proteins were commonly associated with CRP, an established biomarker of inflammation, suggesting the validity of the identified proteins. Our findings have revealed a vast plasma proteome within a free-living population of children that comprise functional biomarkers of homeostatic and induced host defense, nutrient metabolism and tissue repair, representing a set of plasma proteins that may be used to assess dynamics and extent of

  7. Role of pattern recognition receptors of the neurovascular unit in inflamm-aging.

    Science.gov (United States)

    Wilhelm, Imola; Nyúl-Tóth, Ádám; Kozma, Mihály; Farkas, Attila E; Krizbai, István A

    2017-11-01

    Aging is associated with chronic inflammation partly mediated by increased levels of damage-associated molecular patterns, which activate pattern recognition receptors (PRRs) of the innate immune system. Furthermore, many aging-related disorders are associated with inflammation. PRRs, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), are expressed not only in cells of the innate immune system but also in other cells, including cells of the neurovascular unit and cerebral vasculature forming the blood-brain barrier. In this review, we summarize our present knowledge about the relationship between activation of PRRs expressed by cells of the neurovascular unit-blood-brain barrier, chronic inflammation, and aging-related pathologies of the brain. The most important damage-associated molecular pattern-sensing PRRs in the brain are TLR2, TLR4, and NLR family pyrin domain-containing protein-1 and pyrin domain-containing protein-3, which are activated during physiological and pathological aging in microglia, neurons, astrocytes, and possibly endothelial cells and pericytes. Copyright © 2017 the American Physiological Society.

  8. Combined effects of aging and inflammation on renin-angiotensin system mediate mitochondrial dysfunction and phenotypic changes in cardiomyopathies.

    Science.gov (United States)

    Burks, Tyesha N; Marx, Ruth; Powell, Laura; Rucker, Jasma; Bedja, Djahida; Heacock, Elisa; Smith, Barbara J; Foster, D Brian; Kass, David; O'Rourke, Brian; Walston, Jeremy D; Abadir, Peter M

    2015-05-20

    Although the effects of aging and inflammation on the health of the cardiac muscle are well documented, the combined effects of aging and chronic inflammation on cardiac muscle are largely unknown. The renin-angiotensin system (RAS) has been linked independently to both aging and inflammation, but is understudied in the context of their collective effect. Thus, we investigated localized cardiac angiotensin II type I and type II receptors (AT(1)R, AT(2)R), downstream effectors, and phenotypic outcomes using mouse models of the combination of aging and inflammation and compared it to a model of aging and a model of inflammation. We show molecular distinction in the combined effect of aging and inflammation as compared to each independently. The combination maintained an increased AT(1)R:AT(2)R and expression of Nox2 and exhibited the lowest activity of antioxidants. Despite signaling pathway differences, the combined effect shared phenotypic similarities with aging including oxidative damage, fibrosis, and hypertrophy. These phenotypic similarities have dubbed inflammatory conditions as premature aging, but they are, in fact, molecularly distinct. Moreover, treatment with an AT(1)R blocker, losartan, selectively reversed the signaling changes and ameliorated adverse phenotypic effects in the combination of aging and inflammation as well as each independently.

  9. 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.

  10. Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

    Science.gov (United States)

    Massa, Christopher B; Groves, Angela M; Jaggernauth, Smita U; Laskin, Debra L; Gow, Andrew J

    2017-08-01

    Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd) develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs), however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group). An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical alteration at

  11. Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?

    Science.gov (United States)

    Fulop, Tamas; Larbi, Anis; Dupuis, Gilles; Le Page, Aurélie; Frost, Eric H; Cohen, Alan A; Witkowski, Jacek M; Franceschi, Claudio

    2017-01-01

    The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro-endocrine-immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.

  12. Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

    Directory of Open Access Journals (Sweden)

    Christopher B Massa

    2017-08-01

    Full Text Available Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs, however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group. An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical

  13. Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?

    Science.gov (United States)

    Fulop, Tamas; Larbi, Anis; Dupuis, Gilles; Le Page, Aurélie; Frost, Eric H.; Cohen, Alan A.; Witkowski, Jacek M.; Franceschi, Claudio

    2018-01-01

    The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro–endocrine–immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions. PMID:29375577

  14. Cognitive ability in early adulthood is associated with systemic inflammation in middle age: the Vietnam experience study

    DEFF Research Database (Denmark)

    Phillips, Anna C; Batty, G David; van Zanten, Jet J C S Veldhuijzen

    2011-01-01

    , and place of service were extracted from enlistment files. Smoking behaviour, alcohol consumption, basic socio-demographics, and whether participants suffered from a physician diagnosed chronic disease were determined by telephone interview in middle-age in 1985. Erythrocyte sedimentation rate, cholesterol...... erythrocyte sedimentation rate in middle age, ß=-.09. Thus, it would appear that not only does systemic inflammation influence cognition, but also that poor cognitive ability earlier in life is associated with inflammation in middle-age....

  15. Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease.

    Directory of Open Access Journals (Sweden)

    Stephanie Georgina Dakin

    Full Text Available The contribution of inflammation to the pathogenesis of tendinopathy and high prevalence of re-injury is not well established, although recent evidence suggests involvement of prostaglandins. We investigated the roles of prostaglandins and inflammation-resolving mediators in naturally occurring equine tendon injury with disease stage and age. Levels of prostaglandins E(2 (PGE(2, F(2α (PGF(2α, lipoxin A(4 (LXA(4 and its receptor FPR2/ALX were analysed in extracts of normal, sub-acute and chronic injured tendons. To assess whether potential changes were associated with altered PGE(2 metabolism, microsomal prostaglandin E synthase-1 (mPGES-1, prostaglandin dehydrogenase (PGDH, COX-2 and EP(4 receptor expression were investigated. The ability of tendons to resolve inflammation was determined by assessing FPR2/ALX expression in natural injury and IL-1β stimulated tendon explants.Alterations in the profile of lipid mediators during sub-acute injury included low PGE(2 and elevated LXA(4 levels compared to normal and chronic injuries. In contrast, PGF(2α levels remained unchanged and were three-fold lower than PGE(2. The synthetic capacity of PGE(2 as measured by the ratio of mPGES-1:PGDH was elevated in sub-acute injury, suggesting aberrations in tendon prostaglandin metabolism, whilst COX-2 and EP(4 receptor were unchanged. Paradoxically low tendon PGE(2 levels in early injury may be attributed to increased local clearance via PGDH or the class switching of lipid mediators from the prostaglandin to the lipoxin axis. PGE(2 is therefore implicated in the development of tendon inflammation and its ensuing resolution. Whilst there was no relationship between age and tendon LXA(4 levels, there was an age-associated decline in FPR2/ALX receptor expression with concurrent increased PGE(2 levels in injury. Furthermore, uninjured tendon explants from younger (<10 years but not older horses (≥10 years treated with IL-1β responded by increasing FPR2/ALX

  16. Curcumin-mediated regulation of intestinal barrier function: The mechanism underlying its beneficial effects.

    Science.gov (United States)

    Ghosh, Siddhartha S; He, Hongliang; Wang, Jing; Gehr, Todd W; Ghosh, Shobha

    2018-01-02

    Curcumin has anti-inflammatory, anti-oxidant and anti-proliferative properties established largely by in vitro studies. Accordingly, oral administration of curcumin beneficially modulates many diseases including diabetes, fatty-liver disease, atherosclerosis, arthritis, cancer and neurological disorders such as depression, Alzheimer's or Parkinson's disease. However, limited bioavailability and inability to detect curcumin in circulation or target tissues has hindered the validation of a causal role. We established curcumin-mediated decrease in the release of gut bacteria-derived lipopolysaccharide (LPS) into circulation by maintaining the integrity of the intestinal barrier function as the mechanism underlying the attenuation of metabolic diseases (diabetes, atherosclerosis, kidney disease) by curcumin supplementation precluding the need for curcumin absorption. In view of the causative role of circulating LPS and resulting chronic inflammation in the development of diseases listed above, this review summarizes the mechanism by which curcumin affects the several layers of the intestinal barrier and, despite negligible absorption, can beneficially modulate these diseases.

  17. Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain

    Directory of Open Access Journals (Sweden)

    Divya Raj

    2017-06-01

    Full Text Available Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer’s disease (AD-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis and HLA-DR (associated with antigen presentation, in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years. This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

  18. Influence of fitness and age on the endothelial response to acute inflammation.

    Science.gov (United States)

    Schroeder, Elizabeth C; Lane-Cordova, Abbi D; Ranadive, Sushant M; Baynard, Tracy; Fernhall, Bo

    2018-04-16

    What is the central question of the study? The purpose of this study was to determine the effect of age and fitness on the vascular response to acute inflammation in younger and older adults. What is the main finding and its importance? In older adults, cardiorespiratory fitness level has a differential impact on endothelial function following acute inflammation: older moderately fit adults have a greater decrease in endothelial function, similar to that of younger adults. These findings have important implications of further supporting the beneficial effects of higher cardiorespiratory fitness in maintaining vascular reactivity and the ability to respond to stressors. Inflammation is associated with greater risk of cardiovascular events and reduced vascular function with aging. Higher cardiorespiratory fitness is associated with lower risk of cardiovascular events and better vascular function. We evaluated the role of fitness in the vascular response to acute inflammation in 26 younger (YA) and 62 older (OA) adults. We used an influenza vaccine to induce acute inflammation. Blood pressure, flow-mediated dilation (FMD), augmentation index (AIx@75), carotid elastic modulus (Ep) and inflammatory markers were measured before and 24-hours after vaccination. VO 2 peak was measured via a treadmill test. Fit was defined as a VO 2 peak greater than the age- and sex-determined 50 th percentile according to the American College of Sports Medicine. An interaction effect existed for the FMD response during acute inflammation (p fit: 11.5 ± 1.8 to 9.2 ± 1.3%; moderately fit: 11.9 ± 0.8 to 9.0 ± 0.8%) and moderately fit OA (7.5 ± 1.0 to 3.9 ± 0.8%) had similar reductions in FMD at 24h (p fit OA did not reduce FMD at 24h (5.5 ± 0.4 to 5.2 ± 0.5%, p > 0.05). The reduction in FMD in YA was similar between fitness groups (p > 0.05). All groups had similar reductions in mean arterial pressure and increases in inflammatory markers. AIx@75 and Ep did not

  19. Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis

    Directory of Open Access Journals (Sweden)

    Yanxiong Gan

    2015-11-01

    Full Text Available Curcumin, the medically active component from Curcuma longa (Turmeric, is widely used to treat inflammatory diseases. Protein interaction network (PIN analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein–protein interactions (PPIs were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO enrichment analysis based on molecular complex detection (MCODE. A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation.

  20. Understanding How Dogs Age: Longitudinal Analysis of Markers of Inflammation, Immune Function, and Oxidative Stress.

    Science.gov (United States)

    Alexander, Janet E; Colyer, Alison; Haydock, Richard M; Hayek, Michael G; Park, JeanSoon

    2018-05-09

    As in human populations, advances in nutrition and veterinary care have led to an increase in the lifespan of companion animals. Detrimental physiological changes occurring later in life must be understood before interventions can be made to slow or reduce them. One important aspect of human aging is upregulation of the inflammatory response and increase in oxidative damage resulting in pathologies linked to chronic inflammation. To determine whether similar processes occur in the aging dog, changes in markers of inflammation and oxidative stress were investigated in 80 Labrador retrievers from adulthood to the end of life. Serum levels of immunoglobulin M (p immunoglobulin G or C-reactive protein unless the last year of life was included in the analysis (p = .002). Baseline levels of heat shock protein 70 decreased with age (p < .001) while those after exposure to heat stress were maintained (p = .018). However, when excluding final year of life data, a decline in the heat shock protein 70 response after heat stress was observed (p = .004). These findings indicate that aging dogs undergo changes similar to human inflammaging and offer the possibility of nutritional or pharmacological intervention to delay or reduce these effects.

  1. High level of fecal calprotectin at age 2 months as a marker of intestinal inflammation predicts atopic dermatitis and asthma by age 6

    NARCIS (Netherlands)

    Orivuori, L.; Mustonen, K.; de Goffau, M. C.; Hakala, S.; Paasela, M.; Roduit, C.; Dalphin, J. -C.; Genuneit, J.; Lauener, R.; Riedler, J.; Weber, J.; von Mutius, E.; Pekkanen, J.; Harmsen, H. J. M.; Vaarala, O.

    BackgroundGut microbiota and intestinal inflammation regulate the development of immune-mediated diseases, such as allergies. Fecal calprotectin is a biomarker of intestinal inflammation. ObjectiveWe evaluated the association of early-age fecal calprotectin levels to the later development of

  2. AGE and their receptor RAGE in systemic autoimmune diseases : An inflammation propagating factor contributing to accelerated atherosclerosis

    NARCIS (Netherlands)

    Nienhuis, Hans L. A.; Westra, Johanna; Smit, Andries J.; Limburg, Pieter C.; Kallenberg, Cees G. M.; Bijl, Marc

    2009-01-01

    Systemic autoimmune diseases are associated with inflammation, and oxidative stress favouring the formation of advanced glycation endproducts (AGE), able to modulate cellular functions by activation of receptor for advanced glycation endproducts (RAGE). As RAGE expression is increased in an

  3. 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.

  4. Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation

    Directory of Open Access Journals (Sweden)

    Małgorzata Nita

    2014-01-01

    Full Text Available The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH and facilitates chronic inflammation mediated by C-reactive protein (CRP. Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2 and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages; however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages.

  5. Exploring the cross talk between ER stress and inflammation in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Samira Kheitan

    Full Text Available Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER stress is implicated in the development and progression of age-related macular degeneration (AMD, a multifactorial neurodegenerative disease. However the cross talk between these cellular mechanisms has not been clearly and fully understood. The present study investigates a possible intersection between ER stress and inflammation in AMD. In this study, we recruited two collections of involved protein markers to retrieve their interaction information from IMEx-curated databases, which are the most well- known protein-protein interaction collections, allowing us to design an intersection network for AMD that is unprecedented. In order to find expression activated subnetworks, we utilized AMD expression profiles in our network. In addition, we studied topological characteristics of the most expressed active subnetworks to identify the hubs. With regard to topological quantifications and expressional activity, we reported a list of the most pivotal hubs which are potentially applicable as probable therapeutic targets. Furthermore, we introduced MAPK signaling pathway as a significantly involved pathway in the association between ER stress and inflammation, leading to promising new directions in discovering AMD formation mechanisms and possible treatments.

  6. Exploring the cross talk between ER stress and inflammation in age-related macular degeneration.

    Science.gov (United States)

    Kheitan, Samira; Minuchehr, Zarrin; Soheili, Zahra-Soheila

    2017-01-01

    Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER) stress is implicated in the development and progression of age-related macular degeneration (AMD), a multifactorial neurodegenerative disease. However the cross talk between these cellular mechanisms has not been clearly and fully understood. The present study investigates a possible intersection between ER stress and inflammation in AMD. In this study, we recruited two collections of involved protein markers to retrieve their interaction information from IMEx-curated databases, which are the most well- known protein-protein interaction collections, allowing us to design an intersection network for AMD that is unprecedented. In order to find expression activated subnetworks, we utilized AMD expression profiles in our network. In addition, we studied topological characteristics of the most expressed active subnetworks to identify the hubs. With regard to topological quantifications and expressional activity, we reported a list of the most pivotal hubs which are potentially applicable as probable therapeutic targets. Furthermore, we introduced MAPK signaling pathway as a significantly involved pathway in the association between ER stress and inflammation, leading to promising new directions in discovering AMD formation mechanisms and possible treatments.

  7. Systemic inflammation in the extremely low gestational age newborn following maternal genitourinary infections

    Science.gov (United States)

    Fichorova, Raina N.; Beatty, Noah; Sassi, Rita R. S.; Yamamoto, Hidemi S.; Allred, Elizabeth N.; Leviton, Alan

    2014-01-01

    Problem Gestational genitourinary infections are associated with life-long disabilities, but it is unknown if neonatal inflammation is involved. Method Mothers of 914 infants born before 28th gestation week reported cervical/vaginal infection (CVI), and/or urine/bladder/kidney infection (UTI), or neither. Inflammation proteins measured in baby’s blood on postnatal days 1, 7 and 14 were considered elevated if in the top quartile for gestational age. Logistic regression models adjusting for potential confounders assessed odds ratios. Results Compared to neither UTI/CVI, mothers with CVI were more likely to have infants with elevated CRP, SAA, MPO, IL-1β, IL-6, IL-6R, TNF-α, RANTES, ICAM-3, E-selectin and VEGF-R2 on day 1; those with UTI were more likely to have infants with elevated MPO, IL-6R, TNF-R1, TNF-R2, and RANTES on day 7. Placental anaerobes and genital micoplasma were more common in pregnancies with CVI. Conclusion Gestational UTI/CVI should be targeted for preventing systemic inflammation in the very preterm newborn. PMID:25164433

  8. 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...

  9. Short-term Treatment of Daumone Improves Hepatic Inflammation in Aged Mice.

    Science.gov (United States)

    Park, Jong Hee; Ha, Hunjoo

    2015-05-01

    Chronic inflammation has been proposed as one of the main molecular mechanisms of aging and age-related diseases. Although evidence in humans is limited, short-term calorie restriction (CR) has been shown to have anti-inflammatory effects in aged experimental animals. We reported on the long-term treatment of daumone, a synthetic pheromone secreted by Caenorhabditis elegans in an energy deficient environment, extends the life-span and attenuates liver injury in aged mice. The present study examined whether late onset short-term treatment of daumone exerts anti-inflammatory effects in the livers of aged mice. Daumone was administered orally at doses of 2 or 20 mg/kg/day for 5 weeks to 24-month-old male C57BL/6J mice. Increased liver macrophage infiltration and gene expression of proinflammatory cytokines in aged mice were significantly attenuated by daumone treatment, suggesting that short-term oral administration of daumone may have hepatoprotective effects. Daumone also dose-dependently suppressed tumor necrosis factor-α (TNF-α)-induced nuclear factor-κB (NF-κB) phosphorylation in HepG2 cells. The present data demonstrated that short-term treatment of daumone has anti-inflammatory effects in aged mouse livers possibly through suppression of NF-κB signaling and suggest that daumone may become a lead compound targeting aging and age-associated diseases.

  10. Role of PGC-1α in exercise training- and resveratrol-induced prevention of age-associated inflammation

    DEFF Research Database (Denmark)

    Olesen, Jesper; Jørgensen, Stine Ringholm; Nielsen, Maja Munk

    2013-01-01

    Age-related metabolic diseases are often associated with low-grade inflammation. The aim of the present study was to investigate the role of the transcriptional co-activator PGC-1α in the potential beneficial effects of exercise training and/or resveratrol in the prevention of age-associated low......-grade inflammation. To address this, a long-term voluntary exercise training and resveratrol supplementation study was conducted....

  11. 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.

  12. Sleep deprivation and divergent toll-like receptor-4 activation of cellular inflammation in aging.

    Science.gov (United States)

    Carroll, Judith E; Carrillo, Carmen; Olmstead, Richard; Witarama, Tuff; Breen, Elizabeth C; Yokomizo, Megumi; Seeman, Teresa; Irwin, Michael R

    2015-02-01

    Sleep disturbance and aging are associated with increases in inflammation, as well as increased risk of infectious disease. However, there is limited understanding of the role of sleep loss on age-related differences in immune responses. This study examines the effects of sleep deprivation on toll-like receptor activation of monocytic inflammation in younger compared to older adults. Community-dwelling adults (n = 70) who were categorized as younger (25-39 y old, n = 21) and older (60-84 y old, n = 49) participants, underwent a sleep laboratory-based experimental partial sleep deprivation (PSD) protocol including adaptation, an uninterrupted night of sleep, sleep deprivation (sleep restricted to 03:00-07:00), and recovery. Blood samples were obtained each morning to measure toll-like receptor-4 activation of monocyte intracellular production of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Partial sleep deprivation induced a significant increase in the production of IL-6 and/or TNF-α that persisted after a night of recovery sleep (F(2,121.2) = 3.8, P sleep loss, such that younger adults had an increase in inflammatory cytokine production that was not present in older adults (F(2,121.2) = 4.0, P sleep loss. Whereas sleep loss increases cellular inflammation in younger adults and may contribute to inflammatory disorders, blunted toll-like receptor activation in older adults may increase the risk of infectious disease seen with aging. © 2015 Associated Professional Sleep Societies, LLC.

  13. 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.

  14. Curcumin suppresses intestinal polyps in APC Min mice fed a high fat diet

    Directory of Open Access Journals (Sweden)

    Christina Pettan-Brewer

    2011-06-01

    Full Text Available Colorectal cancer (CRC is a leading cause of cancer deaths in the United States. Various risk factors have been associated with CRC including increasing age and diet. Epidemiological and experimental studies have implicated a diet high in fat as an important risk factor for colon cancer. High fat diets can promote obesity resulting in insulin resistance and inflammation and the development of oxidative stress, increased cell proliferation, and suppression of apoptosis. Because of the high consumption of dietary fats, especially saturated fats, by Western countries, it is of interest to see if non-nutrient food factors might be effective in preventing or delaying CRC in the presence of high saturated fat intake. Curcumin (Curcuma longa, the main yellow pigment in turmeric, was selected to test because of its reported anti-tumor activity. APC Min mice, which develop intestinal polyps and have many molecular features of CRC, were fed a diet containing 35% pork fat, 33% sucrose, and a protein and vitamin mineral mixture (HFD with or without 0.5% curcumin. These cohorts were compared to APC Min mice receiving standard rodent chow (RC with 8% fat. APC Min mice fed the HFD for 3 months had a 23% increase in total number of polyps compared to APC Min mice on RC. Curcumin was able to significantly reverse the accelerated polyp development associated with the HFD suggesting it may be effective clinically in helping prevent colon cancer even when ingesting high amounts of fatty foods. The anti-tumor effect of curcumin was shown to be associated with enhanced apoptosis and increased efficiency of DNA repair. Since curcumin prevented the gain in body weight seen in APC Min mice ingesting the HFD, modulation of energy metabolism may also be a factor.

  15. 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.

  16. Gene expression markers of age-related inflammation in two human cohorts.

    Science.gov (United States)

    Pilling, Luke C; Joehanes, Roby; Melzer, David; Harries, Lorna W; Henley, William; Dupuis, Josée; Lin, Honghuang; Mitchell, Marcus; Hernandez, Dena; Ying, Sai-Xia; Lunetta, Kathryn L; Benjamin, Emelia J; Singleton, Andrew; Levy, Daniel; Munson, Peter; Murabito, Joanne M; Ferrucci, Luigi

    2015-10-01

    Chronically elevated circulating inflammatory markers are common in older persons but mechanisms are unclear. Many blood transcripts (>800 genes) are associated with interleukin-6 protein levels (IL6) independent of age. We aimed to identify gene transcripts statistically mediating, as drivers or responders, the increasing levels of IL6 protein in blood at older ages. Blood derived in-vivo RNA from the Framingham Heart Study (FHS, n=2422, ages 40-92 yrs) and InCHIANTI study (n=694, ages 30-104 yrs), with Affymetrix and Illumina expression arrays respectively (>17,000 genes tested), were tested for statistical mediation of the age-IL6 association using resampling techniques, adjusted for confounders and multiple testing. In FHS, IL6 expression was not associated with IL6 protein levels in blood. 102 genes (0.6% of 17,324 expressed) statistically mediated the age-IL6 association of which 25 replicated in InCHIANTI (including 5 of the 10 largest effect genes). The largest effect gene (SLC4A10, coding for NCBE, a sodium bicarbonate transporter) mediated 19% (adjusted CI 8.9 to 34.1%) and replicated by PCR in InCHIANTI (n=194, 35.6% mediated, p=0.01). Other replicated mediators included PRF1 (perforin, a cytolytic protein in cytotoxic T lymphocytes and NK cells) and IL1B (Interleukin 1 beta): few other cytokines were significant mediators. This transcriptome-wide study on human blood identified a small distinct set of genes that statistically mediate the age-IL6 association. Findings are robust across two cohorts and different expression technologies. Raised IL6 levels may not derive from circulating white cells in age related inflammation. Published by Elsevier Inc.

  17. 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.

  18. The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: A systems biology approach

    NARCIS (Netherlands)

    Calçada, D.; Vianello, D.; Giampieri, E.; Sala, C.; Castellani, G.; Graaf, A.A. de; Kremer, S.H.A.; Ommen, B. van; Feskens, E.; Santoro, A.; Franceschi, C.; Bouwman, J.

    2014-01-01

    Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic

  19. [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).

  20. Curcumin-mediated decrease in the expression of nucleolar organizer regions in cervical cancer (HeLa) cells.

    Science.gov (United States)

    Lewinska, Anna; Adamczyk, Jagoda; Pajak, Justyna; Stoklosa, Sylwia; Kubis, Barbara; Pastuszek, Paulina; Slota, Ewa; Wnuk, Maciej

    2014-09-01

    Curcumin, the major yellow-orange pigment of turmeric derived from the rhizome of Curcuma longa, is a highly pleiotropic molecule with the potential to modulate inflammation, oxidative stress, cell survival, cell secretion, homeostasis and proliferation. Curcumin, at relatively high concentrations, was repeatedly reported to be a potent inducer of apoptosis in cancer cells and thus considered a promising anticancer agent. In the present paper, the effects of low concentrations of curcumin on human cervical cancer (HeLa) cells were studied. We found curcumin-mediated decrease in the cell number and viability, and increase in apoptotic events and superoxide level. In contrast to previously shown curcumin cytotoxicity toward different cervical cancer lines, we observed toxic effects when even as low as 1 μM concentration of curcumin was used. Curcumin was not genotoxic to HeLa cells. Because argyrophilic nucleolar protein (AgNOR protein) expression is elevated in malignant cells compared to normal cells reflecting the rapidity of cancer cell proliferation, we evaluated curcumin-associated changes in size (area) and number of silver deposits. We showed curcumin-induced decrease in AgNOR protein pools, which may be mediated by global DNA hypermethylation observed after low concentration curcumin treatment. In summary, we have shown for the first time that curcumin at low micromolar range may be effective against HeLa cells, which may have implications for curcumin-based treatment of cervical cancer in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. 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.

  2. Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

    OpenAIRE

    Ahn, Joong Kyong; Kim, Sooah; Hwang, Jiwon; Kim, Jungyeon; Lee, You Sun; Koh, Eun-Mi; Kim, Kyoung Heon; Cha, Hoon-Suk

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF)-α...

