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Sample records for caffeic acid inhibits

  1. Inhibition of multiplication of herpes simplex virus by caffeic acid.

    Science.gov (United States)

    Ikeda, Keiko; Tsujimoto, Kazuko; Uozaki, Misao; Nishide, Mitsunori; Suzuki, Yukiko; Koyama, A Hajime; Yamasaki, Hisashi

    2011-10-01

    Hot water extracts of coffee grinds and commercial instant coffee solutions have been shown to exhibit marked antiviral and virucidal activities against herpes simplex virus type 1 (HSV-1). Specifically, it has been shown that caffeine and N-methyl-pyridinium formate inhibit the multiplication of HSV-1 in HEp-2 cells. The present study examined the virological properties and the antiviral activity of caffeic acid against HSV-1. Caffeic acid inhibited the multiplication of HSV-1 in vitro, while chlorogenic acid, a caffeic acid ester with quinic acid, did not. These reagents did not have a direct virucidal effect. The one-step growth curve of HSV-1 showed that the addition of caffeic acid at 8 h post infection (h p.i.) did not significantly affect the formation of progeny viruses. An analysis of the influence of the time of caffeic acid addition, revealed that addition at an early time post infection remarkably inhibited the formation of progeny infectious virus in the infected cells, but its addition after 6 h p.i. (i.e., the time of the completion of viral genome replication) did not efficiently inhibit this process. These results indicate that caffeic acid inhibits HSV-1 multiplication mainly before the completion of viral DNA replication, but not thereafter. Although caffeic acid showed some cytotoxicity by prolonged incubation, the observed antiviral activity is likely not the secondary result of the cytotoxic effect of the reagent, because the inhibition of the virus multiplication was observed before appearance of the notable cytotoxicity.

  2. Caffeic Acid Inhibits NFkappaB Activation of Osteoclastogenesis Signaling Pathway

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    Ferry Sandra

    2011-12-01

    Full Text Available BACKGROUND: Caffeic acid (3,4-dihydroxycinnamic acids is involved in various green plants. Based on our previous report, a major component of sweet potato extracts, possibly caffeic acid, was shown as a promising inhibitor of osteoclastogenesis. However, the effect of caffeic acid in inhibiting osteoclastogenesis needs to be confirmed. The underlying mechanism needs to be disclosed as well. METHODS: Caffeic acid in various concentrations was added to in vitro osteoclastogenesis of receptor activator nuclear factor kB ligand (RANKL-tumor necrosis factor alpha (TNF-α-macrophage colony stimulating factor (M-CSF-induced bone marrow-derived monocyte/macrophage precursor cells (BMMs and RANKL-TNF-α-induced RAW264 cells D-Clone (RAW-D cells. Tartrate resistant acid phosphatase (TRAP staining was performed and TRAP-positive polynucleated cells (PNCs were counted. For apoptosis analysis, caffeic acid-treated BMMs, RAW-D cells and osteoclast-like PNCs were subjected to Sub-G1 Apoptosis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assays. To measure NFkB activity, RAW-D cells were transfected with pNFkB-TA-Luc and subjected to Dual Luciferase Reporter Assay System. RESULTS: Caffeic acid inhibited osteoclastogenesis of RANKL-TNF-α-M-CSF-induced BMMs as well as RANKL-TNF-α-induced RAW-D cells in a dose dependent manner. Caffeic acid did not induce apoptosis in BMMs, RAW-D cells and osteoclast-like PNCs. RANKL-TNF-α-induced NFkB activity in RAW-D was diminished by caffeic acid in a dose dependent manner. Significant NFkB activity inhibtion was observed starting from 1µg/mL caffeic acid. CONCLUSIONS: Caffeic acid could be a potent osteoclastogenesis inhibitor through inhibition of NFkB activity. Our present study should be further followed up to disclose caffeic acid's possible overlying signaling pathways in inhibiting osteoclastogenesis. KEYWORDS: caffeic acid, osteoclastogenesis, NFkB, RANKL, TNF-α.

  3. Caffeic and chlorogenic acids inhibit key enzymes linked to type 2 diabetes (in vitro): a comparative study.

    Science.gov (United States)

    Oboh, Ganiyu; Agunloye, Odunayo M; Adefegha, Stephen A; Akinyemi, Ayodele J; Ademiluyi, Adedayo O

    2015-03-01

    Chlorogenic acid is a major phenolic compound that forms a substantial part of plant foods and is an ester of caffeic acid and quinic acid. However, the effect of the structures of both chlorogenic and caffeic acids on their antioxidant and antidiabetic potentials have not been fully understood. Thus, this study sought to investigate and compare the interaction of caffeic acid and chlorogenic acid with α-amylase and α-glucosidase (key enzymes linked to type 2 diabetes) activities in vitro. The inhibitory effect of the phenolic acids on α-amylase and α-glucosidase activities was evaluated. Thereafter, their antioxidant activities as typified by their 1,1-diphenyl-2 picrylhydrazyl radical scavenging ability and ferric reducing antioxidant properties were determined. The results revealed that both phenolic acids inhibited α-amylase and α-glucosidase activities in a dose-dependent manner (2-8 μg/mL). However, caffeic acid had a significantly (pchlorogenic acid (α-amylase IC50=9.10 μg/mL and α-glucosidase IC50=9.24 μg/mL). Furthermore, both phenolic acids exhibited high antioxidant properties, with caffeic acid showing higher effects. The esterification of caffeic acid with quinic acid, producing chlorogenic acid, reduces their ability to inhibit α-amylase and α-glucosidase activities. Thus, the inhibition of α-amylase and α-glucosidase activities by the phenolic acids could be part of the possible mechanism by which the phenolic acids exert their antidiabetic effects.

  4. Substituted Caffeic and Ferulic Acid Phenethyl Esters: Synthesis, Leukotrienes Biosynthesis Inhibition, and Cytotoxic Activity

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    Pier Morin

    2017-07-01

    Full Text Available Glioblastoma multiforme (GBM is an aggressive brain tumor that correlates with short patient survival and for which therapeutic options are limited. Polyphenolic compounds, including caffeic acid phenethyl ester (CAPE, 1a, have been investigated for their anticancer properties in several types of cancer. To further explore these properties in brain cancer cells, a series of caffeic and ferulic acid esters bearing additional oxygens moieties (OH or OCH3 were designed and synthesized. (CAPE, 1a, but not ferulic acid phenethyl ester (FAPE, 1b, displayed substantial cytotoxicity against two glioma cell lines. Some but not all selected compounds derived from both (CAPE, 1a and (FAPE, 1b also displayed cytotoxicity. All CAPE-derived compounds were able to significantly inhibit 5-lipoxygenase (5-LO, however FAPE-derived compounds were largely ineffective 5-LO inhibitors. Molecular docking revealed new hydrogen bonds and π-π interactions between the enzyme and some of the investigated compounds. Overall, this work highlights the relevance of exploring polyphenolic compounds in cancer models and provides additional leads in the development of novel therapeutic strategies in gliomas.

  5. Caffeic acid phenethyl ester downregulates phospholipase D1 via direct binding and inhibition of NFκB transactivation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mi Hee; Kang, Dong Woo [Department of Molecular Biology, Pusan National University, Busan 609-735 (Korea, Republic of); Jung, Yunjin [College of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of); Choi, Kang-Yell [Translational Research Center for Protein Function Control, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Min, Do Sik, E-mail: minds@pusan.ac.kr [Department of Molecular Biology, Pusan National University, Busan 609-735 (Korea, Republic of)

    2013-12-06

    Highlights: •We found CAFÉ, a natural product that suppresses expression and activity of PLD1. •CAPE decreased PLD1 expression by inhibiting NFκB transactivation. •CAPE rapidly inhibited PLD activity via its binding to a Cys837 of PLD1. •PLD1 downregulation by CAPE inhibited invasion and proliferation of glioma cells. -- Abstract: Upregulation of phospholipase D (PLD) is functionally linked with oncogenic signals and tumorigenesis. Caffeic acid phenethyl ester (CAPE) is an active compound of propolis extract that exhibits anti-proliferative, anti-inflammatory, anti-oxidant, and antineoplastic properties. In this study, we demonstrated that CAPE suppressed the expression of PLD1 at the transcriptional level via inhibition of binding of NFκB to PLD1 promoter. Moreover, CAPE, but not its analogs, bound to a Cys837 residue of PLD1 and inhibited enzymatic activity of PLD. CAPE also decreased activation of matrix metalloproteinases-2 induced by phosphatidic acid, a product of PLD activity. Ultimately, CAPE-induced downregulation of PLD1 suppressed invasion and proliferation of glioma cells. Taken together, the results of this study indicate that CAPE might contribute to anti-neoplastic effect by targeting PLD1.

  6. Caffeic Acid Induces Apoptosis in Human Cervical Cancer Cells Through the Mitochondrial Pathway

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    Wei-Chun Chang

    2010-12-01

    Conclusion: Caffeic acid induces apoptosis by inhibiting Bcl-2 activity, leading to release of cytochrome c and subsequent activation of caspase-3, indicating that caffeic acid induces apoptosis via the mitochondrial apoptotic pathway. This also suggests that caffeic acid has a strong anti-tumor effect and may be a promising chemopreventive or chemotherapeutic agent.

  7. Caffeic acid, morin hydrate and quercetin partially attenuate sulfur mustard-induced cell death by inhibiting the lipoxygenase pathway.

    Science.gov (United States)

    Kim, Shin; Jeong, Kwang-Joon; Cho, Sung Kweon; Park, Joo-Won; Park, Woo-Jae

    2016-11-01

    Sulfur mustard (SM) is an alkylating agent, which has been used as in chemical warfare in a number of conflicts. As the generation of reactive oxygen species (ROS), and adducts in DNA and proteins have been suggested as the mechanism underlying SM‑induced cytotoxicity, the present study screened several antioxidant candidates, including tannic acid, deferoxamine mesylate, trolox, vitamin C, ellagic acid and caffeic acid (CA) to assess their potential as therapeutic agents for SM‑induced cell death. Among several antioxidants, CA partially alleviated SM‑induced cell death in a dose‑dependent manner. Although CA treatment decreased the phosphorylation of p38 mitogen‑activated protein (MAP) kinase and p53, p38 MAP kinase inhibition by SB203580 did not affect SM‑induced cell death. As CA has also been reported as a 15‑lipoxygenase (15‑LOX) inhibitor, the role of 15‑LOX in SM‑induced cytotoxicity was also examined. Similar to the results observed with CA, treatment with PD146176, a specific 15‑LOX inhibitor, decreased SM‑induced cytotoxicity, accompanied by decreases in the production of tumor necrosis factor‑α and 15‑hydroxyeicosatetraenoic acid. Furthermore, the present study investigated the protective effects of two natural 15‑LOX inhibitors, morin hydrate and quercetin, in SM‑induced cytotoxicity. As expected, these inhibitors had similar protective effects against SM‑induced cytotoxicity. These antioxidants also reduced the generation of ROS and nitrate/nitrite. Therefore, the results of the present study indicated that the natural products, CA, quercetin and morin hydrate, offer potential as adjuvant therapeutic agents for SM‑induced toxicity, not only by reducing inflammation mediated by the p38 and LOX signaling pathways, but also by decreasing the generation of ROS and nitrate/nitrite.

  8. Butylated caffeic acid: An efficient novel antioxidant

    International Nuclear Information System (INIS)

    Shi, G.; Liao, X.; Olajide, T.M.; Liu, J.; Jiang, X.; Weng, X.

    2017-01-01

    A novel antioxidant, butylated caffeic acid (BCA) was rationally designed by adding a tert-butyl group to caffeic acid, which was synthesized at a high yield (36.2%) from 2-methoxy-4-methylphenol (1) by a four-step reaction including Friedel-Crafts alkylation, bromine oxidation, ether bond hydrolysis and Knoevenagel condensation. Its antioxidant capacity was much stronger than common commercial antioxidant tert-butyl hydroquinone (TBHQ) and its mother compound, caffeic acid, in both rancimat and deep frying tests. When investigated via the DPPH method, the antioxidant capacity of BCA was almost equal to TBHQ, but lower than caffeic acid. BCA could be a potentially strong antioxidant, especially for food processing at high temperatures such as deep frying and baking. [es

  9. Caffeic Acid Induced Apoptosis in MG63 Osteosarcoma Cells Through Activation of Caspases

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    Ferry Sandra

    2017-03-01

    Full Text Available Background: Caffeic acid has been reported that when it is combined with all-trans retinoic acid, it can inhibit proliferation activity of SaOS-2 or OSA-01 cells. In addition, caffeic acid merely could reduce cell viability of SaOS-2 cells. However, there is not any study in caffeic acid's possible effect to induce apoptosis in osteosarcoma cell. Materials and Methods: MG-63 cells were cultured in Dulbecco’s Modified Eagle Medium containing 10% fetal bovine serum. Cells were treated with various concentrations of caffeic acid. Apoptosis were analyzed with Sub-G1 assay and activation of caspase-8, -9, and -3 were analyzed with immunoblotting. Caffeic acid-induced percentage of apoptotic cells and cleaved-8, -9, -3 were then statistically analyzed. Results: Sub-G1 results showed that caffeic acid significantly induced apoptosis in MG-63 osteosarcoma cells in concentration dependent manner. Immunoblotting results showed that caffeic acid induced cleavage of caspase-8, -9 and -3. Cleaved-caspase-8 and -9 were increased at 1-hour treatment of caffeic acid, while cleaved-caspase 3 was increased markedly at 6-hours treatment of caffeic acid. Conclusions: Caffeic acid induces apoptosis significantly in concentration dependent manner through caspase-dependent intrinsic apoptotic pathway. Keywords: caffeic acid, osteosarcoma, MG-63, apoptosis, caspase

  10. Chlorogenic acid and caffeic acid are absorbed in humans

    OpenAIRE

    Olthof, M.R.; Hollman, P.C.H.; Katan, M.B.

    2001-01-01

    Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the absorption of chlorogenic acid and caffeic acid in humans are lacking. We determined the absorption of chlorogenic acid and caffeic acid in a cross-over study with 4 female and 3 male healthy ileo...

  11. Chlorogenic acid and caffeic acid are absorbed in humans

    NARCIS (Netherlands)

    Olthof, Margreet R.; Hollman, Peter C H; Katan, Martijn B.

    2001-01-01

    Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the

  12. Caffeic Acid Phenethyl Ester (CAPE) mediated decrease in ...

    African Journals Online (AJOL)

    Background: Caffeic acid phenethyl ester (CAPE) is a phytochemically active component obtained from honeybee hive propolis. CAPE has been reported to show antimitogenic, anticancer, and other beneficial medicinal properties. Many of its activities have been reported to be mediated by inhibiting levels of matrix ...

  13. Engineering E. coli for caffeic acid biosynthesis from renewable sugars.

    Science.gov (United States)

    Zhang, Haoran; Stephanopoulos, Gregory

    2013-04-01

    Caffeic acid is a valuable aromatic compound that possesses many important pharmacological activities. In structure, caffeic acid belongs to the hydroxycinnamic acid family and can be biosynthesized from the aromatic amino acid tyrosine. In the present paper, the caffeic acid biosynthesis pathway was reconstituted in engineered Escherichia coli to produce caffeic acid from simple biomass sugar glucose and xylose. Different engineering approaches were utilized to optimize the production. Specifically, two parallel biosynthesis routes leading from tyrosine to caffeic acid were studied. The copy number of the intermediate biosynthesis genes was varied to find appropriate gene doses for caffeic acid biosynthesis. Three different media, including a MOPS medium, a synthetic medium, and a rich medium, were also examined to improve the production. The highest specific caffeic acid production achieved was 38 mg/L/OD. Lastly, cultivation of engineered E. coli in a bioreactor resulted in a production of 106 mg/L caffeic acid after 4 days.

  14. Caffeic acid and ferulic acid inhibit UVA-induced matrix metalloproteinase-1 through regulation of antioxidant defense system in keratinocyte HaCaT cells.

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    Pluemsamran, Thanyawan; Onkoksoong, Tasanee; Panich, Uraiwan

    2012-01-01

    Ultraviolet A (UVA) plays a vital role in the pathogenesis of premature skin aging through keratinocyte cytotoxicity and degradation of collagen, a main component of the extracellular matrix providing structural support. Oxidative stress caused by UVA irradiation can mediate induction of matrix metalloprotease-1 (MMP-1), a major enzyme responsible for collagen damage. Protection against UV-mediated disturbance of antioxidant defense system has been proposed as a possible mechanism by which botanical compounds slow down skin aging process. This study therefore aimed to assess inhibitory effects of caffeic acid (CA) and ferulic acid (FA), powerful plant-based phenolic antioxidants, on UVA-induced cytotoxicity and MMP-1 activity and mRNA level through modulation of antioxidant defense mechanism in immortalized human keratinocyte (HaCaT) cells. Pretreatment of the cells with CA or FA prior to UVA irradiation inhibited cytotoxicity, induction of MMP-1 activity and mRNA and oxidant formation. Moreover, CA and FA were able to up-regulate glutathione (GSH) content, γ-glutamate cysteine ligase (γ-GCL) mRNA as well as activities and mRNA expression of catalase and glutathione peroxidase (GPx) in irradiated cells. In conclusion, CA and FA provided protective effects on UVA-mediated MMP-1 induction in HaCaT cells possibly through restoration of antioxidant defense system at the cellular and molecular level. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  15. Caffeic acid phenethyl ester inhibits 3-MC-induced CYP1A1 expression through induction of hypoxia-inducible factor-1α

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    Kim, Hyung Gyun [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Han, Eun Hee [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of); Im, Ji Hye; Lee, Eun Ji; Jin, Sun Woo [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2015-09-25

    Caffeic acid phenethyl ester (CAPE), a natural component of propolis, is reported to have anticarcinogenic properties, although its precise chemopreventive mechanism remains unclear. In this study, we examined the effects of CAPE on 3-methylcholanthrene (3-MC)-induced CYP1A1 expression and activities. CAPE reduced the formation of the benzo[a]pyrene-DNA adduct. Moreover, CAPE inhibited 3-MC-induced CYP1A1 activity, mRNA expression, protein level, and promoter activity. CAPE treatment also decreased 3-MC-inducible xenobiotic-response element (XRE)-linked luciferase, aryl hydrocarbons receptor (AhR) transactivation and nuclear localization. CAPE induced hypoxia inducible factor-1α (HIF-1α) protein level and HIF-1α responsible element (HRE) transcriptional activity. CAPE-mediated HIF-1α reduced 3-MC-inducible CYP1A1 protein expression. Taken together, CAPE decreases 3-MC-mediated CYP1A1 expression, and this inhibitory response is associated with inhibition of AhR and HIF-1α induction. - Highlights: • CAPE reduced the formation of the benzo[a]pyrene-DNA adduct. • CAPE inhibited 3-MC-induced CYP1A1 expression. • CAPE induced HIF-1α induction. • CAPE-mediated HIF-1α reduced 3-MC-inducible CYP1A1 expression.

  16. Caffeic Acid Phenethyl Ester Inhibits Oral Cancer Cell Metastasis by Regulating Matrix Metalloproteinase-2 and the Mitogen-Activated Protein Kinase Pathway

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    Chih-Yu Peng

    2012-01-01

    Full Text Available Caffeic acid phenethyl ester (CAPE, an active component extracted from honeybee hives, exhibits anti-inflammatory and anticancer activities. However, the molecular mechanism by which CAPE affects oral cancer cell metastasis has yet to be elucidated. In this study, we investigated the potential mechanisms underlying the effects of CAPE on the invasive ability of SCC-9 oral cancer cells. Results showed that CAPE attenuated SCC-9 cell migration and invasion at noncytotoxic concentrations (0 μM to 40 μM. Western blot and gelatin zymography analysis findings further indicated that CAPE downregulated matrix metalloproteinase-2 (MMP-2 protein expression and inhibited its enzymatic activity. CAPE exerted its inhibitory effects on MMP-2 expression and activity by upregulating tissue inhibitor of metalloproteinase-2 (TIMP-2 and potently decreased migration by reducing focal adhesion kinase (FAK phosphorylation and the activation of its downstream signaling molecules p38/MAPK and JNK. These data indicate that CAPE could potentially be used as a chemoagent to prevent oral cancer metastasis.

  17. Toxicity and biodegradability of caffeic acid in anaerobic digesting ...

    African Journals Online (AJOL)

    Caffeic acid in waste comes from a variety of industries, and its disposal is likely to increase due to emerging processes such as graphene production and use in healthcare products. The current sustainable option to treat waste caffeic acid and prevent its natural transformation in soil to greenhouse gases, is anaerobic ...

  18. Toxicity and biodegradability of caffeic acid in anaerobic digesting ...

    African Journals Online (AJOL)

    inhibitory effects of caffeic acid on biogas production as well as its ultimate anaerobic biodegradability; or about the reactive- adsorptive ... and reductive dehydroxylation were the initial activation reactions transforming caffeic acid into typical polyphenol structural ... may lead to products acting differently in terms of toxicity or.