  3. Exercise, Arterial Crosstalk-Modulation, and Inflammation in an Aging Population: The ExAMIN AGE Study.

    Science.gov (United States)

    Streese, Lukas; Deiseroth, Arne; Schäfer, Juliane; Schmidt-Trucksäss, Arno; Hanssen, Henner

    2018-01-01

    Background: Age is a key determinant for the development of cardiovascular disease and higher age coincides with an increased prevalence of obesity and physical inactivity. The study examines the influence of physical activity on aging processes of physiological systems focusing on the mechanisms of vascular aging. Methods/Design: The study consists of two parts. The cross-sectional approach aims at examining the association of physical fitness and cardiovascular risk with large and small artery function in healthy older active (HOA, n = 40) and sedentary (HOS, n = 40) persons as well as older sedentary individuals with increased cardiovascular risk (OSR, n = 80) aged 50-80 years. In the interventional approach, the OSR group is randomized into a 12-week walking-based high intensity interval training (HIIT) group or a control condition, aiming at examining the effects of HIIT on arterial function in diseased older adults. Active lifestyle is defined as >9 metabolic equivalent of task (MET) per week and sedentary as ≤3 MET/week. Inclusion criteria for OSR are overweight or obesity (body mass index ≥30 kg/m 2 ) plus at least one additional cardiovascular risk factor. The primary outcome is arterial stiffness as determined by aortic pulse wave velocity (PWV). The secondary outcomes are retinal arterial and venous diameters. Further cardiovascular assessments include peripheral PWV, central haemodynamics, retinal endothelial function, carotid intima media thickness, cardiac strain and diastolic function as well as autonomic function and inflammation. Physical fitness is measured by a treadmill-based spiroergometry to determine peak oxygen uptake. Discussion: The aim of the study is to demonstrate the importance of and need for specific physical activity programs for seniors to achieve healthier aging as a long-term goal. Vascular function defines disease- and age-related end organ damage and represents the potential to contain health at older age. This research

  4. Exercise, Arterial Crosstalk-Modulation, and Inflammation in an Aging Population: The ExAMIN AGE Study

    Directory of Open Access Journals (Sweden)

    Lukas Streese

    2018-02-01

    Full Text Available Background: Age is a key determinant for the development of cardiovascular disease and higher age coincides with an increased prevalence of obesity and physical inactivity. The study examines the influence of physical activity on aging processes of physiological systems focusing on the mechanisms of vascular aging.Methods/Design: The study consists of two parts. The cross-sectional approach aims at examining the association of physical fitness and cardiovascular risk with large and small artery function in healthy older active (HOA, n = 40 and sedentary (HOS, n = 40 persons as well as older sedentary individuals with increased cardiovascular risk (OSR, n = 80 aged 50–80 years. In the interventional approach, the OSR group is randomized into a 12-week walking-based high intensity interval training (HIIT group or a control condition, aiming at examining the effects of HIIT on arterial function in diseased older adults. Active lifestyle is defined as >9 metabolic equivalent of task (MET per week and sedentary as ≤3 MET/week. Inclusion criteria for OSR are overweight or obesity (body mass index ≥30 kg/m2 plus at least one additional cardiovascular risk factor. The primary outcome is arterial stiffness as determined by aortic pulse wave velocity (PWV. The secondary outcomes are retinal arterial and venous diameters. Further cardiovascular assessments include peripheral PWV, central haemodynamics, retinal endothelial function, carotid intima media thickness, cardiac strain and diastolic function as well as autonomic function and inflammation. Physical fitness is measured by a treadmill-based spiroergometry to determine peak oxygen uptake.Discussion: The aim of the study is to demonstrate the importance of and need for specific physical activity programs for seniors to achieve healthier aging as a long-term goal. Vascular function defines disease- and age-related end organ damage and represents the potential to contain health at older age. This

  5. Biomarkers of oxidative stress and inflammation after wood smoke exposure in a reconstructed Viking Age house.

    Science.gov (United States)

    Jensen, Annie; Karottki, Dorina Gabriela; Christensen, Jannie Marie; Bønløkke, Jakob Hjort; Sigsgaard, Torben; Glasius, Marianne; Loft, Steffen; Møller, Peter

    2014-10-01

    Exposure to particles from combustion of wood is associated with respiratory symptoms, whereas there is limited knowledge about systemic effects. We investigated effects on systemic inflammation, oxidative stress and DNA damage in humans who lived in a reconstructed Viking Age house, with indoor combustion of wood for heating and cooking. The subjects were exposed to high indoor concentrations of PM2.5 (700-3,600 µg/m(3)), CO (10.7-15.3 ppm) and NO2 (140-154 µg/m(3)) during a 1-week stay. Nevertheless, there were unaltered levels of genotoxicity, determined as DNA strand breaks and formamidopyrimidine DNA glycosylase and oxoguanine DNA glycosylase 1 sensitive sites in peripheral blood mononuclear cells. There were also unaltered expression levels of OGG1, HMOX1, CCL2, IL8, and TNF levels in leukocytes. In serum, there were unaltered levels of C-reactive protein, IL6, IL8, TNF, lactate dehydrogenase, cholesterol, triglycerides, and high-density lipoproteins. The wood smoke exposure was associated with decreased serum levels of sICAM-1, and a tendency to decreased sVCAM-1 levels. There was a minor increase in the levels of circulating monocytes expressing CD31, whereas there were unaltered expression levels of CD11b, CD49d, and CD62L on monocytes after the stay in the house. In conclusion, even a high inhalation exposure to wood smoke was associated with limited systemic effects on markers of oxidative stress, DNA damage, inflammation, and monocyte activation. © 2014 Wiley Periodicals, Inc.

  6. Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Nada Sallam

    2016-01-01

    Full Text Available Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual’s characteristics; therefore, the development of personalized exercise programs is essential.

  7. 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

  8. 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.

  9. 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.

  10. SYSTEMIC INFLAMMATION IMPAIRS ATTENTION AND COGNITIVE FLEXIBILITY BUT NOT ASSOCIATIVE LEARNING IN AGED RATS: Possible Implications for Delirium

    Directory of Open Access Journals (Sweden)

    Deborah J Culley

    2014-06-01

    Full Text Available Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that systemic inflammation impairs prefrontal cortex function by assessing attention and executive function in aged animals. Aged (24-month-old Fischer-344 rats received a single intraperitoneal injection of lipopolysaccharide (LPS; 50 ug/kg or saline and were tested on the attentional shifting task (AST, an index of integrity of the prefrontal cortex, on days 1-3 post-injection. Plasma and frontal cortex concentrations of the cytokine TNFα and the chemokine CCL2 were measured by ELISA in separate groups of identically treated, age-matched rats. LPS selectively impaired reversal learning and attentional shifts without affecting discrimination learning in the AST, indicating a deficit in attention and cognitive flexibility but not learning globally. LPS increased plasma TNFα and CCL2 acutely but this resolved within 24-48 h. TNFα in the frontal cortex did not change whereas CCL2 increased nearly 3-fold 2 h after LPS but normalized by the time behavioral testing started 24 h later. Together, our data indicate that systemic inflammation selectively impairs attention and executive function in aged rodents and that the cognitive deficit is independent of concurrent changes in frontal cortical TNFα and CCL2. Because inattention is a prominent feature of clinical delirium, our data support a role for inflammation in the pathogenesis of this clinical syndrome and suggest this animal model could be useful for studying that relationship further.

  11. Aging and low-grade inflammation reduce renal function in middle-aged and older adults in Japan and the USA.

    Science.gov (United States)

    Costello-White, Reagan; Ryff, Carol D; Coe, Christopher L

    2015-08-01

    The objective of this study was to investigate the effects of low-grade inflammation on age-related changes in glomerular filtration rate (GFR) in middle-aged and older white Americans, African-Americans, and Japanese adults. Serum creatinine, C-reactive protein (CRP), and interleukin-6 (IL-6) levels were determined for 1570 adult participants in two surveys of aging in the USA and Japan (N = 1188 and 382, respectively). Kidney function declined with age in both countries and was associated with IL-6 and CRP. IL-6 and CRP also influenced the extent of the arithmetic bias when calculating the GFR using the chronic kidney disease epidemiology (CKD-EPI) formula with just serum creatinine. Younger African-Americans initially had the highest GFR but showed a steep age-related decrement that was associated with elevated inflammation. Japanese adults had the lowest average GFR but evinced a large effect of increased inflammatory activity when over 70 years of age. Importantly, our results also indicate that low-grade inflammation is important to consider when evaluating kidney function solely from serum creatinine.

  12. The whole body cryostimulation modifies irisin concentration and reduces inflammation in middle aged, obese men.

    Science.gov (United States)

    Dulian, Katarzyna; Laskowski, Radosław; Grzywacz, Tomasz; Kujach, Sylwester; Flis, Damian J; Smaruj, Mirosław; Ziemann, Ewa

    2015-12-01

    The anti-inflammatory effect induced by exposure to low temperature might trigger the endocrine function of muscle and fat tissue. Thus, the aim of this study was to investigate the influence of the whole body cryostimulation (CRY) on irisin, a myokine which activates oxygen consumption in fat cells as well as thermogenesis. In addition, the relationship between hepcidin (Hpc) - hormone regulating iron metabolism, and inflammation was studied. A group of middle aged men (n = 12, 38 ± 9 years old, BMI > 30 kg m(-2)) participated in the study. Subjects were exposed to a series of 10 sessions in a cryogenic chamber (once a day at 9:30 am, for 3 min, at temperature -110 °C). Blood samples were collected before the first cryostimulation and after completing the last one. Prior to treatment body composition and fitness level were determined. The applied protocol of cryostimulation lead to rise the blood irisin in obese non-active men (338.8 ± 42.2 vs 407.6 ± 118.5 ng mL(-1)), whereas has no effect in obese active men (371.5 ± 30.0 vs 343.3 ± 47.6 ng mL(-1)). Values recorded 24 h after the last cryo-session correlated significantly with the fat tissue, yet inversely with the skeletal muscle mass. Therefore, we concluded the subcutaneous fat tissue to be the main source of irisin in response to cold exposures. The applied cold treatment reduced the high sensitivity C-reactive protein (hsCRP) and Hpc concentration confirming its anti-inflammatory effect. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. 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

  14. 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.

  15. Curcumin Protects Against the Acute Inflammatory Process in Irradiated Rats

    International Nuclear Information System (INIS)

    El-Ghazaly, M.A.; Nada, A.S.; Hegazy, M.E.; Kenawy, S.A.

    2010-01-01

    Nutraceuticals that provide medical or health benefits, including prevention and treatment of disease may be advantageous in inflammation and exposure to radiation. The aim of this study was to investigate the potential of curcumin to modulate, counteract or prevent the inflammatory response induced in irradiated and non-irradiated rats using the carrageenan air-pouch model as an acute model. Diclofenac was used as a reference standard non-steroidal anti-inflammatory drug (NSAID). Results indicated that exposure of rats to a single dose of gamma-radiation (6 Gy) before induction of inflammation increased production of prostaglandin E2 (PGE2), tumour necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) levels in serum. Blood glutathione (GSH) was shown to be reduced in irradiated animals. Curcumin suppressed the elevated levels of TNF-alpha, PGE2 and MDA and was able to restore blood GSH levels. Reduction in liver contents of copper (Cu), zinc (Zn), selenium (Se) and iron (Fe) was recorded after irradiation of animals before induction of inflammation. Curcumin restored the hepatic concentrations of these trace elements. The present results suggest that irradiation of rats caused marked changes in the inflammatory response while curcumin suppressed the inflammatory response in both irradiated and control animals.

  16. Mechanism of Inflammation in Age-Related Macular Degeneration: An Up-to-Date on Genetic Landmarks

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2013-01-01

    Full Text Available Age-related macular degeneration (AMD is the most common cause of irreversible visual impairment among people over 50 years of age, accounting for up to 50% of all cases of legal blindness in Western countries. Although the aging represents the main determinant of AMD, it must be considered a multifaceted disease caused by interactions among environmental risk factors and genetic backgrounds. Mounting evidence and/or arguments document the crucial role of inflammation and immune-mediated processes in the pathogenesis of AMD. Proinflammatory effects secondary to chronic inflammation (e.g., alternative complement activation and heterogeneous types of oxidative stress (e.g., impaired cholesterol homeostasis can result in degenerative damages at the level of crucial macular structures, that is photoreceptors, retinal pigment epithelium, and Bruch’s membrane. In the most recent years, the association of AMD with genes, directly or indirectly, involved in immunoinflammatory pathways is increasingly becoming an essential core for AMD knowledge. Starting from the key basic-research notions detectable at the root of AMD pathogenesis, the present up-to-date paper reviews the best-known and/or the most attractive genetic findings linked to the mechanisms of inflammation of this complex disease.

  17. Does Inflammation Determine Whether Obesity Is Metabolically Healthy or Unhealthy? The Aging Perspective

    Directory of Open Access Journals (Sweden)

    Iftikhar Alam

    2012-01-01

    Full Text Available Obesity is a major health issue in developed as well as developing countries. While obesity is associated with relatively good health status in some individuals, it may become a health issue for others. Obesity in the context of inflammation has been studied extensively. However, whether obesity in its various forms has the same adverse effects is a matter of debate and requires further research. During its natural history, metabolically healthy obesity (MHO converts into metabolically unhealthy obesity (MUHO. What causes this transition to occur and what is the role of obesity-related mediators of inflammation during this transition is discussed in this paper.

  18. Modulation of Erythrocyte Plasma Membrane Redox System Activity by Curcumin

    Directory of Open Access Journals (Sweden)

    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.

  19. Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

    Directory of Open Access Journals (Sweden)

    Joong Kyong Ahn

    Full Text Available Rheumatoid arthritis (RA is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3, which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin. Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA.

  20. Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

    Science.gov (United States)

    Ahn, Joong Kyong; Kim, Sooah; Hwang, Jiwon; Kim, Jungyeon; Lee, You Sun; Koh, Eun-Mi; Kim, Kyoung Heon; Cha, Hoon-Suk

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF)-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin). Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA.

  1. From lymphopoiesis to plasma cells differentiation, the age-related modifications of B cell compartment are influenced by "inflamm-ageing".

    Science.gov (United States)

    Bulati, Matteo; Caruso, Calogero; Colonna-Romano, Giuseppina

    2017-07-01

    Ageing is a complex process characterized by a general decline in physiological functions with increasing morbidity and mortality. The most important aspect of ageing is the chronic inflammatory status, named "inflamm-ageing", strictly associated with the deterioration of the immune function, termed "immunosenescence". Both are causes of increased susceptibility of elderly to infectious diseases, cancer, dementia, cardiovascular diseases and autoimmunity, and of a decreased response to vaccination. It has been widely demonstrated that ageing has a strong impact on the remodelling of the B cell branch of immune system. The first evident effect is the significant decrease in circulating B cells, primarily due to the reduction of new B cell coming from bone marrow (BM) progenitors, as inflammation directly impacts on B lymphopoiesis. Besides, in aged individuals, there is a shift from naïve to memory immunoglobulins production, accompanied by the impaired ability to produce high affinity protective antibodies against newly encountered antigens. This is accompanied by the increase of expanded clones of B cells, which correlates with poor health status. Age-related modifications also occur in naïve/memory B cells subsets. Indeed, in the elderly, there is a reduction of naïve B cells, accompanied by the expansion of memory B cells that show a senescence-associated phenotype. Finally, elderly show the impaired ability of memory B cells to differentiate into plasma cells. It can be concluded that inflammation is the leading cause of the age-related impairment of B cell compartment, which play certainly a key role in the development of age-related diseases. This makes study of B cells in the aged an important tool for monitoring immunosenescence, chronic inflammatory disorders and the effectiveness of vaccines or pharmacological therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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

  3. Curcumin-loaded nanoparticles ameliorate glial activation and improve myelin repair in lyolecithin-induced focal demyelination model of rat corpus callosum.

    Science.gov (United States)

    Naeimi, Reza; Safarpour, Fatemeh; Hashemian, Mona; Tashakorian, Hamed; Ahmadian, Seyed Raheleh; Ashrafpour, Manouchehr; Ghasemi-Kasman, Maryam

    2018-05-01

    Curcumin has been introduced as effective anti-inflammatory agent in treatment of several inflammatory disorders. Despite the wide range pharmacological activities, clinical application of curcumin is restricted mainly due to the low water solubility of this substance. More recently, we could remarkably improve the aqueous solubility of curcumin by its encapsulation in chitosan-alginate-sodium tripolyphosphate nanoparticles (CS-ALG-STPP NPs). In this study, the anti-inflammatory and myelin protective effects of curcumin-loaded NPs were evaluated in lysolecithin (LPC)-induced focal demyelination model. Pharmacokinetic of curcumin was assessed using high performance liquid chromatography (HPLC). Local demyelination was induced by injection of LPC into corpus callosum of rats. Animals were pre-treated with intraperitoneal (i.p.) injections of curcumin or curcumin-loaded NPs at dose of 12.5 mg/kg, 10 days prior to LPC injection and the injections were continued for 7 or 14 days post lesion. Hematoxylin and eosin (H&E) staining and immunostaining against activated glial cells including astrocytes and microglia were carried out for assessment of inflammation level in lesion site. Myelin specific staining was performed to evaluate the effect of curcumin-loaded NPs on myelination of LPC receiving animals. HPLC results showed the higher plasma concentration of curcumin after administration of NPs. Histological evaluation demonstrated that, the extent of demyelination areas was reduced in animals under treatment of curcumin-loaded NPs. Furthermore, treatment with curcumin-loaded NPs effectively attenuated glial activation and inflammation in LPC-induced demyelination model compared to curcumin receiving animals. Overall; these findings indicate that treatment with curcumin-loaded NPs preserve myelinated axons through amelioration of glial activation and inflammation in demyelination context. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Maternal Obesity, Inflammation, and Developmental Programming

    Directory of Open Access Journals (Sweden)

    Stephanie A. Segovia

    2014-01-01

    Full Text Available The prevalence of obesity, especially in women of child-bearing age, is a global health concern. In addition to increasing the immediate risk of gestational complications, there is accumulating evidence that maternal obesity also has long-term consequences for the offspring. The concept of developmental programming describes the process in which an environmental stimulus, including altered nutrition, during critical periods of development can program alterations in organogenesis, tissue development, and metabolism, predisposing offspring to obesity and metabolic and cardiovascular disorders in later life. Although the mechanisms underpinning programming of metabolic disorders remain poorly defined, it has become increasingly clear that low-grade inflammation is associated with obesity and its comorbidities. This review will discuss maternal metainflammation as a mediator of programming in insulin sensitive tissues in offspring. Use of nutritional anti-inflammatories in pregnancy including omega 3 fatty acids, resveratrol, curcumin, and taurine may provide beneficial intervention strategies to ameliorate maternal obesity-induced programming.

  5. The effect of aging on aortic atherosclerotic plaque inflammation and molecular calcification: A FDG and NaF PET CT imaging study

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

    2013-01-01

    Objectives: Aging is an important independent determinant of plaque biology. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and calcification metabolism. Methods: Thirteen healthy volunteers without traditional cardiovascular risk factors were...... and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18-FDG and aortic Na-18F avidity. A second order polynomial regression established that aging is a predictor of the degree of aortic plaque inflammation (R = 0.524; F statistic = 4.93; P = 0...... data, a quadratic relationship appears to exist between aging and plaque inflammation. Furthermore, a quadratic relationship was observed between aging and plaque calcification metabolism. In line with these observations, a linear relationship was observed between atherosclerotic plaque inflammation...

  6. Emu oil based nano-emulgel for topical delivery of curcumin.

    Science.gov (United States)

    Jeengar, Manish Kumar; Rompicharla, Sri Vishnu Kiran; Shrivastava, Shweta; Chella, Naveen; Shastri, Nalini R; Naidu, V G M; Sistla, Ramakrishna

    2016-06-15

    Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Anti-Inflammatory Effects of Novel Standardized Solid Lipid Curcumin Formulations

    OpenAIRE

    Nahar, Pragati P.; Slitt, Angela L.; Seeram, Navindra P.

    2015-01-01

    Inflammation and the presence of pro-inflammatory cytokines are associated with numerous chronic diseases such as type-2 diabetes mellitus, cardiovascular disease, Alzheimer's disease, and cancer. An overwhelming amount of data indicates that curcumin, a polyphenol obtained from the Indian spice turmeric, Curcuma longa, is a potential chemopreventive agent for treating certain cancers and other chronic inflammatory diseases. However, the low bioavailability of curcumin, partly due to its low ...

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Spirulina Protects against Hepatic Inflammation in Aging: An Effect Related to the Modulation of the Gut Microbiota?

    Directory of Open Access Journals (Sweden)

    Audrey M. Neyrinck

    2017-06-01

    Full Text Available Aging predisposes to hepatic dysfunction and inflammation that can contribute to the development of non-alcoholic fatty liver disease. Spirulina, a cyanobacterium used as a food additive or food supplement, has been shown to impact immune function. We have tested the potential hepatoprotective effect of a Spirulina in aged mice and to determine whether these effects can be related to a modulation of the gut microbiota. Old mice have been fed a standard diet supplemented with or without 5% Spirulina for six weeks. Among several changes of gut microbiota composition, an increase in Roseburia and Lactobacillus proportions occurs upon Spirulina treatment. Interestingly, parameters related to the innate immunity are upregulated in the small intestine of Spirulina-treated mice. Furthermore, the supplementation with Spirulina reduces several hepatic inflammatory and oxidative stress markers that are upregulated in old mice versus young mice. We conclude that the oral administration of a Spirulina is able to modulate the gut microbiota and to activate the immune system in the gut, a mechanism that may be involved in the improvement of the hepatic inflammation in aged mice. Those data open the way to new therapeutic tools in the management of immune alterations in aging, based on gut microbe-host interactions.

  15. Novel PPARα agonist MHY553 alleviates hepatic steatosis by increasing fatty acid oxidation and decreasing inflammation during aging.

    Science.gov (United States)

    Kim, Seong Min; Lee, Bonggi; An, Hye Jin; Kim, Dae Hyun; Park, Kyung Chul; Noh, Sang-Gyun; Chung, Ki Wung; Lee, Eun Kyeong; Kim, Kyung Mok; Kim, Do Hyun; Kim, Su Jeong; Chun, Pusoon; Lee, Ho Jeong; Moon, Hyung Ryong; Chung, Hae Young

    2017-07-11

    Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells.Docking simulation and Western blotting confirmed that the activity of PPARα, but not that of the other PPAR subtypes, was increased by MHY553 treatment. When administered orally, MHY553 markedly ameliorated aging-induced hepatic steatosis without changes in body weight and serum levels of liver injury markers. Consistent with in vivo results, MHY553 inhibited triglyceride accumulation induced by a liver X receptor agonist in HepG2 cells. Regarding underlying mechanisms, MHY553 stimulated PPARα translocation into the nucleus and increased mRNA levels of its downstream genes related to fatty acid oxidation, including CPT-1A and ACOX1, without apparent change in lipogenesis signaling. Furthermore, MHY553 significantly suppresses inflammatory mRNA expression in old rats. In conclusion, MHY553 is a novel PPARα agonist that improved aged-induced hepatic steatosis, in part by increasing β-oxidation signaling and decreasing inflammation in the liver. MHY553 is a potential pharmaceutical agent for treating hepatic steatosis in aging.

  16. Modulation of cAMP levels by high fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression

    Science.gov (United States)

    Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlr-/- mice fed a high-fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of f...

  17. Curcumin attenuates skeletal muscle mitochondrial impairment in COPD rats: PGC-1α/SIRT3 pathway involved.

    Science.gov (United States)

    Zhang, Ming; Tang, Jingjing; Li, Yali; Xie, Yingying; Shan, Hu; Chen, Mingxia; Zhang, Jie; Yang, Xia; Zhang, Qiuhong; Yang, Xudong

    2017-11-01

    Curcumin has been widely used to treat numerous diseases due to its antioxidant property. The aim of the present study is to investigate the effect of curcumin on skeletal muscle mitochondria in chronic obstructive pulmonary disease (COPD) and its underlying mechanism. The rat model of COPD was established by cigarette smoke exposure combined with intratracheal administration of lipopolysaccharide. Airway inflammation and emphysema were notably ameliorated by the treatment with curcumin. Oral administration of curcumin significantly improved muscle fiber atrophy, myofibril disorganization, interstitial fibrosis and mitochondrial structure damage in the skeletal muscle of COPD rats. Mitochondrial enzyme activities of cytochrome c oxidase, succinate dehydrogenase, Na + /K + -ATPase and Ca 2+ -ATPase in skeletal muscle mitochondria from COPD rats were significantly increased after treatment with curcumin. Moreover, curcumin significantly decreased oxidative stress and inflammation by determining the levels of malondialdehyde, manganese superoxide dismutase, glutathione peroxidase, catalase, IL-6 and TNF-α in skeletal muscle of COPD rats. Furthermore, curcumin significantly increased the mRNA and protein expression of PGC-1α and SIRT3 in the skeletal muscle tissues of COPD rats. These results suggested that curcumin can attenuate skeletal muscle mitochondrial impairment in COPD rats possibly by the up-regulation of PGC-1α/SIRT3 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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.

  19. Predictors of anemia in women of reproductive age: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

    Science.gov (United States)

    Wirth, James P; Woodruff, Bradley A; Engle-Stone, Reina; Namaste, Sorrel Ml; Temple, Victor J; Petry, Nicolai; Macdonald, Barbara; Suchdev, Parminder S; Rohner, Fabian; Aaron, Grant J

    2017-07-01

    Background: Anemia in women of reproductive age (WRA) (age range: 15-49 y) remains a public health problem globally, and reducing anemia in women by 50% by 2025 is a goal of the World Health Assembly. Objective: We assessed the associations between anemia and multiple proximal risk factors (e.g., iron and vitamin A deficiencies, inflammation, malaria, and body mass index) and distal risk factors (e.g., education status, household sanitation and hygiene, and urban or rural residence) in nonpregnant WRA. Design: Cross-sectional, nationally representative data from 10 surveys ( n = 27,018) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and pooled by the infection burden and risk in the country. We examined the severity of anemia and measured the bivariate associations between anemia and factors at the country level and by infection burden, which we classified with the use of the national prevalences of malaria, HIV, schistosomiasis, sanitation, and water-quality indicators. Pooled multivariate logistic regression models were constructed for each infection-burden category to identify independent determinants of anemia (hemoglobin concertation <120 g/L). Results: Anemia prevalence was ∼40% in countries with a high infection burden and 12% and 7% in countries with moderate and low infection burdens, respectively. Iron deficiency was consistently associated with anemia in multivariate models, but the proportion of anemic women who were iron deficient was considerably lower in the high-infection group (35%) than in the moderate- and low-infection groups (65% and 71%, respectively). In the multivariate analysis, inflammation, vitamin A insufficiency, socioeconomic status, and age were also significantly associated with anemia, but malaria and vitamin B-12 and folate deficiencies were not. Conclusions: The contribution of iron deficiency to anemia varies according to a country's infection

  20. Predictors of anemia in women of reproductive age: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

    Science.gov (United States)

    Woodruff, Bradley A; Petry, Nicolai; Macdonald, Barbara; Aaron, Grant J

    2017-01-01

    Background: Anemia in women of reproductive age (WRA) (age range: 15–49 y) remains a public health problem globally, and reducing anemia in women by 50% by 2025 is a goal of the World Health Assembly. Objective: We assessed the associations between anemia and multiple proximal risk factors (e.g., iron and vitamin A deficiencies, inflammation, malaria, and body mass index) and distal risk factors (e.g., education status, household sanitation and hygiene, and urban or rural residence) in nonpregnant WRA. Design: Cross-sectional, nationally representative data from 10 surveys (n = 27,018) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and pooled by the infection burden and risk in the country. We examined the severity of anemia and measured the bivariate associations between anemia and factors at the country level and by infection burden, which we classified with the use of the national prevalences of malaria, HIV, schistosomiasis, sanitation, and water-quality indicators. Pooled multivariate logistic regression models were constructed for each infection-burden category to identify independent determinants of anemia (hemoglobin concertation Anemia prevalence was ∼40% in countries with a high infection burden and 12% and 7% in countries with moderate and low infection burdens, respectively. Iron deficiency was consistently associated with anemia in multivariate models, but the proportion of anemic women who were iron deficient was considerably lower in the high-infection group (35%) than in the moderate- and low-infection groups (65% and 71%, respectively). In the multivariate analysis, inflammation, vitamin A insufficiency, socioeconomic status, and age were also significantly associated with anemia, but malaria and vitamin B-12 and folate deficiencies were not. Conclusions: The contribution of iron deficiency to anemia varies according to a country’s infection burden. Anemia

  1. 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

  2. Association between local inflammation and breast tissue age-related lobular involution among premenopausal and postmenopausal breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Mirette Hanna

    Full Text Available Increased levels of pro-inflammatory markers and decreased levels of anti-inflammatory markers in the breast tissue can result in local inflammation. We aimed to investigate whether local inflammation in the breast tissue is associated with age-related lobular involution, a process inversely related to breast cancer risk. Levels of eleven pro- and anti-inflammatory markers were assessed by immunohistochemistry in normal breast tissue obtained from 164 pre- and postmenopausal breast cancer patients. Involution status of the breast (degree of lobular involution and the predominant lobule type was microscopically assessed in normal breast tissue on hematoxylin-eosin stained mastectomy slides. Multivariate generalized linear models were used to assess the associations. In age-adjusted analyses, higher levels of pro-inflammatory markers IL-6, TNF-α, CRP, COX-2, leptin, SAA1 and IL-8; and anti-inflammatory marker IL-10, were inversely associated with the prevalence of complete lobular involution (all P≤0.04. Higher levels of the pro-inflammatory marker COX-2 were also associated with lower prevalence of predominant type 1/no type 3 lobules in the breast, an indicator of complete involution, in age-adjusted analysis (P = 0.017. Higher tissue levels of inflammatory markers, mainly the pro-inflammatory ones, are associated with less involuted breasts and may consequently be associated with an increased risk of developing breast cancer.

  3. 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...

  4. Twenty-four hours hypothermia has temporary efficacy in reducing brain infarction and inflammation in aged rats

    DEFF Research Database (Denmark)

    Sandu, Raluca Elena; Buga, Ana Maria; Balseanu, Adrian Tudor

    2016-01-01

    in aged animals. Because the duration of hypothermia in most clinical trials is between 24 and 48 hours, we questioned whether 24 hours exposure to gaseous hypothermia confers the same neuroprotective efficacy as 48 hours exposure. We found that a shorter exposure to hypothermia transiently reduced both...... inflammation and infarct size. However, after 1 week, the infarct size became even larger than in controls and after 2 weeks there was no beneficial effect on regenerative processes such as neurogenesis. Behaviorally, hypothermia also had a limited beneficial effect. Finally, after hydrogen sulfide......-induced hypothermia, the poststroke aged rats experienced a persistent sleep impairment during their active nocturnal period. Our data suggest that cellular events that are delayed by hypothermia in aged rats may, in the long term, rebound, and diminish the beneficial effects....

  5. Curcumin use in pulmonary diseases: State of the art and future perspectives.

    Science.gov (United States)

    Lelli, Diana; Sahebkar, Amirhossein; Johnston, Thomas P; Pedone, Claudio

    2017-01-01

    Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa). It has been used for centuries in Ayurveda (Indian traditional medicine) for the treatment of several diseases. Over the last several decades, the therapeutic properties of curcumin have slowly been elucidated. It has been shown that curcumin has pleiotropic effects, regulating transcription factors (e.g., NF-kB), cytokines (e.g., IL6, TNF-alpha), adhesion molecules (e.g., ICAM-1), and enzymes (e.g., MMPs) that play a major role in inflammation and cancerogenesis. These effects may be relevant for several pulmonary diseases that are characterized by abnormal inflammatory responses, such as asthma or chronic obstructive pulmonary disease, acute respiratory distress syndrome, pulmonary fibrosis, and acute lung injury. Furthermore, some preliminary evidence suggests that curcumin may have a role in the treatment of lung cancer. The evidence for the use of curcumin in pulmonary disease is still sparse and has mostly been obtained using either in vitro or animal models. The most important issue with the use of curcumin in humans is its poor bioavailability, which makes it necessary to use adjuvants or curcumin nanoparticles or liposomes. The aim of this review is to summarize the available evidence on curcumin's effectiveness in pulmonary diseases, including lung cancer, and to provide our perspective on future research with curcumin so as to improve its pharmacological effects, as well as provide additional evidence of curcumin's efficacy in the treatment of pulmonary diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  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. Neuroprotective properties of curcumin in Alzheimer's disease--merits and limitations.

    Science.gov (United States)

    Chin, Dawn; Huebbe, Patricia; Pallauf, Kathrin; Rimbach, Gerald

    2013-01-01

    As demographics in developed nations shift towards an aging population, neurodegenerative pathologies, especially dementias such as Alzheimer's disease, pose one of the largest challenges to the modern health care system. Since there is yet no cure for dementia, there is great pressure to discover potential therapeutics for these diseases. One popular candidate is curcumin or diferuloylmethane, a polyphenolic compound that is the main curcuminoid found in Curcuma longa (family Zingiberaceae). In recent years, curcumin has been reported to possess anti-amyloidogenic, antiinflammatory, anti-oxidative, and metal chelating properties that may result in potential neuroprotective effects. Particularly, the hydrophobicity of the curcumin molecule hints at the possibility of blood-brain barrier penetration and accumulation in the brain. However, curcumin exhibits extremely low bioavailability, mainly due to its poor aqueous solubility, poor stability in solution, and rapid intestinal first-pass and hepatic metabolism. Despite the many efforts that are currently being made to improve the bioavailability of curcumin, brain concentration of curcumin remains low. Furthermore, although many have reported that curcumin possesses a relatively low toxicity profile, curcumin applied at high doses, which is not uncommon practice in many in vivo and clinical studies, may present certain dangers that in our opinion have not been addressed sufficiently. Herein, the neuroprotective potential of curcumin, with emphasis on Alzheimer's disease, as well as its limitations will be discussed in detail.

  8. 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.

  9. Excess ω-6 fatty acids influx in aging drives metabolic dysregulation, electrocardiographic alterations, and low-grade chronic inflammation.

    Science.gov (United States)

    Kain, Vasundhara; Ingle, Kevin A; Kachman, Maureen; Baum, Heidi; Shanmugam, Gobinath; Rajasekaran, Namakkal S; Young, Martin E; Halade, Ganesh V

    2018-02-01

    Maintaining a balance of ω-6 and ω-3 fatty acids is essential for cardiac health. Current ω-6 and ω-3 fatty acids in the American diet have shifted from the ideal ratio of 2:1 to almost 20:1; while there is a body of evidence that suggests the negative impact of such a shift in younger organisms, the underlying age-related metabolic signaling in response to the excess influx of ω-6 fatty acids is incompletely understood. In the present study, young (6 mo old) and aging (≥18 mo old) mice were fed for 2 mo with a ω-6-enriched diet. Excess intake of ω-6 enrichment decreased the total lean mass and increased nighttime carbohydrate utilization, with higher levels of cardiac cytokines indicating low-grade chronic inflammation. Dobutamine-induced stress tests displayed an increase in PR interval, a sign of an atrioventricular defect in ω-6-fed aging mice. Excess ω-6 fatty acid intake in aging mice showed decreased 12-lipoxygenase with a concomitant increase in 15-lipoxygenase levels, resulting in the generation of 15( S)-hydroxyeicosatetraenoic acid, whereas cyclooxygenase-1 and -2 generated prostaglandin E 2 , leukotriene B 4, and thromboxane B 2 . Furthermore, excessive ω-6 fatty acids led to dysregulated nuclear erythroid 2-related factor 2/antioxidant-responsive element in aging mice. Moreover, ω-6 fatty acid-mediated changes were profound in aging mice with respect to the eicosanoid profile while minimal changes were observed in the size and shape of cardiomyocytes. These findings provide compelling evidence that surplus consumption of ω-6 fatty acids, coupled with insufficient intake of ω-3 fatty acids, is linked to abnormal changes in ECG. These manifestations contribute to functional deficiencies and expansion of the inflammatory mediator milieu during later stages of aging. NEW & NOTEWORTHY Aging has a profound impact on the metabolism of fatty acids to maintain heart function. The excess influx of ω-6 fatty acids in aging perturbed

  10. Aging augments the impact of influenza respiratory tract infection on mobility impairments, muscle-localized inflammation, and muscle atrophy.

    Science.gov (United States)

    Bartley, Jenna M; Pan, Sarah J; Keilich, Spencer R; Hopkins, Jacob W; Al-Naggar, Iman M; Kuchel, George A; Haynes, Laura

    2016-04-01

    Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized that upon challenge with influenza, aging would be associated with functional impairments, as well as upregulation of skeletal muscle inflammatory and atrophy genes. Infected young and aged mice demonstrated decreased mobility and altered gait kinetics. These declines were more prominent in hind limbs and in aged mice. Skeletal muscle expression of genes involved in inflammation, as well as muscle atrophy and proteolysis, increased during influenza infection with an elevated and prolonged peak in aged mice. Infection also decreased expression of positive regulators of muscle mass and myogenesis components to a greater degree in aged mice. Gene expression correlated to influenza-induced body mass loss, although evidence did not support direct muscle infection. Overall, influenza leads to mobility impairments with induction of inflammatory and muscle degradation genes and downregulation of positive regulators of muscle. These effects are augmented and prolonged with aging, providing a molecular link between influenza infection, decreased resilience and increased risk of disability in the elderly.

  11. Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers.

    Directory of Open Access Journals (Sweden)

    Mohsen Khademi

    Full Text Available Inflammatory mediators have crucial roles in leukocyte recruitment and subsequent central nervous system (CNS neuroinflammation. The extent of neuronal injury and axonal loss are associated with the degree of CNS inflammation and determine physical disability in multiple sclerosis (MS. The aim of this study was to explore possible associations between a panel of selected cerebrospinal fluid biomarkers and robust clinical and demographic parameters in a large cohort of patients with MS and controls (n = 1066 using data-driven multivariate analysis. Levels of matrix metalloproteinase 9 (MMP9, chemokine (C-X-C motif ligand 13 (CXCL13, osteopontin (OPN and neurofilament-light chain (NFL were measured by ELISA in 548 subjects comprising different MS subtypes (relapsing-remitting, secondary progressive and primary progressive, clinically isolated syndrome and persons with other neurological diseases with or without signs of inflammation/infection. Principal component analyses and orthogonal partial least squares methods were used for unsupervised and supervised interrogation of the data. Models were validated using data from a further 518 subjects in which one or more of the four selected markers were measured. There was a significant association between increased patient age and lower levels of CXCL13, MMP9 and NFL. CXCL13 levels correlated well with MMP9 in the younger age groups, but less so in older patients, and after approximately 54 years of age the levels of CXCL13 and MMP9 were consistently low. CXCL13 and MMP9 levels also correlated well with both NFL and OPN in younger patients. We demonstrate a strong effect of age on both inflammatory and neurodegenerative biomarkers in a large cohort of MS patients. The findings support an early use of adequate immunomodulatory disease modifying drugs, especially in younger patients, and may provide a biological explanation for the relative inefficacy of such treatments in older patients at later

  12. Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility.

    Science.gov (United States)

    Wu, Y; Dong, G; Xiao, W; Xiao, E; Miao, F; Syverson, A; Missaghian, N; Vafa, R; Cabrera-Ortega, A A; Rossa, C; Graves, D T

    2016-04-01

    Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. © International & American Associations for Dental Research 2016.

  13. Elevated estimated arterial age is associated with metabolic syndrome and low-grade inflammation

    DEFF Research Database (Denmark)

    Greve, Sara V; Blicher, Marie K; Kruger, Ruan

    2016-01-01

    BACKGROUND: Arterial age can be estimated from equations relating arterial stiffness to age and blood pressure in large cohorts. We investigated whether estimated arterial age (eAA) was elevated in patients with the metabolic syndrome and/or known cardiovascular disease (CVD), which factors were...... of metabolic syndrome, Systematic COronary Risk Evaluation, or Framingham risk score. From age, mean blood pressure, and cfPWV, eAA and estimated cfPWV (ePWV) were calculated. In 2006, the combined cardiovascular endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke...

  14. Curcumin ameliorates cardiac dysfunction induced by mechanical trauma.

    Science.gov (United States)

    Li, Xintao; Cao, Tingting; Ma, Shuo; Jing, Zehao; Bi, Yue; Zhou, Jicheng; Chen, Chong; Yu, Deqin; Zhu, Liang; Li, Shuzhuang

    2017-11-05

    Curcumin, a phytochemical component derived from turmeric (Carcuma longa), has been extensively investigated because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play critical roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This research was designed to identify the protective effect of curcumin on posttraumatic cardiac dysfunction and investigate its underlying mechanism. Noble-Collip drum was used to prepare a mechanical trauma (MT) model of rats, and the hemodynamic responses of traumatized rats were observed by ventricular intubation 12h after trauma. Myocardial apoptosis was determined through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay. Tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) generated by monocytes and myocardial cells were identified through enzyme-linked immunosorbent assay (ELISA), and the intracellular alteration of Ca 2+ in cardiomyocytes was examined through confocal microscopy. In vivo, curcumin effectively ameliorated MT-induced secondary cardiac dysfunction and significantly decreased the apoptotic indices of the traumatized myocardial cells. In vitro, curcumin inhibited TNF-α production by monocytes and reduced the circulating TNF-α levels. With curcumin pretreatment, ROS production and Ca 2+ overload in H9c2 cells were attenuated when these cells were incubated with traumatic plasma. Therefore, curcumin can effectively ameliorate MT-induced cardiac dysfunction mainly by inhibiting systemic inflammatory responses and by weakening oxidative stress reaction and Ca 2+ overload in cardiomyocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Anti Inflammatory and Anti Arthritic Activity of Different Milk Based Formulation of Curcumin in Rat Model.

    Science.gov (United States)

    Sumeet, Gupta; Rachna, Kumria; Samrat, Chauhan; Ipshita, Chattopadhyaya; Vikas, Jhawat; Manu, Sharma

    2018-02-14

    Inflammation is the key mediator for arthritis. Plant based products are most useful for treating various disorders, but at the same time drug absorption is utmost important for effective therapy. The present aim of our study was to find out the therapeutic concern in pharmacokinetic and pharmacodynamic parameters in an arthritis induced rat model. Carregenan and complete Freud's adjuvant, both were used for an arthritis induction as an animal model. Formulation of curcumin was prepared in different quality of milk brand, high fat milk with ghee and in an aqueous suspension. They were administered orally to the rats for 21 days continuously. Different pharmacodyanmic parameters were analyzed which include percentage inhibition of inflammation, cytokines (IL-6 and TNF-α), hematological levels, X-Rays and histology condition. Pharmacokinetics was also determined like Cmax, Tmax and Kel using HPLC method. The result concludes that, curcumin in full fat milk with ghee and full fat curcumin formulation treated group showed a higher statistical significant effect in the prevention of inflammation in both the models. The presence of curcumin in plasma was higher only in full fat with ghee formulation and full fat milk formulation treated group when compared to the other groups. Hence, it concludes that the presence of adjuvant act as an enhancer can increase the bioavailability of curcumin for achieving maximum effectiveness. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Effect of Leisure Activities on Inflammation and Cognitive Function in an Aging Sample

    Science.gov (United States)

    Friedman, Elliot; Quinn, Jill; Chen, Ding-Geng (Din); Mapstone, Mark

    2012-01-01

    Cardiovascular disease risk factors (CVDRFs) increase the risk of dementia. The purpose of this study was to examine whether leisure activities (mental, physical, and social activities) modified the effect of CVDRFs on inflammatory markers and cognitive function in middle and old age. A secondary-data analysis study was conducted using data from 405 middle-age participants (40 –59 years) and 342 old-age participants (60 – 84 years) who participated in the Survey of Midlife Development in the United States. CVDRFs were obtained from a combination of self-report medical history and blood-based biomarkers. Three CVDRF groups (≤1, 2, and ≥3 CVDRFs) were identified. More CVDRFs were significantly associated with higher levels of inflammatory markers in both age groups, and associated with lower levels of executive function in the old age group. CVDRFs were not related to the frequency of leisure activities in either age group. After controlling for covariates, higher levels of physical activities were significantly associated with lower levels of inflammatory markers, and higher levels of mental activities were associated with higher levels of cognitive function. In the old age group, physical activities also moderated the effect of CVDRFs on episodic memory, and mental activities moderated the effect of CVDRFs on interleukin-6. Multiple CVDRFs may be associated with poorer cognitive function and higher inflammatory markers, but middle-age and older adults with CVDRFs may not engage in frequent physical and cognitive activities that may be protective. It is important to develop strategies to facilitate engagement in these activities from midlife. PMID:22377120

  17. Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination.

    Science.gov (United States)

    Ono, Taisuke; Takada, Shingo; Kinugawa, Shintaro; Tsutsui, Hiroyuki

    2015-09-01

    What is the central question of this study? We sought to examine whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. What is the main finding and its importance? We found that curcumin ameliorated skeletal muscle atrophy in streptozotocin-induced diabetic mice by inhibiting protein ubiquitination without affecting protein synthesis. This favourable effect of curcumin was possibly due to the inhibition of inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 diabetes mellitus. Skeletal muscle atrophy develops in patients with diabetes mellitus (DM), especially in type 1 DM, which is associated with chronic inflammation. Curcumin, the active ingredient of turmeric, has various biological actions, including anti-inflammatory and antioxidant properties. We hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with streptozotocin-induced type 1 DM. C57BL/6 J mice were injected with streptozotocin (200 mg kg(-1) i.p.; DM group) or vehicle (control group). Each group of mice was randomly subdivided into two groups of 10 mice each and fed a diet with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks. There were significant decreases in body weight, skeletal muscle weight and cellular cross-sectional area of the skeletal muscle in DM mice compared with control mice, and these changes were significantly attenuated in DM+Curcumin mice without affecting plasma glucose and insulin concentrations. Ubiquitination of protein was increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene expressions of muscle-specific ubiquitin E3 ligase atrogin-1/MAFbx and MuRF1 were increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor-κB activation, concentrations of the inflammatory cytokines tumour necrosis factor-α and interleukin-1β and oxidative

  18. Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

    Science.gov (United States)

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-01-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

  19. The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation

    Science.gov (United States)

    Machova Urdzikova, Lucia; Karova, Kristyna; Ruzicka, Jiri; Kloudova, Anna; Shannon, Craig; Dubisova, Jana; Murali, Raj; Kubinova, Sarka; Sykova, Eva; Jhanwar-Uniyal, Meena; Jendelova, Pavla

    2015-01-01

    Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9–T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury. PMID:26729105

  20. Implication of Free Fatty Acids in Thrombin Generation and Fibrinolysis in Vascular Inflammation in Zucker Rats and Evolution with Aging

    Directory of Open Access Journals (Sweden)

    Jérémy Lagrange

    2017-11-01

    Full Text Available Background: The metabolic syndrome (MetS and aging are associated with modifications in blood coagulation factors, vascular inflammation, and increased risk of thrombosis.Objectives: Our aim was to determine concomitant changes in thrombin generation in the blood compartment and at the surface of vascular smooth muscle cells (VSMCs and its interplay with adipokines, free fatty acids (FFA, and metalloproteinases (MMPs in obese Zucker rats that share features of the human MetS.Methods: Obese and age-matched lean Zucker rats were compared at 25 and 80 weeks of age. Thrombin generation was assessed by calibrated automated thrombography (CAT.Results: Endogenous thrombin potential (ETP was increased in obese rats independent of platelets and age. Clot half-lysis time was delayed with obesity and age. Interleukin (IL-1β and IL-13 were increased with obesity and age respectively. Addition of exogenous fibrinogen, leptin, linoleic, or palmitic acid increased thrombin generation in plasma whereas adiponectin had an opposite effect. ETP was increased at the surface of VSMCs from obese rats and addition of exogenous palmitic acid further enhanced ETP values. Gelatinase activity was increased in aorta at both ages in obese rats and MMP-2 activity was increased in VSMCs from obese rats.Conclusions: Our study demonstrated in MetS an early prothrombotic phenotype of the blood compartment reinforced by procoagulant properties of dedifferentiated and inflammatory VSMCs. Mechanisms involved (1 increased fibrinogen and impaired fibrinolysis and (2 increased saturated fatty acids responsible for additive procoagulant effects. Whether specifically targeting this hypercoagulability using direct thrombin inhibitors would improve outcome in MetS is worth investigating.

  1. Amelioration of FCA induced arthritis on topical application of curcumin in combination with emu oil.

    Science.gov (United States)

    Jeengar, Manish Kumar; Shrivastava, Shweta; Mouli Veeravalli, S Chandra; Naidu, V G M; Sistla, Ramakrishna

    2016-09-01

    The aim of the present study was to investigate the skin penetration potential of emu oil and the possibility of enhancing the antiarthritic potential of lipophilic bioactive curcumin, which has poor permeability through biological membranes. Solubility and ex vivo skin permeation studies were performed with water, corn oil, and emu oil as a vehicle using curcumin as a model drug. Carrageenan induced inflammation and Freund's complete adjuvant-induced arthritic rat models were used to evaluate enhanced antiinflammatory and antiarthritic effect of curcumin in combination of emu oil via topical route. The skin permeation study resulted in the combination of emu oil with curcumin enhancing the flux 1.84 and 4.25 times through the rat skin compared to corn oil and water, respectively. Results of carrageenan induced rat paw edema model demonstrated that percentage of paw inhibition shown by curcumin-emu oil combination was 1.42-fold more compared to the total effect shown by both groups treated with curcumin aqueous suspension and emu oil per se. In Freund's complete adjuvant-induced arthritic model, the combined treatment was effective in bringing significant changes in the functional, biochemical, histopathologic, and radiologic parameters. Topical application of curcumin-emu oil combination resulted in significant reduced levels of proinflammatory mediators TNF-α, IL-1 β, and IL-6 (P curcumin with emu oil holds promise as a noninvasive and efficacious intervention for the treatment of inflammatory arthritis and it assists in further development of a topical formulation of curcumin using emu oil as a vehicle. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. 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...

  3. 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).

  4. Polyphenols found in berry fruit improve age-associated changes in cognitive function and brain inflammation

    Science.gov (United States)

    Research has demonstrated, in both human and animals, that cognitive functioning decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associat...

  5. Curcumin Attenuates Methotrexate-Induced Hepatic Oxidative Damage in Rats

    International Nuclear Information System (INIS)

    HEMEIDA, R.A.M.; MOHAFEZ, O.M.

    2008-01-01

    In the present study, we have addressed the ability of curcumin to suppress MTX-induced liver damage. Hepatotoxicity was induced by injection of a single dose of MTX (20 mg/kg I.P.). MTX challenge induced liver damage that was well characterized histopathologically and biochemically. MTX increased relative liver/body weight ratio. Histologically, MTX produced fatty changes in hepatocytes and sinusoidal lining cells, mild necrosis and inflammation. Biochemically, the test battery entailed elevated activities of serum ALT and AST. Liver activities of superoxide dismutase (SOD), catalase (CAT) and level of reduced glutathione (GSH), were notably reduced, while lipid peroxidation, expressed as malondialdhyde (MDA) level was significantly increased. Administration of curcumin (100mg/kg, I.P.) once daily for 5 consecutive days after MTX challenge mitigated the injurious effects of MTX and ameliorated all the altered biochemical parameters. These results showed that administration of curcumin decreases MTX-induced liver damage probably via regulation of oxidant/anti-oxidant balance. In conclusion, the present study indicates that curcumin may be of therapeutic benefit against MTX-cytotoxicity.

  6. Aging of in vitro pulp illustrates change of inflammation and dentinogenesis.

    Science.gov (United States)

    Lee, Young-Hee; Kim, Go-Eun; Cho, Hye-Jin; Yu, Mi-Kyoung; Bhattarai, Govinda; Lee, Nan-Hee; Yi, Ho-Keun

    2013-03-01

    Dental pulp functions include pulp cell activity involvement in dentin formation. In this study we investigated the age-related changes in dental pulp cells that may influence pulp cell activity for restoring pulp function. Human dental pulp cells (HDPCs) were serially subcultured until spontaneously arrested. Altered expression of chronic inflammatory molecules and age-related molecules were determined by Western blotting. Odontogenic functions impaired by senescence were assayed by Western blotting, reverse transcriptase polymerase chain reaction, alkaline phosphatase activity, and alizarin red S staining. To understand the mechanism of aging process by stress-induced premature senescence (SIPS), the cells were treated with H(2)O(2). Replicative senescence and SIPS were also compared. Replicative senescence of HDPCs was characterized by senescence-associated β-galactosidase activity and reactive oxygen species formation. These cells exhibited altered expression of chronic inflammatory molecules such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1, peroxisome proliferator activated receptor-gamma, and heme oxygenase-1 and age-related molecules such as p53, p21, phosphorylated-extracellular signal-regulated kinase, and c-myb. SIPS cell results were similar to replicative senescence. Furthermore, HDPCs decreased odontogenic markers such as dentin sialophosphoprotein and dentin matrix-1 and osteogenic markers such as bone morphogenetic protein-2 and -7, runt-related transcription factor-2, osteopontin, alkaline phosphatase activity, and mineralized nodule formation by replicative senescence and SIPS. This study suggests that development of aging-related molecules in pulp cells offers understanding of cellular mechanisms and biological events responsible for tooth preservation and maintenance strategies for healthy teeth across the life span. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Long-term trihexyphenidyl exposure alters neuroimmune response and inflammation in aging rat: relevance to age and Alzheimer's disease.

    Science.gov (United States)

    Huang, Yuqi; Zhao, Zhe; Wei, Xiaoli; Zheng, Yong; Yu, Jianqiang; Zheng, Jianquan; Wang, Liyun

    2016-07-01

    Clinical studies have shown an association between long-term anticholinergic (AC) drug exposure and Alzheimer's disease (AD) pathogenesis, which has been primarily investigated in Parkinson's disease (PD). However, long-term AC exposure as a risk factor for developing neurodegenerative disorders and the exact mechanisms and potential for disease progression remain unclear. Here, we have addressed the issue using trihexyphenidyl (THP), a commonly used AC drug in PD patients, to determine if THP can accelerate AD-like neurodegenerative progression and study potential mechanisms involved. Male Sprague-Dawley rats (SD) were intraperitoneally injected with THP (0.3 and 1.0 mg/kg) or normal saline (NS) for 7 months. Alterations in cognitive and behavioral performance were assessed using the Morris water maze (MWM) and open field tests. After behavior tests, whole genome oligo microarrays, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunofluorescence-confocal were used to investigate the global mechanisms underlying THP-induced neuropathology with aging. Compared with NS controls, the MWM test results showed that THP-treated rats exhibited significantly extended mean latencies during the initial 3 months of testing; however, this behavioral deficit was restored between the fourth and sixth month of MWM testing. The same tendencies were confirmed by MWM probe and open field tests. Gene microarray analysis identified 68 (47 %) upregulated and 176 (53 %) downregulated genes in the "THP-aging" vs. "NS-aging" group. The most significant populations of genes downregulated by THP were the immune response-, antigen processing and presentation-, and major histocompatibility complex (MHC)-related genes, as validated by qRT-PCR. The decreased expression of MHC class I in THP-treated aging brains was confirmed by confocal analysis. Notably, long-term THP treatment primed hippocampal and cortical microglia to

  8. Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease.

    Science.gov (United States)

    Reddy, P Hemachandra; Manczak, Maria; Yin, Xiangling; Grady, Mary Catherine; Mitchell, Andrew; Tonk, Sahil; Kuruva, Chandra Sekhar; Bhatti, Jasvinder Singh; Kandimalla, Ramesh; Vijayan, Murali; Kumar, Subodh; Wang, Rui; Pradeepkiran, Jangampalli Adi; Ogunmokun, Gilbert; Thamarai, Kavya; Quesada, Kandi; Boles, Annette; Reddy, Arubala P

    2018-01-01

    The purpose of our article is to assess the current understanding of Indian spice, curcumin, against amyloid-β (Aβ)-induced toxicity in Alzheimer's disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes, and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on Aβ and curcumin has revealed that curcumin prevents Aβ aggregation and crosses the blood-brain barrier, reach brain cells, and protect neurons from various toxic insults of aging and Aβ in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin's bioavailability and urgent need for new formulations to increase its brain levels to treat patients with AD.

  9. The effect of astaxanthin on the aging rat brain: gender-related differences in modulating inflammation.

    Science.gov (United States)

    Balietti, Marta; Giannubilo, Stefano R; Giorgetti, Belinda; Solazzi, Moreno; Turi, Angelo; Casoli, Tiziana; Ciavattini, Andrea; Fattorettia, Patrizia

    2016-01-30

    Astaxanthin (Ax) is a ketocarotenoid of the xanthophyll family with activities such as antioxidation, preservation of the integrity of cell membranes and protection of the redox state and functional integrity of mitochondria. The aim of this study was to investigate potential gender-related differences in the effect of Ax on the aging rat brain. In females, interleukin 1 beta (IL1β) was significantly lower in treated rats in both cerebral areas, and in the cerebellum, treated animals also had significantly higher IL10. In males, no differences were found in the cerebellum, but in the hippocampus, IL1β and IL10 were significantly higher in treated rats. These are the first results to show gender-related differences in the effect of Ax on the aging brain, emphasizing the necessity to carefully analyze female and male peculiarities when the anti-aging potentialities of this ketocarotenoid are evaluated. The observations lead to the hypothesis that Ax exerts different anti-inflammatory effects in female and male brains. © 2015 Society of Chemical Industry.