  19. Activity of caffeic acid in different fish lipid matrices: A review

    DEFF Research Database (Denmark)

    Medina, Isabel; Undeland, Ingrid; Larsson, Karin

    2012-01-01

    was however clearly dependent on the lipid to antioxidant ratio. In these systems, an important redox cycle between caffeic acid and the endogenous reducing agents ascorbic acid and tocopherol were further thought to play an important role for the protective effects. The effect of caffeic acid was also highly......Caffeic acid, a hydroxycinnamic acid common in different vegetable sources, has been employed as a natural antioxidant for inhibiting oxidation of fish lipids present in different food matrices. The aim of this review is to discuss the mechanisms involved in the antioxidative and prooxidative...... effects of caffeic acid found in different model systems containing fish lipids. These model systems include bulk fish oils, liposomes from cod roe phospholipids, fish oil emulsions, washed cod mince, regular horse mackerel mince and a fish oil fortified fitness bar. The data reported show...

  20. In vitro antiviral efficacy of caffeic acid against canine distemper virus.

    Science.gov (United States)

    Wu, Zong-Mei; Yu, Zhen-Jiang; Cui, Zhen-Qiang; Peng, Lu-Yuan; Li, Hao-Ran; Zhang, Chun-Lei; Shen, Hai-Qing; Yi, Peng-Fei; Fu, Ben-Dong

    2017-09-01

    Canine distemper (CD) is a highly contagious disease caused by the canine distemper virus (CDV), and mortality can be as high as 100%. However, there is no specific treatment for CD. In this study, the antiviral activity of the caffeic acid against CDV was evaluated in vitro. The results showed that the IC 50 of the caffeic acid against CDV at 1 and 2 h post infection (PI) is 23.3 and 32.3 μg/mL, respectively. Consistently, at 1 and 2 h PI, the caffeic acid exhibited a reduced (23.3-57.0% and 37.2-38.1%) viral inhibitory effect in vero cells. Furthermore, the caffeic acid plus Ribavirin (RBV) has greater antiviral activity against CDV than the caffeic acid or RBV individually. In addition, the caffeic acid reduced the total viral RNA synthesis by 59-86% at 24-72 h. Therefore, our data provided the experimental evidence that the caffeic acid effectively inhibited CDV infection in vero cells, which may potentially be used to treat clinical disease associated with CDV infection. Copyright © 2017. Published by Elsevier Ltd.

  1. Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells.

    Science.gov (United States)

    Cho, Mi Suk; Park, Won Sun; Jung, Won-Kyo; Qian, Zhong-Ji; Lee, Dae-Sung; Choi, Jung-Sik; Lee, Da-Young; Park, Sae-Gwang; Seo, Su-Kil; Kim, Hak-Ju; Won, Jun Yeon; Yu, Byeng Chul; Choi, Il-Whan

    2014-07-01

    Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown. The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells in vitro. To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used. CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1β (4.775 versus 0.713 pg/ml, IC50 = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC50 = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC50 = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation. Our results indicated that CAPE can modulate mast cell-mediated allergic disease.

  2. Pharmacokinetics of Caffeic Acid from Methanol Seed Extract of ...

    African Journals Online (AJOL)

    Pharmacokinetics of Caffeic Acid from Methanol Seed Extract of Syzygium cumini L in Rats. Muhammad Islam, Naureen Shehzadi, Muhammad Salman, Fakhra Zahid, Humaira M. Khan, Sohail Amjad, Muhammad T. Khan, Muhammad Z. Danish, Nadeem I. Bukhari, Khalid Hussain ...

  3. Caffeic acid derivative from Clinopodium umbrosum

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    M. Esfahanizadeh

    2017-11-01

    Full Text Available Background and objectives: Plants of genus Clinopodium have been used in different cultures as traditional medicines.Due to theimportance of medicinal properties of the genus Clinopodium, C. umbrosum was selected for phytochemical analysis along with evaluation of its antioxidant property. Methods: The aerial parts of C. umbrosum were extracted with petroleum ether, chloroform, and methanol. Later, the methanol extract was fractionated via solid phase extraction and reversed phase high performance liquid chromatography. Consequently, structure of the isolated compound was analyzed through spectral analysis of 1D and 2D NMR data. Besides, the essential oil of C. umbrosum achieved through hydrodistillation was analyzed via gas chromatography-mass spectrometry (GC-MS. Additionally, the antioxidant property of C. umbrosum methanol extracttogether with its phenolics and flavonoids content were assessed. Results: Structure elucidation of the purified compound revealed presence of a caffeic acid derivative in C. umbrosum methanol extract. GC-MS analysis of the essential oil showed limonene, acetophenone, palmitic acid and phytol as the most frequent components of the essential oil. Moreover, the RC50 value for free radical scavenging activity of  the methanol extract was determined as 38.52 µg/mL and values for the total phenolics and flavonoids contact were calculated as 5.14 g gallic acid equivalent and 4.25 g quercetin equivalent per 100 g of dried plant material, respectively.  Conclusion: Overall, the present study was the first report on the phytochemical analysis of C. umbrosum whichrevealed presence of rosmarinic acid as the main component of the methanol extract with prominent antioxidant activity.

  4. Caffeic acid decomposition products: antioxidants or pro-oxidants?

    OpenAIRE

    Andueza, S. (Susana); Manzocco, L. (Lara); Peña, M.P. (María Paz) de; Cid, C. (Concepción); Nicoli, C. (Cristina)

    2009-01-01

    The potential of phenol antioxidants to suffer decomposition reactions leading to the formation of products exerting pro-oxidant activity was studied. A hydroalcoholic solution containing caffeic acid was assessed for antioxidant and pro-oxidant activity during heating at 90 degrees C to simulate the heat maintenance of the coffee brews in thermos. Decomposition products were also evaluated by HPLC analysis. In the early steps of caffeic acid decomposition. a decrease in antioxidant capacity ...

  5. Caffeic acid phenethyl ester causes p21 induction, Akt signaling reduction, and growth inhibition in PC-3 human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Hui-Ping Lin

    Full Text Available Caffeic acid phenethyl ester (CAPE treatment suppressed proliferation, colony formation, and cell cycle progression in PC-3 human prostate cancer cells. CAPE decreased protein expression of cyclin D1, cyclin E, SKP2, c-Myc, Akt1, Akt2, Akt3, total Akt, mTOR, Bcl-2, Rb, as well as phosphorylation of Rb, ERK1/2, Akt, mTOR, GSK3α, GSK3β, PDK1; but increased protein expression of KLF6 and p21(Cip1. Microarray analysis indicated that pathways involved in cellular movement, cell death, proliferation, and cell cycle were affected by CAPE. Co-treatment of CAPE with chemotherapeutic drugs vinblastine, paclitaxol, and estramustine indicated synergistic suppression effect. CAPE administration may serve as a potential adjuvant therapy for prostate cancer.

  6. Novel Caffeic Acid Nanocarrier: Production, Characterization, and Release Modeling

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    Milad Fathi

    2013-01-01

    Full Text Available This paper deals with the development of novel nanocarriers using layer by layer carbohydrate coating of caffeic acid loaded solid lipid nanoparticles (SLNs to improve stability and colon delivery of the poorly water-soluble caffeic acid. Three biopolymers (chitosan, alginate, and pectin in different concentrations (0.1, 0.25, and 0.5% were electrostatically coated over the SLN surface. The size and zeta potential of produced nanocarriers were measured using photon correlation spectroscopy. Mathematical models (i.e., zero-order, first-order, Higuchi, Ritger-Peppas, reciprocal powered time, Weibull, and quadratic models were used to describe the release and kinetic modeling in gastrointestinal solution (GIS. Also, antioxidant activity of caffeic acid during the release in GIS was investigated using DPPH and reducing activity methods. The prepared treatments coated by alginate-chitosan as well as pectin-chitosan coated SLN at the concentration of 0.1% showed nanosized bead; the latter efficiently retarded the release of caffeic acid in gastric media up to 2.5 times higher than that of SLN. Zeta potential values of coated samples were found to significantly increase in comparison to SLN indicating the higher stability of produced nanocarriers. Antioxidant activity of caffeic acid after gastric release did not result in the same trend as observed for caffeic acid release from different treatments; however, in line with less caffeic acid release in the intestine solution by the effect of coating, lower antioxidant activity was determined at the end stage of the experiment.

  7. Biosynthesis of caffeic acid in Escherichia coli using its endogenous hydroxylase complex

    Science.gov (United States)

    2012-01-01

    Background Caffeic acid (3,4-dihydroxycinnamic acid) is a natural phenolic compound derived from the plant phenylpropanoid pathway. Caffeic acid and its phenethyl ester (CAPE) have attracted increasing attention for their various pharmaceutical properties and health-promoting effects. Nowadays, large-scale production of drugs or drug precursors via microbial approaches provides a promising alternative to chemical synthesis and extraction from plant sources. Results We first identified that an Escherichia coli native hydroxylase complex previously characterized as the 4-hydroxyphenylacetate 3-hydroxylase (4HPA3H) was able to convert p-coumaric acid to caffeic acid efficiently. This critical enzymatic step catalyzed in plants by a membrane-associated cytochrome P450 enzyme, p-coumarate 3-hydroxylase (C3H), is difficult to be functionally expressed in prokaryotic systems. Moreover, the performances of two tyrosine ammonia lyases (TALs) from Rhodobacter species were compared after overexpression in E. coli. The results indicated that the TAL from R. capsulatus (Rc) possesses higher activity towards both tyrosine and L-dopa. Based on these findings, we further designed a dual pathway leading from tyrosine to caffeic acid consisting of the enzymes 4HPA3H and RcTAL. This heterologous pathway extended E. coli native tyrosine biosynthesis machinery and was able to produce caffeic acid (12.1 mg/L) in minimal salt medium. Further improvement in production was accomplished by boosting tyrosine biosynthesis in E. coli, which involved the alleviation of tyrosine-induced feedback inhibition and carbon flux redirection. Finally, the titer of caffeic acid reached 50.2 mg/L in shake flasks after 48-hour cultivation. Conclusion We have successfully established a novel pathway and constructed an E. coli strain for the production of caffeic acid. This work forms a basis for further improvement in production, as well as opens the possibility of microbial synthesis of more complex plant

  8. Biosynthesis of caffeic acid in Escherichia coli using its endogenous hydroxylase complex

    Directory of Open Access Journals (Sweden)

    Lin Yuheng

    2012-04-01

    Full Text Available Abstract Background Caffeic acid (3,4-dihydroxycinnamic acid is a natural phenolic compound derived from the plant phenylpropanoid pathway. Caffeic acid and its phenethyl ester (CAPE have attracted increasing attention for their various pharmaceutical properties and health-promoting effects. Nowadays, large-scale production of drugs or drug precursors via microbial approaches provides a promising alternative to chemical synthesis and extraction from plant sources. Results We first identified that an Escherichia coli native hydroxylase complex previously characterized as the 4-hydroxyphenylacetate 3-hydroxylase (4HPA3H was able to convert p-coumaric acid to caffeic acid efficiently. This critical enzymatic step catalyzed in plants by a membrane-associated cytochrome P450 enzyme, p-coumarate 3-hydroxylase (C3H, is difficult to be functionally expressed in prokaryotic systems. Moreover, the performances of two tyrosine ammonia lyases (TALs from Rhodobacter species were compared after overexpression in E. coli. The results indicated that the TAL from R. capsulatus (Rc possesses higher activity towards both tyrosine and L-dopa. Based on these findings, we further designed a dual pathway leading from tyrosine to caffeic acid consisting of the enzymes 4HPA3H and RcTAL. This heterologous pathway extended E. coli native tyrosine biosynthesis machinery and was able to produce caffeic acid (12.1 mg/L in minimal salt medium. Further improvement in production was accomplished by boosting tyrosine biosynthesis in E. coli, which involved the alleviation of tyrosine-induced feedback inhibition and carbon flux redirection. Finally, the titer of caffeic acid reached 50.2 mg/L in shake flasks after 48-hour cultivation. Conclusion We have successfully established a novel pathway and constructed an E. coli strain for the production of caffeic acid. This work forms a basis for further improvement in production, as well as opens the possibility of microbial synthesis

  9. Caffeic Acid Derivatives in Dried Lamiaceae and Echinacea purpurea Products

    Science.gov (United States)

    The concentrations of caffeic acid derivatives within Lamiaceae and Echinacea (herb, spice, tea, and dietary supplement forms) readily available in the U.S. marketplace (n=72) were determined. After the first identification of chicoric acid in Ocimum basilicum (basil), the extent to which chicoric a...

  10. Pharmacokinetics of Caffeic Acid from Methanol Seed Extract of ...

    African Journals Online (AJOL)

    4.00 and 12.00 h. The plasma was collected after centrifugation of blood at 2700rpm for 10 min at. 25 oC, which was then processed and analyzed as mentioned above. Determination of pharmacokinetic parameters. Analytical data of each rat were used to plot a curve between plasma concentration of caffeic acid and time.

  11. Synthesis of a Series of Caffeic Acid Phenethyl Amide (CAPA) Fluorinated Derivatives: Comparison of Cytoprotective Effects to Caffeic Acid Phenethyl Ester (CAPE)

    Science.gov (United States)

    2010-06-11

    Synthesis of a series of caffeic acid phenethyl amide (CAPA) fluorinated derivatives: Comparison of cytoprotective effects to caffeic acid phenethyl...to induce genes with the downstream effect of counter- acting oxidative stress.5,6 Caffeic acid phenethyl ester (CAPE), a plant polyphenolic con... synthesis and investigation of catechol ring-fluorinated derivatives of CAPE with regard to cytoprotective ability against oxidative stress in vitro.14

  12. Inhibitory mechanism against oxidative stress of caffeic acid

    Directory of Open Access Journals (Sweden)

    Farhan Ahmed Khan

    2016-10-01

    Full Text Available The purpose of this article is to summarize the reported antioxidant activities of a naturally abundant bioactive phenolic acid, caffeic acid (CA, 3,4-dihydroxycinnamic acid, so that new avenues for future research involving CA can be explored. CA is abundantly found in coffee, fruits, vegetables, oils, and tea. CA is among the most potential and abundantly found in nature, hydroxycinnamic acids with the potential of antioxidant behavior. Reactive oxygen species produced as a result of endogenous processes can lead to pathophysiological disturbances in the human body. Foods containing phenolic substances are a potential source for free radical scavenging; these chemicals are known as antioxidants. This review is focused on CA's structure, availability, and potential as an antioxidant along with its mode of action. A brief overview of the literature published about the prooxidant potential of caffeic acid as well as the future perspectives of caffeic acid research is described. CA can be effectively employed as a natural antioxidant in various food products such as oils.

  13. Ethanol extract of propolis and its constituent caffeic acid phenethyl ester inhibit breast cancer cells proliferation in inflammatory microenvironment by inhibiting TLR4 signal pathway and inducing apoptosis and autophagy.

    Science.gov (United States)

    Chang, Huasong; Wang, Yuehua; Yin, Xusheng; Liu, Xinying; Xuan, Hongzhuan

    2017-09-26

    Propolis and its major constituent - caffeic acid phenethyl ester (CAPE) have good abilities on antitumor and anti-inflammation. However, little is known about the actions of propolis and CAPE on tumor in inflammatory microenvironment, and inflammatory responses play decisive roles at different stages of tumor development. To understand the effects and mechanisms of ethanol-extracted Chinese propolis (EECP) and its major constituent - CAPE in inflammation-stimulated tumor, we investigated their effects on Toll-like receptor 4 (TLR4) signaling pathway which plays a crucial role in breast cancer MDA-MB-231 cell line. 80% confluent breast cancer MDA-MB-231 cells were stimulated with 1 μg/mL lipopolysaccaride (LPS). Then the cells were divided for treatment by CAPE (25 μg/mL) and EECP (25, 50 and 100 μg/mL), respectively. Cell viability, nitric oxide (NO) production and cell migration were measured by sulforhodamine B assay, chemical method and scratch assay. The levels of TLR4, MyD88, IRAK4, TRIF, caspase 3, PARP, LC3B and p62 were investigated through western blotting. The expression of TLR4, LC3B and nuclear factor-κB p65 (NF-κB p65) were tested by immunofluorescence microscopy assay. Treatment of different concentrations of EECP (25, 50 and 100 μg/mL) and CAPE (25 μg/mL) significantly inhibited LPS-stimulated MDA-MB-231 cell line proliferation, migration and NO production. Furthermore, EECP and CAPE activated caspase3 and PARP to induce cell apoptosis, and also upregulated LC3-II and decreased p62 level to induce autophagy during the process. TLR4 signaling pathway molecules such as TLR4, MyD88, IRAK4, TRIF and NF-κB p65 were all down-regulated after EECP and CAPE treatment in LPS-stimulated MDA-MB-231 cells. These findings indicated that EECP and its major constituent - CAPE inhibited breast cancer MDA-MB-231 cells proliferation in inflammatory microenvironment through activating apoptosis, autophagy and inhibiting TLR4 signaling pathway. EECP and

  14. Grape skins (Vitis vinifera L.) catalyze the in vitro enzymatic hydroxylation of p-coumaric acid to caffeic acid

    DEFF Research Database (Denmark)

    Arnous, Anis; Meyer, Anne S.

    2009-01-01

    The ability of grape skins to catalyze in vitro conversion of p-coumaric acid to the more potent antioxidant caffeic acid was studied. Addition of different concentrations of p-coumaric to red grape skins (Cabernet Sauvignon) resulted in formation of caffeic acid. This caffeic acid formation (Y...

  15. Immobilization of caffeic acid on a polypropylene film: synthesis and antioxidant properties.

    Science.gov (United States)

    Arrua, Dario; Strumia, Miriam Cristina; Nazareno, Mónica Azucena

    2010-08-25

    The immobilization of caffeic acid (CA) on a polypropylene (PP) film was successfully performed through the covalent binding of the caffeoyl chloride on a modified polymeric surface of PP films grafted with hydroxyethyl methacrylate as monomer (PP-g-HEMA). The different reaction steps were monitored by FT-IR spectroscopy. The synthesized films were characterized by Folin-Ciocalteu method by measuring the available phenolic groups as caffeic acid equivalents linked to the surface. The antioxidant efficiency of the modified polymers was evaluated by typical spectrophometric methods, such as the bleaching of radicals DPPH(•) and ABTS(•+), and the inhibition of the enzymatically induced coupled oxidation of linoleic acid and betacarotene. The available phenolic groups on the modified film presented a good correlation with the antiradical activity toward DPPH(•). Moreover, the polymer synthesized in this work showed a good protective activity against ascorbic acid oxidation in real samples of orange juice.

  16. Antioxidative activity of caffeic acid: Mechanistic DFT study

    OpenAIRE

    Redžepović, Izudin; Marković, Svetlana; Tošović, Jelena

    2017-01-01

    This paper reports the results of comprehensive mechanistic investigations of the hydrogen atom transfer (HAT), radical adduct formation (RAF), single electron transfer – proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) mechanisms of caffeic acid (CA). The goals of the work were achieved by simulating the reactions of CA with hydroxyl radical in benzene and water solutions. It was found that SET-PT is not a favourable antioxidative mechanism of CA. On the other h...

  17. Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats.

    Science.gov (United States)

    Anwar, Javed; Spanevello, Roselia Maria; Pimentel, Victor Camera; Gutierres, Jessié; Thomé, Gustavo; Cardoso, Andreia; Zanini, Daniela; Martins, Caroline; Palma, Heloisa Einloft; Bagatini, Margarete Dulce; Baldissarelli, Jucimara; Schmatz, Roberta; Leal, Cláudio Alberto Martins; da Costa, Pauline; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2013-06-01

    This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase (nucleoside triphosphate diphosphohydrolase), Ecto-NPP (nucleotide pyrophosphatase/phosphodiesterase), 5'-nucleotidase and adenosine deaminase (ADA) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation. Animals were divided into five groups: I (control); II (oil); III (caffeic acid 10 mg/kg); IV (caffeic acid 50 mg/kg); and V (caffeic acid 100 mg/kg). Animals were treated with caffeic acid diluted in oil for 30 days. In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control (P<0.05). The 5'-nucleotidase activity was decreased, while E-NPP and ADA activities were increased in platelets of rats of groups III, IV and V (P<0.05). Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I (P<0.05). In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control (P<0.05). These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Antioxidant and prooxidant nature of hydroxycinnamic acid derivatives ferulic and caffeic acids.