  10. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    Directory of Open Access Journals (Sweden)

    Funamoto M

    2016-08-01

    Full Text Available Masafumi Funamoto,1,2 Yoichi Sunagawa,1–3 Yasufumi Katanasaka,1–3 Yusuke Miyazaki,1,2 Atsushi Imaizumi,4 Hideaki Kakeya,5 Hajime Yamakage,2 Noriko Satoh-Asahara,2 Maki Komiyama,2 Hiromichi Wada,2 Koji Hasegawa,2 Tatsuya Morimoto1–3 1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 2Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, 3Shizuoka General Hospital, Shizuoka, 4Theravalues Corporation, Kioicho, Tokyo, 5Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan Purpose: COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD.Patients and methods: This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated.Results: There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure

  11. Ursodeoxycholic acid decreases age-related adiposity and inflammation in mice

    Science.gov (United States)

    Oh, Ah-Reum; Bae, Jin-Sik; Lee, Junghoon; Shin, Eunji; Oh, Byung-Chul; Park, Sang-Chul; Cha, Ji-Young

    2016-01-01

    Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli. [BMB Reports 2016; 49(2): 105-110] PMID:26350747

  12. Curcumin Attenuates on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Modulation of the Nrf2/HO-1 and TGF-β1/Smad3 Pathway

    Directory of Open Access Journals (Sweden)

    Xinyan Peng

    2018-01-01

    Full Text Available This study aimed to investigate the protective effect of curcumin against carbon tetrachloride (CCl4-induced acute liver injury in a mouse model, and to explain the underlying mechanism. Curcumin at doses of 50, 100 and 200 mg/kg/day were administered orally once daily for seven days prior to CCl4 exposure. At 24 h, curcumin-attenuated CCl4 induced elevated serum transaminase activities and histopathological damage in the mouse’s liver. Curcumin pre-treatment at 50, 100 and 200 mg/kg significantly ameliorated CCl4-induced oxidative stress, characterized by decreased malondialdehyde (MDA formations, and increased superoxide dismutase (SOD, catalase (CAT activities and glutathione (GSH content, followed by a decrease in caspase-9 and -3 activities. Curcumin pre-treatment significantly decreased CCl4-induced inflammation. Furthermore, curcumin pre-treatment significantly down-regulated the expression of TGF-β1 and Smad3 mRNAs (both p < 0.01, and up-regulated the expression of nuclear-factor erythroid 2-related factor 2 (Nrf2 and HO-1 mRNA (both p < 0.01 in the liver. Inhibition of HO-1 attenuated the protective effect of curcumin on CCl4-induced acute liver injury. Given these outcomes, curcumin could protect against CCl4-induced acute liver injury by inhibiting oxidative stress and inflammation, which may partly involve the activation of Nrf2/HO-1 and inhibition of TGF-β1/Smad3 pathways.

  13. Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium

    International Nuclear Information System (INIS)

    Rennolds, Jessica; Malireddy, Smitha; Hassan, Fatemat; Tridandapani, Susheela; Parinandi, Narasimham; Boyaka, Prosper N.; Cormet-Boyaka, Estelle

    2012-01-01

    Highlights: ► Cadmium induces secretion of IL-6 and IL-8 by two distinct pathways. ► Cadmium increases NAPDH oxidase activity leading to Erk activation and IL-8 secretion. ► Curcumin prevents cadmium-induced secretion of both IL-6 and IL-8 by airway cells. ► Curcumin could be use to suppress lung inflammation due to cadmium inhalation. -- Abstract: Cadmium is a toxic metal present in the environment and its inhalation can lead to pulmonary disease such as lung cancer and chronic obstructive pulmonary disease. These lung diseases are characterized by chronic inflammation. Here we show that exposure of human airway epithelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory cytokines known to play an important role in pulmonary inflammation. We also determined that two distinct pathways controlled secretion of these proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL-6 secretion occurs via an NF-κB dependent pathway, whereas IL-8 secretion involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human airway epithelial cells. In conclusion, curcumin could be used to prevent airway inflammation due to cadmium inhalation.

  14. Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Rennolds, Jessica; Malireddy, Smitha; Hassan, Fatemat; Tridandapani, Susheela; Parinandi, Narasimham [Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210 (United States); Boyaka, Prosper N. [Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210 (United States); Cormet-Boyaka, Estelle, E-mail: Estelle.boyaka@osumc.edu [Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210 (United States)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Cadmium induces secretion of IL-6 and IL-8 by two distinct pathways. Black-Right-Pointing-Pointer Cadmium increases NAPDH oxidase activity leading to Erk activation and IL-8 secretion. Black-Right-Pointing-Pointer Curcumin prevents cadmium-induced secretion of both IL-6 and IL-8 by airway cells. Black-Right-Pointing-Pointer Curcumin could be use to suppress lung inflammation due to cadmium inhalation. -- Abstract: Cadmium is a toxic metal present in the environment and its inhalation can lead to pulmonary disease such as lung cancer and chronic obstructive pulmonary disease. These lung diseases are characterized by chronic inflammation. Here we show that exposure of human airway epithelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory cytokines known to play an important role in pulmonary inflammation. We also determined that two distinct pathways controlled secretion of these proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL-6 secretion occurs via an NF-{kappa}B dependent pathway, whereas IL-8 secretion involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human airway epithelial cells. In conclusion, curcumin could be used to prevent airway inflammation due to cadmium inhalation.

  15. Potential Role of Curcumin Against Biofilm-Producing Organisms on the Skin: A Review.

    Science.gov (United States)

    Vaughn, Alexandra R; Haas, Kelly N; Burney, Waqas; Andersen, Erich; Clark, Ashley K; Crawford, Robert; Sivamani, Raja K

    2017-12-01

    Turmeric root (Curcuma longa) is predominantly used as a spice, but has also long been known to possess antimicrobial, analgesic, antiinflammatory, and anticancer properties. One predominant group of active compounds in turmeric are curcuminoids, namely bright yellow-pigmented curcumin. While modern science has yet to fully investigate the therapeutic claims of turmeric and its derivatives, results have proven promising in decreasing pain and inflammation in arthritis, improving insulin sensitivity in diabetes, and even curing a variety of infections. The purpose of this review is to discuss the potential for curcumin as an agent against microbial infections, with a special focus on the skin and in the development of bacterial biofilms. Curcumin has demonstrated bactericidal efficacy against a variety of infections when administered with antibiotics in several clinical studies, with consistent antimicrobial activity demonstrated in vitro, as well as in urinary tract infections, gingival infections, and chronic wound infections. Hypothesized mechanisms of action include curcumin's ability to perturb bacterial membranes, disturb protofillament assembly, and even impair bacterial virulence factors. Further investigation is needed to fully understand which organisms are most susceptible to the effects of curcumin and how curcumin can be implemented in dermatology to treat skin conditions such as chronic wounds and acne vulgaris. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Inhibition of 12/15 lipoxygenase by curcumin and an extract from Curcuma longa L.

    Science.gov (United States)

    Bezáková, Lýdia; Košťálová, Daniela; Obložinský, Marek; Hoffman, Peter; Pekárová, Mária; Kollárová, Renáta; Holková, Ivana; Mošovská, Silvia; Sturdík, Ernest

    2014-02-01

    Curcumin (diferuloylmethane) is an orange-yellow secondary metabolic compound from the rhizome of turmeric (Curcuma longa L.), a spice often found in curry powder. It is one of the major curcuminoids of turmeric. For centuries, curcumin has been used in some medicinal preparations or as a food colouring agent. A variety of enzymes that are closely associated with inflammation and cancer were found to be modulated by curcumin. This paper summarized the results of the inhibitory effect of curcumin and a Curcuma longa L. ethanolic extract on lipoxygenase from the rat lung cytosolic fraction. The positional specificity determination of arachidonic acid dioxygenation by RP- and SP-HPLC methods showed that in a purified enzyme preparation from the rat lung cytosol the specific form of lipoxygenase (LOX) is present exhibiting 12/15-LOX dual specificity (with predominant 15-LOX activity). The inhibitory activity of curcumin and Curcuma longa extract on LOX from cytosolic fraction of rat lung was expressed in the percentage of inhibition and as IC50. Lineweaver-Burk plot analysis has indicated that curcumin is the competitive inhibitor of 12/15 LOX from the rat lung cytosolic fraction.

  17. Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis

    Directory of Open Access Journals (Sweden)

    Xuejiao Sun

    2017-01-01

    Full Text Available Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E-1,5-bis(2-bromophenyl penta-1,4-dien-3-one(B06 in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years. Curcumin exerts antifibrotic effect through reducing inflammation related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and cav-1 and inducing the expression of anti-inflammation factors (HO-1, M6PRBP1, and NEDD4 as well as targeting TGF-β/Smads, MAPK/ERK, and PPAR-γ pathways in animal models. As a food derived compound, curcumin is becoming a promising drug candidate for improving renal health.

  18. Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin.

    Science.gov (United States)

    Deck, Lorraine M; Hunsaker, Lucy A; Vander Jagt, Thomas A; Whalen, Lisa J; Royer, Robert E; Vander Jagt, David L

    2018-01-01

    Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC 50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues. Copyright © 2017. Published by Elsevier Masson SAS.

  19. Curcumin Attenuates Lipopolysaccharide-Induced Hepatic Lipid Metabolism Disorder by Modification of m6 A RNA Methylation in Piglets.

    Science.gov (United States)

    Lu, Na; Li, Xingmei; Yu, Jiayao; Li, Yi; Wang, Chao; Zhang, Lili; Wang, Tian; Zhong, Xiang

    2018-01-01

    N 6 -methyladenosine (m 6 A) regulates gene expression and affects cellular metabolism. In this study, we checked whether the regulation of lipid metabolism by curcumin is associated with m 6 A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)-induced liver injury and lipid metabolism disorder, and on m 6 A RNA methylation in weaned piglets. A total of 24 Duroc × Large White × Landrace piglets were randomly assigned to control, LPS, and CurL (LPS challenge and 200 mg/kg dietary curcumin) groups (n = 8/group). The results showed that curcumin reduced the increase in relative liver weight as well as the concentrations of aspartate aminotransferase and lactate dehydrogenase induced by LPS injection in the plasma and liver of weaning piglets (p < 0.05). The amounts of total cholesterol and triacylglycerols were decreased by curcumin compared to that by the LPS injection (p < 0.05). Additionally, curcumin reduced the expression of Bcl-2 and Bax mRNA, whereas it increased the p53 mRNA level in the liver (p < 0.05). Curcumin inhibited the enhancement of SREBP-1c and SCD-1 mRNA levels induced by LPS in the liver. Notably, dietary curcumin affected the expression of METTL3, METTL14, ALKBH5, FTO, and YTHDF2 mRNA, and increased the abundance of m 6 A in the liver of piglets. In conclusion, the protective effect of curcumin in LPS-induced liver injury and hepatic lipid metabolism disruption might be due to the increase in m 6 A RNA methylation. Our study provides mechanistic insights into the effect of curcumin in protecting against hepatic injury during inflammation and metabolic diseases. © 2018 AOCS.

  20. Curcumin reverses neurochemical, histological and immuno-histochemical alterations in the model of global brain ischemia

    Directory of Open Access Journals (Sweden)

    Glaura Fernandes Teixeira de Alcântara

    2017-01-01

    Full Text Available Curcumin, a curcuminoid from Curcuma longa, presents antioxidant and anti-inflammatory actions and, among pathological changes of cerebral ischemic injury, inflammation is an important one. The objectives were to study the neuroprotective action of curcumin, in a model of global ischemia. Male Wistar rats (sham-operated, ischemic untreated and ischemic treated with curcumin, 25 or 50 mg/kg, p.o. were anesthesized and their carotid arteries occluded, for 30 min. The SO group had the same procedure, except for carotid occlusion. In the 1st protocol, animals were treated 1 h before ischemia and 24 h later; and in the 2nd protocol, treatments began 1 h before ischemia, continuing for 7 days. Twenty four hours after the last administration, animals were euthanized and measurements for striatal monoamines were performed, at the 1st and 7th days after ischemia, as well as histological and immunohistochemical assays in hippocampi. We showed in both protocols, depletions of DA and its metabolites (DOPAC and HVA, in the ischemic group, but these effects were reversed by curcumin. Additionally, a decrease seen in 5-HT contents, 1 day after ischemia, was also reversed by curcumin. This reversion was not seen 7 days later. On the other hand, a decrease observed in NE levels, at the 7th day, was totally reversed by curcumin. Furthermore, curcumin treatments increased neuronal viability and attenuated the immunoreactivity for COX-2 and TNF-alpha, in the hippocampus in both protocols. We showed that curcumin exerts neuroprotective actions, in a model of brain ischemia that are probably related to its anti-inflammatory activity.

  1. 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

  2. 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.

  3. Inflammation and prolonged QT time: results from the Cardiovascular Disease, Living and Ageing in Halle (CARLA study.

    Directory of Open Access Journals (Sweden)

    Daniel Medenwald

    Full Text Available Previous research found an association of CRP with QT time in population based samples. Even more, there is evidence of a substantial involvement of the tumor necrosis factor-alpha system in the pathophysiology of cardiac arrhythmia, while the role of Interleukin 6 remains inconclusive.To determine the association between inflammation with an abnormally prolonged QT-time (APQT in men and women of the elderly general population.Data descend from the baseline examination of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA Study. After exclusion of subjects with atrial fibrillation and missing ECG recording the final study cohort consisted of 919 men and 797 women. Blood parameters of inflammation were the soluble TNF-Receptor 1 (sTNF-R1, the high-sensitive C-reactive protein (hsCRP, and Interleukin 6 (IL-6. In accordance with major cardiologic societies we defined an APQT above a QT time of 460 ms in women and 450 ms in men. Effect sizes and the corresponding 95% confidence intervals (CI were estimated by performing multiple linear and logistic regression analyses including the analysis of sex differences by interaction terms.After covariate adjustment we found an odds ratio (OR of 1.89 (95% CI: 1.13, 3.17 per 1000 pg/mL increase of sTNF-R1 in women, and 0.74 (95% CI: 0.48, 1.15 in men. In the covariate adjusted linear regression sTNF-R1 was again positively associated with QT time in women (5.75 ms per 1000 pg/mL, 95% CI: 1.32, 10.18, but not in men. Taking possible confounders into account IL-6 and hsCRP were not significantly related to APQT in both sexes.Our findings from cross-sectional analyses give evidence for an involvement of TNF-alpha in the pathology of APQT in women.

  4. Effects of curcumin consumption on human chronic diseases: A narrative review of the most recent clinical data.

    Science.gov (United States)

    Mantzorou, Maria; Pavlidou, Eleni; Vasios, George; Tsagalioti, Eftychia; Giaginis, Constantinos

    2018-06-01

    Numerous clinical trials have investigated the potential beneficial effects of curcumin supplementation against several human chronic diseases. Up to now, it has been claimed that curcumin consumption may exert beneficial effects against several chronic diseases by promoting human health and preventing diseases. In this aspect, the present review aims to critically collect and in-depth summarize the most recent, well-designed clinical studies evaluating the potential beneficial effects of curcumin consumption on human health promotion and disease prevention. According to recent and well-designed clinical studies, curcumin consumption may benefit against obesity, metabolic syndrome, and diabetes. Moreover, curcumin consumption seems to exert a positive effect on people suffering from various types of cancer, fatty liver disease, depression, arthritis, skin diseases, gut inflammation, and symptoms of premenstrual syndrome. Due to the strong heterogeneity among the clinical studies concerning the exact effective curcumin dose and formulation, as well as the recommended treatment duration for each chronic disease, no precise and definitive conclusions could be drawn. Further large-scale prospective studies are strongly recommended, being well-designed as far as follow-up times, dosage, formulation, and duration of curcumin supplementation are concerned. Moreover, potential confounders in each specific chronic disease should carefully be taken into account in future studies. Copyright © 2018 John Wiley & Sons, Ltd.

  5. Oral administration of curcumin (Curcuma longa) can attenuate the neutrophil inflammatory response in zymosan-induced arthritis in rats.

    Science.gov (United States)

    Nonose, Nilson; Pereira, José Aires; Machado, Paulo Roberto Moura; Rodrigues, Murilo Rocha; Sato, Daniela Tiemi; Martinez, Carlos Augusto Real

    2014-11-01

    To evaluate the effect of curcumin in the acute phase of zymosan-induced arthritis. Twenty-eight male rats were subjected to intra-articular infiltration of zymosan of both knees and, in four the infiltration was made with saline. The animals were divided into five groups second received every six hours by gavage: corn oil by (positive and negative control); curcumin (100 mg/kg); prednisone 1 mg/kg/day; prednisone 8 mg/kg. All animals were sacrificed after six, 12, 24 and 48 hours of the infiltration. The knees were removed for evaluation of neutrophil infiltration. The number of neutrophils was counted by computer-assisted analysis of the images. The neutrophil infiltrate was stratified into four grades: 0 = normal; + = mild; ++/+++ = moderate; > ++++ = severe. The results were compared using the Mann-Whitney test and the variance by Kruskal-Wallis test adopting a significance level of 5% (pCurcumin reduces inflammatory activity in the first six hours after zymosan-induced arthritis when compared to saline (pCurcumin was more effective than lower doses of prednisone in the first six hours after induction of the arthritis. After 12, 24 and 48 hours, curcumin does not have the same anti-inflammatory effects when compared to prednisone. After 48 hours, prednisone is more effective than curcumin in reducing the inflammatory infiltrate regardless of the dose of prednisone used. Oral administration of curcumin reduces inflammation in the first six hours after experimentally zymosan-induced arthritis.

  6. The Potential Therapeutic Effect of Curcumin on the Adjuvant-induced Arthritis in Irradiated Rats

    International Nuclear Information System (INIS)

    El-Ghazaly, M.A.; Nada, A.S.; Hegazy, M.E.; Kenawy, S.A.

    2010-01-01

    Naturalistic that provide medical or health benefits, including prevention and treatment of diseases. They may be advantageous in inflammation and exposure to radiation. The study was conducted to investigate curcumin potential to modulate, counteract or prevent the inflammatory response induced in arthritic irradiated and non-irradiated rats using the adjuvant-induced arthritis model. Diclofenac was used as a reference standard non-steroidal anti-inflammatory drug (NSAID). Results indicated that exposure of rats to single dose of gamma-radiation (6 Gy) before induction of inflammation increased production of prostaglandin E2 (PGE2), tumour necrosis factor-gamma (TNF-gamma) and malondialdehyde (MDA) levels in serum. Blood glutathione (GSH) was shown to be reduced in irradiated animals. Curcumin suppressed the elevated levels of TNF-gamma, PGE2 and MDA and was able to restore blood GSH level. Reduction in liver contents of copper (Cu), zinc (Zn), selenium (Se) and iron (Fe) was recorded in animals irradiated before induction of inflammation. In addition, curcumin restored the hepatic contents of these trace elements. The present results suggest that irradiation of rats caused marked changes in the inflammatory response, while curcumin suppressed the inflammatory response in both irradiated and normal rats

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. Effect of inhaled hydrosoluble curcumin on inflammatory markers in broncho-alveolar lavage fluid of horses with LPS-induced lung neutrophilia

    OpenAIRE

    Sandersen, Charlotte; Bienzle, Dorothee; Cerri, Simona; Franck, Thierry; Derochette, Sandrine; Neven, Philippe; Mouytis-Mickalad, Ange; Serteyn, Didier

    2015-01-01

    Background Horses commonly suffer from chronic respiratory disease and are also used in large animal models of spontaneous or induced airway inflammation. The anti-inflammatory properties of curcumin are largely described but its low bioavailability precludes its clinical use. NDS27, a lysin salt of curcumin incorporated in beta-cyclodextrine, has high bioavailability and can be administered by inhalation. The aim of this study was to investigate the effects of inhaled NDS27 on inflammatory c...

  12. Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis.

    Science.gov (United States)

    Kalinkovich, Alexander; Livshits, Gregory

    2017-05-01

    Sarcopenia, an age-associated decline in skeletal muscle mass coupled with functional deterioration, may be exacerbated by obesity leading to higher disability, frailty, morbidity and mortality rates. In the combination of sarcopenia and obesity, the state called sarcopenic obesity (SOB), some key age- and obesity-mediated factors and pathways may aggravate sarcopenia. This review will analyze the mechanisms underlying the pathogenesis of SOB. In obese adipose tissue (AT), adipocytes undergo hypertrophy, hyperplasia and activation resulted in accumulation of pro-inflammatory macrophages and other immune cells as well as dysregulated production of various adipokines that together with senescent cells and the immune cell-released cytokines and chemokines create a local pro-inflammatory status. In addition, obese AT is characterized by excessive production and disturbed capacity to store lipids, which accumulate ectopically in skeletal muscle. These intramuscular lipids and their derivatives induce mitochondrial dysfunction characterized by impaired β-oxidation capacity and increased reactive oxygen species formation providing lipotoxic environment and insulin resistance as well as enhanced secretion of some pro-inflammatory myokines capable of inducing muscle dysfunction by auto/paracrine manner. In turn, by endocrine manner, these myokines may exacerbate AT inflammation and also support chronic low grade systemic inflammation (inflammaging), overall establishing a detrimental vicious circle maintaining AT and skeletal muscle inflammation, thus triggering and supporting SOB development. Under these circumstances, we believe that AT inflammation dominates over skeletal muscle inflammation. Thus, in essence, it redirects the vector of processes from "sarcopenia→obesity" to "obesity→sarcopenia". We therefore propose that this condition be defined as "obese sarcopenia", to reflect the direction of the pathological pathway. Copyright © 2016 Elsevier B.V. All rights

  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. Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus.

    Science.gov (United States)

    Hong, Yan; Shen, Chao; Yin, Qingqing; Sun, Menghan; Ma, Yingjuan; Liu, Xueping

    2016-05-01

    An increased level of advanced glycation end products (AGEs) is observed in brains of patients with Alzheimer's disease (AD). AGEs and receptor for AGEs (RAGE) play important roles in the pathogenesis of AD. FPS-ZM1 is a high-affinity RAGE-specific blocker that inhibits amyloid-β binding to RAGE, neurological damage and inflammation in the APP(sw/0) transgenic mouse model of AD. FPS-ZM1 is not toxic to mice and can easily cross the blood-brain barrier. In this study, an AGEs-RAGE-activated rat model were established by intrahippocampal injection of AGEs, then these rats were treated with intraperitoneal administration of FPS-ZM1 and the possible neuroprotective effects were investigated. We found that AGEs administration induced an-regulation of Abeta production, inflammation, and oxidative stress, and an increased escape latency of rats in the Morris water maze test, all of these are significantly reduced by FPS-ZM1 treatment. Our results suggest that the AGEs-RAGE pathway is responsible for cognitive deficits, and therefore may be a potential treatment target. FPS-ZM1 might be a novel therapeutic agent to treat AD patients.

  15. The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention

    Science.gov (United States)

    McFadden, Rita-Marie T.; Larmonier, Claire B.; Shehab, Kareem W.; Midura-Kiela, Monica; Ramalingam, Rajalakshmy; Harrison, Christy A.; Besselsen, David G.; Chase, John H.; Caporaso, J. Gregory; Jobin, Christian; Ghishan, Fayez K.; Kiela, Pawel R.

    2015-01-01

    Background Intestinal microbiota influences the progression of colitis-associated colorectal cancer (CAC). With diet being a key determinant of the gut microbial ecology, dietary interventions are an attractive avenue for the prevention of CAC. Curcumin is the most active constituent of the ground rhizome of the Curcuma Longa plant, which has been demonstrated to have anti-inflammatory, anti-oxidative and anti-proliferative properties. Methods Il10−/− mice on 129/SvEv background were used as a model of CAC. Starting at 10 weeks of age, WT or Il10−/− mice received six weekly i.p. injections of azoxymethane (AOM) or saline, and were started on either a control or curcumin-supplemented diet. Stools were collected every 4 weeks for microbial community analysis. Mice were sacrificed at 30 weeks of age. Results Curcumin-supplemented diet increased survival, decreased colon weight/length ratio, and at 0.5%, entirely eliminated tumor burden. Although colonic histology indicated improvement with curcumin, no effects of mucosal immune responses have been observed in PBS/Il10−/− mice, and limited effects were seen in AOM/Il10−/− mice. In WT and in Il10−/− mice, curcumin increased bacterial richness, prevented age-related decrease in alpha diversity, increased the relative abundance of Lactobacillales, and decreased Coriobacterales order. Taxonomic profile of AOM/Il10−/− mice receiving curcumin was more similar to those of wild-type mice than those fed control diet. Conclusions In AOM/Il10−/− model, curcumin reduced or eliminated colonic tumor burden with limited effects on mucosal immune responses. The beneficial effect of curcumin on tumorigenesis was associated with the maintenance of a more diverse colonic microbial ecology. PMID:26218141

  16. 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".

  17. Curcumin elevates sirtuin level but does not postpone in vitro senescence of human cells building the vasculature

    Science.gov (United States)

    Grabowska, Wioleta; Suszek, Małgorzata; Wnuk, Maciej; Lewinska, Anna; Wasiak, Emilia; Sikora, Ewa; Bielak-Zmijewska, Anna

    2016-01-01

    It is believed that curcumin, a component of the turmeric that belongs to hormetins, possesses anti-aging propensity. This property of curcumin can be partially explained by its influence on the level of sirtuins. Previously, we have shown that relatively high (2.5-10 μM) doses of curcumin induce senescence of cancer cells and cells building the vasculature. In the present study we examined whether curcumin at low doses (0.1 and 1 μM) is able to delay cell senescence and upregulate the level of sirtuins in human cells building the vasculature, namely vascular smooth muscle (VSMC) and endothelial (EC) cells. To this end we used cells senescing in a replicative and premature manner. We showed that low doses of curcumin in case of VSMC neither postponed the replicative senescence nor protected from premature senescence induced by doxorubicin. Moreover, curcumin slightly accelerated replicative senescence of EC. Despite some fluctuations, a clear increasing tendency in the level of sirtuins was observed in curcumin-treated young, senescing or already senescent cells. Sirtuin activation could be caused by the activation of AMPK resulting from superoxide elevation and ATP reduction. Our results show that curcumin at low doses can increase the level of sirtuins without delaying senescence of VSMC. PMID:27034011

  18. Curcumin: An Anti-Inflammatory Molecule from a Curry Spice on the Path to Cancer Treatment

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    Purusotam Basnet

    2011-06-01

    Full Text Available Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer’s disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer.

  19. Curcumin: an anti-inflammatory molecule from a curry spice on the path to cancer treatment.

    Science.gov (United States)

    Basnet, Purusotam; Skalko-Basnet, Natasa

    2011-06-03

    Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer's disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice) showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer.

  20. Curcumin Prevents Acute Neuroinflammation and Long-Term Memory Impairment Induced by Systemic Lipopolysaccharide in Mice

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    Vincenzo Sorrenti

    2018-03-01

    Full Text Available Systemic lipopolysaccharide (LPS induces an acute inflammatory response in the central nervous system (CNS (“neuroinflammation” characterized by altered functions of microglial cells, the major resident immune cells of the CNS, and an increased inflammatory profile that can result in long-term neuronal cell damage and severe behavioral and cognitive consequences. Curcumin, a natural compound, exerts CNS anti-inflammatory and neuroprotective functions mainly after chronic treatment. However, its effect after acute treatment has not been well investigated. In the present study, we provide evidence that 50 mg/kg of curcumin, orally administered for 2 consecutive days before a single intraperitoneal injection of a high dose of LPS (5 mg/kg in young adult mice prevents the CNS immune response. Curcumin, able to enter brain tissue in biologically relevant concentrations, reduced acute and transient microglia activation, pro-inflammatory mediator production, and the behavioral symptoms of sickness. In addition, short-term treatment with curcumin, administered at the time of LPS challenge, anticipated the recovery from memory impairments observed 1 month after the inflammatory stimulus, when mice had completely recovered from the acute neuroinflammation. Together, these results suggest that the preventive effect of curcumin in inhibiting the acute effects of neuroinflammation could be of value in reducing the long-term consequences of brain inflammation, including cognitive deficits such as memory dysfunction.

  1. Curcumin: a potential neuroprotective agent in Parkinson's disease.

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    Mythri, R B; Bharath, M M Srinivas

    2012-01-01

    Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD.

  2. Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts

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    Zhang Dongwei

    2011-11-01

    Full Text Available Abstract Background Lung fibrosis is characterized by fibroblast proliferation and the deposition of collagens. Curcumin, a polyphenol antioxidant from the spice tumeric, has been shown to effectively counteract fibroblast proliferation and reducing inflammation and fibrotic progression in animal models of bleomycin-induced lung injury. However, there is little mechanistic insight in the biological activity of curcumin. Here, we study the effects of curcumin on the expression and activity of cathepsins which have been implicated in the development of fibrotic lung diseases. Methods We investigated the effects of curcumin administration to bleomycin stimulated C57BL/6 mice and human fetal lung fibroblasts (HFL-1 on the expression of cathepsins K and L which have been implicated in matrix degradation, TGF-β1 modulation, and apoptosis. Lung tissues were evaluated for their contents of cathepsins K and L, collagen, and TGF-β1. HFL-1 cells were used to investigate the effects of curcumin and cathepsin inhibition on cell proliferation, migration, apoptosis, and the expression of cathepsins K and L and TGF-β1. Results Collagen deposition in lungs was decreased by 17-28% after curcumin treatment which was accompanied by increased expression levels of cathepsins L (25%-39% and K (41%-76% and a 30% decrease in TGF-β1 expression. Moreover, Tunel staining of lung tissue revealed a 33-41% increase in apoptotic cells after curcumin treatment. These in vivo data correlated well with data obtained from the human fibroblast line, HFL-1. Here, cathepsin K and L expression increased 190% and 240%, respectively, in the presence of curcumin and the expression of TGF-β1 decreased by 34%. Furthermore, curcumin significantly decreased cell proliferation and migration and increased the expression of surrogate markers of apoptosis. In contrast, these curcumin effects were partly reversed by a potent cathepsin inhibitor. Conclusion This study demonstrates that

  3. The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation.

    Czech Academy of Sciences Publication Activity Database

    Machová-Urdzíková, Lucia; Kárová, Kristýna; Růžička, Jiří; Kloudová, Anna; Shannon, C.; Dubišová, Jana; Murali, R.; Kubinová, Šárka; Syková, Eva; Jhanwar-Uniyal, M.; Jendelová, Pavla

    2016-01-01

    Roč. 17, č. 1 (2016) ISSN 1661-6596 R&D Projects: GA ČR(CZ) GP13-15031P; GA ČR(CZ) GA13-00939S; GA MŠk(CZ) LH12024; GA MŠk(CZ) 7F14057; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378041 Keywords : spinal cord injury * curcumin * inflammation * inflammation * cytokines Subject RIV: FH - Neurology

  4. Curcumin inhibits epigen and amphiregulin upregulated by 2,4,6-trinitrochlorobenzene associated with attenuation of skin swelling.