    Science.gov (United States)

    Maurya, Dharmendra Kumar; Devasagayam, Thomas Paul Asir

    2010-12-01

    Dietary polyphenols are beneficial to human health by exerting various biological effects. Ferulic and caffeic acids are hydroxycinnamic acid derivatives widely distributed in plant-derived food products. Studies indicate that some dietary compounds may have concentration-dependent antioxidant or prooxidant activities. The present study concerns such activities of ferulic and caffeic acids. They have concentration-dependent antioxidant effects in terms of inhibition of lipid peroxidation and reactive oxygen species-scavenging after 2,2'-azobis-amidinopropane dihydrochloride-induced damage in mouse liver microsomes and splenic lymphocytes respectively. They also show differential scavenging of nitric oxide, superoxide and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid radical (ABTS*(+)). In DPPH (1,1-diphenyl picrylhydrazyl) assay above 20 μM the absorbance start increasing due to the formation of an unknown adduct which has a shoulder at 517 nm. However, in Fenton reaction, above 5 μM, they behave as prooxidants and the possible mechanisms responsible for their prooxidant property may be related to their ferric reducing ability. These findings may have significant health implications where these natural compounds are being used/consumed. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Impact of caffeic acid on aluminium chloride-induced dementia in rats.

    Science.gov (United States)

    Khan, Kafeel A; Kumar, Nitesh; Nayak, Pawan G; Nampoothiri, Madhavan; Shenoy, Rekha R; Krishnadas, Nandakumar; Rao, C Mallikarjuna; Mudgal, Jayesh

    2013-12-01

    Literature favours the in vitro neuroprotective role of caffeic acid, a naturally derived polyphenolic compound. This study was aimed to investigate the role of caffeic acid in experimental model of Alzheimer's disease. Firstly, caffeic acid was tested for in vitro anticholinesterase potential using rat brain homogenate. Later, in vivo antidementia activity of caffeic acid was assessed against aluminium chloride (AlCl3 )-induced dementia in rats. Behavioural (Morris water maze test) and brain biochemical parameters (acetylcholinesterase (AChE), catalase, glutathione-S-transferase (GST) activity, glutathione (GSH) and nitrite levels) were assessed to correlate the cognitive function with cholinergic transmission and oxidative stress. Rats administered with caffeic acid showed improved cognitive function in Morris water maze test. The antidementia activity of caffeic acid was confirmed by the reduction in brain AChE activity and nitrite levels. Further, caffeic acid corrected the diminished level of antioxidant enzymes such as catalase, GSH and GST in brain. These findings suggest the antidementia activity of caffeic acid against AlCl3 -induced dementia in rats. The outcome of present study offers a wider scope to screen caffeic acid against neurodegeneration associated disorders. © 2013 Royal Pharmaceutical Society.

  20. Synthesis, Preliminary Bioevaluation and Computational Analysis of Caffeic Acid Analogues

    Directory of Open Access Journals (Sweden)

    Zhiqian Liu

    2014-05-01

    Full Text Available A series of caffeic acid amides were designed, synthesized and evaluated for anti-inflammatory activity. Most of them exhibited promising anti-inflammatory activity against nitric oxide (NO generation in murine macrophage RAW264.7 cells. A 3D pharmacophore model was created based on the biological results for further structural optimization. Moreover, predication of the potential targets was also carried out by the PharmMapper server. These amide analogues represent a promising class of anti-inflammatory scaffold for further exploration and target identification.

  1. Caffeic Acid Phenethyl Ester (Propolis Extract) Ameliorates Insulin Resistance by Inhibiting JNK and NF-κB Inflammatory Pathways in Diabetic Mice and HepG2 Cell Models.

    Science.gov (United States)

    Nie, Jiarui; Chang, Yaning; Li, Yujia; Zhou, Yingjun; Qin, Jiawen; Sun, Zhen; Li, Haibin

    2017-10-18

    Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated for the ameliorative effects on insulin resistance and the mechanisms were identified, using non-insulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5 weeks of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Proinflammatory cytokines in serum and the expressions of tumor necrosis factor-alpha (TNF-α) mRNA in tissues were markedly downregulated from CAPE-treated mice. In vitro, CAPE supplement significantly improved glucose consumption, glucose uptake, glycogen content, and oxidative stress and decreased expression of glucose-6-phosphatase (G6Pase) mRNA in cells. Both in vivo and in vitro, CAPE enhanced p-Akt (Ser473) and p-insulin receptor substrate (IRS)-1 (Tyr612), but inhibited p-JNK (Thr183/Tyr185), p-NF-κB p65 (Ser536), and nuclear translocation of p-NF-κB p65 (Ser536). In summary, CAPE can ameliorate insulin resistance through modulation of JNK and NF-κB signaling pathway in mice and HepG2 cells.

  2. Cytotoxic caffeic acid derivatives from the rhizomes of Cimicifuga heracleifolia.

    Science.gov (United States)

    Yim, Soon-Ho; Kim, Hyun Jung; Park, Si-Hwan; Kim, Jinmi; Williams, Darren R; Jung, Da-Woon; Lee, Ik-Soo

    2012-09-01

    Activity profiling of the n-BuOH extract from Cimicifuga heracleifolia rhizomes led to the identification of three cytotoxic caffeic acid derivatives, carboxymethyl isoferulate (2), cimicifugic acid A (3), and cimicifugic acid B (4) together with a series of structurally related inactive compounds. The extract was separated by time-based fractionation in a gradient HPLC condition, and cytotoxicity of each fraction was evaluated using HCT116 colon cancer cells in vitro. HPLChyphenated spectroscopy including LC/NMR and LC/PDA/MS provided structural information for phenolic compounds contained in the extract, and further preparative isolation of active compounds 2-4 was achieved by semi-preparative HPLC. Compounds 2-4 showed cytotoxic activity against cancer cells in a dose-dependent manner at the concentrations of 2.5-40 μM, and western blotting analysis showed that these compounds increased expression of cleaved poly ADP ribose polymerase (PARP), a critical apoptosis marker.

  3. Synthesis and Biological Activity of Arylspiroborate Salts Derived from Caffeic Acid Phenethyl Ester

    Directory of Open Access Journals (Sweden)

    Martin J. G. Hébert

    2015-01-01

    Full Text Available Two novel boron compounds containing caffeic acid phenethyl ester (CAPE derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE.

  4. Synthesis and evaluation of multifunctional ferulic and caffeic acid dimers for Alzheimer's disease.

    Science.gov (United States)

    He, Xi-Xin; Yang, Xiao-Hong; Ou, Rui-Ying; Ouyang, Ying; Wang, Sheng-Nan; Chen, Zi-Wei; Wen, Shi-Jun; Pi, Rong-Biao

    2017-03-01

    In this study, a series of novel ferulic and caffeic acid dimers was designed and synthesised, and their multifunctional properties against Alzheimer's disease (AD) were evaluated. Results showed that our multifunctional strategy was great supported by enhancing the inhibition of Aβ 1-42 self-induced aggregation. Moreover, 7b also had potent protective effects against glutamate-induced cell death without significant cell toxicity in mouse hippocampal neuronal HT22 cells and 10c effectively scavenged diphenylpicrylhydrazyl free radicals. Collectively, these data strongly encourage further optimisation of 7b as a new hit to develop multifunctional agents for the treatment of AD.

  5. Antioxidative activity of caffeic acid: Mechanistic DFT study

    Directory of Open Access Journals (Sweden)

    Redžepović Izudin

    2017-01-01

    Full Text Available This paper reports the results of comprehensive mechanistic investigations of the hydrogen atom transfer (HAT, radical adduct formation (RAF, single electron transfer – proton transfer (SET-PT, and sequential proton loss electron transfer (SPLET mechanisms of caffeic acid (CA. The goals of the work were achieved by simulating the reactions of CA with hydroxyl radical in benzene and water solutions. It was found that SET-PT is not a favourable antioxidative mechanism of CA. On the other hand, HAT and RAF are competitive, because HAT pathways yield thermodynamically more stable radical products, and RAF pathways require smaller activation barriers. In polar basic environment SPLET is a probable antioxidative mechanism of CA, with exceptionally large rate.

  6. Preparation of MIP-based QCM nanosensor for detection of caffeic acid.

    Science.gov (United States)

    Gültekin, Aytaç; Karanfil, Gamze; Kuş, Mahmut; Sönmezoğlu, Savaş; Say, Rıdvan

    2014-02-01

    In the present work, a new caffeic acid imprinted quartz crystal microbalance (QCM) nanosensor has been designed for selective assignation of caffeic acid in plant materials. Methacrylamidoantipyrine-iron(III) [MAAP-Fe(III)] as metal-chelating monomer has been used to prepare selective molecular imprinted polymer (MIP). MIP film for detection of caffeic acid has been developed on QCM electrode and selectivity experiments and analytical performance of caffeic acid imprinted QCM nanosensor has been studied. The caffeic acid imprinted QCM nanosensor has been characterized by AFM. After the characterization studies, imprinted and non-imprinted nanosensors was connected to QCM system for studies of connection of the target molecule, selectivity and the detection of amount of target molecule in real samples. The detection limit was found to be 7.8 nM. The value of Langmuir constant (b) (4.06 × 10(6)) that was acquired using Langmuir graph demonstrated that the affinity of binding sites was strong. Also, selectivity of prepared caffeic acid imprinted nanosensor was found as being high compared to chlorogenic acid. Finally, the caffeic acid levels in plant materials was determined by the prepared QCM nanosensor. © 2013 Published by Elsevier B.V.

  7. Modulatory effect of caffeic acid on cholinesterases inhibitory properties of donepezil.

    Science.gov (United States)

    Agunloye, Odunayo Michael; Oboh, Ganiyu

    2017-09-22

    Background Donepezil hydrochloride commonly used in the management of Alzheimer's disease (AD), exhibiting its inhibitory effects on acetylcholinesterase and butyrylcholinesterase activity thereby enhance cognitive function. Caffeic acid member of hydroxycinnamic acid is widely present in human diet. This study aims to investigate influence of caffeic acid on acetylcholinesterase and butyrylcholinesterase inhibitory properties of donepezil (in vitro). Methods 5 mg of donepezil was dissolved in 50 mL distilled water while 10 mg of caffeic acid was dissolved in 100 mL distilled water. Therefore, mixtures of samples were prepared as follows: A2=donepezil 0.075 mg/mL+caffeic acid 0.025 mg/mL; A3=donepezil 0.050 mg/mL+caffeic acid 0.050 mg/mL; A4=donepezil 0.025 mg/mL+caffeic acid 0.075 mg/mL. All samples were kept in the refrigerator at 4 °C for subsequent analysis. Results The result showed that all the combinations show an inhibitory effect on acetylcholinesterase and butyrylcholinesterase activity in vitro, with the combination A4=donepezil 0.025 mg/mL+caffeic acid 0.075 mg/mL had significant (pdonepezil 0.025 mg/mL+caffeic acid 0.075 mg/mL and A3=donepezil 0.050 mg/mL+caffeic acid 0.050 mg/mL had highest inhibitory effect against FeSO4 and SNP induced lipid peroxidation in rat brain homogenate in vitro respectively. Moreover, all the samples exhibit antioxidant properties as typified by their ability to chelate iron (II) ion (Fe2+), hydroxyl radical (OH٭) radical scavenging ability and ferric reducing property (FRAP). Conclusions Therefore, the combination of caffeic acid with donepezil enhances the antioxidant properties of donepezil. The combination of caffeic acid with donepezil could be a therapeutic aid in the management of AD, possibly with fewer side effects of donepezil. Nevertheless, the combination donepezil 0.025 mg/mL+caffeic acid 0.075 mg/mL acid look promising.

  8. Caffeic acid production by simultaneous saccharification and fermentation of kraft pulp using recombinant Escherichia coli.

    Science.gov (United States)

    Kawaguchi, Hideo; Katsuyama, Yohei; Danyao, Du; Kahar, Prihardi; Nakamura-Tsuruta, Sachiko; Teramura, Hiroshi; Wakai, Keiko; Yoshihara, Kumiko; Minami, Hiromichi; Ogino, Chiaki; Ohnishi, Yasuo; Kondo, Ahikiko

    2017-07-01

    Caffeic acid (3,4-dihydroxycinnamic acid) serves as a building block for thermoplastics and a precursor for biologically active compounds and was recently produced from glucose by microbial fermentation. To produce caffeic acid from inedible cellulose, separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) reactions were compared using kraft pulp as lignocellulosic feedstock. Here, a tyrosine-overproducing Escherichia coli strain was metabolically engineered to produce caffeic acid from glucose by introducing the genes encoding a 4-hydroxyphenyllactate 3-hydroxylase (hpaBC) from Pseudomonas aeruginosa and tyrosine ammonia lyase (fevV) from Streptomyces sp. WK-5344. Using the resulting recombinant strain, the maximum yield of caffeic acid in SSF (233 mg/L) far exceeded that by SHF (37.9 mg/L). In the SSF with low cellulase loads (≤2.5 filter paper unit/g glucan), caffeic acid production was markedly increased, while almost no glucose accumulation was detected, indicating that the E. coli cells experienced glucose limitation in this culture condition. Caffeic acid yield was also negatively correlated with the glucose concentration in the fermentation medium. In SHF, the formation of by-product acetate and the accumulation of potential fermentation inhibitors increased significantly with kraft pulp hydrolysate than filter paper hydrolysate. The combination of these inhibitors had synergistic effects on caffeic acid fermentation at low concentrations. With lower loads of cellulase in SSF, less potential fermentation inhibitors (furfural, 5-hydroxymethyfurfural, and 4-hydroxylbenzoic acid) accumulated in the medium. These observations suggest that glucose limitation in SSF is crucial for improving caffeic acid yield, owing to reduced by-product formation and fermentation inhibitor accumulation.

  9. Interactive effects of gallic/ferulic/caffeic acids and anthocyanins on pigment thermal stabilities.

    Science.gov (United States)

    Qian, Bing-Jun; Liu, Jian-Hua; Zhao, Shu-Juan; Cai, Jian-Xiong; Jing, Pu

    2017-06-01

    The data presented in this article are related to the research article entitled "The effects of gallic/ferulic/caffeic acids on colour intensification and anthocyanin stability" (Qian et al., 2017) [1]. This paper described preparation and isolation of anthocyanins from purple sweet potatoes (PSP) and the time-course of anthocyanin profiles treated with gallic, ferulic, or caffeic acids at 95 °C. The color appearance of PSPanthocyanins alone, or with gallic, ferulic, or caffeic acids was described after the 15 h of thermal treatment. The high resolution mass spectrographs of PSP anthocyanins were determined using UPLC-ESI-HRMS. The spatial interaction of peonidin 3-O-(2-O-β-D-glucopyranocyl-β-D-glucopyranoide)-5-O-β-D-glucopyranoside and gallic/ferulic/caffeic acids was illustrated by molecular dynamic simulation.

  10. The effects of caffeic, coumaric and ferulic acids on proliferation, superoxide production, adhesion and migration of human tumor cells in vitro.

    Science.gov (United States)

    Nasr Bouzaiene, Nouha; Kilani Jaziri, Soumaya; Kovacic, Hervé; Chekir-Ghedira, Leila; Ghedira, Kamel; Luis, José

    2015-11-05

    Reactive oxygen species are well-known mediators of various biological responses. In this study, we examined the effect of three phenolic acids, caffeic, coumaric and ferulic acids, on superoxide anion production, adhesion and migration of human lung (A549) and colon adenocarcinoma (HT29-D4) cancer cell lines. Proliferation of both tumor cells was inhibited by phenolic acids. Caffeic, coumaric and ferulic acids also significantly inhibited superoxide production in A549 and HT29-D4 cells. Superoxide anion production decreased by 92% and 77% at the highest tested concentration (200 µM) of caffeic acid in A549 and HT29-D4 cell lines respectively. Furthermore, A549 and HT29-D4 cell adhesion was reduced by 77.9% and 79.8% respectively at the higher tested concentration of ferulic acid (200 µM). Migration assay performed towards A549 cell line, revealed that tested compounds reduced significantly cell migration. At the highest concentration tested (200 µM), the covered surface was 7.7%, 9.5% and 35% for caffeic, coumaric or ferulic acids, respectively. These results demonstrate that caffeic, coumaric and ferulic acids may participate as active ingredients in anticancer agents against lung and colon cancer development, at adhesion and migration steps of tumor progression. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Synthesis of labelled compound of ferulic acid and caffeic acid with tritium

    International Nuclear Information System (INIS)

    Yi Mingguang; Wang Caiyun

    1986-01-01

    Effective components of Chinese traditional herbs consist of many compounds, but some of the compounds usually contain unsaturated carbon-carbon double bonds. The unsaturated organic compounds 3 H-Ferulic acid and 3 H-Caffeic acid are prepared with their tritiated intermediates made by electric-dischange exposure method, which ensures the compounds contaning double bonds not hydrogenated. The 3 H-Ferulic acid is composed of 3 H-vanillin and Malonic acid. The 3 H-Caffeic acid is composed of 3 H-protocatechuyl aldehyde and Malonic acid and the specific activity of the products is 0.2 mCi/mg. The radiochemicaly purity is greater than 90%

  12. Preparation and characterization of SPION functionalized via caffeic acid

    Science.gov (United States)

    Baykal, A.; Amir, Md.; Günerb, S.; Sözeri, H.

    2015-12-01

    Caffeic acid coated superparamagnetic iron oxide nanoparticles (SPION-CFA) was synthesized by reflux method. The structural, spectroscopic and magnetic properties were studied by X-ray diffraction (XRD), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), and Vibrating sample magnetometer (VSM) techniques. Thermal gravimetric analysis (TG) and Fourier transform infrared spectroscopy (FT-IR) confirmed the presence of CA on the surface of SPION. The theoretical analyzes performed on recorded room temperature VSM spectrum confirmed the formation of superparamagnetic nature of SPION-CFA. The particle size dependent Langevin function was applied to determine the average magnetic particle dimension (Dmag) around 11.93 nm. In accordance, the average crystallite and particle sizes were obtained as 11.40 nm and ~12.00 nm from XRD and TEM measurements. The extrapolated specific saturation magnetization (σs) is 44.11 emu/g and measured magnetic moment is 1.83 μB. These parameters assign small order of magnetization for NPs with respect to bulk Fe3O4. Magnetic anisotropy was offered as uniaxial and calculated effective anisotropy constant (Keff) is 34.82×104 Erg/g. The size-dependent saturation magnetization suggests the existence of a magnetically inactive layer as 1.035 nm for SPION-CFA.

  13. Aspergillus niger whole-cell catalyzed synthesis of caffeic acid phenethyl ester in ionic liquids.

    Science.gov (United States)

    Rajapriya, Govindaraju; Morya, Vivek Kumar; Mai, Ngoc Lan; Koo, Yoon-Mo

    2018-04-01

    Synthesis of caffeic acid ester essentially requires an efficient esterification process to produce various kinds of medicinally important ester derivatives. In the present study, a comprehensive and comparative analysis of whole-cell catalyzed caffeic acid esters production in ionic liquids (ILs) media was performed. Olive oil induced mycelial mass of halotolerant Aspergillus niger (A.niger) EXF 4321 was freeze dried and used as a catalyst. To ensure maximum solubilization of caffeic acid for highest substrate loading several ILs were screened and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Emim][Tf 2 N]) was found to have the maximum solubility and favoured for enzymatic activity of freeze dried mycelia. The whole-cell catalyzed synthesis of caffeic acid phenethyl ester (CAPE) conditions were optimized and bioconversion up to 84% was achieved at a substrate molar ratio of 1:20 (caffeic acid:2-phenyl ethanol), 30°C for 12h. Results obtained during this study were encouraging and helpful to design a bioreactor system to produce caffeic acid derived esters. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Regulatory Effects of Caffeic Acid Phenethyl Ester on Neuroinflammation in Microglial Cells

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    Cheng-Fang Tsai

    2015-03-01

    Full Text Available Microglial activation has been widely demonstrated to mediate inflammatory processes that are crucial in several neurodegenerative disorders. Pharmaceuticals that can deliver direct inhibitory effects on microglia are therefore considered as a potential strategy to counter balance neurodegenerative progression. Caffeic acid phenethyl ester (CAPE, a natural phenol in honeybee propolis, is known to possess antioxidant, anti-inflammatory and anti-microbial properties. Accordingly, the current study intended to probe the effects of CAPE on microglia activation by using in vitro and in vivo models. Western blot and Griess reaction assay revealed CAPE significantly inhibited the expressions of inducible nitric oxide synthase (NOS, cyclooxygenase (COX-2 and the production of nitric oxide (NO. Administration of CAPE resulted in increased expressions of hemeoxygenase (HO-1and erythropoietin (EPO in microglia. The phosphorylated adenosine monophosphate-activated protein kinase (AMPK-α was further found to regulate the anti-inflammatory effects of caffeic acid. In vivo results from immunohistochemistry along with rotarod test also revealed the anti-neuroinflammatory effects of CAPE in microglia activation. The current study has evidenced several possible molecular determinants, AMPKα, EPO, and HO-1, in mediating anti-neuroinflammatory responses in microglial cells.

  15. Phytochemical profile of Orthosiphon aristatus extracts after storage: Rosmarinic acid and other caffeic acid derivatives.