    Science.gov (United States)

    Sakai, Hiroyasu; Sato, Ken; Sato, Fumiaki; Kai, Yuki; Mandokoro, Kazutaka; Matsumoto, Kenjiro; Kato, Shinichi; Yumoto, Tetsuro; Narita, Minoru; Chiba, Yoshihiko

    2017-08-01

    Contact dermatitis model involving repeated application of hapten is used as a tool to assess dermatitis, as characterized by thickening. Involvement of cell proliferation, elicited by repeated hapten-stimulation, in this swelling has been unclear. Curcumin is reported to reduce inflammation. We examined involvement of cell proliferation and the role of extracellular regulated kinase (ERK) in 2,4,6-trinitrochlorobenzene (TNCB) challenge-induced ear swelling. We also examined the effects of curcumin in this model. Mice were sensitized with TNCB to the abdominal skin. Then, they were challenged with TNCB to the ear three times. The ERK activation inhibitor U0126 or curcumin was applied 30 min before each TNCB challenge. TNCB challenge-induced increased epidermal cell number and dermal thickening. Gene expressions of epithelial mitogen (EPGN), amphiregulin (AREG) and heparin-binding-epidermal growth factor (HB-EGF) were increased in the ears after the last TNCB challenge. Ki-67 immunoreactivity was increased in the dermis in TNCB-challenged ears. TNCB-induced swelling was inhibited by U0126 and curcumin. Curcumin also attenuated TNCB-induced ERK phosphorylation and expression of EPGN and AREG genes. Ear swelling induced by TNCB challenge might be mediated, in part, by the EPGN- and AREG-ERK proliferation pathway and was inhibited by curcumin.

  5. Inhibition of enveloped viruses infectivity by curcumin.

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    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.

  6. 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

  7. 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.

  8. Comparison the effects of Ginger and Curcumin in treatment of premenstrual syndrome

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    Samira khayat

    2015-07-01

    Full Text Available Background: Most women at reproductive ages experience the premenstrual syndrome (PMS. Different methods have been suggested for the treatment of this syndrome and one of them is using herbal medicine. This study was carried out to evaluate the effects of ginger and curcumin on severity of symptoms of PMS. Materials and Methods: In this double-blind clinical trial, 105 students with PMS symptoms were randomly assigned to ginger, curcumin and placebo groups. Participants received two capsules daily from seven days before menstruation to three days after menstruation for three cycles and they recorded severity of the symptoms by Daily Record of Severity of Problems (DRSP questionnaire. Data of before interventions and 1, 2 and 3 months after interventions were analyzed by repeated measurement ANOVA and indepented t-test. SPSS-18 software was used for analyses and P<0/05 was considered significant. Results: The mean of PMS symptoms severity were similar in three groups before the intervention [( 110/2±30/7 in ginger group, 103/6±39/1 in curcumin group and106/7±44/65 in placebo group p=0/79], but after interventions there were significant differences between groups [(47/06 ±33/4 in ginger group, 29/74±11/6 in curcumin group and106±48/7 in placebo group P<0/0001]. Also, there was a significant difference between effects of curcumin and ginger (P=0/008. Conclusion: Ginger and curcumin are effective in reduction of severity of psychological, physical and behavioral symptoms of PMS and the effect of curcumin is more than ginger. Results of present study suggest curcumin and ginger as treatment for PMS.

  9. 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.

  10. 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

  11. Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFκB signaling and macrophage migration.

    Directory of Open Access Journals (Sweden)

    Nicholas A Young

    Full Text Available Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

  12. Curcumin Attenuates Amyloid-β Aggregate Toxicity and Modulates Amyloid-β Aggregation Pathway.

    Science.gov (United States)

    Thapa, Arjun; Jett, Stephen D; Chi, Eva Y

    2016-01-20

    The abnormal misfolding and aggregation of amyloid-β (Aβ) peptides into β-sheet enriched insoluble deposits initiates a cascade of events leading to pathological processes and culminating in cognitive decline in Alzheimer's disease (AD). In particular, soluble oligomeric/prefibrillar Aβ have been shown to be potent neurotoxins. The naturally occurring polyphenol curcumin has been shown to exert a neuroprotective effect against age-related neurodegenerative diseases such as AD. However, its protective mechanism remains unclear. In this study, we investigated the effects of curcumin on the aggregation of Aβ40 as well as Aβ40 aggregate induced neurotoxicity. Our results show that the curcumin does not inhibit Aβ fibril formation, but rather enriches the population of "off-pathway" soluble oligomers and prefibrillar aggregates that were nontoxic. Curcumin also exerted a nonspecific neuroprotective effect, reducing toxicities induced by a range of Aβ conformers, including monomeric, oligomeric, prefibrillar, and fibrillar Aβ. The neuroprotective effect is possibly membrane-mediated, as curcumin reduced the extent of cell membrane permeabilization induced by Aβ aggregates. Taken together, our study shows that curcumin exerts its neuroprotective effect against Aβ induced toxicity through at least two concerted pathways, modifying the Aβ aggregation pathway toward the formation of nontoxic aggregates and ameliorating Aβ-induced toxicity possibly through a nonspecific pathway.

  13. 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.

  14. The Neuroprotective Effect of Curcumin Against Nicotine-Induced Neurotoxicity is Mediated by CREB-BDNF Signaling Pathway.

    Science.gov (United States)

    Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Faraji, Fahimeh; Mozaffari, Shiva

    2017-10-01

    Nicotine abuse adversely affects brain and causes apoptotic neurodegeneration. Curcumin- a bright yellow chemical compound found in turmeric is associated with neuroprotective properties. The current study was designed to evaluate the role of CREB-BDNF signaling in mediating the neuroprotective effects of curcumin against nicotine-induced apoptosis, oxidative stress and inflammation in rats. Sixty adult male rats were divided randomly into six groups. Group 1 received 0.7 ml/rat normal saline, group 2 received 6 mg/kg nicotine. Groups 3, 4, 5 and 6 were treated concurrently with nicotine (6 mg/kg) and curcumin (10, 20, 40 and 60 mg/kg i.p. respectively) for 21 days. Open Field Test (OFT) was used to evaluate the motor activity. Hippocampal oxidative, anti-oxidant, inflammatory and apoptotic factors were evaluated. Furthermore, phosphorylated brain cyclic adenosine monophosphate (cAMP) response element binding protein (P-CREB) and brain derived neurotrophic factor (BDNF) levels were studied at gene and protein levels. We found that nicotine disturbed the motor activity in OFT and simultaneous treatment with curcumin (40 and 60 mg/kg) reduced the nicotine-induced motor activity disturbances. In addition, nicotine treatment increased lipid peroxidation and the levels of GSH, IL-1β, TNF-α and Bax, while reducing Bcl-2, P-CREB and BDNF levels in the hippocampus. Nicotine also reduced the activity of superoxide dismutase, glutathione peroxidase and glutathione reductase in hippocampus. In contrast, various doses of curcumin attenuated nicotine-induced apoptosis, oxidative stress and inflammation; while elevating P-CREB and BDNF levels. Thus, curcumin via activation of P-CREB/BDNF signaling pathway, confers neuroprotection against nicotine-induced inflammation, apoptosis and oxidative stress.

  15. [Orbital inflammation].

    Science.gov (United States)

    Mouriaux, F; Coffin-Pichonnet, S; Robert, P-Y; Abad, S; Martin-Silva, N

    2014-12-01

    Orbital inflammation is a generic term encompassing inflammatory pathologies affecting all structures within the orbit : anterior (involvement up to the posterior aspect of the globe), diffuse (involvement of intra- and/or extraconal fat), apical (involvement of the posterior orbit), myositis (involvement of only the extraocular muscles), dacryoadenitis (involvement of the lacrimal gland). We distinguish between specific inflammation and non-specific inflammation, commonly referred to as idiopathic inflammation. Specific orbital inflammation corresponds to a secondary localization of a "generalized" disease (systemic or auto-immune). Idiopathic orbital inflammation corresponds to uniquely orbital inflammation without generalized disease, and thus an unknown etiology. At the top of the differential diagnosis for specific or idiopathic orbital inflammation are malignant tumors, represented most commonly in the adult by lympho-proliferative syndromes and metastases. Treatment of specific orbital inflammation begins with treatment of the underlying disease. For idiopathic orbital inflammation, treatment (most often corticosteroids) is indicated above all in cases of visual loss due to optic neuropathy, in the presence of pain or oculomotor palsy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Association of Dietary Patterns with Components of Metabolic Syndrome and Inflammation among Middle-Aged and Older Adults with Metabolic Syndrome in Taiwan

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    Ahmad Syauqy

    2018-01-01

    Full Text Available This study examined the correlation of dietary patterns with components of metabolic syndrome (MetS and inflammation among middle-aged and older adults with MetS in Taiwan. This cross-sectional study used data from the Mei Jau International Health Management Institution in Taiwan between 2004 and 2013. A total of 26,016 subjects aged 35 years and above were selected for analysis. MetS was defined according to the International Diabetes Federation. Three dietary patterns were identified by principal component analysis. High intake of a meat–instant food dietary pattern (rich in animal protein, saturated fat, sweets, sodium, and food additives was positively associated with components of MetS and C-reactive protein (CRP, while high intake of a vege–seafood dietary pattern (rich in dietary fiber, vitamins, minerals, and unsaturated fat or a cereal–dairy dietary pattern (rich in dietary fiber, antioxidants, phytochemicals, complex carbohydrate, prebiotics, and probiotics was inversely associated with components of MetS and CRP. Our findings suggested that intake of a vege–seafood dietary pattern or a cereal–dairy dietary pattern decreased the risk of developing MetS and inflammation among middle-aged and older adults with MetS.

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

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    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.

  18. 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.

  19. Anti-Inflammatory Effects of Novel Standardized Solid Lipid Curcumin Formulations.

    Science.gov (United States)

    Nahar, Pragati P; Slitt, Angela L; Seeram, Navindra P

    2015-07-01

    Inflammation and the presence of pro-inflammatory cytokines are associated with numerous chronic diseases such as type-2 diabetes mellitus, cardiovascular disease, Alzheimer's disease, and cancer. An overwhelming amount of data indicates that curcumin, a polyphenol obtained from the Indian spice turmeric, Curcuma longa, is a potential chemopreventive agent for treating certain cancers and other chronic inflammatory diseases. However, the low bioavailability of curcumin, partly due to its low solubility and stability in the digestive tract, limits its therapeutic applications. Recent studies have demonstrated increased bioavailability and health-promoting effects of a novel solid lipid particle formulation of curcumin (Curcumin SLCP, Longvida(®)). The goal of this study was to evaluate the aqueous solubility and in vitro anti-inflammatory effects of solid lipid curcumin particle (SLCP) formulations using lipopolysaccharide (LPS)-stimulated RAW 264.7 cultured murine macrophages. SLCPs treatment significantly decreased nitric oxide (NO) and prostaglandin-E2 (PGE2) levels at concentrations ranging from 10 to 50 μg/mL, and reduced interleukin-6 (IL-6) levels in a concentration-dependent manner. Transient transfection experiments using a nuclear factor-kappa B (NF-κB) reporter construct indicate that SLCPs significantly inhibit the transcriptional activity of NF-κB in macrophages. Taken together, these results show that in RAW 264.7 murine macrophages, SLCPs have improved solubility over unformulated curcumin, and significantly decrease the LPS-induced pro-inflammatory mediators NO, PGE2, and IL-6 by inhibiting the activation of NF-κB.

  20. Curcumin inhibits adipogenesis induced by benzyl butyl phthalate in 3T3-L1 cells.

    Science.gov (United States)

    Sakuma, Satoru; Sumida, Maki; Endoh, Yukiko; Kurita, Ayaka; Yamaguchi, Ayana; Watanabe, Tomoki; Kohda, Tetsuya; Tsukiyama, Yui; Fujimoto, Yohko

    2017-08-15

    Phthalates are a group of endocrine disrupting chemicals and may have contributed to the recent global obesity health crisis. Increased adipogenesis via the peroxisome proliferator-activated receptor γ (PPARγ)-CCAAT-enhancer binding protein α (C/EBPα) pathway could be one critical mechanism responsible for phthalate-induced weight gain. On the other hand, curcumin has been shown to inhibit adipogenesis in cells and animal models. The present study was undertaken to evaluate, for the first time, whether curcumin could reduce adipogenesis induced by benzyl butyl phthalate (BBP) via downregulation of the PPARγ-C/EBPα pathway. 3T3-L1 preadipocytes were differentiated by treating them with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine in the presence of BBP, with or without curcumin. Cells that were grown in the presence of BBP alone showed a significant increase in triacylglycerol (TG) levels. In addition, the number of Oil Red O-stained cells and the mRNA expression levels of PPARγ, C/EBPα, adiponectin, and tumor necrosis factor-α (TNFα) were significantly increased. However, treatment with BBP in combination with curcumin resulted in major reductions in TG levels, the numbers of Oil Red O-stained cells, and the mRNA expression levels of the four proteins. These results suggest that curcumin might be an inhibitor of BBP-induced weight gain and inflammation via stimulation of adipocyte differentiation and TNFα generation. Curcumin may, therefore, be a potential medication for preventing the harmful effects of phthalates. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route.

    Science.gov (United States)

    Mangalathillam, Sabitha; Rejinold, N Sanoj; Nair, Amrita; Lakshmanan, Vinoth-Kumar; Nair, Shantikumar V; Jayakumar, Rangasamy

    2012-01-07

    In this study, curcumin loaded chitin nanogels (CCNGs) were developed using biocompatible and biodegradable chitin with an anticancer curcumin drug. Chitin, as well as curcumin, is insoluble in water. However, the developed CCNGs form a very good and stable dispersion in water. The CCNGs were analyzed by DLS, SEM and FTIR and showed spherical particles in a size range of 70-80 nm. The CCNGs showed higher release at acidic pH compared to neutral pH. The cytotoxicity of the nanogels were analyzed on human dermal fibroblast cells (HDF) and A375 (human melanoma) cell lines and the results show that CCNGs have specific toxicity on melanoma in a concentration range of 0.1-1.0 mg mL(-1), but less toxicity towards HDF cells. The confocal analysis confirmed the uptake of CCNGs by A375. The apoptotic effect of CCNGs was analyzed by a flow-cytometric assay and the results indicate that CCNGs at the higher concentration of the cytotoxic range showed comparable apoptosis as the control curcumin, in which there was negligible apoptosis induced by the control chitin nanogels. The CCNGs showed a 4-fold increase in steady state transdermal flux of curcumin as compared to that of control curcumin solution. The histopathology studies of the porcine skin samples treated with the prepared materials showed loosening of the horny layer of the epidermis, facilitating penetration with no observed signs of inflammation. These results suggest that the formulated CCNGs offer specific advantage for the treatment of melanoma, the most common and serious type of skin cancer, by effective transdermal penetration.

  2. Curcumin loaded solid lipid nanoparticles ameliorate adjuvant-induced arthritis in rats.

    Science.gov (United States)

    Arora, R; Kuhad, A; Kaur, I P; Chopra, K

    2015-08-01

    Rheumatoid arthritis (RA), a chronic and systemic inflammation, results in destruction of joints and cartilages. Effectiveness of curcumin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable curcumin loaded solid lipid nanoparticles (C-SLNs) for the treatment of RA. In the present study, the protective effect of curcumin and its SLNs was evaluated in complete Freund's adjuvant (CFA)-induced arthritis in rats. Arthritic rats exhibited marked decrease in paw withdrawal threshold in Randall-Selitto and von Frey hair test along with decreased reaction time in hot plate. Arthritic rats also showed significant joint hyperalgesia, joint stiffness and increased paw volume along with marked decrease in mobility score. Arthritic rats showed a significant increase in blood leukocyte count, oxidative-nitrosative stress, tumour necrosis factor-α, C-reactive protein, cyclic citrullinated peptide antibody levels and radiological alterations in tibiotarsal joint. C-SLN administration (10 and 30 mg/kg), when compared with free curcumin (10 and 30 mg/kg), significantly and dose dependently ameliorated various symptoms of arthritis in rats, improved biochemical markers and preserved radiological alterations in joints of arthritic rats. The current findings suggest the protective potential of curcumin-SLNs in ameliorating CFA-induced arthritis in rats through attenuation of oxido-inflammatory and immunomodulatory cascade. Further, the results emphasize that SLNs are a novel approach to deliver curcumin into the inflamed joints and improve its biopharmaceutical performance. © 2014 European Pain Federation - EFIC®

  3. Reduced inflammatory and muscle damage biomarkers following oral supplementation with bioavailable curcumin.

    Science.gov (United States)

    McFarlin, Brian K; Venable, Adam S; Henning, Andrea L; Sampson, Jill N Best; Pennel, Kathryn; Vingren, Jakob L; Hill, David W

    2016-06-01

    Exercise-Induced Muscle Damage (EIMD) and delayed onset muscle soreness (DOMS) impact subsequent training sessions and activities of daily living (ADL) even in active individuals. In sedentary or diseased individuals, EIMD and DOMS may be even more pronounced and present even in the absence of structured exercise. The purpose of this study was to determine the effects of oral curcumin supplementation (Longvida® 400 mg/days) on muscle & ADL soreness, creatine kinase (CK), and inflammatory cytokines (TNF-α, IL-6, IL-8, IL-10) following EMID (eccentric-only dual-leg press exercise). Subjects (N = 28) were randomly assigned to either curcumin (400 mg/day) or placebo (rice flour) and supplemented 2 days before to 4 days after EMID. Blood samples were collected prior to (PRE), and 1, 2, 3, and 4 days after EIMD to measure CK and inflammatory cytokines. Data were analyzed by ANOVA with P < 0.05. Curcumin supplementation resulted in significantly smaller increases in CK (- 48%), TNF-α (- 25%), and IL-8 (- 21%) following EIMD compared to placebo. We observed no significant differences in IL-6, IL-10, or quadriceps muscle soreness between conditions for this sample size. Collectively, the findings demonstrated that consumption of curcumin reduced biological inflammation, but not quadriceps muscle soreness, during recovery after EIMD. The observed improvements in biological inflammation may translate to faster recovery and improved functional capacity during subsequent exercise sessions. These findings support the use of oral curcumin supplementation to reduce the symptoms of EIMD. The next logical step is to evaluate further the efficacy of an inflammatory clinical disease model.

  4. TGF-β1 induces an age-dependent inflammation of nerve ganglia and fibroplasia in the prostate gland stroma of a novel transgenic mouse.

    Directory of Open Access Journals (Sweden)

    David A Barron

    2010-10-01

    Full Text Available TGF-β1 is overexpressed in wound repair and in most proliferative disorders including benign prostatic hyperplasia and prostate cancer. The stromal microenvironment at these sites is reactive and typified by altered phenotype, matrix deposition, inflammatory responses, and alterations in nerve density and biology. TGF-β1 is known to modulate several stromal responses; however there are few transgenic models to study its integrated biology. To address the actions of TGF-β1 in prostate disorders, we targeted expression of an epitope tagged and constitutively active TGF-β1 via the enhanced probasin promoter to the murine prostate gland epithelium. Transgenic mice developed age-dependent lesions leading to severe, yet focal attenuation of epithelium, and a discontinuous basal lamina. These changes were associated with elevated fibroplasia and frequency of collagenous micronodules in collapsed acini, along with an induced inflammation in nerve ganglia and small vessels. Elevated recruitment of CD115+ myeloid cells but not mature macrophages was observed in nerve ganglia, also in an age-dependent manner. Similar phenotypic changes were observed using a human prostate epithelium tissue recombination xenograft model, where epithelial cells engineered to overexpress TGF-β1 induced fibrosis and altered matrix deposition concurrent with inflammation in the stromal compartment. Together, these data suggest that elevated TGF-β1 expression induces a fibroplasia stromal response associated with breach of epithelial wall structure and inflammatory involvement of nerve ganglia and vessels. The novel findings of ganglia and vessel inflammation associated with formation of collagenous micronodules in collapsed acini is important as each of these are observed in human prostate carcinoma and may play a role in disease progression.

  5. Short term exercise induces PGC-1α, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts.

    Science.gov (United States)

    Botta, Amy; Laher, Ismail; Beam, Julianne; Decoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L; Ghosh, Sanjoy

    2013-01-01

    PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.

  6. Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Avasarala, Sreedevi; Zhang, Fangfang; Liu, Guangliang; Wang, Ruixue; London, Steven D; London, Lucille

    2013-01-01

    Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10(7)pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

  7. Novel dipeptide nanoparticles for effective curcumin delivery

    Directory of Open Access Journals (Sweden)

    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

  8. Anti-Inflammation Activities of Mycosporine-Like Amino Acids (MAAs) in Response to UV Radiation Suggest Potential Anti-Skin Aging Activity

    Science.gov (United States)

    Suh, Sung-Suk; Hwang, Jinik; Park, Mirye; Seo, Hyo Hyun; Kim, Hyoung-Shik; Lee, Jeong Hun; Moh, Sang Hyun; Lee, Taek-Kyun

    2014-01-01

    Certain photosynthetic marine organisms have evolved mechanisms to counteract UV-radiation by synthesizing UV-absorbing compounds, such as mycosporine-like amino acids (MAAs). In this study, MAAs were separated from the extracts of marine green alga Chlamydomonas hedleyi using HPLC and were identified as porphyra-334, shinorine, and mycosporine-glycine (mycosporine-Gly), based on their retention times and maximum absorption wavelengths. Furthermore, their structures were confirmed by triple quadrupole MS/MS. Their roles as UV-absorbing compounds were investigated in the human fibroblast cell line HaCaT by analyzing the expression levels of genes associated with antioxidant activity, inflammation, and skin aging in response to UV irradiation. The mycosporine-Gly extract, but not the other MAAs, had strong antioxidant activity in the 2,2-diphenyl-1-picryhydrazyl (DPPH) assay. Furthermore, treatment with mycosporine-Gly resulted in a significant decrease in COX-2 mRNA levels, which are typically increased in response to inflammation in the skin, in a concentration-dependent manner. Additionally, in the presence of MAAs, the UV-suppressed genes, procollagen C proteinase enhancer (PCOLCE) and elastin, which are related to skin aging, had increased expression levels equal to those in UV-mock treated cells. Interestingly, the increased expression of involucrin after UV exposure was suppressed by treatment with the MAAs mycosporine-Gly and shinorine, but not porphyra-334. This is the first report investigating the biological activities of microalgae-derived MAAs in human cells. PMID:25317535

  9. 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.

  10. 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.

  11. Curcumin derivatives as HIV-1 protease inhibitors

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    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.

  12. 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".

  13. Erythropoietin Attenuates the Memory Deficits in Aging Rats by Rescuing the Oxidative Stress and Inflammation and Promoting BDNF Releasing.

    Science.gov (United States)

    Jia, Zhankui; Xue, Rui; Ma, Shengli; Xu, Jingjing; Guo, Si; Li, Songchao; Zhang, Erwei; Wang, Jun; Yang, Jinjian

    2016-10-01

    Aging is a natural process accompanied with many disorders, including the memory decline. The underlying mechanisms for the age-related memory decline are complicated. Previous work suggested that oxidative stress, inflammatory disturbance, and the neurotropic absence play important roles in the age-related disorders. Thus, to seek a drug to target those abnormalities might be a possible protective approach for aging. Here, we reported that supplements with exogenous erythropoietin (EPO) for 4 weeks could partially rescue the spatial and fear memory impairments in aged rats. The EPO treatment also suppresses the oxidative stress and inflammatory response. Most importantly, EPO supplement restores the mRNA and protein levels of brain-derived neurotrophic factor (BDNF), the critical neurotropic factor for synaptic plasticity and memory. Our study strongly suggests the potential usage of EPO in an anti-aging agent clinically.

  14. 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

  15. 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

  16. 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.

  17. Meta-analysis of Gene Expression in the Mouse Liver Reveals Biomarkers Associated with Inflammation Increased Early During Aging

    Science.gov (United States)

    Aging is associated with a predictable loss of cellular homeostasis, a decline in physiological function and an increase in various diseases. We hypothesized that similar age-related gene expression profiles would be observed in mice across independent studies. Employing a metaan...

  18. Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice

    Science.gov (United States)

    Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic KrasG12D was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activati...

  19. Does RBC Storage Age Effect Inflammation, Immune Function and Susceptibility to Transfusion Associated Microchimerism in Critically Ill Patients? Adverse Effects of RBC Storage in Critically Ill Patients

    Science.gov (United States)

    2015-05-01

    Barnes S, Grizzle W, Miller D, Zhang H-G. A novel nanoparticle drug delivery system: The anti-inflammatory activity of curcumin is enhanced when...Ultracentrifugatio remove impuritie including seru protein an othe solubl contaminant fro th plasma whic ca affec functiona experimenta outcomes...applications. EVs used in functional assays should be ultracentrifuged using the 3-step differential centrifugation protocol, since the soluble serum

  20. Curcumin Stimulates Biochemical Mechanisms of Apis Mellifera Resistance and Extends the Apian Life-Span

    Directory of Open Access Journals (Sweden)

    Strachecka Aneta J.

    2015-06-01

    Full Text Available We examined the influence of curcumin-supplemented feeding on worker lifespan, Nosema resistance, key enzyme activities, metabolic compound concentrations and percentage of the global DNA methylation. Two worker groups (Apis mellifera were set up: 1 control group; workers were fed ad libitum with sucrose syrup; 2 workers were fed with the syrup with the addition of curcumin. Dead workers were removed every two days and the Nosema spp. infection levels were assessed. Hemolymph was taken from living workers for biochemical analyses. The global DNA methylation level was analysed using DNA from worker heads and thoraces. The bees that consumed curcumin lived longer and were less infested with Nosema spp. The curcumin-treated workers had higher concentrations of proteins, non-enzymatic biomarkers (triglycerides, glucose, cholesterol, Mg2+ and Ca2+, uric acid and creatinine, as well as elevated activities of antioxidant enzymes (SOD , GPx, CAT , GST , neutral proteases, protease inhibitors, enzymatic biomarkers (AST , ALT , ALP . The concentrations of albumin and urea, and the activities of acidic and alkaline proteases were higher in the control group. Curcumin decreased global DNA methylation levels especially in older bees in which the natural, age-related level increase was observed. Most of the parameters increased over the apian youth and adulthood, and decreased in older bees. The decrease was markedly delayed in the bees fed with curcumin. Curcumin appeared to be an unexpectedly effective natural bio-stimulator, improving apian health and vitality. This multifactorial effect is caused by the activation of many biochemical processes involved in the formation of apian resistance.