    Science.gov (United States)

    Chua, Lee Suan; Lau, Cher Haan; Chew, Chee Yung; Ismail, Nurul Izzati Mohd; Soontorngun, Nitnipa

    2018-01-15

    Orthosiphon aristatus (Blume) Miq. is a medicinal herb which is traditionally used for the treatment of diabetes and kidney diseases in South East Asia. Previous studies reported higher concentration of antioxidative phytochemicals, especially rosmarinic acid (ester of caffeic acid) and other caffeic acid derivatives in this plant extract than the other herbs such as rosemary and sage which are usually used as raw materials to produce rosmarinic acid supplement in the market. The phytochemical profile of O. aristatus was investigated at different storage durations for quality comparison. The phytochemicals were extracted from the leaves and stems of O. aristatus using a reflux reactor. The extracts were examined for total phenolic and flavonoid contents, as well as their antioxidant capacities, in terms of radical scavenging, metal chelating and reducing power. The phytochemical profiles were also analyzed by unsupervised principal component analysis and hierarchical cluster analysis, in relation to the factor of storage at 4 °C for 5 weeks. The leaf extract was likely to have more phytochemicals than stem extract, particularly caffeic acid derivatives including glycosylated and alkylated caffeic acids. This explains higher ratio of total phenolic content to total flavonoid content with higher antioxidant capacities for the leaf extracts. Rosmarinic acid dimer and salvianolic acid B appeared to be the major constituents, possibly contributing to the previously reported pharmacological properties. However, the phytochemical profiles were found changing, even though the extracts were stored in the refrigerator (4 °C). The change was significantly observed at the fifth week based on the statistical pattern recognition technique. O. aristatus could be a promising source of rosmarinic acid and its dimer, as well as salvianolic acid B with remarkably antioxidant properties. The phytochemical profile was at least stable for a month stored at 4 °C. It is likely to be

  16. Effects of caffeic and chlorogenic acids on the rat skeletal system.

    Science.gov (United States)

    Folwarczna, J; Pytlik, M; Zych, M; Cegieła, U; Nowinska, B; Kaczmarczyk-Sedlak, I; Sliwinski, L; Trzeciak, H; Trzeciak, H I

    2015-02-01

    Caffeic acid, predominantly as esters linked to quinic acid (chlorogenic acids), is a phenolic acid present at high levels in coffee. The aim of the study was to investigate effects of caffeic and chlorogenic acids on the skeletal system of female rats with normal estrogen levels and estrogen-deficient. Caffeic acid (5 and 50 mg/kg p.o. daily) and chlorogenic acid (100 mg/kg p.o. daily) were administered for 4 weeks to non-ovariectomized and bilaterally ovariectomized mature Wistar rats, and their effects were compared with appropriate controls. Moreover, estradiol (0.2 mg/kg p.o. daily) was administered to ovariectomized rats. Bone turnover markers, mass, mineralization and mechanical properties were examined. Although caffeic acid at a low dose exerted some unfavorable effects on the skeletal system, at high doses, caffeic and chlorogenic acids slightly increased mineralization in the tibia and improved mechanical properties of the femoral diaphysis (compact bone). Unlike estradiol, they did not counteract the worsening of the tibial metaphysis bone strength (cancellous bone) and increases in osteocalcin concentration induced by estrogen deficiency. High doses of the phenolic acids slightly favorably affected the rat skeletal system independently of the estrogen status.

  17. Antiepileptogenic, antioxidant and genotoxic evaluation of rosmarinic acid and its metabolite caffeic acid in mice.

    Science.gov (United States)

    Coelho, Vanessa Rodrigues; Vieira, Caroline Gonçalves; de Souza, Luana Pereira; Moysés, Felipe; Basso, Carla; Papke, Débora Kuck Mausolff; Pires, Thienne Rocha; Siqueira, Ionara Rodrigues; Picada, Jaqueline Nascimento; Pereira, Patrícia

    2015-02-01

    Antioxidant compounds have been extensively investigated as a pharmacological alternatives to prevent epileptogenesis. Rosmarinic acid (RA) and caffeic acid (CA) are compounds with antioxidant properties, and RA has been shown to inhibit GABA transaminase activity (in vitro). Our aim was to evaluate the effect of RA and CA on seizures induced by pentylenotetrazole (PTZ) using the kindling model in mice. Male CF-1 mice were treated once every three days during 16days with RA (1, 2 or 4mg/kg; i.p.), or CA (1, 4 or 8mg/kg; i.p.), or positive controls diazepam (1mg/kg; i.p.) or vigabatrin (600mg/kg; p.o.), 30min before PTZ administration (50mg/kg; s.c.). After the last treatment, animals were sacrificed and the cortex was collected to evaluate free radicals (determined by 2',7'-dichlorofluorescein diacetate probe), superoxide dismutase (SOD) and genotoxic activity (Alkaline Comet Assay). Rosmarinic acid 2mg/kg increased latency and decreased percentage of seizures, only on the 4th day of observation. The other tested doses of RA and CA did not show any effect. Rosmarinic acid 1mg/kg, CA 4mg/kg and CA 8mg/kg decreased free radicals, but no dose altered the levels of enzyme SOD. In the comet assay, RA 4mg/kg and CA 4mg/kg reduced the DNA damage index. Some doses of rosmarinic acid and CA tested showed neuroprotective action against oxidative and DNA damage produced in the kindling epilepsy model, although they did not produce antiepileptogenic effect in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells.

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    Lucia Natarelli

    Full Text Available Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG. In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9 and effector caspases (caspase 7 and 3 and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins.

  19. Caffeic acid product from the highly copper-tolerant plant Elsholtzia splendens post-phytoremediation: its extraction, purification, and identification*

    OpenAIRE

    Xing, Yan; Peng, Hong-yun; Zhang, Meng-xi; Li, Xia; Zeng, Wei-wei; Yang, Xiao-e

    2012-01-01

    In the current study, caffeic acid was an important metabolite in the highly copper-tolerant plant Elsholtzia splendens. Preparation and purification of caffeic acid were performed on the dried biomass of the plants by means of sonication/ethanol extraction, followed by purification using a macroporous resin (D101 type) column and silica gel chromatography. The faint-yellow caffeic acid product was yielded with a purity of 98.46%, and it was chemically identified from spectra of Fourier trans...

  20. Quantification of caffeic acid content in 4 species of mullein (Verbascum sp. ecotypes from southwest Iran

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    F. Jamshidi kia

    2017-11-01

    Full Text Available Background and objectives: The Verbascum genus is the largest genus of Scrophulariaceae family which has extensive natural habitat in southwest of Iran. Phenolic acids are one of the most important chemical compounds that have different biological activities including anti-inflammatory, antibacterial, antiviral, anti-tumor and antioxidant. Therefore, this study was conducted with the aim of caffeic acid quantification of 4 species of Verbascum sp. ecotypes from southwest Iran. Methods: Nine ecotypes of the 4 species (V. macrophyllus, V. pseudo- digitalis, V. sinatum, V. songaricum were collected from the southwest of Iran. Quantification of caffeic acid contentusing reversed-phase high-performance liquid chromatography (RP-HPLC with UV PDA 2800 detector, a C18 column with dimensions of 250×4.6 mm was performed. Results: The results showed that Verbascum sp. contained caffeic acid compound and there was a difference among species and ecotypes. The results showed the highest and lowest content of caffeic acid obtained from the V. sinatum species and ecotype Sepidan (7.76 μg/mg extract and V. songaricum species and ecotype Farokhshahr (0.54 μg/mg extract, respectively. Conclusion: The results revealed a high level of variation in caffeic acid among Verbascum sp. which was affected by habitat and climatic. The pattern of habitats of suitable ecotypes superior in terms of composition to should be selected and used for breeding and cropping mullein.

  1. Synergistic antioxidative effects of alkamides, caffeic acid derivatives, and polysaccharide fractions from Echinacea purpurea on in vitro oxidation of human low-density lipoproteins.

    Science.gov (United States)

    Dalby-Brown, Lea; Barsett, Hilde; Landbo, Anne-Katrine R; Meyer, Anne S; Mølgaard, Per

    2005-11-30

    Preparations of Echinacea are widely used as alternative remedies to prevent the common cold and infections in the upper respiratory tract. After extraction, fractionation, and isolation, the antioxidant activity of three extracts, one alkamide fraction, four polysaccharide-containing fractions, and three caffeic acid derivatives from Echinacea purpurea root was evaluated by measuring their inhibition of in vitro Cu(II)-catalyzed oxidation of human low-density lipoprotein (LDL). The antioxidant activities of the isolated caffeic acid derivatives were compared to those of echinacoside, caffeic acid, and rosmarinic acid for reference. The order of antioxidant activity of the tested substances was cichoric acid > echinacoside > or = derivative II > or = caffeic acid > or = rosmarinic acid > derivative I. Among the extracts the 80% aqueous ethanolic extract exhibited a 10 times longer lag phase prolongation (LPP) than the 50% ethanolic extract, which in turn exhibited a longer LPP than the water extract. Following ion-exchange chromatography of the water extract, the majority of its antioxidant activity was found in the latest eluted fraction (H2O-acidic 3). The antioxidant activity of the tested Echinacea extracts, fractions, and isolated compounds was dose dependent. Synergistic antioxidant effects of Echinacea constituents were found when cichoric acid (major caffeic acid derivative in E. purpurea) or echinacoside (major caffeic acid derivative in Echinacea pallida and Echinacea angustifolia) were combined with a natural mixture of alkamides and/or a water extract containing the high molecular weight compounds. This contributes to the hypothesis that the physiologically beneficial effects of Echinacea are exerted by the multitude of constituents present in the preparations.

  2. Effect of three edible oils on the intestinal absorption of caffeic acid: An in vivo and in vitro study

    Science.gov (United States)

    Prasadani, W. Chaturi; Senanayake, Chaturi M.; Jayathilaka, Nimanthi; Ekanayake, Sagarika

    2017-01-01

    Polyphenolic antioxidants are mainly absorbed through passive paracellular permeation regulated by tight junctions. Some fatty acids are known to modulate tight junctions. Fatty acids resulting from the digestion of edible oils may improve the absorption of polyphenolic antioxidants. Therefore, we explored the effect of three edible oils on the intestinal absorption of caffeic acid. Rats were fed with soybean oil and caffeic acid dissolved in distilled water. Caffeic acid contents in the plasma collected up to 1 hr were quantified. The experiment was repeated with coconut oil and olive oil. Component fatty acids of the oils were individually tested in vitro for their effect on permeability of caffeic acid using Caco-2 cell monolayers. Highest absorption of caffeic acid was observed in animals fed with coconut oil. In vitro transport percentages of caffeic acid in 2.5 mmol/L solutions of fatty acids were 22.01±0.12 (lauric), 15.30 ± 0.25 (myristic acid), 13.59 ± 0.35 (linoleic acid), 3.70 ± 0.09 (oleic acid) and 0.10–2.0 (all other fatty acids). Lauric acid and myristic acid are the two major fatty acids present in coconut oil. Therefore, these fatty acids may contribute to the higher absorption of caffeic acid in the presence of coconut oil. PMID:28617858

  3. Degradation of caffeic acid in subcritical water and online HPLC-DPPH assay of degradation products.

    Science.gov (United States)

    Khuwijitjaru, Pramote; Suaylam, Boonyanuch; Adachi, Shuji

    2014-02-26

    Caffeic acid was subjected to degradation under subcritical water conditions within 160-240 °C and at a constant pressure of 5 MPa in a continuous tubular reactor. Caffeic acid degraded quickly at these temperatures; the main products identified by liquid chromatography-diode array detection/mass spectrometry were hydroxytyrosol, protocatechuic aldehyde, and 4-vinylcatechol. The reaction rates for the degradation of caffeic acid and the formation of products were evaluated. Online high-performance liquid chromatography/2,2-diphenyl-1-picryhydrazyl assay was used to determine the antioxidant activity of each product in the solution. It was found that the overall antioxidant activity of the treated solution did not change during the degradation process. This study showed a potential of formation of antioxidants from natural phenolic compounds under these subcritical water conditions, and this may lead to a discovering of novel antioxidants compounds during the extraction by this technique.

  4. [Induction of adventitious roots of Echinacea pallida and accumulation of caffeic acid derivatives].

    Science.gov (United States)

    Wu, Chun-Hua; Huang, Tao; Cui, Xi-Hua; Paek, Keeyoeup

    2012-12-01

    To investigate the effect of auxins 2,4-D,IAA,IBA,NAA on induction of adventitious roots as well as that of IBA concentrations on the growth of adventitious roots and the accumulation of caffeic acid derivatives, with test-tube seedling leaves Echinacea pallida as the explant, and cultivate adventitious roots in bioreactors. 1.0 mg x L(-1) IBA was found the best for the induction of adventitious roots, with the numer of induced adventitious roots up to 22. 5 in each culture dish. Among different concentrations for suspension cultivation of IBA tested, 1.0 mg x L(-1) IBA was found the most suitable for the growth of adventitious roots and the accumulation of caffeic acid derivatives. In a 5 L balloon type bubble bioreactor, 8.98 g x L(-1) dry weight was achieved after one month, which was 2.05 times of 4.38 g x L(-1) dry weight cultivated in a triangular flask. The content of echinacoside cultivated in a bioreactor was 14.08 mg x g(-1) DW, which was 2.4 times of cultivated roots. The contents of chlorogenic acid, chicoric acid and total caffeic acid derivatives were 4.0-25.6 times of ultivated roots. The study can provide high-quality biomedical drugs containing such caffeic acid derivatives as echinacoside for mass production of Echinacea purpurea medicines.

  5. Efficacy of various naturally occurring caffeic acid derivatives in preventing post-harvest protein losses in forages.

    Science.gov (United States)

    Sullivan, Michael L; Zeller, Wayne E

    2013-01-01

    In red clover, oxidation of endogenous o-diphenols by polyphenol oxidase (PPO) inhibits post-harvest proteolyis. This system is transferable to alfalfa by providing PPO (via a transgene) and o-diphenol PPO substrates (via exogenous application). To exploit the PPO system for protein protection, it would be advantageous to produce PPO substrates in alfalfa, which lacks them. We assessed the extent of PPO-mediated proteolytic inhibition by phenolic compounds, especially those whose biosynthesis could be engineered into alfalfa. Tested compounds included o-diphenols (caffeic acid, phaselic acid, chlorogenic acid, clovamide) and monophenols (p-coumaric acid, p-coumaroyl-malic acid). In the presence of PPO, 2 mmol o-diphenol g⁻¹ protein reduced 24 h proteolysis 68-87% (P < 0.001) and as little as 0.25 mmol g⁻¹ protein still decreased 24 h proteolysis 43-60% (P < 0.001). At high concentrations, clovamide inhibited 24 h proteolysis 50% (P < 0.001) in the absence of PPO, likely due to non-PPO oxidation. Monophenol p-coumaric acid did not inhibit 24 h proteolyis, although high levels of its malate ester did exhibit PPO- and oxygen-independent inhibition (37%, P < 0.001). For PPO-mediated proteolytic inhibition, pathways for both phaselic acid and chlorogenic acid may be good targets for engineering into alfalfa. Clovamide may be useful for inhibiting proteolysis without PPO. Published 2012 by John Wiley & Sons, Ltd.

  6. Caffeic acid phenethyl ester induces adrenoleukodystrophy (Abcd2) gene in human X-ALD fibroblasts and inhibits the proinflammatory response in Abcd1/2 silenced mouse primary astrocytes.

    Science.gov (United States)

    Singh, Jaspreet; Khan, Mushfiquddin; Singh, Inderjit

    2013-04-01

    X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene. Accumulation of very long chain fatty acids (VLCFA) that have been attributed to reduced peroxisomal VLCFA β-oxidation activity are the hallmark of the disease. Overexpression of ABCD2 gene, the closest homolog of ABCD1, has been shown to compensate for ABCD1, thus correcting the VLCFA derangement. The accumulation of VLCFA leads to a neuroinflammatory disease process associated with demyelination of the cerebral white matter. The present study underlines the importance of caffeic acid phenethyl ester (CAPE) in inducing the expression of ABCD2 (ALDRP), and normalizing the peroxisomal β-oxidation as well as the levels of saturated and monounsaturated VLCFAs in cultured human skin fibroblasts of X-ALD patients. The expression of ELOVL1, the single elongase catalyzing the synthesis of both saturated VLCFA (C26:0) and mono-unsaturated VLCFA (C26:1), was also reduced by CAPE treatment. Importantly, CAPE upregulated Abcd2 expression and peroxisomal β-oxidation and lowered the VLCFA levels in Abcd1-deficient U87 astrocytes and B12 oligodendrocytes. In addition, using Abcd1/Abcd2-silenced mouse primary astrocytes we examined the effects of CAPE in VLCFA-induced inflammatory response. CAPE treatment decreased the inflammatory response as the expression of inducible nitric oxide synthase, inflammatory cytokine, and activation of NF-κB in Abcd1/Abcd2-silenced mouse primary astrocytes was reduced. The observations indicate that CAPE corrects both the metabolic disease of VLCFA as well as secondary inflammatory disease; therefore, it may be a potential drug candidate to be tested for X-ALD therapy in humans. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Caffeic Acid Phenethyl Ester Induces Adrenoleukodystrophy (Abcd2) Gene in Human X-ALD Fibroblasts and Inhibits the Proinflammatory Response in Abcd1/2 Silenced Mouse Primary Astrocytes

    Science.gov (United States)

    Singh, Jaspreet; Khan, Mushfiquddin; Singh, Inderjit

    2013-01-01

    X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene. Accumulation of very long chain fatty acids (VLCFA) that have been attributed to reduced peroxisomal VLCFA β-oxidation activity are the hallmark of the disease. Overexpression of ABCD2 gene, the closest homolog of ABCD1, has been shown to compensate for ABCD1, thus correcting the VLCFA derrangement. The accumulation of VLCFA leads to a neuroinflammatory disease process associated with demyelination of the cerebral white matter. The present study underlines the importance of caffeic acid phenethyl ester (CAPE) in inducing the expression of ABCD2 (ALDRP), and normalizing the peroxisomal β-oxidation as well as the levels of saturated and monounsaturated VLCFAs in cultured human skin fibroblasts of X-ALD patients. The expression of ELOVL1, the single elongase catalyzing the synthesis of both saturated VLCFA (C26:0) and mono-unsaturated VLCFA (C26:1), was also reduced by CAPE treatment. Importantly, CAPE upregulated Abcd2 expression and peroxisomal β-oxidation and lowered the VLCFA levels in Abcd1-deficient U87 astrocytes and B12 oligodendrocytes. In addition, using Abcd1/Abcd2-silenced mouse primary astrocytes we examined the effects of CAPE in VLCFA-induced inflammatory response. CAPE treatment decreased the inflammatory response as the expression of inducible nitric oxide synthase, inflammatory cytokine, and activation of NF-κB in Abcd1/Abcd2-silenced mouse primary astrocytes was reduced. The observations indicate that CAPE corrects both the metabolic disease of VLCFA as well as secondary inflammatory disease; therefore, it may be a potential drug candidate to be tested for X-ALD therapy in humans. PMID:23318275

  8. Determination of caffeic acid in root and rhizome of Black cohosh (Cimicifuga racemosa (L. Nutt.

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    Zapala Karolina

    2014-06-01

    Full Text Available Cimicifuga racemosa, is a plant with a diverse and long history of medicinal use. Caffeic acid, bioactive compound, which often occurs with other polyphenols can influence the biological activity of this plant. The aim of our work was quantitative analysis of caffeic acid in roots and rhizomes of two varieties of C. racemosa. Analysis was performed by HPLC method. The extracts were separated on C18 reversed-phase column using mixture of methanol, water and formic acid (25:75:0.5 v/v/v as a mobile phase. The flow rate of eluent was 1.0 ml·min-1. The obtained validation parameters such as linearity, linear regression equation and precision expressed as a relative standard deviation were adequate for quantitative determination. Caffeic acid was found in all tested extracts. The highest total amount of caffeic acid was determined in C. racemosa var. racemosa (255.3 μg·g-1 while its concentration in C. racemosa var. cordifolia was significantly lower (213.0 μg·g-1.