  1. Curcumin ameliorates macrophage infiltration by inhibiting NF-κB activation and proinflammatory cytokines in streptozotocin induced-diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Suzuki Kenji

    2011-06-01

    Full Text Available Abstract Background Chronic inflammation plays an important role in the progression of diabetic nephropathy (DN and that the infiltration of macrophages in glomerulus has been implicated in the development of glomerular injury. We hypothesized that the plant polyphenolic compound curcumin, which is known to exert potent anti-inflammatory effect, would ameliorate macrophage infiltration in streptozotocin (STZ-induced diabetic rats. Methods Diabetes was induced with STZ (55 mg/kg by intraperitoneal injection in rats. Three weeks after STZ injection, rats were divided into three groups, namely, control, diabetic, and diabetic treated with curcumin at 100 mg/kg/day, p.o., for 8 weeks. The rats were sacrificed 11 weeks after induction of diabetes. The excised kidney was used to assess macrophage infiltration and expression of various inflammatory markers. Results At 11 weeks after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood glucose, blood urea nitrogen and proteinuria, along with marked reduction in the body weight. All of these abnormalities were significantly reversed by curcumin. Hyperglycemia induced the degradation of IκBα and NF-κB activation and as a result increased infiltration of macrophages (52% as well as increased proinflammatory cytokines: TNF-α and IL-1β. Curcumin treatment significantly reduced macrophage infiltration in the kidneys of diabetic rats, suppressed the expression of above proinflammatory cytokines and degradation of IκBα. In addition, curcumin treatment also markedly decreased ICAM-1, MCP-1 and TGF-β1 protein expression. Moreover, at nuclear level curcumin inhibited the NF-κB activity. Conclusion Our results suggested that curcumin treatment protect against the development of DN in rats by reducing macrophage infiltration through the inhibition of NF-κB activation in STZ-induced diabetic rats.

  2. 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

  3. 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.

  4. Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study.

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    Ringman, John M; Frautschy, Sally A; Teng, Edmond; Begum, Aynun N; Bardens, Jenny; Beigi, Maryam; Gylys, Karen H; Badmaev, Vladimir; Heath, Dennis D; Apostolova, Liana G; Porter, Verna; Vanek, Zeba; Marshall, Gad A; Hellemann, Gerhard; Sugar, Catherine; Masterman, Donna L; Montine, Thomas J; Cummings, Jeffrey L; Cole, Greg M

    2012-01-01

    Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD. We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex(®) with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured. Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex(®) was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between

  5. 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

  6. 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.

  7. Chili Peppers, Curcumins, and Prebiotics in Gastrointestinal Health and Disease.

    Science.gov (United States)

    Patcharatrakul, Tanisa; Gonlachanvit, Sutep

    2016-04-01

    There is growing evidence for the role of several natural products as either useful agents or adjuncts in the management of functional GI disorders (FGIDs). In this review, we examine the medical evidence for three such compounds: chili, a culinary spice; curcumin, another spice and active derivative of a root bark; and prebiotics, which are nondigestible food products. Chili may affect the pathogenesis of abdominal pain especially in functional dyspepsia and cause other symptoms. It may have a therapeutic role in FGIDs through desensitization of transient receptor potential vanilloid-1 receptor. Curcumin, the active ingredient of turmeric rhizome, has been shown in several preclinical studies and uncontrolled clinical trials as having effects on gut inflammation, gut permeability and the brain-gut axis, especially in FGIDs. Prebiotics, the non-digestible food ingredients in dietary fiber, may serve as nutrients and selectively stimulate the growth and/or activity of certain colonic bacteria. The net effect of this change on colonic microbiota may lead to the production of acidic metabolites and other compounds that help to reduce the production of toxins and suppress the growth of harmful or disease-causing enteric pathogens. Although some clinical benefit in IBS has been shown, high dose intake of prebiotics may cause more bloating from bacterial fermentation.

  8. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population.

    Science.gov (United States)

    Cox, Katherine H M; Pipingas, Andrew; Scholey, Andrew B

    2015-05-01

    Curcumin possesses many properties which may prevent or ameliorate pathological processes underlying age-related cognitive decline, dementia or mood disorders. These benefits in preclinical studies have not been established in humans. This randomized, double-blind, placebo-controlled trial examined the acute (1 and 3 h after a single dose), chronic (4 weeks) and acute-on-chronic (1 and 3 h after single dose following chronic treatment) effects of solid lipid curcumin formulation (400 mg as Longvida®) on cognitive function, mood and blood biomarkers in 60 healthy adults aged 60-85. One hour after administration curcumin significantly improved performance on sustained attention and working memory tasks, compared with placebo. Working memory and mood (general fatigue and change in state calmness, contentedness and fatigue induced by psychological stress) were significantly better following chronic treatment. A significant acute-on-chronic treatment effect on alertness and contentedness was also observed. Curcumin was associated with significantly reduced total and LDL cholesterol and had no effect on hematological safety measures. To our knowledge this is the first study to examine the effects of curcumin on cognition and mood in a healthy older population or to examine any acute behavioral effects in humans. Results highlight the need for further investigation of the potential psychological and cognitive benefits of curcumin in an older population. © The Author(s) 2014.

  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. Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases

    Science.gov (United States)

    Aggarwal, Bharat B.; Harikumar, Kuzhuvelil B.

    2009-01-01

    Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that the this activity of turmeric is due to curcumin, a diferuloylmethane. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various pro-inflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further. PMID:18662800

  11. Anti-Inflammation Activities of Mycosporine-Like Amino Acids (MAAs in Response to UV Radiation Suggest Potential Anti-Skin Aging Activity

    Directory of Open Access Journals (Sweden)

    Sung-Suk Suh

    2014-10-01

    Full Text Available Certain photosynthetic marine organisms have evolved mechanisms to counteract UV-radiation by synthesizing UV-absorbing compounds, such as mycosporine-like amino acids (MAAs. In this study, MAAs were separated from the extracts of marine green alga Chlamydomonas hedleyi using HPLC and were identified as porphyra-334, shinorine, and mycosporine-glycine (mycosporine-Gly, based on their retention times and maximum absorption wavelengths. Furthermore, their structures were confirmed by triple quadrupole MS/MS. Their roles as UV-absorbing compounds were investigated in the human fibroblast cell line HaCaT by analyzing the expression levels of genes associated with antioxidant activity, inflammation, and skin aging in response to UV irradiation. The mycosporine-Gly extract, but not the other MAAs, had strong antioxidant activity in the 2,2-diphenyl-1-picryhydrazyl (DPPH assay. Furthermore, treatment with mycosporine-Gly resulted in a significant decrease in COX-2 mRNA levels, which are typically increased in response to inflammation in the skin, in a concentration-dependent manner. Additionally, in the presence of MAAs, the UV-suppressed genes, procollagen C proteinase enhancer (PCOLCE and elastin, which are related to skin aging, had increased expression levels equal to those in UV-mock treated cells. Interestingly, the increased expression of involucrin after UV exposure was suppressed by treatment with the MAAs mycosporine-Gly and shinorine, but not porphyra-334. This is the first report investigating the biological activities of microalgae-derived MAAs in human cells.

  12. Exposure to 16O-particle radiation causes aging-like decrements in rats through increased oxidative stress, inflammation and loss of autophagy.

    Science.gov (United States)

    Poulose, Shibu M; Bielinski, Donna F; Carrihill-Knoll, Kirsty; Rabin, Bernard M; Shukitt-Hale, Barbara

    2011-12-01

    Exposing young rats to particles of high energy and charge (HZE particles), a ground-based model for exposure to cosmic rays, enhances indices of oxidative stress and inflammation, disrupts the functioning of neuronal communication, and alters cognitive behaviors. Even though exposure to HZE particles occurs at low fluence rates, the cumulative effects of long-term exposure result in molecular changes similar to those seen in aged animals. In the present study, we assessed markers of autophagy, a dynamic process for intracellular degradation and recycling of toxic proteins and organelles, as well as stress and inflammatory responses, in the brains of Sprague-Dawley rats irradiated at 2 months of age with 5 and 50 cGy and 1 Gy of ionizing oxygen particles ((16)O) (1000 MeV/n). Compared to nonirradiated controls, exposure to (16)O particles significantly inhibited autophagy function in the hippocampus as measured by accumulation of ubiquitin inclusion bodies such as P62/SQSTM1, autophagosome marker microtubule-associated protein 1 beta light chain 3 (MAP1B-LC3), beclin1 and proteins such as mammalian target of rapamycin (mTOR). The molecular changes measured at short (36 h) and long (75 days) intervals after (16)O-particle exposure indicate that the loss of autophagy function occurred shortly after exposure but was recovered via inhibition of mTOR. However, HZE-particle radiation caused significant sustained loss of protein kinase C alpha (PKC-α), a key G protein modulator involved in neuronal survival and functions of neuronal trophic factors. Exposure to (16)O particles also caused substantial increases in the levels of nuclear factor kappa B (NF-κB) and glial fibrillary acidic protein (GFAP), indicating glial cell activation 75 days after exposure. This is the first report to show the molecular effects of (16)O-particle radiation on oxidative stress, inflammation and loss of autophagy in the brain of young rats.

  13. Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage [v1; ref status: indexed, http://f1000r.es/1cl

    Directory of Open Access Journals (Sweden)

    Abigail L Clutterbuck

    2013-07-01

    Full Text Available Objective: Curcumin (diferuloylmethane is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA. The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β-stimulated inflammation and catabolism in an explant model of cartilage inflammation. Methods: Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E2 (PGE2 and matrix metalloproteinase (MMP-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days. Results: Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001 after 24 hours. After 48 hours and five days, curcumin (≥25μM significantly increased cell death (p<0.001 both time points. In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM significantly reduced IL-1β-stimulated PG (p<0.05 and PGE2 release (p<0.001 from explants, whilst curcumin (≥12μM significantly reduced MMP-3 release (p<0.01. Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

  14. Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence.

    Science.gov (United States)

    Tezze, Caterina; Romanello, Vanina; Desbats, Maria Andrea; Fadini, Gian Paolo; Albiero, Mattia; Favaro, Giulia; Ciciliot, Stefano; Soriano, Maria Eugenia; Morbidoni, Valeria; Cerqua, Cristina; Loefler, Stefan; Kern, Helmut; Franceschi, Claudio; Salvioli, Stefano; Conte, Maria; Blaauw, Bert; Zampieri, Sandra; Salviati, Leonardo; Scorrano, Luca; Sandri, Marco

    2017-06-06

    Mitochondrial dysfunction occurs during aging, but its impact on tissue senescence is unknown. Here, we find that sedentary but not active humans display an age-related decline in the mitochondrial protein, optic atrophy 1 (OPA1), that is associated with muscle loss. In adult mice, acute, muscle-specific deletion of Opa1 induces a precocious senescence phenotype and premature death. Conditional and inducible Opa1 deletion alters mitochondrial morphology and function but not DNA content. Mechanistically, the ablation of Opa1 leads to ER stress, which signals via the unfolded protein response (UPR) and FoxOs, inducing a catabolic program of muscle loss and systemic aging. Pharmacological inhibition of ER stress or muscle-specific deletion of FGF21 compensates for the loss of Opa1, restoring a normal metabolic state and preventing muscle atrophy and premature death. Thus, mitochondrial dysfunction in the muscle can trigger a cascade of signaling initiated at the ER that systemically affects general metabolism and aging. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Anti-Inflamm-Ageing and/or Anti-Age-Related Disease Emerging Treatments: A Historical Alchemy or Revolutionary Effective Procedures?

    Directory of Open Access Journals (Sweden)

    Carmela Rita Balistreri

    2018-01-01

    Full Text Available The “long-life elixir” has long represented for humans a dream, a vanity’s sin for remaining young and to long survive. Today, because of ageing population phenomenon, the research of antiageing interventions appears to be more important than ever, for preserving health in old age and retarding/or delaying the onset of age-related diseases. A hope is given by experimental data, which evidence the possibility of retarding ageing in animal models. In addition, it has been also demonstrated in animal life-extending studies not only the possibility of increasing longevity but also the ability to retard the onset of age-related diseases. Interestingly, this recent evidence is leading to promise of obtaining the same effects in humans and resulting in benefits for their health in old ages. In order to achieve this goal, different approaches have been used ranging from pharmacological targeting of ageing, basic biological assays, and big data analysis to the recent use of young blood, stem cells, cellular, genetic, and epigenetic reprogramming, or other techniques of regenerative medicine. However, only a little fraction of these approaches has the features for being tested in clinical applications. Here, new emerging molecules, drugs, and procedures will be described, by evidencing potential benefits and limitations.

  16. Potential Eye Drop Based on a Calix[4]arene Nanoassembly for Curcumin Delivery: Enhanced Drug Solubility, Stability, and Anti-Inflammatory Effect.

    Science.gov (United States)

    Granata, Giuseppe; Paterniti, Irene; Geraci, Corrada; Cunsolo, Francesca; Esposito, Emanuela; Cordaro, Marika; Blanco, Anna Rita; Cuzzocrea, Salvatore; Consoli, Grazia M L

    2017-05-01

    Curcumin is an Indian spice with a wide spectrum of biological and pharmacological activities but poor aqueous solubility, rapid degradation, and low bioavailability that affect medical benefits. To overcome these limits in ophthalmic application, curcumin was entrapped in a polycationic calix[4]arene-based nanoaggregate by a simple and reproducible method. The calix[4]arene-curcumin supramolecular assembly (Calix-Cur) appeared as a clear colloidal solution consisting in micellar nanoaggregates with size, polydispersity index, surface potential, and drug loading percentage meeting the requirements for an ocular drug delivery system. The encapsulation in the calix[4]arene nanoassembly markedly enhanced the solubility, reduced the degradation, and improved the anti-inflammatory effects of curcumin compared to free curcumin in both in vitro and in vivo experiments. Calix-Cur did not compromise the viability of J774A.1 macrophages and suppressed pro-inflammatory marker expression in J774A.1 macrophages subjected to LPS-induced oxidative stress. Histological and immunohistochemical analyses showed that Calix-Cur reduced signs of inflammation in a rat model of LPS-induced uveitis when topically administrated in the eyes. Overall, the results supported the calix[4]arene nanoassembly as a promising nanocarrier for delivering curcumin to anterior ocular tissues.

  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. Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging-Induced Renal Inflammation and Senescence via NADPH Oxidase-Mediated Reactive Oxygen Generation.

    Science.gov (United States)

    Park, Chan Hum; Shin, Sung Ho; Lee, Eun Kyeong; Kim, Dae Hyun; Kim, Min-Jo; Roh, Seong-Soo; Yokozawa, Takako; Chung, Hae Young

    2017-05-01

    The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22 phox ), phospho-p38, nuclear factor-kappa B p65, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, MLB-treated old rats showed lower levels of senescence-related proteins such as p16, ADP-ribosylation factor 6, p53, and p21 through effects on the mitogen-activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age-related increase in serum urea nitrogen, reflecting renal dysfunction, up-regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Effects of Almond- and Olive Oil-Based Docosahexaenoic- and Vitamin E-Enriched Beverage Dietary Supplementation on Inflammation Associated to Exercise and Age

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    Xavier Capó

    2016-10-01

    Full Text Available n-3-polyunsaturated fatty acids and polyphenols are potential key factors for the treatment and prevention of chronic inflammation associated to ageing and non-communicable diseases. The aim was to analyse effects of an almond and olive oil beverage enriched with α-tocopherol and docosahexaenoic, exercise and age on inflammatory plasma markers, and immune gene expression in peripheral blood mononuclear cells (PBMCs. Five young and five senior athletes who were supplemented for five weeks with a functional beverage performed a stress test under controlled conditions before and after beverage supplementation. Blood samples were taken immediately before and 1 h after each test. Plasma, erythrocytes and PBMCs were isolated. Beverage supplementation increased plasmatic Tumour Necrosis Factor α (TNFα levels depending on age and exercise. Exercise increased plasma non esterified fatty acids (NEFAs, soluble Intercellular adhesion molecule 3 (sICAM3 and soluble L-selectin (sL-Selectin, and this increase was attenuated by the supplementation. Exercise increased PGE2 plasma levels in supplemented young and in senior placebo athletes. Exercise increased NFkβ-activated levels in PBMCs, which are primed to a pro-inflammatory response increasing pro-inflammatory genes expression after the exercise mainly in the young group after the supplementation. The functional beverage supplementation to young athletes enhances a pro-inflammatory circulating environment in response to the exercise that was less evident in the senior group.

  20. Vesicular (liposomal and nanoparticulated delivery of curcumin: a comparative study on carbon tetrachloride–mediated oxidative hepatocellular damage in rat model

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    Choudhury ST

    2016-05-01

    Full Text Available Somsubhra Thakur Choudhury,1 Nirmalendu Das,2 Swarupa Ghosh,2 Debasree Ghosh,2 Somsuta Chakraborty,2 Nahid Ali1 1Infectious Diseases and Immunology, 2Drug Development, Diagnostics and Biotechnology, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India Abstract: The liver plays a vital role in biotransforming and extricating xenobiotics and is thus prone to their toxicities. Short-term administration of carbon tetrachloride (CCl4 causes hepatic inflammation by enhancing cellular reactive oxygen species (ROS level, promoting mitochondrial dysfunction, and inducing cellular apoptosis. Curcumin is well accepted for its antioxidative and anti-inflammatory properties and can be considered as an effective therapeutic agent against hepatotoxicity. However, its therapeutic efficacy is compromised due to its insolubility in water. Vesicular delivery of curcumin can address this limitation and thereby enhance its effectiveness. In this study, it was observed that both liposomal and nanoparticulated formulations of curcumin could increase its efficacy significantly against hepatotoxicity by preventing cellular oxidative stress. However, the best protection could be obtained through the polymeric nanoparticle-mediated delivery of curcumin. Mitochondria have a pivotal role in ROS homeostasis and cell survivability. Along with the maintenance of cellular ROS levels, nanoparticulated curcumin also significantly (P<0.0001 increased cellular antioxidant enzymes, averted excessive mitochondrial destruction, and prevented total liver damage in CCl4-treated rats. The therapy not only prevented cells from oxidative damage but also arrested the intrinsic apoptotic pathway. In addition, it also decreased the fatty changes in hepatocytes, centrizonal necrosis, and portal inflammation evident from the histopathological analysis. To conclude, curcumin-loaded polymeric nanoparticles are more effective in comparison to liposomal curcumin in preventing CCl4

  1. Role of leukotrienes in NSAID induced gastric ulceration and inflammation in wistar rats

    Directory of Open Access Journals (Sweden)

    Maulik N Gandhi

    2012-06-01

    Full Text Available Objective: To evaluate the effects of Montelukast and Curcumin against indomethacin induced gastric damage in rats in order to assess the role of leukotriene (LTs if any, in non steroidal antiinflammatory drug (NSAID induced gastroinflammation. Methods: The effects of Montelukast (10 mg/kg and Curcumin (100 mg/kg were observed on gastric lesion induced by Indomethacin. The blood samples were analyzed for neutrophil adhesion and lipid peroxide levels in gastric tissue measured spectrophotometrically. The skin vascular permeability study was performed by using compound 48/80 induced vascular permeability model. Results: Montelukast and Curcumin significantly reduced Indomethacin induced gastric lesion score. Pretreatment with Montelukast and Curcumin significantly counteracted Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence, through decrease in related production of free radicals that disrupts integrity of stomach mucosa and decrease in vascular permeability as compared to Indomethacin group. The results of the present study further indicates the role of 5-LOX metabolites in NSAIDs induced gastro inflammation and suggests that Montelukast and Curcumin counteracted the Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence and through decrease in related production of free radicals that disrupts integrity of stomach mucosa. Conclusions: Experimental data clearly demonstrated the role of LTs was indomethacin induced gastric ulcers. However, inhibition of ulcerogenic events by Montelukast and Curcumin is suggestive of an important balance between COX and 5-LOX products.

  2. Modulation of cAMP levels by high-fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression.

    Science.gov (United States)

    Zingg, Jean-Marc; Hasan, Syeda T; Nakagawa, Kiyotaka; Canepa, Elisa; Ricciarelli, Roberta; Villacorta, Luis; Azzi, Angelo; Meydani, Mohsen

    2017-01-02

    Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlr -/- mice fed a high-fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of fatty acid transport proteins (CD36/FAT, FABP4/aP2) in peritoneal macrophages. In this study, we analyzed the molecular mechanisms by which curcumin (500, 1000, 1500 mg/kg diet, for 4 months) may influence plasma and tissue lipid levels in Ldlr -/- mice fed an HFD. In liver, HFD significantly suppressed cAMP levels, and curcumin restored almost normal levels. Similar trends were observed in adipose tissues, but not in brain, skeletal muscle, spleen, and kidney. Treatment with curcumin increased phosphorylation of CREB in liver, what may play a role in regulatory effects of curcumin in lipid homeostasis. In cell lines, curcumin increased the level of cAMP, activated the transcription factor CREB and the human CD36 promoter via a sequence containing a consensus CREB response element. Regulatory effects of HFD and Cur on gene expression were observed in liver, less in skeletal muscle and not in brain. Since the cAMP/protein kinase A (PKA)/CREB pathway plays an important role in lipid homeostasis, energy expenditure, and thermogenesis by increasing lipolysis and fatty acid β-oxidation, an increase in cAMP levels induced by curcumin may contribute to its hypolipidemic and anti-atherosclerotic effects. © 2016 BioFactors, 43(1):42-53, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  3. Natural pomegranate juice reduces inflammation, muscle damage and increase platelets blood levels in active healthy Tunisian aged men

    Directory of Open Access Journals (Sweden)

    Ammar Achraf

    2018-03-01

    Paired simple t-test showed a significant difference between PLA and POMj supplementation effects on systolic blood pressure (SAP, creatinine (CRE, hematological and muscle damage parameters and C-reactive protein (CRP (p < 0.01 with lower values using POMj. Similarly, a significant differences were shown for platelets PLT (p < 0.01 with higher values using POMj supplementation. POMj rich in polyphenols seems to have a power anti-inflammatory effect and to be an effective treatment for patients who suffer from the thrombocyto-penia disease. Therefore, aged populations are advised to add natural POMj to their daily nutrition behavior.

  4. Neuroprotective effects of the polyphenolic antioxidant agent, Curcumin, against homocysteine-induced cognitive impairment and oxidative stress in the rat.

    Science.gov (United States)

    Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Kazeminejad, Behrang

    2010-10-01

    Aging is the major risk factor for neurodegenerative diseases and oxidative stress is involved in the pathophysiology of these diseases. In this study, the possible antioxidant and neuroprotective properties of the polyphenolic antioxidant compound, Curcumin against homocysteine (Hcy) neurotoxicity was investigated. Curcumin (5 and 50mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intrahippocampal injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests were studied 24h after the last Curcumin or its vehicle injection. We detected Malondialdehyde (MDA) and Super oxide anion (SOA) in rats' hippocampi. Results indicated that Hcy could induce lipid peroxidation and increase MDA and SOA levels in rats' hippocampi. Additionally, Hcy impaired memory retention in passive avoidance learning test. However, Curcumin treatment decreased MDA and SOA levels significantly as well as improved learning and memory in rats. Histopathological analysis also indicated that Hcy could decrease hippocampus cell count and Curcumin inhibited this toxic effect. These results suggest that Hcy may induce lipid peroxidation in rats' hippocampi and polyphenol treatment (Curcumin) improved learning and memory deficits by protecting the nervous system against Hcy toxicity. (c) 2010 Elsevier Inc. All rights reserved.

  5. Effect of ageing and pulmonary inflammation on the incidence and number of cross-bridging structures in pneumothorax patients

    International Nuclear Information System (INIS)

    Sasaki, Tomoaki; Takahashi, Koji; Aburano, Tamio

    2011-01-01

    Background. There is an improved prognosis for T4 non-small-cell lung cancer in patients who show particular patterns of direct mediastinal invasion. The particular patterns suggest the presence of direct pathways other than the pulmonary hilum between each of the lungs and the mediastinum/chest wall. Purpose. To determine the incidence and number of such direct pathways in pneumothorax patients as well as the factors that affect the development of these pathways. Material and Methods. Two radiologists independently analyzed multidetector computed tomographic images of 81 patients with pneumothorax to assess the incidence and distribution pattern of the cross-bridging structures in the pleural cavity. Results. Cross-bridging structures were observed in the right pneumothorax in 34/54 (63%) patients and in the left pneumothorax in 19/32 (59%) patients. The number of cross-bridging structures was found to be positively correlated with ageing and pulmonary disease. The distribution patterns of cross-bridging structures were found to be specific in formation and often in repeated locations, regardless of the presence of pulmonary disease or the age of the patient. Conclusion. Cross-bridging structures in pneumothoraces were found more frequently in older patients and in patients with pulmonary disease. However, some of the cross-bridging structures may have been congenital because of their specific formations and repeated locations

  6. Effect of ageing and pulmonary inflammation on the incidence and number of cross-bridging structures in pneumothorax patients

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Tomoaki; Takahashi, Koji; Aburano, Tamio (Dept. of Radiology, Asahikawa Medical Univ., Asahikawa, Hokkaido (Japan)), email: tomoaki3est@gmail.com

    2011-12-15

    Background. There is an improved prognosis for T4 non-small-cell lung cancer in patients who show particular patterns of direct mediastinal invasion. The particular patterns suggest the presence of direct pathways other than the pulmonary hilum between each of the lungs and the mediastinum/chest wall. Purpose. To determine the incidence and number of such direct pathways in pneumothorax patients as well as the factors that affect the development of these pathways. Material and Methods. Two radiologists independently analyzed multidetector computed tomographic images of 81 patients with pneumothorax to assess the incidence and distribution pattern of the cross-bridging structures in the pleural cavity. Results. Cross-bridging structures were observed in the right pneumothorax in 34/54 (63%) patients and in the left pneumothorax in 19/32 (59%) patients. The number of cross-bridging structures was found to be positively correlated with ageing and pulmonary disease. The distribution patterns of cross-bridging structures were found to be specific in formation and often in repeated locations, regardless of the presence of pulmonary disease or the age of the patient. Conclusion. Cross-bridging structures in pneumothoraces were found more frequently in older patients and in patients with pulmonary disease. However, some of the cross-bridging structures may have been congenital because of their specific formations and repeated locations

  7. Dietary supplementation with fruit polyphenolics ameliorates age-related deficits in behavior and neuronal markers of inflammation and oxidative stress.

    Science.gov (United States)

    Shukitt-Hale, Barbara; Galli, Rachel L; Meterko, Vanessa; Carey, Amanda; Bielinski, Donna F; McGhie, Tony; Joseph, James A

    2005-03-01

    Dietary supplementation with fruit or vegetable extracts can ameliorate age-related declines in measures of learning, memory, motor performance, and neuronal signal transduction in a rat model. To date, blueberries have proved most effective at improving measures of motor performance, spatial learning and memory, and neuronal functioning in old rats. In an effort to further characterize the bioactive properties of fruits rich in color and correspondingly high in anthocyanins and other polyphenolics, 19-month-old male Fischer rats were fed a well-balanced control diet, or the diet supplemented with 2% extract from either blueberry, cranberry, blackcurrant, or Boysenberry fruit for eight weeks before testing began. The blackcurrant and cranberry diets enhanced neuronal signal transduction as measured by striatal dopamine release, while the blueberry and cranberry diets were effective in ameliorating deficits in motor performance and hippocampal HSP70 neuroprotection; these changes in HSP70 were positively correlated with performance on the inclined screen. It appears that the polyphenols in blueberries and cranberries have the ability to improve muscle tone, strength and balance in aging rats, whereas polyphenols in blueberries, cranberries and blackcurrants have the ability to enhance neuronal functioning and restore the brain's ability to generate a neuroprotective response to stress.

  8. Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder.

    Science.gov (United States)

    Grosse, Laura; Carvalho, Livia A; Wijkhuijs, Annemarie J M; Bellingrath, Silja; Ruland, Tillmann; Ambrée, Oliver; Alferink, Judith; Ehring, Thomas; Drexhage, Hemmo A; Arolt, Volker

    2015-02-01

    Increased inflammatory activation might only be present in a subgroup of depressed individuals in which immune processes are especially relevant to disease development. We aimed to analyze demographic, depression, and trauma characteristics of major depressive disorder (MDD) patients with regard to inflammatory monocyte gene expression. Fifty-six naturalistically treated MDD patients (32 ± 12 years) and 57 healthy controls (HC; 31 ± 11 years) were analyzed by the Inventory of Depressive Symptomatology (IDS) and by the Childhood Trauma Questionnaire (CTQ). We determined the expression of 38 inflammatory and immune activation genes including the glucocorticoid receptor (GR)α and GRβ genes in purified CD14(+) monocytes using quantitative-polymerase chain reaction (RT-qPCR). Monocyte gene expression was age-dependent, particularly in MDD patients. Increased monocyte gene expression and decreased GRα/β ratio were only present in MDD patients aged ⩾ 28 years. Post hoc analyses of monocyte immune activation in patients depression (recurrent type, onset depression, onset ⩾15 years) - additionally characterized by the absence of panic symptoms - that exhibited a strongly reduced inflammatory monocyte activation compared to HC. In conclusion, monocyte immune activation was not uniformly raised in MDD patients but was increased only in patients of 28 years and older. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 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

  10. Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription

    Directory of Open Access Journals (Sweden)

    Santoro Thomas J

    2005-02-01

    Full Text Available Abstract Background In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2 is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS. The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chemokine. Curcumin is a spice principle in, and constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and antioxidant activities suggest that it might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation. Relatively unexplored, but relevant to its potential therapeutic efficacy in neuroinflammatory syndromes is the effect of curcumin on chemokine production. To examine the possibility that curcumin may influence CNS inflammation by mechanisms distinct from its known anti-oxidant activities, we studied the effect of this spice principle on the synthesis of MIP-2 by astrocytes. Methods Primary astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were stimulated with lipopolysaccharide in the presence or absence of various amount of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi-quantitative PCR and MIP-2 protein production in the culture supernatants was quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct, pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of curcumin. Results The induction of MIP-2 gene expression and the production of MIP-2 protein were inhibited by curcumin. Curcumin also inhibited lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene construct in primary astrocytes. However MIP-2 gene induction by lipopolysaccharide was not inhibited by another anti

  11. Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription.

    Science.gov (United States)

    Tomita, Michiyo; Holman, Brita J; Santoro, Christopher P; Santoro, Thomas J

    2005-02-25

    BACKGROUND: In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2) is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS). The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chemokine.Curcumin is a spice principle in, and constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and antioxidant activities suggest that it might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation. Relatively unexplored, but relevant to its potential therapeutic efficacy in neuroinflammatory syndromes is the effect of curcumin on chemokine production. To examine the possibility that curcumin may influence CNS inflammation by mechanisms distinct from its known anti-oxidant activities, we studied the effect of this spice principle on the synthesis of MIP-2 by astrocytes. METHODS: Primary astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were stimulated with lipopolysaccharide in the presence or absence of various amount of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi-quantitative PCR and MIP-2 protein production in the culture supernatants was quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct, pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of curcumin. RESULTS: The induction of MIP-2 gene expression and the production of MIP-2 protein were inhibited by curcumin. Curcumin also inhibited lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene construct in primary astrocytes. However MIP-2 gene induction by lipopolysaccharide was not inhibited by another anti-oxidant, epigallocatechin

  12. CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries.

    Science.gov (United States)

    Lin, Chai-Ching; Chiang, Tien-Huang; Chen, Wei-Jung; Sun, Yu-Yo; Lee, Yi-Hsuan; Lin, Muh-Shi

    2015-12-01

    CISD2 is known to have roles in calcium metabolism, anti-apoptosis, and longevity. However, whether CISD2 is involved in the inflammatory response associated with injuries of the central nervous system (CNS) remains unclear. This issue is particularly relevant for traumatic spinal cord injuries (SCIs), which lack therapeutic targeting and often cause long-term disability in patients. The authors previously demonstrated the neuroprotective effects of curcumin against RANTES-mediated neuroinflammation. In this study, we investigated (1) the role of CISD2 in injury-induced inflammation and (2) whether curcumin influences CISD2 expression in acute SCI. The efficacy of curcumin treatment (40 mg/kg i.p.) was evaluated in an animal model of SCI. In a neural cell culture model, lipopolysaccharide (LPS) was administrated to induce inflammation with the aim of mimicking the situation commonly encountered in SCI. Additionally, knockdown of CISD2 expression by siRNA (siCISD2) in LPS-challenged neural cells was performed to verify the causal relationship between CISD2 and SCI-related inflammation. The injuries were shown to reduce CISD2 mRNA and protein expression in vivo, and CISD2-positive cells were upregulated by the curcumin treatment. LPS led to a decrease in CISD2 expression in vitro; however, treatment with 1 μM curcumin attenuated the downregulation of CISD2. Furthermore, in a cellular model of LPS-induced injury, the loss of CISD2 function caused by siCISD2 resulted in a pronounced iNOS increase as well as a decrease in BCL2 expression. To the best of our knowledge, this is the first study to report the following: (1) CISD2 exerts anti-apoptotic and anti-inflammatory effects in neural cells; and (2) curcumin can attenuate the downregulation of CISD2 in SCI and LPS-treated astrocytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. 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 ...

  14. Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress

    Science.gov (United States)

    Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

    2016-01-01

    Objective The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Methods Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Results Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=−0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=−0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=−0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction

  15. 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 ...

  16. 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...

  17. 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]....

  18. Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration.

    Science.gov (United States)

    Chen, Jiajia; Wang, Wenzhan; Li, Qiuming

    2017-01-01

    Age-related macular degeneration (AMD) is the primary cause of senior blindness in developed countries. Mechanisms underlying initiation and development of AMD remained known. We examined the CD4+ T cell compartments and their functions in AMD patients. AMD patients presented significantly higher frequencies of interferon (IFN)-γ-expressing and interleukin (IL)-17-expressing CD4+ T cells than healthy controls. The levels of IFN-γ and IL-17 expression by CD4+ T cells were significantly higher in AMD patients. These IFN-γ-expressing Th1 cells and IL-17-expressing Th17 cells could be selectively enriched by surface CCR3+ and CCR4+CCR6+ expression, respectively. Th1 and Th17 cells from AMD patients promoted the differentiation of monocytes toward M1 macrophages, which were previously associated with retinal damage. Th1 and Th17 cells also increased the level of MHC class I expression in human retinal pigment epithelial (RPE)-1 cells, while Th1 cells increased the frequency of MHC class II-expressing RPE-1 cells. These proinflammatory effects were partly, but not entirely, induced by the secretion of IFN-γ and IL-17. This study demonstrated an enrichment of Th1 cells and Th17 cells in AMD patients. These Th1 and Th17 cells possessed proinflammatory roles in an IFN-γ- and IL-17-dependent fashion, and could potentially serve as therapeutic targets. © 2017 The Author(s). Published by S. Karger AG, Basel.

  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. 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.

  2. 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.

  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. Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation.

    Science.gov (United States)

    Afrin, Rejina; Arumugam, Somasundaram; Rahman, Azizur; Wahed, Mir Imam Ibne; Karuppagounder, Vengadeshprabhu; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Suzuki, Kenji; Yoneyama, Hiroyuki; Ueno, Kazuyuki; Watanabe, Kenichi

    2017-03-01

    Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro-inflammatory cytokines, and chemokines including interferon (IFN) γ, interleukin-1β and IFNγ-inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF-κB) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican-3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1-NF-κB translocation. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. [Neuroprotective effect of curcumin to Aβ of double transgenic mice with Alzheimer's disease].

    Science.gov (United States)

    Feng, Hui-Li; Fan, Hui; Dang, Hui-Zi; Chen, Xiao-Pei; Ren, Ying; Yang, Jin-Duo; Wang, Peng-Wen

    2014-10-01

    To observe the changes in Aβ40, Aβ42 and ADDLs in brains of 3 month-old APPswe/PS1dE9 double transgenic mice after six-month intervention with curcumin, in order to discuss the neuroprotective effect of curcumin. APPswe/PS1dE9dtg mice were randomly divided into the model group, the Rosiglitazone group (10 mg x kg(-1) x d(-1)) and curcumin high (400 mg x kg9-1) x d(-1)), medium (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dosage groups, with C57/BL6J mice of the same age and the same background in the normal control group. After 6 months, the immunohistochemical staining (IHC) and the Western blot method were used to observe the changes in positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area, their distribution and protein expressions. Both of the immunohistochemical staining and the Western blot method showed more positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area and higher protein expressions in the model group than the normal group (P curcumin high group, the medium group showed a significant decrease (P curcumin can significantly reduce the expressions of hippocampal Aβ40, Aβ42 and ADDLs in brains of APPswe/PS1dE9 double transgenic mice. Whether curcumin can impact Aβ cascade reaction by down-regulating expressions of Aβ40, Aβ42 and ADDLs and show the neuroprotective effect needs further studies.

  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. Design, characterization, and biological evaluation of curcumin-loaded surfactant-based systems for topical drug delivery

    Directory of Open Access Journals (Sweden)

    Fonseca-Santos B

    2016-09-01

    Full Text Available Bruno Fonseca-Santos, Aline Martins dos Santos, Camila Fernanda Rodero, Maria Palmira Daflon Gremião, Marlus Chorilli School of Pharmaceutical Sciences, UNESP – São Paulo State University, Araraquara, São Paulo Brazil Abstract: From previous studies, it has been found that curcumin exhibits an anti-inflammatory activity and is being used for the treatment of skin disorders; however, it is hydrophobic and has weak penetrating ability, resulting in poor drug transport through the stratum corneum. The aim of this study was to develop liquid crystalline systems for topical administration of curcumin for the treatment of inflammation. These liquid crystalline systems were developed from oleic acid, polyoxypropylene (5 polyoxyethylene (20 cetyl alcohol, and water as the surfactant, oil phase, and aqueous phase, respectively. These systems were characterized, and polarized light microscopy showed anisotropy with lamellar mesophases (Formulation 1 and hexagonal mesophases (Formulations 2 and 3, which were confirmed by the peak ratio measured using small-angle X-ray scattering. In addition, rheological tests revealed that the formulations exhibited gel-like behavior (G'>G'', as evidenced by the increased G' values that indicate structured systems. Texture profile analysis showed that hexagonal mesophases have high values of hardness, adhesiveness, and compressibility, which indicate structured systems. In vitro studies on bioadhesion revealed that the hexagonal mesophases increased the bioadhesiveness of the systems to the skin of the pig ear. An in vivo inflammation experiment showed that the curcumin-loaded hexagonal mesophase exhibited an anti-inflammatory activity as compared to the positive control (dexamethasone. The results suggest that this system has a potential to be used as a bioadhesive vehicle for the topical administration of curcumin. Therefore, it is possible to conclude that these systems can be used for the optimization of drug

  9. 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 ...

  10. 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.

  11. 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

  12. 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...

  13. Aging-related renal injury and inflammation are associated with downregulation of Klotho and induction of RIG-I/NF-κB signaling pathway in senescence-accelerated mice.

    Science.gov (United States)

    Zeng, Yi; Wang, Ping-Han; Zhang, Mao; Du, Jun-Rong

    2016-02-01

    The predominant distribution of the antiaging Klotho protein in both the kidneys and brain may point to its essential role in protecting against dysfunction of the kidney-brain axis during the aging process. Our previous study showed that the downregulation of Klotho was involved in aging-related cognitive impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. The present study investigated the potential role of Klotho in aging-associated inflammation and renal injury. Age- and gender-matched groups of SAMP8 mice and their corresponding normal control senescence-accelerated mouse resistant-1 (SAMR1) were used to investigate the potential role of Klotho in aging-associated inflammation and renal injury. Compared with aged SAMR1 controls, early-stage chronic kidney disease (CKD), which is associated with an increase in the urinary albumin-to-creatinine ratio, inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis, was observed in aged SAMP8 mice. Furthermore, the aging-related loss of Klotho-induced activation of the retinoic acid-inducible gene 1/nuclear factor-κB (RIG-I/NF-κB) signaling pathway and subsequent production of the proinflammatory mediators tumor necrosis factor α, interleukin-6, and inducible nitric oxide synthase in the kidneys of aged SAMP8 mice compared with SAMR1 controls. The present results suggest that aging-related inflammation and the development of early-stage CKD are likely associated with the downregulation of Klotho and induction of the RIG-I/NF-κB signaling pathway in 12-month-old SAMP8 mice. Moreover, aged SAMP8 mice with cognitive deficits and renal damage may be a potential mouse model for investigating the kidney-brain axis in the aging process.

  14. 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.

  15. Aging, female sex, migration, elevated HDL-C, and inflammation are associated with prevalence of metabolic syndrome among African bank employees

    Directory of Open Access Journals (Sweden)

    Gombet T

    2012-06-01

    Full Text Available Thierry Gombet,1 Benjamin Longo-Mbenza,2 Bertrand Ellenga-Mbolla,1 Meo Stephane Ikama,3 Etienne Mokondjimobe,4 Gisele Kimbally-Kaky,3 Jean-Louis Nkoua,31Emergency Department, University Hospital Center of Brazzaville, Brazzaville, Congo; 2Faculty of Health Sciences, Walter Sisulu University, Mthatha, Eastern Cape, South Africa; 3Department of Cardiology and Internal Medicine, University Hospital Center of Brazzaville, Brazzaville, Congo; 4Laboratory of Biochemistry and Pharmacology, Faculty of Health Sciences, Brazzaville, CongoBackground: The objective of this study was to compare four different criteria for diagnosing metabolic syndrome (MS and to correlate sociodemographic data, liver enzymes, lipids, inflammation, and insulin resistance with MS definitions.Methods: This cross-sectional study included a random number of 126 African bank employees from Brazzaville, Congo.Results: The prevalence of MS varied according to the different definitions used: 4.8% under World Health Organization (WHO criteria, 8.7% under the National Cholesterol Education Program Adult Treatment Panel III (NECP-ATPIII criteria, 14.3% under the International Diabetes Federation (IDF for Europe, and 15.9% by the IDF for Central Africa. According to the IDF, specific cutoff points for the erythrocyte sedimentation rate, ≥13 mm at first hour and ≥30 mm at second hour, defined MS for Central Africa. The best agreement was observed between the IDF for Europe and the IDF for Central Africa (Kappa = 0.938; P < 0.0001 criteria. The worst agreements were between the WHO and IDF for Central Africa (Kappa = 0.419; P < 0.0001 criteria and between the WHO and IDF for Europe (Kappa = 0.462; P < 0.0001 criteria. The NECP-ATPIII criteria did not agree with either the IDF for Europe or the IDF for Central Africa criteria. There was a significant relationship between female sex, aging, elevated liver enzymes, elevated phospholipids, high homeostasis model assessment of insulin

  16. 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.

  17. Antioxidant and antiinflammatory activities of curcumin on diabetes mellitus and its complications.

    Science.gov (United States)

    Meng, Bo; Li, Jun; Cao, Hong

    2013-01-01

    Diabetes mellitus (DM) has reached pandemic status and shows no signs of abatement. It can severely impair people's quality of life and affects patients all over the world. Since it is a serious, chronic metabolic disease, it can bring about many kinds of complications, which can in turn increase mortality. In recent decades, more and more studies have shown that oxidative stress and inflammatory reactions play critical roles in the pathogenesis of DM. There is an increasing demand for natural antidiabetic medicines that do not have the same side effects as modern drugs. Curcumin, a phytochemical found in the spice turmeric, has been used in India for centuries, and it has no known side effects. It has been shown to have some beneficial effects against various chronic illnesses. Many of these therapeutic actions can be attributed to its potent anti-oxidant and anti-inflammatory activities. In view of the oxidative stress and inflammatory mechanisms of DM, curcumin can be considered suitable for the prevention and amelioration of diabetes. In this review, we summarize the nosogenesis of DM, giving primary focus to oxidative stress and inflammation. We discuss the anti-oxidant and anti-inflammatory activities of curcumin in DM and its ability to mitigate the effects on DM and its associated complications in detail.

  18. Preparation and In Vitro Evaluation of Glycyrrhetinic Acid-Modified Curcumin-Loaded Nanostructured Lipid Carriers

    Directory of Open Access Journals (Sweden)

    Yang Chu

    2014-02-01

    Full Text Available Curcumin, a phenolic antioxidant compound derived from the rhizome of the turmeric plant Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion and apoptosis, revealing its anticancer potential. In this study, a Glycyrrhetinic Acid-Modified Curcumin-Loaded Nanostructured Lipid Carrier (Cur-GA-PEG-NLC was prepared by the film ultrasound method to improve the tumor-targeting ability. The drug content was detected by an UV spectrophotometry method. The encapsulation efficiency of curcumin in the nanostructured lipid carriers (NLCs was determined using a mini-column centrifugation method. The encapsulation efficiency for various Cur-GA-PEG-NLC was within the range of 90.06%–95.31% and particle size was between 123.1 nm and 132.7 nm. An in vitro MTT assay showed that Cur-GA10%-PEG-NLC had significantly high cellular uptake and cytotoxicity against HepG2 cells compared with other groups.

  19. Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations.

    Science.gov (United States)

    Baliga, Manjeshwar Shrinath; Joseph, Nandhini; Venkataranganna, Marikunte V; Saxena, Arpit; Ponemone, Venkatesh; Fayad, Raja

    2012-11-01

    Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.

  20. Red Light Combined with Blue Light Irradiation Regulates Proliferation and Apoptosis in Skin Keratinocytes in Combination with Low Concentrations of Curcumin

    Science.gov (United States)

    Cai, Qing; Ren, Qu; Wei, Lizhao

    2015-01-01

    Curcumin is a widely known natural phytochemical from plant Curcuma longa. In recent years, curcumin has received increasing attention because of its capability to induce apoptosis and inhibit cell proliferation as well as its anti-inflammatory properties in different cancer cells. However, the therapeutic benefits of curcumin are severely hampered due to its particularly low absorption via trans-dermal or oral bioavailability. Phototherapy with visible light is gaining more and more support in dermatological therapy. Red light is part of the visible light spectrum, which is able to deeply penetrate the skin to about 6 mm, and directly affect the fibroblast of the skin dermis. Blue light is UV-free irradiation which is fit for treating chronic inflammation diseases. In this study, we show that curcumin at low concentrations (1.25–3.12 μM) has a strong anti-proliferative effect on TNF-α-induced psoriasis-like inflammation when applied in combination with light-emitting-diode devices. The treatment was especially effective when LED blue light at 405 nm was combined with red light at 630 or 660 nm, which markedly amplified the anti-proliferative and apoptosis-inducing effects of curcumin. The experimental results demonstrated that this treatment reduced the viability of human skin keratinocytes, decreased cell proliferation, induced apoptosis, inhibited NF-κB activity and activated caspase-8 and caspase-9 while preserving the cell membrane integrity. Moreover, the combined treatment also down-regulated the phosphorylation level of Akt and ERK. Taken together, our results indicated that the combination of curcumin with LED blue light united red light irradiation can attain a higher efficiency of regulating proliferation and apoptosis in skin keratinocytes. PMID:26382065

  1. Red Light Combined with Blue Light Irradiation Regulates Proliferation and Apoptosis in Skin Keratinocytes in Combination with Low Concentrations of Curcumin.

    Directory of Open Access Journals (Sweden)

    Tianhui Niu

    Full Text Available Curcumin is a widely known natural phytochemical from plant Curcuma longa. In recent years, curcumin has received increasing attention because of its capability to induce apoptosis and inhibit cell proliferation as well as its anti-inflammatory properties in different cancer cells. However, the therapeutic benefits of curcumin are severely hampered due to its particularly low absorption via trans-dermal or oral bioavailability. Phototherapy with visible light is gaining more and more support in dermatological therapy. Red light is part of the visible light spectrum, which is able to deeply penetrate the skin to about 6 mm, and directly affect the fibroblast of the skin dermis. Blue light is UV-free irradiation which is fit for treating chronic inflammation diseases. In this study, we show that curcumin at low concentrations (1.25-3.12 μM has a strong anti-proliferative effect on TNF-α-induced psoriasis-like inflammation when applied in combination with light-emitting-diode devices. The treatment was especially effective when LED blue light at 405 nm was combined with red light at 630 or 660 nm, which markedly amplified the anti-proliferative and apoptosis-inducing effects of curcumin. The experimental results demonstrated that this treatment reduced the viability of human skin keratinocytes, decreased cell proliferation, induced apoptosis, inhibited NF-κB activity and activated caspase-8 and caspase-9 while preserving the cell membrane integrity. Moreover, the combined treatment also down-regulated the phosphorylation level of Akt and ERK. Taken together, our results indicated that the combination of curcumin with LED blue light united red light irradiation can attain a higher efficiency of regulating proliferation and apoptosis in skin keratinocytes.

  2. Curcumin mediated suppression of nuclear factor-κB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment.

    Science.gov (United States)

    Buhrmann, Constanze; Mobasheri, Ali; Matis, Ulrike; Shakibaei, Mehdi

    2010-01-01

    Osteoarthritis (OA) and rheumatoid arthritis (RA) are characterised by joint inflammation and cartilage degradation. Although mesenchymal stem cell (MSC)-like progenitors are resident in the superficial zone of articular cartilage, damaged tissue does not possess the capacity for regeneration. The high levels of pro-inflammatory cytokines present in OA/RA joints may impede the chondrogenic differentiation of these progenitors. Interleukin (IL)-1β activates the transcription factor nuclear factor-κB (NF-κB), which in turn activates proteins involved in matrix degradation, inflammation and apoptosis. Curcumin is a phytochemical capable of inhibiting IL-1β-induced activation of NF-κB and expression of apoptotic and pro-inflammatory genes in chondrocytes. Therefore, the aim of the present study was to evaluate the influence of curcumin on IL-1β-induced NF-κB signalling pathway in MSCs during chondrogenic differentiation. MSCs were either cultured in a ratio of 1:1 with primary chondrocytes in high-density culture or cultured alone in monolayer with/without curcumin and/or IL-1β. We demonstrate that although curcumin alone does not have chondrogenic effects on MSCs, it inhibits IL-1β-induced activation of NF-κB, activation of caspase-3 and cyclooxygenase-2 in MSCs time and concentration dependently, as it does in chondrocytes. In IL-1β stimulated co-cultures, four-hour pre-treatment with curcumin significantly enhanced the production of collagen type II, cartilage specific proteoglycans (CSPGs), β1-integrin, as well as activating MAPKinase signaling and suppressing caspase-3 and cyclooxygenase-2. Curcumin treatment may help establish a microenvironment in which the effects of pro-inflammatory cytokines are antagonized, thus facilitating chondrogenesis of MSC-like progenitor cells in vivo. This strategy may support the regeneration of articular cartilage.

  3. 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."

  4. Curcumin increased the differentiation rate of neurons in neural stem cells via wnt signaling in vitro study.

    Science.gov (United States)

    Chen, Fei; Wang, Haoxiang; Xiang, Xin; Yuan, Jichao; Chu, Weihua; Xue, Xingsen; Zhu, Haitao; Ge, Hongfei; Zou, Mingming; Feng, Hua; Lin, Jiangkai

    2014-12-01

    The objective of the present study was to clarify the relationship between the neuroprotective effects of curcumin and the classical wnt signaling pathway. Using Sprague-Dawley rats at a gestational age of 14.5 d, we isolated neural stem cells from the anterior two-thirds of the fetal rat brain. The neural stem cells were passaged three times using the half media replacement method and identified using cellular immunofluorescence. After passaging for three generations, we cultured cells in media without basic fibroblast growth factor and epidermal growth factor. Then we treated cells in five different ways, including a blank control group, a group treated with IWR1 (10 μmol/L), a group treated with curcumin (500 nmol/L), a group treated with IWR1 + curcumin, and a group treated with dimethyl sulfoxide (10 μmol/L). We then measured the protein and RNA expression levels for wnt3a and β-catenin using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). Western-blotting: after the third generation of cells had been treated for 72 h, we observed that wnt3a and β-catenin expression was significantly increased in the group receiving 500 nmol/L curcumin but not in the other groups. Furthermore, cells in the IWR1-treated group showed decreased wnt3a and β-catenin expression, and wnt3a and β-catenin was also decreased in the IWR1 + 500 nmol/L curcumin group. No obvious change was observed in the dimethyl sulfoxide group. RT-PCR showed similar changes to those observed with the Western blotting experiments. Our study suggests that curcumin can activate the wnt signaling pathway, which provides evidence that curcumin exhibits a neuroprotective effect through the classical wnt signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

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    Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

    2012-05-01

    Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  6. 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.

  7. A PPARγ, NF-κB and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver.

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    Jiménez-Flores, Lizbeth M; López-Briones, Sergio; Macías-Cervantes, Maciste H; Ramírez-Emiliano, Joel; Pérez-Vázquez, Victoriano

    2014-06-18

    Turmeric (Curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family which has been used to treat biliary disorders, anorexia, cough, rheumatism, cancer, sinusitis, hepatic disorders, hyperglycemia, obesity, and diabetes in both Ayurvedic and Traditional Chinese Medicine. Suggested mechanisms of action include the modulation of signal transduction cascades and effects on gene expression, however they remain to be elucidated. In this study, the expression of some proteins responsible for transcription factors, inflammation, and metabolic control were evaluated by western blot in 15-week-old db/db mice livers treated with curcumin 0.75% mixed in their diet for 8 weeks. In addition, nitrosative stress was evaluated. Curcumin increased the expression of AMPK and PPARγ, and diminished NF-κB protein in db/db mice. However, it did not modify the expression of PGC-1α or SIRT1. Nitrosative stress present in db/db mice livers was determined by a unique nitrotyrosylated protein band (75 kDa) and was not reverted with curcumin. In conclusion, curcumin regulates the expression of AMPK, PPARγ, and NF-κB; suggesting a beneficial effect for treatment of T2DM complications. In order to observe best beneficial effects it is desirable to administer curcumin in the earlier states of T2DM.

  8. A PPARγ, NF-κB and AMPK-Dependent Mechanism May Be Involved in the Beneficial Effects of Curcumin in the Diabetic db/db Mice Liver

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    Lizbeth M. Jiménez-Flores

    2014-06-01

    Full Text Available Turmeric (Curcuma longa is a rhizomatous herbaceous perennial plant of the ginger family which has been used to treat biliary disorders, anorexia, cough, rheumatism, cancer, sinusitis, hepatic disorders, hyperglycemia, obesity, and diabetes in both Ayurvedic and Traditional Chinese Medicine. Suggested mechanisms of action include the modulation of signal transduction cascades and effects on gene expression, however they remain to be elucidated. In this study, the expression of some proteins responsible for transcription factors, inflammation, and metabolic control were evaluated by western blot in 15-week-old db/db mice livers treated with curcumin 0.75% mixed in their diet for 8 weeks. In addition, nitrosative stress was evaluated. Curcumin increased the expression of AMPK and PPARγ, and diminished NF-κB protein in db/db mice. However, it did not modify the expression of PGC-1α or SIRT1. Nitrosative stress present in db/db mice livers was determined by a unique nitrotyrosylated protein band (75 kDa and was not reverted with curcumin. In conclusion, curcumin regulates the expression of AMPK, PPARγ, and NF-κB; suggesting a beneficial effect for treatment of T2DM complications. In order to observe best beneficial effects it is desirable to administer curcumin in the earlier states of T2DM.

  9. Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia

    International Nuclear Information System (INIS)

    Rajasingh, Johnson; Raikwar, Himanshu P.; Muthian, Gladson; Johnson, Caroline; Bright, John J.

    2006-01-01

    Adult T cell leukemia is an aggressive and frequently fatal malignancy that expressess constitutively activated growth-signaling pathways in association with deregulated growth and resistance to apoptosis. Curcumin (diferuloylmethane) is a naturally occurring yellow pigment, isolated from the rhizomes of the plant Curcuma longa that has traditionally been used in the treatment of injury and inflammation. But the effect and mechanism of action of curcumin on T cell leukemia is not known. To investigate the antitumor activity of curcumin in T cell leukemia, we examined its effect on constitutive phosphorylation of JAK and STAT proteins, proliferation, and apoptosis in HTLV-I-transformed T cell lines. HTLV-I-transformed T cell leukemia lines, MT-2, HuT-102, and SLB-1, express constitutively phosphorylated JAK3, TYK2, STAT3, and STAT5 signaling proteins. In vitro treatment with curcumin induced a dose-dependent decrease in JAK and STAT phosphorylation resulting in the induction of growth-arrest and apoptosis in T cell leukemia. The induction of growth-arrest and apoptosis in association with the blockade of constitutively active JAK-STAT pathway suggests this be a mechanism by which curcumin induces antitumor activity in T cell leukemia

  10. Multiple antidepressant potential modes of action of curcumin: a review of its anti-inflammatory, monoaminergic, antioxidant, immune-modulating and neuroprotective effects.

    Science.gov (United States)

    Lopresti, Adrian L; Hood, Sean D; Drummond, Peter D

    2012-12-01

    Curcumin is the principal curcuminoid of the popular Indian spice turmeric and has attracted increasing attention for the treatment of a range of conditions. Research into its potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. Research completed to date on the multiple effects of curcumin is reviewed in this paper, with a specific emphasis on the biological systems that are compromised in depression. The antidepressant effects of curcumin in animal models of depression are summarised, and its influence on neurotransmitters such as serotonin and dopamine is detailed. The effects of curcumin in moderating hypothalamus-pituitary-adrenal disturbances, lowering inflammation and protecting against oxidative stress, mitochondrial damage, neuroprogression and intestinal hyperpermeability, all of which are compromised in major depressive disorder, are also summarised. With increasing interest in natural treatments for depression, and efforts to enhance current treatment outcomes, curcumin is presented as a promising novel, adjunctive or stand-alone natural antidepressant.