  9. Mechanism and kinetics in reactions of caffeic acid with radicals by pulse radiolysis and calculation

    International Nuclear Information System (INIS)

    Li, Xifeng; Cai, Zhongli; Katsumura, Yosuke

    2000-01-01

    The interaction of caffeic acid with e aq - , (CH 3 ) 2 (OH) CCH 2 · , CO 2 ·- , H · , ·OH and N 3 · radicals were studied by γ-, pulse radiolysis and molecular orbital calculation. UV-visible spectra of electron/·OH adducts, semi-quinone radicals of caffeic ions, and the stable products from the reactions were derived. The rate constants were determined. The attacked sites and the most favorable structures of the transient radicals were predicted. Reaction mechanisms were proposed. (author)

  10. HIGH PERFORMANCE THIN LAYER CHROMATOGRAPHIC DETERMINATION OF CAFFEIC ACID AND ROSMARINIC ACID FROM THE LEAVES OF Orthosiphon stamineus

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    M. Amzad Hossain

    2010-06-01

    Full Text Available This paper presents the studies performed on extraction of Orthosiphon stamineus, Benth by using different solvent for the identification and quantification of the caffeic acid derivatives such as caffeic acid  and rosmarinic acid which confers to the leaves of this plant with remarkable pharmaceutical properties. High performance thin-layer chromatographic (HPTLC allows the identification and the quantification of more than 20 samples in the same chromatographic run. The analysis of the samples requires 15-30 min compared with more than 2 h using a typical HPLC method. Using the techniques of the HPTLC and the UV-VIS spectra we have found that the extraction of this herb plant contain, the caffeic acid and rosmarinic acid ranging between 0.029% up to 0.506% and up to 0.24% to 2.24% respectively.     Keywords: Caffice acid derivatives, quantification, Malaysian Orthosiphon stamineus, HPTLC

  11. Chitosan-caffeic acid-genipin films presenting enhanced antioxidant activity and stability in acidic media.

    Science.gov (United States)

    Nunes, Cláudia; Maricato, Élia; Cunha, Ângela; Nunes, Alexandra; da Silva, José A Lopes; Coimbra, Manuel A

    2013-01-02

    The use of chitosan films has been limited due to their high degradability in aqueous acidic media. In order to produce chitosan films with high antioxidant activity and insoluble in acid solutions caffeic acid was grafted to chitosan by a radical mechanism using ammonium cerium (IV) nitrate (60 mM). Genipin was used as cross-linker. This methodology originated films with 80% higher antioxidant activity than the pristine film. Also, these films only lost 11% of their mass upon seven days immersion into an aqueous solution at pH 3.5 under stirring. The films surface wettability (contact angle 105°), mechanical properties (68 MPa of tensile strength and 4% of elongation at break), and thermal stability for temperatures lower than 300 °C were not significantly influenced by the covalent linkage of caffeic acid and genipin to chitosan. Due to their characteristics, mainly higher antioxidant activity and lower solubility, these are promising materials to be used as active films. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Reduction of the DNA damages, Hepatoprotective Effect and Antioxidant Potential of the Coconut Water, ascorbic and Caffeic Acids in Oxidative Stress Mediated by Ethanol

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    VANDERSON S. BISPO

    Full Text Available ABSTRACT Hepatic disorders such as steatosis and alcoholic steatohepatitis are common diseases that affect thousands of people around the globe. This study aims to identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to evaluate some oxidative stress parameters and the hepatoprotective action of green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of rats treated with ethanol. The results showed five polyphenols in the lyophilized coconut water spiked with standards: chlorogenic acid (0.18 µM, caffeic acid (1.1 µM, methyl caffeate (0.03 µM, quercetin (0.08 µM and ferulic acid (0.02 µM isomers. In the animals, the activity of the serum γ-glutamyltranspeptidase (γ-GT was reduced to 1.8 I.U/L in the coconut water group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid groups, when compared with the ethanol group (5.1 I.U/L, p<0.05. Still in liver, the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol group of 36.2% and 48.0% for pretreated and post treated coconut water group respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid reactive substances (TBARS in the liver by 16.5% in comparison with the ethanol group. These data indicate that the green dwarf coconut water, caffeic and ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage properties, thus decreasing the oxidative stress induced by ethanol metabolism.

  13. Biotechnological production of caffeic acid derivatives from cell and organ cultures of Echinacea species.

    Science.gov (United States)

    Murthy, Hosakatte Niranjana; Kim, Yun-Soo; Park, So-Young; Paek, Kee-Yoeup

    2014-09-01

    Caffeic acid derivatives (CADs) are a group of bioactive compounds which are produced in Echinacea species especially Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida. Echinacea is a popular herbal medicine used in the treatment of common cold and it is also a prominent dietary supplement used throughout the world. Caffeic acid, chlorogenic acid (5-O-caffeoylquinic acid), caftaric acid (2-O-caffeoyltartaric acid), cichoric acid (2, 3-O-dicaffeoyltartaric acid), cynarin, and echinacoside are some of the important CADs which have varied pharmacological activities. The concentrations of these bioactive compounds are species specific and also they vary considerably with the cultivated Echinacea species due to geographical location, stage of development, time of harvest, and growth conditions. Due to these reasons, plant cell and organ cultures have become attractive alternative for the production of biomass and caffeic acid derivatives. Adventitious and hairy roots have been induced in E. pupurea and E. angustifolia, and suspension cultures have been established from flask to bioreactor scale for the production of biomass and CADs. Tremendous progress has been made in this area; various bioprocess methods and strategies have been developed for constant high-quality productivity of biomass and secondary products. This review is aimed to discuss biotechnological methods and approaches employed for the sustainable production of CADs.

  14. Caffeic acid attenuates oxidative stress, learning and memory deficit in intra-cerebroventricular streptozotocin induced experimental dementia in rats.

    Science.gov (United States)

    Deshmukh, Rahul; Kaundal, Madhu; Bansal, Vikas; Samardeep

    2016-07-01

    Oxidative stress has been implicated in cognitive decline as seen during normal aging and in sporadic Alzheimer's disease (AD). Caffeic acid, a polyphenolic compound, has been reported to possess potent antioxidant and neuroprotective properties. The role of caffeic acid in experimental dementia is not fully understood. Thus the present study was designed to investigate the therapeutic potential of caffeic acid in streptozotocin (STZ)-induced experimental dementia of Alzheimer's type in rats. Streptozotocin (STZ) was administered intracerebroventrically (ICV) on day 1 and 3 (3mg/kg, ICV bilaterally) in Wistar rats. Caffeic acid was administered (10, 20 and 40mg/kg/day p.o.) 1h following STZ infusion upto 21st day. Morris water maze and object recognition task were used to assess learning and memory in rats. Terminally, acetylcholinesterase (AChE) activity and the levels of oxido-nitrosative stress markers were determined in cortical and hippocampal brain regions of rats. STZ produced significant (plearning and memory impairment, oxido-nitrosative stress and cholinergic deficit in rats. Whereas, caffeic acid treatment significantly (p<0.001) and dose dependently attenuated STZ induced behavioral and biochemical abnormalities in rats. The observed cognitive improvement following caffeic acid in STZ treated rats may be due to its antioxidant activity and restoration of cholinergic functions. Our results suggest the therapeutic potential of caffeic acid in cognitive disorders such as AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. A Comparative Study of the Radical-scavenging Activity of the Phenolcarboxylic Acids Caffeic Acid, p-Coumaric Acid, Chlorogenic Acid and Ferulic Acid, With or Without 2-Mercaptoethanol, a Thiol, Using the Induction Period Method

    Directory of Open Access Journals (Sweden)

    Seiichiro Fujisawa

    2008-10-01

    Full Text Available Phenolcarboxylic acid antioxidants do not act in vivo as radical-scavengers in isolation, but rather together with GSH (glutathione, a coantioxidant, they constitute an intricate antioxidant network. Caffeic acid, p-coumaric acid, ferulic acid and chlorogenic acid with or without 2-mercaptoethanol (ME, as a substitute for GSH, was investigated by the induction period (IP method for polymerization of methyl methacrylate (MMA initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN, a source of alkyl radicals, R. and benzoyl peroxide (BPO, a source of peroxy radicals, PhCOO. using differential scanning calorimetry (DSC. Upon PhCOO. radical scavenging, the stoichiometric factors (n, number of free radical trapped by one mole of antioxidant for caffeic acid, ferulic acid, p-coumaric acid and chlorogenic acid were 2.4, 1.8, 1.7 and 0.9, whereas upon R. radical scavenging, the corresponding values were 1.3, 1.2, 1.0 and 0.8, respectively. Antioxidants with n values close to 2 suggest the stepwise formation of semiquinone radicals and quinones. By contrast, those with n values close to 1 suggest the formation of dimers after single-electron oxidation, possibly due to recombination of corresponding aryloxy radicals. The ratio of the rate constant of inhibition to that of propagation (kinh/kp declined in the order chlorogenic acid > p-coumaric acid > ferulic acid > caffeic acid. The ratio of the observed IP for the phenolcarboxylic acid/2-mercapto-ethanol (ME mixture (1:1 molar ratio (A to the calculated IP (the simple sum of phenol acid antioxidant and ME (B was investigated. Upon R. scavenging, the caffeic acid or p-coumaric acid/ME mixture was A/B > 1, particularly the former was 1.2, suggesting a synergic effect. By contrast, upon PhCOO. scavenging, the corresponding mixture was A/B < 1, particularly the latter was 0.7, suggesting an antagonistic effect. Upon both radicals scavenging, the A/B for the ferulic acid or chlorogenic acid

  16. Comparative study on the inhibitory effect of caffeic and chlorogenic acids on key enzymes linked to Alzheimer's disease and some pro-oxidant induced oxidative stress in rats' brain-in vitro.

    Science.gov (United States)

    Oboh, Ganiyu; Agunloye, Odunayo M; Akinyemi, Ayodele J; Ademiluyi, Adedayo O; Adefegha, Stephen A

    2013-02-01

    This study sought to investigate and compare the interaction of caffeic acid and chlorogenic acid on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and some pro-oxidants (FeSO(4), sodium nitroprusside and quinolinic acid) induced oxidative stress in rat brain in vitro. The result revealed that caffeic acid and chlorogenic acid inhibited AChE and BChE activities in dose-dependent manner; however, caffeic acid had a higher inhibitory effect on AChE and BChE activities than chlorogenic acid. Combination of the phenolic acids inhibited AChE and BChE activities antagonistically. Furthermore, pro-oxidants such as, FeSO(4), sodium nitroprusside and quinolinic acid caused increase in the malondialdehyde (MDA) contents of the brain which was significantly decreased dose-dependently by the phenolic acids. Inhibition of AChE and BChE activities slows down acetylcholine and butyrylcholine breakdown in the brain. Therefore, one possible mechanism through which the phenolic acids exert their neuroprotective properties is by inhibiting AChE and BChE activities as well as preventing oxidative stress-induced neurodegeneration. However, esterification of caffeic acid with quinic acid producing chlorogenic acid affects these neuroprotective properties.

  17. Caffeic Acid Phenethyl Ester Regulates PPAR’s Levels in Stem Cells-Derived Adipocytes

    Directory of Open Access Journals (Sweden)

    Luca Vanella

    2016-01-01

    Full Text Available Hypertrophic obesity inhibits activation of peroxisome proliferators-activated receptor gamma (PPARγ, considered the key mediator of the fully differentiated and insulin sensitive adipocyte phenotype. We examined the effects of Caffeic Acid Phenethyl Ester (Cape, isolated from propolis, a honeybee hive product, on Adipose Stem Cells (ASCs differentiation to the adipocyte lineage. Finally we tested the effects of Cape on insulin-resistant adipocytes. Quantification of Oil Red O-stained cells showed that lipid droplets decreased following Cape treatment as well as radical oxygen species formation. Additionally, exposure of ASC to high glucose levels decreased adiponectin and increased proinflammatory cytokines mRNA levels, which were reversed by Cape-mediated increase of insulin sensitivity. Cape treatment resulted in decreased triglycerides synthesis and increased beta-oxidation. Exposure of ASCs to Lipopolysaccharide (LPS induced a reduction of PPARγ, an increase of IL-6 levels associated with a well-known stimulation of lipolysis; Cape partially attenuated the LPS-mediated effects. These observations reveal the main role of PPARγ in the adipocyte function and during ASC differentiation. As there is now substantial interest in functional food and nutraceutical products, the observed therapeutic value of Cape in insulin-resistance related diseases should be taken into consideration.

  18. Caffeic acid phenethyl ester (CAPE): scavenger of peroxynitrite in vitro and in sepsis models.

    Science.gov (United States)

    Kassim, Mustafa; Mansor, Marzida; Kamalden, Tengku Ain; Shariffuddin, Ina Ismiarti; Hasan, Mohd Shahnaz; Ong, Gracie; Sekaran, Shamala Devi; Suhaimi, Anwar; Al-Abd, Nazeh; Yusoff, Kamaruddin Mohd

    2014-08-01

    Excessive free radical production by immune cells has been linked to cell death and tissue injury during sepsis. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death that has been identified in several pathological conditions. Caffeic acid phenethyl ester (CAPE) is an active component of honeybee products and exhibits antioxidant, anti-inflammatory, and immunomodulatory activities. The present study examined the ability of CAPE to scavenge peroxynitrite in RAW 264.7 murine macrophages stimulated with lipopolysaccharide/interferon-γ that was used as an in vitro model. Conversion of 123-dihydrorhodamine to its oxidation product 123-rhodamine was used to measure peroxynitrite production. Two mouse models of sepsis (endotoxemia and cecal ligation and puncture) were used as in vivo models. The level of serum 3-nitrotyrosine was used as an in vivo marker of peroxynitrite. The results demonstrated that CAPE significantly improved the viability of lipopolysaccharide/interferon-γ-treated RAW 264.7 cells and significantly inhibited nitric oxide production, with effects similar to those observed with an inhibitor of inducible nitric oxide synthase (1400W). In addition, CAPE exclusively inhibited the synthesis of peroxynitrite from the artificial substrate SIN-1 and directly prevented the peroxynitrite-mediated conversion of dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In both sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as evidenced by the absence of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite. Thus, CAPE attenuates the inflammatory responses that lead to cell damage and, potentially, cell death through suppression of the production of cytotoxic molecules such as nitric oxide and peroxynitrite. These observations provide evidence of the therapeutic potential of CAPE treatment for a wide range of inflammatory disorders.

  19. Possible molecular targets for therapeutic applications of caffeic acid phenethyl ester in inflammation and cancer

    Directory of Open Access Journals (Sweden)

    Ghulam Murtaza

    2015-03-01

    Full Text Available Of the various derivatives of caffeic acid, caffeic acid phenethyl ester (CAPE is a hydrophobic, bioactive polyphenolic ester obtained from propolis extract. The objective in writing this review article was to summarize all published studies on therapeutics of CAPE in inflammation and cancer to extract direction for future research. The possible molecular targets for the action of CAPE, include various transcription factors such as nuclear factor-κB, tissue necrosis factor-α, interleukin-6, cyclooxygenase-2, Nrf2, inducible nitric oxide synthase, nuclear factor of activated T cells, hypoxia-inducible factor-1α, and signal transducers and activators of transcription. Based on the valuable data on its therapeutics in inflammation and cancer, clinical studies of CAPE should also be conducted to explore its toxicities, if any.

  20. Antioxidative effect of lipophilized caffeic acid in fish oil enriched mayonnaise and milk

    DEFF Research Database (Denmark)

    Alemán, Mercedes; Bou, Ricard; Guardiola, Francesc

    2015-01-01

    The antioxidative effect of lipophilized caffeic acid was assessed in two different fish oil enriched food products: mayonnaise and milk. In both emulsion systems, caffeic acid esterified with fatty alcohols of different chain lengths (C1–C20) were better antioxidants than the original phenolic...... compound. The optimal chain length with respect to protection against oxidation was, however, different for the two food systems. Fish oil enriched mayonnaise with caffeates of medium alkyl chain length (butyl, octyl and dodecyl) added resulted in a better oxidative stability than caffeates with shorter...... (methyl) or longer (octadecyl) alkyl chains. Whereas in fish oil enriched milk emulsions the most effective caffeates were those with shorter alkyl chains (methyl and butyl) rather than the ones with medium and long chains (octyl, dodecyl, hexadecyl and eicosyl). These results demonstrate that there might...

  1. Caffeic acid product from the highly copper-tolerant plant Elsholtzia splendens post-phytoremediation: its extraction, purification, and identification*

    Science.gov (United States)

    Xing, Yan; Peng, Hong-yun; Zhang, Meng-xi; Li, Xia; Zeng, Wei-wei; Yang, Xiao-e

    2012-01-01

    In the current study, caffeic acid was an important metabolite in the highly copper-tolerant plant Elsholtzia splendens. Preparation and purification of caffeic acid were performed on the dried biomass of the plants by means of sonication/ethanol extraction, followed by purification using a macroporous resin (D101 type) column and silica gel chromatography. The faint-yellow caffeic acid product was yielded with a purity of 98.46%, and it was chemically identified from spectra of Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR)/carbon nuclear magnetic resonance (13C NMR), and electrospray ionization mass spectrometry (ESI-MS). Caffeic acid is a possible product from the post-harvest processing of Elsholtzia splendens biomass. PMID:22661211

  2. Caffeic acid product from the highly copper-tolerant plant Elsholtzia splendens post-phytoremediation: its extraction, purification, and identification.

    Science.gov (United States)

    Xing, Yan; Peng, Hong-yun; Zhang, Meng-xi; Li, Xia; Zeng, Wei-wei; Yang, Xiao-e

    2012-06-01

    In the current study, caffeic acid was an important metabolite in the highly copper-tolerant plant Elsholtzia splendens. Preparation and purification of caffeic acid were performed on the dried biomass of the plants by means of sonication/ethanol extraction, followed by purification using a macroporous resin (D101 type) column and silica gel chromatography. The faint-yellow caffeic acid product was yielded with a purity of 98.46%, and it was chemically identified from spectra of Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance ((1)H NMR)/carbon nuclear magnetic resonance ((13)C NMR), and electrospray ionization mass spectrometry (ESI-MS). Caffeic acid is a possible product from the post-harvest processing of Elsholtzia splendens biomass.

  3. Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice.

    Science.gov (United States)

    Bocco, B M; Fernandes, G W; Lorena, F B; Cysneiros, R M; Christoffolete, M A; Grecco, S S; Lancellotti, C L; Romoff, P; Lago, J H G; Bianco, A C; Ribeiro, M O

    2016-03-01

    Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

  4. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation--A Chemical Approach.

    Directory of Open Access Journals (Sweden)

    Thiago C Genaro-Mattos

    Full Text Available Caffeic acid (CA is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here--in association with its reported signaling effects--could be an explanation to its

  5. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation—A Chemical Approach

    Science.gov (United States)

    Genaro-Mattos, Thiago C.; Maurício, Ângelo Q.; Rettori, Daniel; Alonso, Antonio; Hermes-Lima, Marcelo

    2015-01-01

    Caffeic acid (CA) is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR) oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here—in association with its reported signaling effects—could be an explanation to its beneficial effects

  6. Mechanism and kinetics in reactions of caffeic acid with radicals by pulse radiolysis and calculation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xifeng; Cai, Zhongli; Katsumura, Yosuke [Tokyo Univ., Tokai, Ibaraki (Japan). Nuclear Engineering Research Lab

    2000-03-01

    The interaction of caffeic acid with e{sub aq}{sup -}, (CH{sub 3}){sub 2}(OH) CCH{sub 2}{sup {center_dot}}, CO{sub 2}{sup {center_dot}}{sup -}, H{sup {center_dot}}, {center_dot}OH and N{sub 3}{sup {center_dot}} radicals were studied by {gamma}-, pulse radiolysis and molecular orbital calculation. UV-visible spectra of electron/{center_dot}OH adducts, semi-quinone radicals of caffeic ions, and the stable products from the reactions were derived. The rate constants were determined. The attacked sites and the most favorable structures of the transient radicals were predicted. Reaction mechanisms were proposed. (author)

  7. Effects of roasting temperatures and gamma irradiation on the content of chlorogenic acid, caffeic acid and soluble carbohydrates of coffee

    International Nuclear Information System (INIS)

    Deshpande, S.N.; Aguilar, A.A.

    1975-01-01

    Two varieties of Puerto Rican coffee, Coffea canephora L. var. Robusta, and Coffea arabica L. var. Borbon, were subjected to four different doses of radiation and roasted at two different temperatures. Aqueous extracts of the ground coffee beans were analyzed for chlorogenic acid and caffeic acid at 324 nm and 360 nm wavelength settings, respectively. Samples subjected to the roasting treatments in conjuction with irradiation treatments were treated with basic lead acetate prior to the colorimetric analyses in order to eliminate interfering substances. The total carbohydrate content was also determined by colorimetric techniques with anthrone reagent. The total nitrogen content of the pulverized samples were determined by the micro-Kjeldahl method. While roasting treatments caused a reduction in the concentrations of the chlorogenic acid, caffeic acid, and the carbohydrates, the radiation treatments increased the concentrations of soluble carbohydrates without affecting the concentrations of chlorogenic acid or caffeic acid. It therefore appears that radiation treatments seem to cause degradation of the acid-polysaccharide complexes liberating soluble sugars. There were no noticable changes in the total content of nitrogen caused by roasting or the radiation treatments as indicated by the statistical analysis employing the split plot design. (author)

  8. The effects of gallic/ferulic/caffeic acids on colour intensification and anthocyanin stability.

    Science.gov (United States)

    Qian, Bing-Jun; Liu, Jian-Hua; Zhao, Shu-Juan; Cai, Jian-Xiong; Jing, Pu

    2017-08-01

    The mechanism by which copigments stabilize colour, by protecting anthocyanin chromophores from nucleophilic attack, seems well accepted. This study was to determine effects of gallic/ferulic/caffeic acids on colour intensification and anthocyanin stability. Molecular dynamics simulations were applied to explore molecular interactions. Phenolic acids intensified the colour by 19%∼27%. Colour fading during heating followed first-order reactions with half-lives of 3.66, 9.64, 3.50, and 3.39h, whereas anthocyanin degradation, determined by the pH differential method (or HPLC-PDA), followed second-order reactions with half-lives of 3.29 (3.40), 3.43 (3.39), 2.29 (0.39), and 2.72 (0.32)h alone or with gallic/ferulic/caffeic acids, respectively, suggesting that anthocyanin degradation was faster than the colour fading. The strongest protection of gallic acids might be attributed to the shortest distance (4.37Å) of its aromatic ring to the anthocyanin (AC) panel. Hyperchromic effects induced by phenolic acids were pronounced and they obscured the accelerated anthocyanin degradation due to self-association interruption. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Effects of propolis, caffeic acid phenethyl ester, and pollen on renal injury in hypertensive rat: An experimental and theoretical approach.

    Science.gov (United States)

    Salmas, Ramin Ekhteiari; Gulhan, Mehmet Fuat; Durdagi, Serdar; Sahna, Engin; Abdullah, Huda I; Selamoglu, Zeliha

    2017-08-01

    The objective of this study was to evaluate the antioxidant effects of propolis, caffeic acid phenethyl ester (CAPE; active compound in propolis), and pollen on biochemical oxidative stress biomarkers in rat kidney tissue inhibited by N ω -nitro-L-arginine methyl ester (L-NAME). The biomarkers evaluated were paraoxonase (PON1), oxidative stress index (OSI), total antioxidant status (TAS), total oxidant status (TOS), asymmetric dimethylarginine (ADMA), and nuclear factor kappa B (NF-κB). TAS levels and PON1 activity were significantly decreased in kidney tissue samples in the L-NAME-treated group (P propolis, CAPE, and pollen groups compared with the L-NAME-treated group. TOS, ADMA, and NF-κB levels were significantly increased in the kidney tissue samples of the L-NAME-treated group (P propolis, CAPE, and pollen groups (P propolis, CAPE administration. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Protective role of caffeic acid in an Aβ25-35-induced Alzheimer's disease model

    OpenAIRE

    Kim, Ji Hyun; Wang, Qian; Choi, Ji Myung; Lee, Sanghyun; Cho, Eun Ju

    2015-01-01

    BACKGROUND/OBJECTIVES Alzheimer's disease (AD) is characterized by deficits in memory and cognitive functions. The accumulation of amyloid beta peptide (Aβ) and oxidative stress in the brain are the most common causes of AD. MATERIALS/METHODS Caffeic acid (CA) is an active phenolic compound that has a variety of pharmacological actions. We studied the protective abilities of CA in an Aβ25-35-injected AD mouse model. CA was administered at an oral dose of 10 or 50 mg/kg/day for 2 weeks. Behavi...

  11. Comparative studies on the interaction of caffeic acid, chlorogenic acid and ferulic acid with bovine serum albumin

    Science.gov (United States)

    Li, Shuang; Huang, Kelong; Zhong, Ming; Guo, Jun; Wang, Wei-zheng; Zhu, Ronghua

    2010-10-01

    The substitution of the hydrogen on aromatic and esterification of carboxyl group of the phenol compounds plays an important role in their bio-activities. In this paper, caffeic acid (CaA), chlorogenic acid (ChA) and ferulic acid (FA) were selected to investigate the binding to bovine serum albumin (BSA) using UV absorption spectroscopy, fluorescence spectroscopy and synchronous fluorescence spectroscopy. It was found that the methoxyl group substituting for the 3-hydroxyl group of CaA decreased the affinity for BSA and the esterification of carboxyl group of CaA with quinic acid increased the affinities. The affinities of ChA and FA with BSA were more sensitive to the temperature than that of CaA with BSA. Synchronous fluorescence spectroscopy and time-resolved fluorescence indicated that the Stern-Volmer plots largely deviated from linearity at high concentrations and were caused by complete quenching of the tyrosine fluorescence of BSA.

  12. Polydopamine-coated magnetic molecularly imprinted polymer for the selective solid-phase extraction of cinnamic acid, ferulic acid and caffeic acid from radix scrophulariae sample.

    Science.gov (United States)

    Yin, Yuli; Yan, Liang; Zhang, Zhaohui; Wang, Jing; Luo, Ningjing

    2016-04-01

    We describe novel cinnamic acid polydopamine-coated magnetic imprinted polymers for the simultaneous selective extraction of cinnamic acid, ferulic acid and caffeic acid from radix scrophulariae sample. The novel magnetic imprinted polymers were synthesized by surface imprinting polymerization using magnetic multi-walled carbon nanotubes as the support material, cinnamic acid as the template and dopamine as the functional monomer. The magnetic imprinted polymers were characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy and vibrating sample magnetometry. The results revealed that the magnetic imprinted polymers had outstanding magnetic properties, high adsorption capacity, selectivity and fast kinetic binding toward cinnamic acid, ferulic acid and caffeic acid. Coupled with high-performance liquid chromatography, the extraction conditions of the magnetic imprinted polymers as a magnetic solid-phase extraction sorbent were investigated in detail. The proposed imprinted magnetic solid phase extraction procedure has been used for the purification and enrichment of cinnamic acid, ferulic acid and caffeic acid successfully from radix scrophulariae extraction sample with recoveries of 92.4-115.0% for cinnamic acid, 89.4-103.0% for ferulic acid and 86.6-96.0% for caffeic acid. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Chemical Properties of Caffeic and Ferulic Acids in Biological System: Implications in Cancer Therapy. A Review.

    Science.gov (United States)

    Damasceno, Sarah S; Dantas, Bruna B; Ribeiro-Filho, Jaime; Antônio M Araújo, Demetrius; Galberto M da Costa, José

    2017-01-01

    The antioxidant properties of caffeic and ferulic acids in biological systems have been extensively demonstrated. As antioxidants, these compounds prevent the production of reactive oxygen species (ROS), which cause cell lesions that are associated with the development of several diseases, including cancer. Recent findings suggest that the chemoprotective action of these phenolic acids occurs through the following mechanisms: regulation of gene expression, chelation and / or reduction of transition metals, formation of covalent adducts and direct toxicity. The biological efficacy of these promising chemoprotective agents is strongly related with their chemical structure. Therefore, in this study, we discuss the structural characteristics of ferulic and caffeic acids that are responsible for their biological activities, as well as the mechanisms of action involved with the anti-cancer activity. Several reports indicated that the antioxidant effect of these phenylpropanoids results from reactions with free radicals with formation of stable products in the cells. The chelating effect of these compounds was also reported as an important protective mechanism against oxidative. Finally, the lipophilicity of these agents facilitates their entry into the cells, and thus, contributes to the anticancer activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Synthesis and Antiradical/Antioxidant Activities of Caffeic Acid Phenethyl Ester and Its Related Propionic, Acetic, and Benzoic Acid Analoguesc

    Directory of Open Access Journals (Sweden)

    Mohamed Touaibia

    2012-12-01

    Full Text Available Caffeic acid phenethyl ester (CAPE is a bioactive component isolated from propolis. A series of CAPE analogues was synthesized and their antiradical/antioxidant effects analyzed. The effect of the presence of the double bond and of the conjugated system on the antioxidant effect is evaluated with the analogues obtained from 3-(3,4-dihydroxyphenyl propanoic acid. Those obtained from 2-(3,4-dihydroxyphenyl acetic acid and 3,4-dihydroxybenzoic acid allow the evaluation of the effect of the presence of two carbons between the carbonyl and aromatic system.

  15. Synthesis and antiradical/antioxidant activities of caffeic acid phenethyl ester and its related propionic, acetic, and benzoic acid analogues.

    Science.gov (United States)

    LeBlanc, Luc M; Paré, Aurélie F; Jean-François, Jacques; Hébert, Martin J G; Surette, Marc E; Touaibia, Mohamed

    2012-12-10

    Caffeic acid phenethyl ester (CAPE) is a bioactive component isolated from propolis. A series of CAPE analogues was synthesized and their antiradical/antioxidant effects analyzed. The effect of the presence of the double bond and of the conjugated system on the antioxidant effect is evaluated with the analogues obtained from 3-(3,4-dihydroxyphenyl) propanoic acid. Those obtained from 2-(3,4-dihydroxyphenyl) acetic acid and 3,4-dihydroxybenzoic acid allow the evaluation of the effect of the presence of two carbons between the carbonyl and aromatic system.

  16. Choline chloride-based deep eutectic solvents as additives for optimizing chromatographic behavior of caffeic acid

    International Nuclear Information System (INIS)

    Li, Guizhen; Zhu, Tao; Lei, Yingjie

    2015-01-01

    A series of deep eutectic solvents (DESs) were prepared using glycerol and choline chloride (ChCl), and Fourier transform infrared spectrometer (FT-IR) was used to analyze the spectra of glycerol, choline chloride and DESs based on glycerol and choline chloride. Then DESs were used as the additives of mobile phase to optimize chromatographic behavior of caffeic acid in high performance liquid chromatography (HPLC). A 17-run Box-Behnken design (BBD) was employed to evaluate effect of DESs as additives by analyzing the maximum theoretical plate number. Three factors, reaction temperature (60 .deg. C, 80 .deg. C, 100 .deg. C), molar ratio of glycerol and choline chloride (2 : 1, 3 : 1, 4 : 1, n/n), and volume percent of additives (0.05%, 0.10%, 0.15%, v/v), were investigated in BBD. The optimum experiment condition was that of reaction temperature (80 .deg. C), molar ratio of glycerol and ChCl (3 : 1, n/n), and volume percent of additive (0.10%, v/v). The mean chromatographic theoretical plate number of the caffeic acid this condition was 1567.5, and DESs as additives shorten the retention time and modify the chromatogram shape, proving DESs as additives for effective theoretical plate number and column efficiency in HPLC.

  17. Choline chloride-based deep eutectic solvents as additives for optimizing chromatographic behavior of caffeic acid

    Energy Technology Data Exchange (ETDEWEB)

    Li, Guizhen; Zhu, Tao; Lei, Yingjie [Tianjin University of Technology, Tianjin (China)

    2015-10-15

    A series of deep eutectic solvents (DESs) were prepared using glycerol and choline chloride (ChCl), and Fourier transform infrared spectrometer (FT-IR) was used to analyze the spectra of glycerol, choline chloride and DESs based on glycerol and choline chloride. Then DESs were used as the additives of mobile phase to optimize chromatographic behavior of caffeic acid in high performance liquid chromatography (HPLC). A 17-run Box-Behnken design (BBD) was employed to evaluate effect of DESs as additives by analyzing the maximum theoretical plate number. Three factors, reaction temperature (60 .deg. C, 80 .deg. C, 100 .deg. C), molar ratio of glycerol and choline chloride (2 : 1, 3 : 1, 4 : 1, n/n), and volume percent of additives (0.05%, 0.10%, 0.15%, v/v), were investigated in BBD. The optimum experiment condition was that of reaction temperature (80 .deg. C), molar ratio of glycerol and ChCl (3 : 1, n/n), and volume percent of additive (0.10%, v/v). The mean chromatographic theoretical plate number of the caffeic acid this condition was 1567.5, and DESs as additives shorten the retention time and modify the chromatogram shape, proving DESs as additives for effective theoretical plate number and column efficiency in HPLC.

  18. Caffeic Acid Reduces the Viability and Migration Rate of Oral Carcinoma Cells (SCC-25 Exposed to Low Concentrations of Ethanol

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    Arkadiusz Dziedzic

    2014-10-01

    Full Text Available Alcohol increases the risk of carcinoma originated from oral epithelium, but the biological effects of ultra-low doses of ethanol on existing carcinoma cells in combination with natural substances are still unclear. A role for ethanol (EtOH, taken in small amounts as an ingredient of some beverages or mouthwashes to change the growth behavior of established squamous cell carcinoma, has still not been examined sufficiently. We designed an in vitro study to determine the effect of caffeic acid (CFA on viability and migration ability of malignant oral epithelial keratinocytes, exposed to ultra-low concentrations (maximum 100 mmol/L EtOH. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-dimethyltetrazolium bromide and LDH (lactate dehydrogenase assays were used to assess the cytotoxic effect of EtOH/CFA and the viability of squamous carcinoma SCC-25 cells (ATCC CRL-1628, mobile part of the tongue. Tested EtOH concentrations were: 2.5, 5, 10, 25, 50, and 100 mmol/L, along with an equal CFA concentration of 50 μmol/L. Carcinoma cells’ migration was investigated by monolayer “wound” healing assay. We demonstrated that very low concentrations of EtOH ranging between 2.5 and 10 mmol/L may induce the viability of oral squamous cell carcinoma cells, while the results following addition of CFA reveal an antagonistic effect, attenuating pro-proliferative EtOH activity. The migration rate of oral squamous carcinoma cells can be significantly inhibited by the biological activity of caffeic acid.

  19. Thermal transformation of bioactive caffeic acid on fumed silica seen by UV-Vis spectroscopy, thermogravimetric analysis, temperature programmed desorption mass spectrometry and quantum chemical methods.

    Science.gov (United States)

    Kulik, Tetiana V; Lipkovska, Natalia O; Barvinchenko, Valentyna M; Palyanytsya, Borys B; Kazakova, Olga A; Dudik, Olesia O; Menyhárd, Alfréd; László, Krisztina

    2016-05-15

    Thermochemical studies of hydroxycinnamic acid derivatives and their surface complexes are important for the pharmaceutical industry, medicine and for the development of technologies of heterogeneous biomass pyrolysis. In this study, structural and thermal transformations of caffeic acid complexes on silica surfaces were studied by UV-Vis spectroscopy, thermogravimetric analysis, temperature programmed desorption mass spectrometry (TPD MS) and quantum chemical methods. Two types of caffeic acid surface complexes are found to form through phenolic or carboxyl groups. The kinetic parameters of the chemical reactions of caffeic acid on silica surface are calculated. The mechanisms of thermal transformations of the caffeic chemisorbed surface complexes are proposed. Thermal decomposition of caffeic acid complex chemisorbed through grafted ester group proceeds via three parallel reactions, producing ketene, vinyl and acetylene derivatives of 1,2-dihydroxybenzene. Immobilization of phenolic acids on the silica surface improves greatly their thermal stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Analysis of Caffeic Acid Extraction From Ocimum gratissimum Linn. by High Performance Liquid Chromatography and its Effects on a Cervical Cancer Cell Line

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    Je-Chiuan Ye

    2010-09-01

    Conclusion: This paper shows that high performance liquid chromatography is a suitable analytical method for determining caffeic acid levels in O. gratissimum, Ju ZenTa, and several vegetable oils. Caffeic acid can suppress the proliferation of HeLa cells.

  1. Caffeic Acid Phenethyl Ester Induces Adrenoleukodystrophy (Abcd2) Gene in Human X-ALD Fibroblasts and Inhibits the Proinflammatory Response in Abcd1/2 Silenced Mouse Primary Astrocytes

    OpenAIRE

    Singh, Jaspreet; Khan, Mushfiquddin; Singh, Inderjit

    2013-01-01

    X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene. Accumulation of very long chain fatty acids (VLCFA) that have been attributed to reduced peroxisomal VLCFA β-oxidation activity are the hallmark of the disease. Overexpression of ABCD2 gene, the closest homolog of ABCD1, has been shown to compensate for ABCD1, thus correcting the VLCFA derrangement. The accumulation of VLCFA leads to a neuroinflammatory disease process associated with demyel...

  2. Evaluation of Chemical Constituents and Antioxidant Activity of Coconut Water (Cocus nucifera L. and Caffeic Acid in Cell Culture

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    JOAO L.A. SANTOS

    2013-09-01

    Full Text Available Coconut water contains several uncharacterized substances and is widely used in the human consumption. In this paper we detected and quantified ascorbic acid and caffeic acid and total phenolics in several varieties of coconut using HPLS/MS/MS (25.8 ± 0.6 µg/mL and 1.078 ± 0.013 µg/mL and 99.7 µg/mL, respectively, in the green dwarf coconut water, or 10 mg and 539 µg and 39.8 mg for units of coconut consumed, 500 ± 50 mL. The antioxidant potential of four coconut varieties (green dwarf, yellow dwarf, red dwarf and yellow Malaysian was compared with two industrialized coconut waters and the lyophilized water of the green dwarf variety. All varieties were effective in scavenging the DPPH radical (IC50=73 µL and oxide nitric (0.1 mL with an IP of 29.9% as well as in inhibiting the in vitro production of thiobarbituric acid reactive substances (1 mL with an IP of 34.4%, highlighting the antioxidant properties of the green dwarf which it is the most common used. In cell culture, the green dwarf water was efficient in protecting against oxidative damages induced by hydrogen peroxide.

  3. Molecular cloning, characterization and expression of the caffeic acid O-methyltransferase (COMT) ortholog from kenaf (Hibiscus cannabinus)

    Science.gov (United States)

    We cloned the full-length of the gene putatively encoding caffeic acid O-methyltransferase (COMT) from kenaf (Hibiscus cannabinus L.) using degenerate primers and the RACE (rapid amplification of cDNA ends) method. Kenaf is an herbaceous and rapidly growing dicotyledonous plant with great potential ...

  4. Antihyperglycemic effect of a natural chicoric acid extract of chicory (Cichorium intybus L.): a comparative in vitro study with the effects of caffeic and ferulic acids.

    Science.gov (United States)

    Azay-Milhau, Jacqueline; Ferrare, Karine; Leroy, Jeremy; Aubaterre, Jordan; Tournier, Michel; Lajoix, Anne-Dominique; Tousch, Didier

    2013-11-25

    In Eurasia folk medicine, roots of chicory (Cichorium intybus L.) have been reported to exert antidiabetic benefits. In vitro, a natural chicoric acid extract (NCRAE) from Cichorium intybus root has been shown to increase insulin secretion by pancreatic β-cells and glucose uptake by muscle cells. In vitro experiments were designed to compare the effects of two hydroxycinnamic acids, caffeic and ferulic acids, to those obtained with NCRAE (50 and 100 µg.mL(-1)) on the three major tissues implicated in glycemic regulation (pancreas, muscle and liver). In vivo experiments were performed in Wistar rats submitted to a daily intraperitoneal injection of NCRAE (3, 15 or 30 mg kg(-1)) for 4 days. On the fourth day, an intraperitoneal glucose tolerance test (IPGTT; 1 g kg(-1)) was carried out. Our results show that the three compounds we used are able each to induce an original response. Caffeic acid mainly promotes a decrease in hepatic glycogenolysis. Ferulic acid elicits a clear increase of insulin release and a reduction of hepatic glycogenolysis. However, this compound induces an inhibition of muscle glucose uptake. NCRAE provokes an increase of insulin release and glucose uptake without any effect on hepatic glycogenolysis. We could also show that none of these compounds implicates hepatic glucose 6-phosphatase in contrast to chlorogenic acid, known as an inhibitor of glucose 6-phosphatase and which is able to decrease glucose output from hepatocytes. Our results point out that NCRAE is able to decrease blood glucose without any effect hepatic effect. Our in vivo experiments bring evidence that 4 daily IP administrations of NCRAE improve IP glucose tolerance in a dose-dependent manner and mainly via an insulin sensitizing effect. We conclude that NCRAE presents an antihyperglycemic effect essentially due to a peripheral effect on muscle glucose uptake. © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Evolution of novel O-methyltransferases from the Vanilla planifolia caffeic acid O-methyltransferase.

    Science.gov (United States)

    Li, Huaijun Michael; Rotter, David; Hartman, Thomas G; Pak, Fulya E; Havkin-Frenkel, Daphna; Belanger, Faith C

    2006-06-01

    The biosynthesis of many plant secondary compounds involves the methylation of one or more hydroxyl groups, catalyzed by O-methyltransferases (OMTs). Here, we report the characterization of two OMTs, Van OMT-2 and Van OMT-3, from the orchid Vanilla planifolia Andrews. These enzymes catalyze the methylation of a single outer hydroxyl group in substrates possessing a 1,2,3-trihydroxybenzene moiety, such as methyl gallate and myricetin. This is a substrate requirement not previously reported for any OMTs. Based on sequence analysis these enzymes are most similar to caffeic acid O-methyltransferases (COMTs), but they have negligible activity with typical COMT substrates. Seven of 12 conserved substrate-binding residues in COMTs are altered in Van OMT-2 and Van OMT-3. Phylogenetic analysis of the sequences suggests that Van OMT-2 and Van OMT-3 evolved from the V. planifolia COMT. These V. planifolia OMTs are new instances of COMT-like enzymes with novel substrate preferences.

  6. Antiviral properties of caffeic acid phenethyl ester and its potential application.

    Science.gov (United States)

    Erdemli, Hacı Kemal; Akyol, Sumeyya; Armutcu, Ferah; Akyol, Omer

    2015-01-01

    Caffeic acid phenethyl ester (CAPE) is found in a variety of plants and well-known the active ingredient of the honeybee propolis. CAPE showed anti-inflammatory, anticarcinogenic, antimitogenic, antiviral, and immunomodulatory properties in several studies. The beneficial effects of CAPE on different health issues attracted scientists to make more studies on CAPE. Specifically, the anti-viral effects of CAPE and its molecular mechanisms may reveal the important properties of virus-induced diseases. CAPE and its targets may have important roles to design new therapeutics and understand the molecular mechanisms of virus-related diseases. In this mini-review, we summarize the antiviral effects of CAPE under the light of medical and chemical literature.