  11. Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

    Science.gov (United States)

    Joe, Bina; Nagaraju, Anitha; Gowda, Lalitha R; Basrur, Venkatesha; Lokesh, Belur R

    2014-01-01

    Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I.

  12. Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

    Directory of Open Access Journals (Sweden)

    Bina Joe

    Full Text Available Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I.

  13. The effects of curcumin (diferuloylmethane) on body composition of patients with advanced pancreatic cancer.

    Science.gov (United States)

    Parsons, Henrique A; Baracos, Vickie E; Hong, David S; Abbruzzese, James; Bruera, Eduardo; Kurzrock, Razelle

    2016-04-12

    Curcumin is a natural product that is often explored by patients with cancer. Weight loss due to fat and muscle depletion is a hallmark of pancreatic cancer and is associated with worse outcomes. Studies of curcumin's effects on muscularity show conflicting results in animal models. Retrospective matched 1:2 case-control study to evaluate the effects of curcumin on body composition (determined by computerized tomography) of 66 patients with advanced pancreatic cancer (22 treated,44 controls). Average age (SEM) was 63(1.8) years, 30/66(45%) women, median number of prior therapies was 2, median (IQR) time from advanced pancreatic cancer diagnosis to baseline image was 7(2-13.5) months (p>0.2, all variables). All patients lost weight (3.3% and 1.3%, treated vs. control, p=0.13). Treated patients lost more muscle (median [IQR] percent change -4.8[-9.1,-0.1] vs. -0.05%[-4.2, 2.6] in controls,pcancer treated with curcumin showed significantly greater loss of subcutaneous fat and muscle than matched untreated controls.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Neonatal systemic inflammation and the risk of low scores on measures of reading and mathematics achievement at age 10 years among children born extremely preterm.

    Science.gov (United States)

    Leviton, Alan; Dammann, Olaf; Allred, Elizabeth N; Joseph, Robert M; Fichorova, Raina N; O'Shea, T Michael; Kuban, Karl C K

    2018-05-01

    Difficulties with reading and math occur more commonly among children born extremely preterm than among children born at term. Reasons for this are unclear. We measured the concentrations of 27 inflammatory-related and neurotrophic/angiogenic proteins (angio-neurotrophic proteins) in multiple blood specimens collected a week apart during the first postnatal month from 660 children born before the 28th week of gestation who at age 10 years had an IQ ≥ 70 and a Wechsler Individual Achievement Test 3rd edition (WIAT-III) assessment. We identified four groups of children, those who had a Z-score ≤ -1 on the Word Reading assessment only, on the Numerical Operations assessment only, on both of these assessments, and on neither, which served as the referent group. We then modeled the risk of each learning limitation associated with a top quartile concentration of each protein, and with high and lower concentrations of multiple proteins. The protein profile of low reading scores was confined to the third and fourth postnatal weeks when increased risks were associated with high concentrations of IL-8 and ICAM-1 in the presence of low concentrations of angio-neurotrophic proteins. The profile of low math scores was very similar, except it did not include ICAM-1. In contrast, the profile of low scores on both assessments was present in each of the first four postnatal weeks. The increased risks associated with high concentrations of TNF-α in the first two weeks and of IL-8 and ICAM-1 in the next two weeks were modulated down by high concentrations of angio-neurotrophic proteins. High concentrations of angio-neurotrophic proteins appear to reduce/moderate the risk of each learning limitation associated with systemic inflammation. The three categories of limitations have protein profiles with some similarities, and yet some differences, too. Copyright © 2018 ISDN. Published by Elsevier Ltd. All rights reserved.

  16. Curcumin mitigates lithium-induced thyroid dysfunction by modulating antioxidant status, apoptosis and inflammatory cytokines

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    Sanaa M. Abd El-Twab

    2016-08-01

    Full Text Available Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. It has also been shown to reduce suicidal risk and short term mortality. Few experimental studies have demonstrated the thyroid toxicity caused by lithium as well as the possible protective effect of curcumin. Twenty four male albino rats were divided into three groups; group I (control group, group II received lithium carbonate daily for 6 weeks and group III received the same dose of lithium carbonate as group II concomitantly with curcumin for 6 weeks. The specimens were prepared for histopathological, immunohistochemical and biochemical examination. Lithium-induced thyroid dysfunction evidenced by the histopathological and immunohistochemical changes represented by detached cells and vacuolated cytoplasm of some follicular cells and highly significant increase in positive immunostained of thyroglobulin and caspase-3 respectively. Moreover, a significant decrease in serum free triiodothyonine (FT3, free thyroxine (FT4 concomitant with significantly increased thyroid stimulating hormone (TSH and pro-inflammatory cytokines, and thyroid lipid peroxidation (MDA and nitric oxide (NO levels. Curcumin counteracted lithium-induced oxidative stress and inflammation as assessed by restoration of the antioxidant defenses and diminishing of pro-inflammatory cytokines and improvements in the degenerative changes of the thyroid gland. In conclusion, the present study provides evidence that curcumin exerts thyroprotective effects against lithium carbonate mediated by its antioxidant, anti-inflammatory and anti-apoptotic effect as indicated by caspase-3. This report also confers that the use of this drug should be justified for long treatment under direct medical supervision.

  17. 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.

  18. Curcumin Inhibits NTHi-Induced MUC5AC Mucin Overproduction in Otitis Media via Upregulation of MAPK Phosphatase MKP-1

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    Anuhya Sharma Konduru

    2017-01-01

    Full Text Available Otitis media (OM, characterized by the presence of mucus overproduction and excess inflammation in the middle ear, is the most common childhood infection. Nontypeable Haemophilus influenzae (NTHi pathogen is responsible for approximately one-third of episodes of bacteria-caused OM. Current treatments for bacterial OM rely on the systemic use of antibiotics, which often leads to the emergence of multidrug resistant bacterial strains. Therefore there is an urgent need for developing alternative therapies strategies for controlling mucus overproduction in OM. MUC5AC mucin has been shown to play a critical role in the pathogenesis of OM. Here we show that curcumin derived from Curcuma longa plant is a potent inhibitor of NTHi-induced MUC5AC mucin expression in middle ear epithelial cells. Curcumin inhibited MUC5AC expression by suppressing activation of p38 MAPK by upregulating MAPK phosphatase MKP-1. Thus, our study identified curcumin as a potential therapeutic for inhibiting mucin overproduction in OM by upregulating MKP-1, a known negative regulator of inflammation.

  19. Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress

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    Machi JF

    2016-03-01

    groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=-0.6, P<0.003. Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009 and vagal tonus (r=-0.7, P<0.0002; and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002, sympathetic tonus (r=0.55, P<0.006, and physical capacity (r=-0.55, P<0.003. The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction, inflammation, and oxidative stress. Keywords: autonomic nervous system, aging, aerobic exercise, female rats

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

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    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)

  1. 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)

  2. 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.

  3. Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impairment and oxidative stress in rat brain.

    Science.gov (United States)

    Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Ataee, Ramin; Moghaddam, Shiva Nasiraei

    2010-08-01

    Aging is the major risk factor for neurodegenerative diseases and oxidative stress and is involved in their pathophysiology. Oxidative stress can induce neuronal damage and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study we investigated the neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (5, 15, or 45 mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intracerebroventricular injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests, were evaluated 24 hours after the last injection of curcumin or vehicle. Results indicated that Hcy induces lipid peroxidation and increases malondialdehyde (MDA) and superoxide anion (SOA) levels in whole rat brain. In addition, Hcy impaired memory retention in the passive avoidance learning test. However, curcumin treatment significantly decreased MDA and SOA levels and improved learning and memory in rats. These results suggest that Hcy may induce lipid peroxidation in rat brain and that polyphenol treatment (curcumin) improves learning and memory deficits by protecting the nervous system against oxidative stress.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers

    Science.gov (United States)

    Aggarwal, Bharat B; Gupta, Subash C; Sung, Bokyung

    2013-01-01

    TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8 PMID:23425071

  10. Curcumin Mimics the Neurocognitive and Anti-Inflammatory Effects of Caloric Restriction in a Mouse Model of Midlife Obesity.

    Directory of Open Access Journals (Sweden)

    Marjana Rahman Sarker

    Full Text Available Dietary curcumin was studied for its potential to decrease adiposity and reverse obesity- associated cognitive impairment in a mouse model of midlife sedentary obesity. We hypothesized that curcumin intake, by decreasing adiposity, would improve cognitive function in a manner comparable to caloric restriction (CR, a weight loss regimen. 15-month-old male C57BL/6 mice were assigned in groups to receive the following dietary regimens for 12 weeks: (i a base diet (Ain93M fed ad libitum (AL, (ii the base diet restricted to 70% of ad libitum (CR or (iii the base diet containing curcumin fed AL (1000 mg/kg diet, CURAL. Blood markers of inflammation, interleukin 6 (IL-6 and C-reactive protein (CRP, as well as an indicator of redox stress (GSH: GSSG ratio, were determined at different time points during the treatments, and visceral and subcutaneous adipose tissue were measured upon completion of the experiment. After 8 weeks of dietary treatment, the mice were tested for spatial cognition (Morris water maze and cognitive flexibility (discriminated active avoidance. The CR group showed significant weight loss and reduced adiposity, whereas CURAL mice had stable weight throughout the experiment, consumed more food than the AL group, with no reduction of adiposity. However, both CR and CURAL groups took fewer trials than AL to reach criterion during the reversal sessions of the active avoidance task, suggesting an improvement in cognitive flexibility. The AL mice had higher levels of CRP compared to CURAL and CR, and GSH as well as the GSH: GSSG ratio were increased during curcumin intake, suggesting a reducing shift in the redox state. The results suggest that, independent of their effects on adiposity; dietary curcumin and caloric restriction have positive effects on frontal cortical functions that could be linked to anti-inflammatory or antioxidant actions.

  11. Accelerated Recovery of Endothelium Function after Stent Implantation with the Use of a Novel Systemic Nanoparticle Curcumin

    Directory of Open Access Journals (Sweden)

    Qi Lu

    2015-01-01

    Full Text Available Curcumin was reported to exhibit a wide range of pharmacological effects including antioxidant, anti-inflammatory, and antiproliferative activities and significantly prevent smooth muscle cells migration. In the present study, a novel kind of curcumin loaded nanoparticles (Cur-NP has been prepared and characterized with the aim of inhibiting inflammation formation and accelerating the healing process of the stented arteries. Cur-NP was administrated intravenously after stent implantation twice a week and detailed tissue responses were evaluated. The results demonstrated that intravenous administration of Cur-NP after stent implantation accelerated endothelial cells restoration and endothelium function recovery and may potentially be an effective therapeutic alternative to reduce adverse events for currently available drug eluting stents.

  12. 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

  13. 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.

  14. 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 ...

  15. Inflammation and Heart Disease

    Science.gov (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More Inflammation and Heart Disease Updated:Jun 13,2017 Understand the risks of ... inflammation causes cardiovascular disease, inflammation is common for heart disease and stroke patients and is thought to be ...

  16. The effect of aging on aortic atherosclerotic plaque inflammation and molecular calcification: A FDG and NaF PET CT imaging study

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

    2013-01-01

    prospectively assessed by 18-FDG (inflammation) and Sodium 18-Fluoride (Na-18F) (calcification metabolism) PET CT imaging. Global aortic uptake of 18-FDG and Na-18F was quantified by subtracting the blood pool SUVmean from the aortic SUVmax (cSUV) [maximum SUVaorta - mean SUVblood pool]. Calculating regression...

  17. Protective effect of curcumin on pulmonary and cardiovascular effects induced by repeated exposure to diesel exhaust particles in mice.

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    Full Text Available Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15 µg/animal every 2(nd day for 6 days (a total of 4 exposures, and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor α (TNF α in the bronchoalveolar lavage (BAL fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP and TNF α concentrations, systolic blood pressure (SBP as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1. Pretreatment with curcumin by oral gavage (45 mg/kg 1 h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF α in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF α, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNFα release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNFα and protects against the pulmonary and cardiovascular effects of DEP.

  18. Design, characterization, and biological evaluation of curcumin-loaded surfactant-based systems for topical drug delivery.

    Science.gov (United States)

    Fonseca-Santos, Bruno; Dos Santos, Aline Martins; Rodero, Camila Fernanda; Gremião, Maria Palmira Daflon; Chorilli, Marlus

    From previous studies, it has been found that curcumin exhibits an anti-inflammatory activity and is being used for the treatment of skin disorders; however, it is hydrophobic and has weak penetrating ability, resulting in poor drug transport through the stratum corneum. The aim of this study was to develop liquid crystalline systems for topical administration of curcumin for the treatment of inflammation. These liquid crystalline systems were developed from oleic acid, polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol, and water as the surfactant, oil phase, and aqueous phase, respectively. These systems were characterized, and polarized light microscopy showed anisotropy with lamellar mesophases (Formulation 1) and hexagonal mesophases (Formulations 2 and 3), which were confirmed by the peak ratio measured using small-angle X-ray scattering. In addition, rheological tests revealed that the formulations exhibited gel-like behavior (G'>G″), as evidenced by the increased G' values that indicate structured systems. Texture profile analysis showed that hexagonal mesophases have high values of hardness, adhesiveness, and compressibility, which indicate structured systems. In vitro studies on bioadhesion revealed that the hexagonal mesophases increased the bioadhesiveness of the systems to the skin of the pig ear. An in vivo inflammation experiment showed that the curcumin-loaded hexagonal mesophase exhibited an anti-inflammatory activity as compared to the positive control (dexamethasone). The results suggest that this system has a potential to be used as a bioadhesive vehicle for the topical administration of curcumin. Therefore, it is possible to conclude that these systems can be used for the optimization of drug delivery systems to the skin.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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...

  8. 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...

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Zou, Xuan [Center for Translational Medicine, FIST, Xi' an Jiaotong University, Xi' an (China); Cao, Ke; Xu, Jie; Yue, Tingting [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Dai, Fang; Zhou, Bo [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou (China); Lu, Wuyuan [Center for Translational Medicine, FIST, Xi' an Jiaotong University, Xi' an (China); Feng, Zhihui, E-mail: zhfeng@mail.xjtu.edu.cn [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Liu, Jiankang, E-mail: j.liu@mail.xjtu.edu.cn [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China)

    2013-11-01

    Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 μM, which was much more efficient than curcumin. Both 0.5 μM C3 and 5 μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. - Highlights: • We examine toxicity effects of cigarette smoking component acrolein in retina cells. • We report a more efficient curcumin analog (C3) protecting cellular function. • Mitochondrial function and phase II enzyme activation are the

  15. Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity

    International Nuclear Information System (INIS)

    Li, Yuan; Zou, Xuan; Cao, Ke; Xu, Jie; Yue, Tingting; Dai, Fang; Zhou, Bo; Lu, Wuyuan; Feng, Zhihui; Liu, Jiankang

    2013-01-01

    Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 μM, which was much more efficient than curcumin. Both 0.5 μM C3 and 5 μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. - Highlights: • We examine toxicity effects of cigarette smoking component acrolein in retina cells. • We report a more efficient curcumin analog (C3) protecting cellular function. • Mitochondrial function and phase II enzyme activation are the major

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

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

    Science.gov (United States)

    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.

  4. Curcumin in Alzheimer's disease: Can we think to new strategies and perspectives for this molecule?

    Science.gov (United States)

    Serafini, Melania Maria; Catanzaro, Michele; Rosini, Michela; Racchi, Marco; Lanni, Cristina

    2017-10-01

    Population aging is an irreversible global trend with economic and socio-political consequences. One of the most invalidating outcomes of aging in the elderly is cognitive decline, leading to dementia and often related to neurodegenerative disorders. Among these latter, Alzheimer's disease (AD) is the major cause of dementia, affecting more than 30 million of individuals worldwide. To date, the treatment of AD remains a challenge because of an incomplete understanding of the events that lead to the selective neurodegeneration typical of Alzheimer's brains. There is an enormous global demand for new effective therapies and researchers are investigating new fields. One promising strategy is the use of nutraceuticals as integrative, complementary and preventive therapy. Curcumin is one example of natural product with anti-AD properties, with promising potential for prevention, treatment and diagnostic. The limitations in the use of curcumin as therapeutic are represented by its pharmacokinetics profile and the low bioavailability after oral administration. However, curcumin has been the focus of intense research for new drug development. Here we analyzed some new approaches that have been applied in the attempt to improve its use, particularly new formulations, changes in the way of administration, nanotechnology-based delivery systems and the hybridization strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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 ...

  10. 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...

  11. 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...

  12. 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...

  13. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. 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 ...

  17. 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 ...

  18. 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

  19. 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 ...

  20. 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 ...

  1. 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

  2. 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

  3. Curcumin Induces Nrf2 Nuclear Translocation and Prevents Glomerular Hypertension, Hyperfiltration, Oxidant Stress, and the Decrease in Antioxidant Enzymes in 5/6 Nephrectomized Rats

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    Edilia Tapia

    2012-01-01

    Full Text Available Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1 control, (2 5/6NX, (3 5/6NX +CUR, and (4 CUR (n=8–10. Curcumin was given by gavage to NX5/6 +CUR and CUR groups (60 mg/kg/day starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes.

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

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    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.

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

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    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.

  6. Facile synthesis of water-soluble curcumin nanocrystals

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    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

  7. Neuroprotective role of curcumin on the hippocampus against the structural and serological alterations of streptozotocin-induced diabetes in sprague dawely rats

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    Nermeen Mohammed Faheem

    2017-06-01

    Full Text Available Objective(s: Diabetes mellitus causes impaired memory and cognitive functions. The hippocampus plays a key role in memory and learning. Curcumin attenuates diabetic nephropathy in vivo. Curcumin has shown a neurogenic effect and cognition-enhancing potential in aged rats. The aim of this study is to evaluate the possible protective role of curcumin on the histological and serologicalchanges of the hippocampus in diabetic rats. Materials and Methods: Forty albino rats were divided into four groups, ten rats each. Group 1 control rats, group 2 rats received curcumin orally (200 mg/kg/day for six weeks, group 3 rats were injected intraperitoneally with streptozotocin (STZ (100 mg/kg, single dose, group 4 received a single injection of STZ and received curcumin orally for six weeks. Paraffin sections of hippocampus were prepared and stained with hematoxylin and eosin stain, and immnunohistochemical staining for GFAP and caspase-3. Morphometrical and statistical analyses were performed. Glycemic status and parameters of oxidative stress was measured. Results: Examination of hippocampus of diabetic rats showed disorganization of small pyramidal cells in CA1, many cellular losses in the pyramidal cells of CA3, many degenerated granule cells in the dentate gyrus. GFAP positive astrocyte and caspase-3 positive neuron counts were significantly increased.  There were significant serum glucose elevation and significant lowered levels of oxidative stress parameters as compared to control rats. Curcumin administration improved the structural and serological alterationsof the hippocampuswith significant reduction in serum glucose level. Conclusion: Curcumin ameliorates the deterious effect of diabetes on the hippocampus through its antioxidant, antiapoptotic and anti-inflammatory efficacies.

  8. Neuroprotective role of curcumin on the hippocampus against the structural and serological alterations of streptozotocin-induced diabetes in Sprague Dawely rats.

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    Faheem, Nermeen Mohammed; El Askary, Ahmad

    2017-06-01

    Diabetes mellitus causes impaired memory and cognitive functions. The hippocampus plays a key role in memory and learning. Curcumin attenuates diabetic nephropathy in vivo . Curcumin has shown a neurogenic effect and cognition-enhancing potential in aged rats. The aim of this study is to evaluate the possible protective role of curcumin on the histological and serological changes of the hippocampus in diabetic rats. Forty albino rats were divided into four groups, ten rats each. Group 1 control rats, group 2 rats received curcumin orally (200 mg/kg/day for six weeks), group 3 rats were injected intraperitoneally with streptozotocin (STZ) (100 mg/kg, single dose), group 4 received a single injection of STZ and received curcumin orally for six weeks. Paraffin sections of hippocampus were prepared and stained with hematoxylin and eosin stain, and immnunohistochemical staining for GFAP and caspase-3. Morphometrical and statistical analyses were performed. Glycemic status and parameters of oxidative stress was measured. Examination of hippocampus of diabetic rats showed disorganization of small pyramidal cells in CA1, many cellular losses in the pyramidal cells of CA3, many degenerated granule cells in the dentate gyrus. GFAP positive astrocyte and caspase-3 positive neuron counts were significantly increased. There were significant serum glucose elevation and significant lowered levels of oxidative stress parameters as compared to control rats. Curcumin administration improved the structural and serological alterations of the hippocampus with significant reduction in serum glucose level. Curcumin ameliorates the deterious effect of diabetes on the hippocampus through its antioxidant, antiapoptotic and anti-inflammatory efficacies.

  9. Molecular complexation of curcumin with pH sensitive cationic copolymer enhances the aqueous solubility, stability and bioavailability of curcumin.

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    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.

  10. Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in Aβ1-42 insult in vitro.

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    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.

  11. 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.

  12. Telomerase: A Target for Therapeutic Effects of Curcumin and a Curcumin Derivative in Aβ1-42 Insult In Vitro

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    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

  13. Curcuma longa extract associated with white pepper lessens high fat diet-induced inflammation in subcutaneous adipose tissue.

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    Audrey M Neyrinck

    Full Text Available Supra-nutritional doses of curcumin, derived from the spice Curcuma longa, have been proposed as a potential treatment of inflammation and metabolic disorders related to obesity. The aim of the present study was to test whether Curcuma longa extract rich in curcumin and associated with white pepper (Curcuma-P®, at doses compatible with human use, could modulate systemic inflammation in diet-induced obese mice. We questioned the potential relevance of changes in adiposity and gut microbiota in the effect of Curcuma-P® in obesity.Mice were fed either a control diet (CT, a high fat (HF diet or a HF diet containing Curcuma longa extract (0.1 % of curcumin in the HF diet associated with white pepper (0.01 % for four weeks. Curcumin has been usually combined with white pepper, which contain piperine, in order to improve its bioavailability. This combination did not significantly modify body weight gain, glycemia, insulinemia, serum lipids and intestinal inflammatory markers. Tetrahydrocurcumin, but not curcumin accumulated in the subcutaneous adipose tissue. Importantly, the co-supplementation in curcuma extract and white pepper decreased HF-induced pro-inflammatory cytokines expression in the subcutaneous adipose tissue, an effect independent of adiposity, immune cells recruitment, angiogenesis, or modulation of gut bacteria controlling inflammation.These findings support that nutritional doses of Curcuma longa, associated with white pepper, is able to decrease inflammatory cytokines expression in the adipose tissue and this effect could be rather linked to a direct effect of bioactive metabolites reaching the adipose tissue, than from changes in the gut microbiota composition.

  14. Curcuma longa extract associated with white pepper lessens high fat diet-induced inflammation in subcutaneous adipose tissue.

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    Neyrinck, Audrey M; Alligier, Maud; Memvanga, Patrick B; Névraumont, Elodie; Larondelle, Yvan; Préat, Véronique; Cani, Patrice D; Delzenne, Nathalie M

    2013-01-01

    Supra-nutritional doses of curcumin, derived from the spice Curcuma longa, have been proposed as a potential treatment of inflammation and metabolic disorders related to obesity. The aim of the present study was to test whether Curcuma longa extract rich in curcumin and associated with white pepper (Curcuma-P®), at doses compatible with human use, could modulate systemic inflammation in diet-induced obese mice. We questioned the potential relevance of changes in adiposity and gut microbiota in the effect of Curcuma-P® in obesity. Mice were fed either a control diet (CT), a high fat (HF) diet or a HF diet containing Curcuma longa extract (0.1 % of curcumin in the HF diet) associated with white pepper (0.01 %) for four weeks. Curcumin has been usually combined with white pepper, which contain piperine, in order to improve its bioavailability. This combination did not significantly modify body weight gain, glycemia, insulinemia, serum lipids and intestinal inflammatory markers. Tetrahydrocurcumin, but not curcumin accumulated in the subcutaneous adipose tissue. Importantly, the co-supplementation in curcuma extract and white pepper decreased HF-induced pro-inflammatory cytokines expression in the subcutaneous adipose tissue, an effect independent of adiposity, immune cells recruitment, angiogenesis, or modulation of gut bacteria controlling inflammation. These findings support that nutritional doses of Curcuma longa, associated with white pepper, is able to decrease inflammatory cytokines expression in the adipose tissue and this effect could be rather linked to a direct effect of bioactive metabolites reaching the adipose tissue, than from changes in the gut microbiota composition.

  15. Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

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    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

  16. Curcumin exerts its antitumor effects in a context dependent fashion.

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    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.

  17. (Cationic + nonionic) mixed surfactant aggregates for solubilisation of curcumin

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    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.

  18. 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.

  19. 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

  20. Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats.

    Science.gov (United States)

    Sharma, Sameer; Kulkarni, Shrinivas K; Chopra, Kanwaljit

    2006-10-01

    Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals and evidence is increasing that these contribute to the development of diabetic nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring and colouring agent in the indian diet every day and is known to possess anti-oxidant properties. The present study was designed to examine the effect of curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ injection, rats were divided into four groups, namely control rats, diabetic rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks. Renal function was assessed by creatinine, blood urea nitrogen, creatinine and urea clearance and urine albumin excretion. Oxidative stress was measured by renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide dismutase and catalase. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria and a decrease in bodyweight compared with age-matched control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance and proteinuria, along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Chronic treatment with curcumin significantly attenuated both renal dysfunction and oxidative stress in diabetic rats. These results provide confirmatory evidence of oxidative stress in diabetic nephropathy and point towards the possible anti-oxidative mechanism being responsible for the nephroprotective action of curcumin.

  1. 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.

  2. A multi-nutrient supplement reduced markers of inflammation and improved physical performance in active individuals of middle to older age: a randomized, double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Szivak Tunde K

    2011-09-01

    Full Text Available Abstract Background While exercise acts to combat inflammation and aging, the ability to exercise may itself be compromised by inflammation and inflammation's impact on muscle recovery and joint inflammation. A number of nutritional supplements have been shown to reduce inflammation and improve recovery. The purpose of the current investigation was to examine the effect of a multi-nutrient supplement containing branched chain amino acids, taurine, anti-inflammatory plant extracts, and B vitamins on inflammatory status, endothelial function, physical function, and mood in middle-aged individuals. Methods Thirty-one healthy and active men (N = 16, mean age 56 ± 6.0 yrs and women (N = 15, mean age = 52 ± 7.5 yrs participated in this investigation. Subjects completed one 28 day cycle of placebo supplementation and one 28 day cycle of multi-nutrient supplementation (separated by a one week washout period in a balanced, randomized, double-blind, cross-over design. Subjects completed weekly perceptual logs (PROMIS-57, KOOS and pre- and post- testing around the supplementation period. Testing consisted of brachial artery flow mediated dilation (FMD, blood measures, and physical performance on vertical jump, handgrip strength, and balance (dispersion from center of pressure. Significance for the investigation was p ≤ 0.05. Results IL-6 significantly decreased in both men (from 1.2 ± 0.2 to 0.7 ± 0.4 pg·mL-1 and women (from 1.16 ± 0.04 to 0.7 ± 0.4 pg·mL-1. Perceived energy also improved for both men (placebo: 1.8 ± 0.7; supplement: 3.7 ± 0.8 AUC and women (placebo: 1.2 ± 0.7; supplement: 2.8 ± 0.8 AUC. Alpha-1-antichymotrypsin (from 108.9 ± 38.6 to 55.5 ± 22.2 ug·mL-1, Creatine Kinase (from 96 ± 34 to 67 ± 23 IU·L-1, general pain, and joint pain decreased in men only, while anxiety and balance (from 0.52 ± 0.13 to 0.45 ± 0.12 cm improved in women only. Men showed increased performance in vertical jump power (from 2642 ± 244 to 3134

  3. Niosome Encapsulation of Curcumin: Characterization and Cytotoxic Effect on Ovarian Cancer Cells

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    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.

  4. 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.

  5. 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.

  6. 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.

  7. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

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    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.

  8. 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.

  9. Identification of proteins regulated by curcumin in cerebral ischemia.

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    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.

  10. Curcumin phytosomal softgel formulation: Development, optimization and physicochemical characterization

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    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.

  11. Renoprotective effect of the antioxidant curcumin: Recent findings☆

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    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

  12. Novel water-soluble curcumin derivative mediating erectile signaling.

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    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 mo