  7. Effect of caffeic acid phenethyl ester on bone formation in the expanded inter-premaxillary suture

    Directory of Open Access Journals (Sweden)

    Kazancioglu HO

    2015-12-01

    Full Text Available Hakki Oguz Kazancioglu,1 Sertac Aksakalli,2 Seref Ezirganli,1 Muhammet Birlik,2 Mukaddes Esrefoglu,3 Ahmet Hüseyin Acar1 1Department of Oral and Maxillofacial Surgery, 2Department of Orthodontics, Faculty of Dentistry, 3Department of Histology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey Background: Narrow maxilla is a common problem in orthodontics and dentofacial orthopedics. To solve this problem, a procedure called rapid maxillary expansion (RME has been used. However, relapse tendency is a major problem of RME. Although relapse tendency is not clearly understood, various treatment procedures and new application has been investigated. The present study aimed to investigate the possible effectiveness of caffeic acid phenethyl ester (CAPE on new bone formation in rat midpalatal suture after RME.Materials and methods: Twenty male Sprague Dawley rats were used in this study. The animals were randomly divided into two groups as control and CAPE group. In CAPE group, CAPE was administered systemically via intraperitoneal injection. RME procedure was performed on all animals. For this purpose, the springs were placed on the maxillary incisors of rats and activated for 5 days. After then, the springs were removed and replaced with short lengths of rectangular retaining wire for consolidation period of 15 days. At the end of the study, histomorphometric analysis was carried out to assess of new bone formation.Results: New bone formation was significantly greater in CAPE group than the control group (P<0.05. CAPE enhances new bone formation in midpalatal suture after RME.Conclusion: These results show that CAPE may decrease the time needed for retention. Keywords: rapid maxillary expansion, bone formation, caffeic acid phenethyl ester, midpalatal suture, histopathology

  8. Fungal biotransformation of chlorogenic and caffeic acids by Fusarium graminearum: New insights in the contribution of phenolic acids to resistance to deoxynivalenol accumulation in cereals.

    Science.gov (United States)

    Gauthier, Léa; Bonnin-Verdal, Marie-Noelle; Marchegay, Gisèle; Pinson-Gadais, Laetitia; Ducos, Christine; Richard-Forget, Florence; Atanasova-Penichon, Vessela

    2016-03-16

    Fusarium Head Blight and Gibberella Ear Rot, mainly caused by the fungi Fusarium graminearum and Fusarium culmorum, are two of the most devastating diseases of small-grain cereals and maize. In addition to yield loss, these diseases frequently result in contamination of kernels with toxic type B trichothecenes. The potential involvement of chlorogenic acid in cereal resistance to Fusarium Head Blight and Gibberella Ear Rot and to trichothecene accumulation was the focus of this study. The effects of chlorogenic acid and one of its hydrolyzed products, caffeic acid, on fungal growth and type B trichothecenes biosynthesis were studied using concentrations close to physiological amounts quantified in kernels and a set of F. graminearum and F. culmorum strains. Both chlorogenic and caffeic acids negatively impact fungal growth and mycotoxin production, with caffeic acid being significantly more toxic. Inhibitory efficiencies of both phenolic acids were strain-dependent. To further investigate the antifungal and anti "mycotoxin" effect of chlorogenic and caffeic acids, the metabolic fate of these two phenolic acids was characterized in supplemented F. graminearum broths. For the first time, our results demonstrated the ability of F. graminearum to degrade chlorogenic acid into caffeic, hydroxychlorogenic and protocatechuic acids and caffeic acid into protocatechuic and hydroxycaffeic acids. Some of these metabolic products can contribute to the inhibitory efficiency of chlorogenic acid that, therefore, can be compared as a "pro-drug". As a whole, our data corroborate the contribution of chlorogenic acid to the chemical defense that cereals employ to counteract F. graminearum and its production of mycotoxins. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Antioxidant activity of phenolic acids and their metabolites: synthesis and antioxidant properties of the sulfate derivatives of ferulic and caffeic acids and of the acyl glucuronide of ferulic acid.

    Science.gov (United States)

    Piazzon, A; Vrhovsek, U; Masuero, D; Mattivi, F; Mandoj, F; Nardini, M

    2012-12-19

    The main metabolites of caffeic and ferulic acids (ferulic acid-4'-O-sulfate, caffeic acid-4'-O-sulfate, and caffeic acid-3'-O-sulfate), the most representative phenolic acids in fruits and vegetables, and the acyl glucuronide of ferulic acid were synthesized, purified, and tested for their antioxidant activity in comparison with those of their parent compounds and other related phenolics. Both the ferric reducing antioxidant power (FRAP) assay and the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging method were used. Ferulic acid-4'-O-sulfate and ferulic acid-4'-O-glucuronide exhibited very low antioxidant activity, while the monosulfate derivatives of caffeic acid were 4-fold less efficient as the antioxidant than caffeic acid. The acyl glucuronide of ferulic acid showed strong antioxidant action. The antioxidant activity of caffeic acid-3'-O-glucuronide and caffeic acid-4'-O-glucuronide was also studied. Our results demonstrate that some of the products of phenolic acid metabolism still retain strong antioxidant properties. Moreover, we first demonstrate the ex vivo synthesis of the acyl glucuronide of ferulic acid by mouse liver microsomes, in addition to the phenyl glucuronide.

  10. Caffeic Acid-PLGA Conjugate to Design Protein Drug Delivery Systems Stable to Irradiation

    Directory of Open Access Journals (Sweden)

    Francesca Selmin

    2015-01-01

    Full Text Available This work reports the feasibility of caffeic acid grafted PLGA (g-CA-PLGA to design biodegradable sterile microspheres for the delivery of proteins. Ovalbumin (OVA was selected as model compound because of its sensitiveness of γ-radiation. The adopted grafting procedure allowed us to obtain a material with good free radical scavenging properties, without a significant modification of Mw and Tg of the starting PLGA (Mw PLGA = 26.3 ± 1.3 kDa vs. Mw g-CA-PLGA = 22.8 ± 0.7 kDa; Tg PLGA = 47.7 ± 0.8 °C vs. Tg g-CA-PLGA = 47.4 ± 0.2 °C. By using a W1/O/W2 technique, g-CA-PLGA improved the encapsulation efficiency (EE, suggesting that the presence of caffeic residues improved the compatibility between components (EEPLGA = 35.0% ± 0.7% vs. EEg-CA-PLGA = 95.6% ± 2.7%. Microspheres particle size distribution ranged from 15 to 50 µm. The zeta-potential values of placebo and loaded microspheres were −25 mV and −15 mV, respectively. The irradiation of g-CA-PLGA at the dose of 25 kGy caused a less than 1% variation of Mw and the degradation patterns of the non-irradiated and irradiated microspheres were superimposable. The OVA content in g-CA-PLGA microspheres decreased to a lower extent with respect to PLGA microspheres. These results suggest that g-CA-PLGA is a promising biodegradable material to microencapsulate biological drugs.

  11. Sensitive Determination of 6-Thioguanine Using Caffeic Acid-functionalized Fe3O4 Nanoparticles as an Electrochemical Sensor

    Science.gov (United States)

    Amir, Md.; Tunesi, Mawada M.; Soomro, Razium A.; Baykal, Abdülhadi; Kalwar, Nazar H.

    2018-01-01

    The study demonstrates the potential application of caffeic acid-functionalized magnetite nanoparticles (CA-Fe3O4 NPs) as an effective electrode modifying material for the electrochemical oxidation of the 6-thioguanine (6-TG) drug. The functionalized Fe3O4 NPs were prepared using simple wet-chemical methodology where the used caffeic acid acted simultaneously as growth controlling and functionalizing agent. The study discusses the influence of an effective functionalization on the signal sensitivity observed for the electro-oxidation of 6-TG over CA-Fe3O4 NPs in comparison to a glassy carbon electrode modified with bare and nicotinic acid (NA)-functionalized Fe3O4 NPs. The experiment results provided sufficient evidence to support the importance of favorable functionality to achieve higher signal sensitivity for the electro-oxidation of 6-TG. The presence of favorable interactions between the active functional moieties of caffeic acid and 6-TG synergized with the greater surface area of magnetic NPs produces a stable electro-oxidation signal within the working range of 0.01-0.23 μM with sensitive up to 0.001 μM. Additionally, the sensor showed the strong anti-interference potential against the common co-existing drug molecules such as benzoic acid, acetaminophen, epinephrine, norepinephrine, glucose, ascorbic acid and uc(l)-cysteine. In addition, the successful quantification of 6-TG from the commercial tablets obtained from local pharmacy further signified the practical capability of the discussed sensor.

  12. Sensitive Determination of 6-Thioguanine Using Caffeic Acid-functionalized Fe3O4 Nanoparticles as an Electrochemical Sensor

    Science.gov (United States)

    Amir, Md.; Tunesi, Mawada M.; Soomro, Razium A.; Baykal, Abdülhadi; Kalwar, Nazar H.

    2018-04-01

    The study demonstrates the potential application of caffeic acid-functionalized magnetite nanoparticles (CA-Fe3O4 NPs) as an effective electrode modifying material for the electrochemical oxidation of the 6-thioguanine (6-TG) drug. The functionalized Fe3O4 NPs were prepared using simple wet-chemical methodology where the used caffeic acid acted simultaneously as growth controlling and functionalizing agent. The study discusses the influence of an effective functionalization on the signal sensitivity observed for the electro-oxidation of 6-TG over CA-Fe3O4 NPs in comparison to a glassy carbon electrode modified with bare and nicotinic acid (NA)-functionalized Fe3O4 NPs. The experiment results provided sufficient evidence to support the importance of favorable functionality to achieve higher signal sensitivity for the electro-oxidation of 6-TG. The presence of favorable interactions between the active functional moieties of caffeic acid and 6-TG synergized with the greater surface area of magnetic NPs produces a stable electro-oxidation signal within the working range of 0.01-0.23 μM with sensitive up to 0.001 μM. Additionally, the sensor showed the strong anti-interference potential against the common co-existing drug molecules such as benzoic acid, acetaminophen, epinephrine, norepinephrine, glucose, ascorbic acid and l-cysteine. In addition, the successful quantification of 6-TG from the commercial tablets obtained from local pharmacy further signified the practical capability of the discussed sensor.

  13. Natural product-inspired esters and amides of ferulic and caffeic acid as dual inhibitors of HIV-1 reverse transcriptase.

    Science.gov (United States)

    Sonar, Vijay P; Corona, Angela; Distinto, Simona; Maccioni, Elias; Meleddu, Rita; Fois, Benedetta; Floris, Costantino; Malpure, Nilesh V; Alcaro, Stefano; Tramontano, Enzo; Cottiglia, Filippo

    2017-04-21

    Using an HIV-1 Reverse Transcriptase (RT)-associated RNase H inhibition assay as lead, bioguided fractionation of the dichloromethane extract of the Ocimum sanctum leaves led to the isolation of five triterpenes (1-5) along with three 3-methoxy-4-hydroxy phenyl derivatives (6-8). The structure of this isolates were determined by 1D and 2D NMR experiments as well as ESI-MS. Tetradecyl ferulate (8) showed an interesting RNase H IC 50 value of 12.4 μM and due to the synthetic accessibility of this secondary metabolite, a structure-activity relationship study was carried out. A series of esters and amides of ferulic and caffeic acids were synthesized and, among all, the most active was N-oleylcaffeamide displaying a strong inhibitory activity towards both RT-associated functions, ribonuclease H and DNA polymerase. Molecular modeling studies together with Yonetani-Theorell analysis, demonstrated that N-oleylcaffeamide is able to bind both two allosteric site located one close to the NNRTI binding pocket and the other close to RNase H catalytic site. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Caffeic acid and quercetin exert caspases-independent apoptotic effects on Leishmania major promastigotes, and reactivate the death of infected phagocytes derived from BALB/c mice

    Directory of Open Access Journals (Sweden)

    Radia Belkhelfa-Slimani

    2017-04-01

    Conclusions: The leishmanicidal effect of caffeic acid and quercetin on promastigotes and amastigotes, as well as reactivation of infected phagocytes apoptosis, suggested a potential therapeutic role against cutaneous leishmaniasis.

  15. Butylated caffeic acid: An efficient novel antioxidant; Ácido cafeico butilado: un nuevo y eficaz antioxidante.

    Energy Technology Data Exchange (ETDEWEB)

    Shi, G.; Liao, X.; Olajide, T.M.; Liu, J.; Jiang, X.; Weng, X.

    2017-07-01

    A novel antioxidant, butylated caffeic acid (BCA) was rationally designed by adding a tert-butyl group to caffeic acid, which was synthesized at a high yield (36.2%) from 2-methoxy-4-methylphenol (1) by a four-step reaction including Friedel-Crafts alkylation, bromine oxidation, ether bond hydrolysis and Knoevenagel condensation. Its antioxidant capacity was much stronger than common commercial antioxidant tert-butyl hydroquinone (TBHQ) and its mother compound, caffeic acid, in both rancimat and deep frying tests. When investigated via the DPPH method, the antioxidant capacity of BCA was almost equal to TBHQ, but lower than caffeic acid. BCA could be a potentially strong antioxidant, especially for food processing at high temperatures such as deep frying and baking. [Spanish] Se diseñó razonadamente un nuevo antioxidante, el ácido cafeico butilado (BCA) mediante la adición de un grupo terc-butilo al ácido cafeico, que se sintetizó con un alto rendimiento (36,2%) a partir de 2-metoxi-4-metilfenol, reacción de Friedel-Crafts, oxidación de bromo, hidrólisis del enlace éter y condensación de Knoevenagel. Su capacidad antioxidante fué mucho más fuerte que la del antioxidante comercial mas común el terc-butil hidroquinona (TBHQ) y la de su compuesto madre el ácido cafeico, tanto en rancimat como en pruebas de fritura. Cuando se investigó mediante el método DPPH, la capacidad antioxidante de BCA fue casi igual a TBHQ, pero menor que la del ácido cafeico. BCA podría ser un fuerte antioxidante potencial, especialmente para el procesamiento de alimentos a alta temperatura, tales como freír y hornear.

  16. Protective Effects of Intralipid and Caffeic Acid Phenethyl Ester on Nephrotoxicity Caused by Dichlorvos in Rats

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    Muhammet Murat Celik

    2015-01-01

    Full Text Available The protective effects of Caffeic Acid Phenethyl Ester (CAPE and intralipid (IL on nephrotoxicity caused by acute Dichlorvos (D toxicity were investigated in this study. Forty-eight Wistar Albino rats were divided into 7 groups as follows: Control, D, CAPE, intralipid, D + CAPE, D + IL, and D + CAPE + IL. When compared to D group, the oxidative stress index (OSI values were significantly lower in Control, CAPE, and D + IL + CAPE groups. When compared to D + IL + CAPE group, the TOS and OSI values were significantly higher in D group (P<0.05. When mitotic cell counts were assessed in the renal tissues, it was found that mitotic cell count was significantly higher in the D group while it was lower in the D + CAPE, D + IL, and D + IL + CAPE groups when compared to the control group (P<0.05. Also, immune reactivity showed increased apoptosis in D group and low profile of apoptosis in the D + CAPE group when compared to the Control group. The apoptosis level was significantly lower in D + IL + CAPE compared to D group (P<0.05 in the kidneys. As a result, we concluded that Dichlorvos can be used either alone or in combination with CAPE and IL as supportive therapy or as facilitator for the therapeutic effect of the routine treatment in the patients presenting with pesticide poisoning.

  17. Variation in intron length in caffeic acid O-methyltransferase (COMT) in Vanilla species (Orchidaceae).

    Science.gov (United States)

    Besse, Pascale; Da Silva, Denis; Bory, Séverine; Noirot, Michel; Grisoni, Michel

    2009-04-01

    Variation in intron length in caffeic acid O-methyltransferase (COMT) in Vanilla was studied and demonstrated that COMT genes in Vanilla are organized with four exons and three introns. At least two to four different versions (either allelic or paralogous) of the COMT multigenic family in the genus Vanilla (in terms of intron sizes) were detected. The three introns were differentially variable, with intron-1 being the most length-polymorphic. Patterns of variations were in accordance with known phylogenetic relationships in the genus obtained with neutral markers. In particular, the genus displayed a strong Old World versus New World differentiation with American fragrant species being characterized by a specific 99bp intron-1 size-variant and a unique 226bp intron-3 variant. Conversely, leafless species of the genus displayed unexpected variations in intron lengths. Due to their role in primary (lignin) and secondary (phenolics, e.g., vanillin, alkaloids) metabolisms, COMT genes might not be neutral markers, and represent candidate functional markers for resistance, aromatic or medicinal properties of Vanilla species. Investigating the orthologous/paralogous status of the different genes revealed (in terms of intron size) will allow the evolution of the COMT genes to be studied. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  18. Early Treatment of radiation-Induced Heart Damage in Rats by Caffeic acid phenethyl Ester

    International Nuclear Information System (INIS)

    Tawfik, S.S.; Mansour, H. H.

    2012-12-01

    The study designed to determine the therapeutic effect of caffeic acid phenethyl ester (CAPE) in minimising radiation-induced injuries in rats. Rats were exposed to 7 Gy γ-rays, 30 minutes later; rats were injected with CAPE (10μmol/ kg body, i.p.) for 7 consecutive days. Rats were sacrificed at 8 and 15 days after starting the experiment. Gamma-irradiation induced significant increase in malonaldehyde (MDA) level and xanthine oxidase (XO) and adenosine deaminase (ADA) activities, and significant decrease in total nitrate/nitrate (NO (x)) level and glutathione peroxidise (Gpx), superoxide dismutase (SOD)and catalase (CAT) activities in heart tissue and augmented activities of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and aspartate transaminase (AST) in serum. Irradiated rats early treated with CAPE showed significant decrease in MDA, XO and ADA and significant increase in group. Cardiac enzymes were restored. Conclusion, CAPE could exhibits curable effect on gamma irradiation-induced cardiac-oxidative impairment in rats. (Author)

  19. EFFECTS OF EXERCISE AND CAFFEIC ACID PHENETHYL ESTER AFTER CHRONIC EXERCISE RAT MODEL

    Directory of Open Access Journals (Sweden)

    Ayse Alp

    2011-01-01

    Full Text Available In order to understand whether exercise and caffeic acid phenethyl ester (CAPE has an effect on obesity and weight control, we investigated the effects of CAPE, and exercise on lipid parameters (triglyceride, total cholesterol, HDL-C, LDL-C, and adipokine substances such as leptin and resistin in rats. 40 male rat were randomly assigned into 4 groups. It was determined that CAPE does not have any significant effect on these parameters but that lipid parameters and leptin values in exercise groups decreased considerably, while no significant change occurred in resistin levels. In order to understand whether diet has an effect on exercise, body weights of all animal groups in pre and post-exercise were compared. A significant weight gain was observed (p = 0.005 in all groups. This study concluded that exercise has a considerable effect on leptin and lipid parameters; however, exercise alone was not sufficient for weight control and could be effective in weight control only when accompanied by a restricted diet.

  20. Modulation of Tamoxifen Cytotoxicity by Caffeic Acid Phenethyl Ester in MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Tarek K. Motawi

    2016-01-01

    Full Text Available Although Tamoxifen (TAM is one of the most widely used drugs in managing breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE is a polyphenolic compound present in many medicinal plants and in propolis. The present study examined the effect of CAPE on TAM cytotoxicity in MCF-7 cells. MCF-7 cells were treated with different concentrations of TAM and/or CAPE for 48 h. This novel combination exerted synergistic cytotoxic effects against MCF-7 cells via induction of apoptotic machinery with activation of caspases and DNA fragmentation, along with downregulation of Bcl-2 and Beclin 1 expression levels. However, the mammalian microtubule-associated protein light chain LC 3-II level was unchanged. Vascular endothelial growth factor level was also decreased, whereas levels of glutathione and nitric oxide were increased. In conclusion, CAPE augmented TAM cytotoxicity via multiple mechanisms, providing a novel therapeutic approach for breast cancer treatment that can overcome resistance and lower toxicity. This effect provides a rationale for further investigation of this combination.

  1. Release and permeation profiles of spray-dried chitosan microparticles containing caffeic acid

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    Caroline Magnani Spagnol

    2018-03-01

    Full Text Available Caffeic acid (CA, a phenolic compound found in plants with antioxidant and antimicrobial activity, induces collagen production and prevents premature aging of the skin. The objective of this study was to develop two types of chitosan microparticles (MP containing CA and to relate the morphology with the release and permeation profiles. One type of MP was prepared from a hydroalcoholic solution (MPI and the other from an aqueous solution (MPII. Their morphology and size was evaluated by high-resolution scanning electron microscopy. The release profile of CA was evaluated using the cellulose membrane from the two MPs in Franz diffusion cells and the permeation profile was evaluated using human abdominal skin samples; the epidermal membranes were prepared by the heat-separation technique. MPII was spherical with a smooth surface, suitable for the controlled release of substances, whereas MPI was porous with non-internalized residual material. This result was consistent with their release and permeation profiles because MPII exhibited a slower and more controlled release than MPI. Thus, the method of preparation of MP and their composition influence the release profile of CA. Therefore, the production conditions must be closely controlled.

  2. Release and permeation profiles of spray-dried chitosan microparticles containing caffeic acid.

    Science.gov (United States)

    Spagnol, Caroline Magnani; Zaera, Ana Melero; Isaac, Vera Lucia Borges; Corrêa, Marcos Antonio; Salgado, Hérida Regina Nunes

    2018-03-01

    Caffeic acid (CA), a phenolic compound found in plants with antioxidant and antimicrobial activity, induces collagen production and prevents premature aging of the skin. The objective of this study was to develop two types of chitosan microparticles (MP) containing CA and to relate the morphology with the release and permeation profiles. One type of MP was prepared from a hydroalcoholic solution (MPI) and the other from an aqueous solution (MPII). Their morphology and size was evaluated by high-resolution scanning electron microscopy. The release profile of CA was evaluated using the cellulose membrane from the two MPs in Franz diffusion cells and the permeation profile was evaluated using human abdominal skin samples; the epidermal membranes were prepared by the heat-separation technique. MPII was spherical with a smooth surface, suitable for the controlled release of substances, whereas MPI was porous with non-internalized residual material. This result was consistent with their release and permeation profiles because MPII exhibited a slower and more controlled release than MPI. Thus, the method of preparation of MP and their composition influence the release profile of CA. Therefore, the production conditions must be closely controlled.

  3. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

    International Nuclear Information System (INIS)

    Chen, Y.-J.; Liao, H.-F.; Tsai, T.-H.; Wang, S.-Y.; Shiao, M.-S.

    2005-01-01

    Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-κB activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or γ-glutamyl transpeptidase activity. Radiation activated NF-κB was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-κB activity, without toxicity to bone marrow, liver, and kidney

  4. Down-regulation of the caffeic acid O-methyltransferase gene in switchgrass reveals a novel monolignol analog

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    Tschaplinski Timothy J

    2012-09-01

    Full Text Available Abstract Background Down-regulation of the caffeic acid 3-O-methyltransferase EC 2.1.1.68 (COMT gene in the lignin biosynthetic pathway of switchgrass (Panicum virgatum resulted in cell walls of transgenic plants releasing more constituent sugars after pretreatment by dilute acid and treatment with glycosyl hydrolases from an added enzyme preparation and from Clostridium thermocellum. Fermentation of both wild-type and transgenic switchgrass after milder hot water pretreatment with no water washing showed that only the transgenic switchgrass inhibited C. thermocellum. Gas chromatography–mass spectrometry (GCMS-based metabolomics were undertaken on cell wall aqueous extracts to determine the nature of the microbial inhibitors. Results GCMS confirmed the increased concentration of a number of phenolic acids and aldehydes that are known inhibitors of microbial fermentation. Metabolomic analyses of the transgenic biomass additionally revealed the presence of a novel monolignol-like metabolite, identified as trans-3, 4-dimethoxy-5-hydroxycinnamyl alcohol (iso-sinapyl alcohol in both non-pretreated, as well as hot water pretreated samples. iso-Sinapyl alcohol and its glucoside were subsequently generated by organic synthesis and the identity of natural and synthetic materials were confirmed by mass spectrometric and NMR analyses. The additional novel presence of iso-sinapic acid, iso-sinapyl aldehyde, and iso-syringin suggest the increased activity of a para-methyltransferase, concomitant with the reduced COMT activity, a strict meta-methyltransferase. Quantum chemical calculations were used to predict the most likely homodimeric lignans generated from dehydration reactions, but these products were not evident in plant samples. Conclusions Down-regulation of COMT activity in switchgrass resulted in the accumulation of previously undetected metabolites resembling sinapyl alcohol and its related metabolites, but that are derived from para

  5. Equilibrium adsorption of caffeic, chlorogenic and rosmarinic acids on cationic cross-linked starch with quaternary ammonium groups.

    Science.gov (United States)

    Simanaviciute, Deimante; Klimaviciute, Rima; Rutkaite, Ramune

    2017-02-01

    In the present study, the equilibrium adsorption of caffeic acid (CA) and its derivatives, namely, chlorogenic (CGA) and rosmarinic (RA) acids on cationic cross-linked starch (CCS) with degree of substitution of quaternary ammonium groups of 0.42 have been investigated in relation to the structure and acidity of phenolic acids. The Langmuir, Freundlich and Dubinin-Radushkevich adsorption models have been used to describe the equilibrium adsorption of CA, CGA and RA from their initial solutions and solutions having the equimolar amount of NaOH at different temperatures. In the case of adsorption from the initial solutions of acids the values of adsorption parameters were closely related to the dissociation constants of investigated acids. According to the increasing effectiveness of adsorption, phenolic acids could be arranged in the following order: CAacids solutions changed their sorption properties which became mostly related to the acids structure. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities.

    Science.gov (United States)

    Otero, Elver; García, Elisa; Palacios, Genesis; Yepes, Lina M; Carda, Miguel; Agut, Raúl; Vélez, Iván D; Cardona, Wilson I; Robledo, Sara M

    2017-12-01

    The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of twelve triclosan-caffeic acid hybrids are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Eight compounds were active against L. (V) panamensis (18-23, 26 and 30) and eight of them against T. cruzi (19-22, 24 and 28-30) with EC 50 values lower than 40 μM. Compounds 19-22, 24 and 28-30 showed higher activities than benznidazole (BNZ). Esters 19 and 21 were the most active compounds for both L. (V) panamensis and T. cruzi with 3.82 and 11.65 μM and 8.25 and 8.69 μM, respectively. Compounds 19-22, 24 and 28-30 showed higher activities than benznidazole (BNZ). Most of the compounds showed antiprotozoal activity and with exception of 18, 26 and 28, the remaining compounds were toxic for mammalian cells, yet they have potential to be considered as candidates for anti-trypanosomal and anti-leishmanial drug development. The activity is dependent on the length of the alkyl linker with compound 19, bearing a four-carbon alkyl chain, the most performing hybrid. In general, hydroxyl groups increase both activity and cytotoxicity and the presence of the double bond in the side chain is not decisive for cytotoxicity and anti-protozoal activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Potential Effects of Caffeic Acid in Suppression of Matrix Metalloproteinases Activities in Irradiated Rats

    International Nuclear Information System (INIS)

    Zahran, A.M.

    2008-01-01

    Great Number of researches on the potential role of antioxidant nutrients and phenolic compounds in the prevention of chronic diseases has been accumulated over the past several decades. Despite this effort, there is much that remains uncertain. Bio markers research in this field has the potential to help fill the gaps in current knowledge. The present study was designed to evaluate, in one aspect, the probable direction expression of proteolytic enzymes as indices for gamma-irradiation-induced oxidative stress and their relationship, in other aspect with one antioxidant micro nutrient phenolic compound: caffeic acid (CA). Sprague Dawley male albino rats were administrated CA intraperitoneally (i.p.) 10 μmol/ kg body wt/ day for 8 consecutive days pre irradiation exposure (fractionated doses, instalment as 1 Gy every day up to total dose of 8 Gy). The treatment was continued for 15 successive days following irradiation processing. Quantitative assay of gelatinolytic zymo graphic analysis of serum and hepatic tissues showed that exposure to gamma-rays yields a marked significant increase in the activities of both latent and active MMP-9 (92 and 86 kDa), respectively, and both latent and active MMP-2 (72 and 66 kDa), respectively. Administration of CA significantly decreased the activities of MMP-2 and MMP-9 in gamma-irradiated rats. Conclusion: the present findings demonstrated that irradiation-exposure leads to enhancement of enzymatic activities of MMP-2 and MMP-9 in their inactive and active forms in the serum and liver. Meanwhile, administration of CA exhibits protective effects in gamma-irradiated rats through down-regulation of MMP-2 and MMP-9 activities

  8. Effects of novel hybrids of caffeic acid phenethyl ester and NSAIDs on experimental ocular inflammation.

    Science.gov (United States)

    Pittalà, Valeria; Salerno, Loredana; Romeo, Giuseppe; Siracusa, Maria Angela; Modica, Maria Nunziata; Romano, Giovanni Luca; Salomone, Salvatore; Drago, Filippo; Bucolo, Claudio

    2015-04-05

    In this study, we report the design and synthesis of novel hybrids of caffeic acid phenetyl ester (CAPE) and non-steroidal anti-inflammatory drugs (NSAIDs). We assessed their effects on an experimental ocular inflammation in New Zealand rabbits. The formulations of CAPE-aspirin and CAPE-indomethacin hybrids were topical instilled in the rabbit׳s eye. Afterwards, the anti-inflammatory activity was evaluated by grading the clinical signs and by assessing the inflammatory cell count, protein, PGE2 and TNFα levels in the aqueous humor. Furthermore, ocular tolerability of hybrids formulations was evaluated in a separate set of animals by using a modified Draize test. The ocular inflammation in the control group was significantly higher than in both the hybrid-treated groups, as indicated by clinical grading and biomarkers assessment. However, only the CAPE-aspirin hybrid reduced, in a significant dose-dependent manner, the ocular inflammation elicited by paracentesis. CAPE-indomethacin hybrid was able to significantly attenuate the clinical grading and the PGE2 aqueous levels only at the highest dose (0.1%). CAPE-aspirin significantly reduced PGE2 and TNFα levels in the aqueous humor as well as proteins and PMNs. Finally, all formulations showed no ocular irritation compared with vehicle-treated group. In conclusion, CAPE-aspirin shows full anti-inflammatory efficacy in experimental model of ocular inflammation demonstrating an optimal pharmacological and safety profile. Taken together these data indicate that CAPE-aspirin hybrid represents a valid and safe new chemical entity potentially useful for the treatment of ocular inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo

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    Yang Cheng-Ta

    2005-12-01

    Full Text Available Abstract Background Lung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose. We previously showed that Caffeic acid phenethyl ester (CAPE induces apoptosis and increases radiosensitivity in lung cancer. To determine whether CAPE, an antioxidant and an inhibitor of NF-kappa B, could be a useful adjuvant agent for lung cancer treatment, we examine the effects of CAPE on irradiated normal lung tissue in this study. Methods We compared the effects of CAPE on cytotoxicity and intracellular oxidative stress in normal lung fibroblast and a lung cancer cell line. For in vivo analysis, whole thorax radiation (single dose 10 Gy and 20 Gy was delivered to BALB/c male mice with or without CAPE pretreatment. NF- kappaB activation and the expression levels of acute inflammatory cytokines were evaluated in mice after irradiation. Results The in vitro studies showed that CAPE cause no significant cytotoxicity in normal lung as compared to lung cancer cells. This is probably due to the differential effect on the expression of NF-kappa B between normal and malignant lung cells. The results from in vivo study showed that CAPE treatment decreased the expression of inflammatory cytokines including IL-1 alpha and beta, IL-6, TNF-alpha and TGF- beta, after irradiation. Moreover, histological and immunochemical data revealed that CAPE decreased radiation- induced interstitial pneumonitis and TGF-beta expression. Conclusion This study suggests that CAPE decreases the cascade of inflammatory responses induced by thoracic irradiation without causing toxicity in normal lung tissue. This provides a rationale for combining CAPE and thoracic radiotherapy for lung cancer treatment in further clinical studies.

  10. Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo.

    Science.gov (United States)

    Chen, Miao-Fen; Keng, Peter C; Lin, Paul-Yang; Yang, Cheng-Ta; Liao, Shuen-Kuei; Chen, Wen-Cheng

    2005-12-09

    Lung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose. We previously showed that Caffeic acid phenethyl ester (CAPE) induces apoptosis and increases radiosensitivity in lung cancer. To determine whether CAPE, an antioxidant and an inhibitor of NF-kappa B, could be a useful adjuvant agent for lung cancer treatment, we examine the effects of CAPE on irradiated normal lung tissue in this study. We compared the effects of CAPE on cytotoxicity and intracellular oxidative stress in normal lung fibroblast and a lung cancer cell line. For in vivo analysis, whole thorax radiation (single dose 10 Gy and 20 Gy) was delivered to BALB/c male mice with or without CAPE pretreatment. NF- kappaB activation and the expression levels of acute inflammatory cytokines were evaluated in mice after irradiation. The in vitro studies showed that CAPE cause no significant cytotoxicity in normal lung as compared to lung cancer cells. This is probably due to the differential effect on the expression of NF-kappa B between normal and malignant lung cells. The results from in vivo study showed that CAPE treatment decreased the expression of inflammatory cytokines including IL-1 alpha and beta, IL-6, TNF-alpha and TGF- beta, after irradiation. Moreover, histological and immunochemical data revealed that CAPE decreased radiation- induced interstitial pneumonitis and TGF-beta expression. This study suggests that CAPE decreases the cascade of inflammatory responses induced by thoracic irradiation without causing toxicity in normal lung tissue. This provides a rationale for combining CAPE and thoracic radiotherapy for lung cancer treatment in further clinical studies.

  11. Effect of antioxidant activity of caffeic acid with cyclodextrins using ground mixture method

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    Ryota Shiozawa

    2018-01-01

    Full Text Available In the current study, we prepared a ground mixture (GM of caffeic acid (CA with α-cyclodextrin (αCD and with β-cyclodextrin (βCD, and then comparatively assessed the physicochemical properties and antioxidant capacities of these GMs. Phase solubility diagrams indicated that both CA/αCD and CA/βCD formed a complex at a molar ratio of 1/1. In addition, stability constants suggested that CA was more stable inside the cavity of αCD than inside the cavity of βCD. Results of powder X-ray diffraction (PXRD indicated that the characteristic diffraction peaks of CA and CD disappeared and a halo pattern was produced by the GMs of CA/αCD and CA/βCD (molar ratios = 1/1. Dissolution testing revealed that both GMs had a higher rate of dissolution than CA alone did. Based on the 1H-1H NOESY NMR spectra for the GM of CA/αCD, the vinylene group of the CA molecule appeared to be included from the wider to the narrower rim of the αCD ring. Based on spectra for the GM of CA/βCD, the aromatic ring of the CA molecule appeared to be included from the wider to the narrower rim of the βCD ring. This suggests that the structures of the CA inclusion complexes differed between those involving αCD rings and those involving βCD rings. Results of a DPPH radical-scavenging activity test indicated that the GM of CA/αCD had a higher antioxidant capacity than that of the GM of CA/βCD. The differences in the antioxidant capacities of the GMs of CA/αCD and CA/βCD are presumably due to differences in stability constants and structures of the inclusion complexes.

  12. Genomic study of the absorption mechanism of p-coumaric acid and caffeic acid of extract of Ananas comosus L. leaves.

    Science.gov (United States)

    Dang, Yun-jie; Zhu, Chun-yan

    2015-03-01

    Cardiac disease has emerged as the leading cause of death worldwide, and food rich in phenolic acids has drawn much attention as sources of active substances of hypolipidemic drug. Ananas comosus L. (pineapple) is one of the most popular tropical and subtropical fruits. Isolated from pineapple leaves, EAL(Extract of Ananas Comosus L. Leaves) is rich in phenolic acids, such as p-coumaric acid, caffeic acid, and other phenolics, highly relevant to the putative cardiovascular-protective effects, which suggests its potential to be a new plant medicine for treatment of cardiac disease, but little is known about absorption, distribution, metabolism, and excretion of EAL in animals or human beings. In this study, we employed cDNA microarray, Caco-2 cell lines, and rat intestinal model to explore the absorption behavior of p-coumaric acid and caffeic acid in EAL. The permeation of 2 substances was concentration and time dependent. Results also indicated that monocarboxylic acid transporter was involved in the transepithelial transport of p-coumaric acid and caffeic acid. © 2015 Institute of Food Technologists®

  13. Mechanism of Action of Isolated Caffeic Acid and Epicatechin 3-gallate fromEuphorbia hirtaagainstPseudomonas aeruginosa.

    Science.gov (United States)

    Perumal, Shanmugapriya; Mahmud, Roziahanim; Ismail, Sabariah

    2017-07-01

    The escalating dominance of resistant Pseudomonas aeruginosa strains as infectious pathogen had urged the researchers to look for alternative and complementary drugs. The objective of this study is to address the biological targets and probable mechanisms of action underlying the potent antibacterial effect of the isolated compounds from Euphorbia hirta (L.) against P. aeruginosa . The action mechanisms of caffeic acid (CA) and epicatechin 3-gallate (ECG) on P. aeruginosa cells were investigated by several bacterial physiological manifestations involving outer membrane permeabilization, intracellular potassium ion efflux, and nucleotide leakage. The findings revealed that ECG and CA targeted both cell wall and cytoplasmic membrane of P. aeruginosa . The cellular membrane destruction and ensuing membrane permeability perturbation of P. aeruginosa had led to the ascending access of hydrophobic antibiotics, release of potassium ions, and leakages of nucleotides. The overall study concludes that ECG and CA isolated from E. hirta possess remarkable anti-infective potentials which can be exploited as drug template for the development of new antibacterial agent against resistant P. aeruginosa pathogen. Epicatechin 3-gallate (ECG) and caffeic acid (CA) exhibited remarkable bactericidal abilities by increasing the outer membrane and plasma membrane permeability of Pseudomonas aeruginosa pathogenECG and CA had facilitated the entry of hydrophobic antibiotics into P. aeruginosa by disintegrating the lipopolysaccharides layer of the outer membraneECG-induced potassium efflux with efficiency close to that obtained with cefepime suggesting mode of action through membrane disruptionBoth ECG and CA had caused consistent leakage of intracellular nucleotide content with the increase in time. Abbreviations used: ECG: Epicatechin 3-gallate; CA: Caffeic acid; E. hirta : Euphoria hirta.

  14. Mechanism of Action of Isolated Caffeic Acid and Epicatechin 3-gallate from Euphorbia hirta against Pseudomonas aeruginosa

    Science.gov (United States)

    Perumal, Shanmugapriya; Mahmud, Roziahanim; Ismail, Sabariah

    2017-01-01

    Background: The escalating dominance of resistant Pseudomonas aeruginosa strains as infectious pathogen had urged the researchers to look for alternative and complementary drugs. Objective: The objective of this study is to address the biological targets and probable mechanisms of action underlying the potent antibacterial effect of the isolated compounds from Euphorbia hirta (L.) against P. aeruginosa. Materials and Methods: The action mechanisms of caffeic acid (CA) and epicatechin 3-gallate (ECG) on P. aeruginosa cells were investigated by several bacterial physiological manifestations involving outer membrane permeabilization, intracellular potassium ion efflux, and nucleotide leakage. Results: The findings revealed that ECG and CA targeted both cell wall and cytoplasmic membrane of P. aeruginosa. The cellular membrane destruction and ensuing membrane permeability perturbation of P. aeruginosa had led to the ascending access of hydrophobic antibiotics, release of potassium ions, and leakages of nucleotides. Conclusion: The overall study concludes that ECG and CA isolated from E. hirta possess remarkable anti-infective potentials which can be exploited as drug template for the development of new antibacterial agent against resistant P. aeruginosa pathogen. SUMMARY Epicatechin 3-gallate (ECG) and caffeic acid (CA) exhibited remarkable bactericidal abilities by increasing the outer membrane and plasma membrane permeability of Pseudomonas aeruginosa pathogenECG and CA had facilitated the entry of hydrophobic antibiotics into P. aeruginosa by disintegrating the lipopolysaccharides layer of the outer membraneECG-induced potassium efflux with efficiency close to that obtained with cefepime suggesting mode of action through membrane disruptionBoth ECG and CA had caused consistent leakage of intracellular nucleotide content with the increase in time. Abbreviations used: ECG: Epicatechin 3-gallate; CA: Caffeic acid; E. hirta: Euphoria hirta. PMID:28808398

  15. Development of an Electrochemical Sensor for NADH Determination Based on a Caffeic Acid Redox Mediator Supported on Carbon Black

    Directory of Open Access Journals (Sweden)

    Chiara Zanardi

    2015-04-01

    Full Text Available Screen-printed electrode (SPE modified with carbon black nanoparticles (CB has been tested as a new platform for the stable deposition of caffeic acid (CFA on the electrode surface. The electrochemical performance from varying the amount of CFA/CB composite has been tested with respect to NADH determination. The electrocatalytic activity of CFA/CB has also been compared with that of SPEs modified by a single component of the coating, i.e., either CFA or CB. Finally, glycerol dehydrogenase, a typical NADH-dependent enzyme, was deposited on the CFA/CB coating in order to test the applicability of the sensor in glycerol determination.

  16. A study of esterification of caffeic acid with methanol using p-toluenesulfonic acid as a catalyst

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    Wang Jun

    2013-01-01

    Full Text Available Caffeic acid (CA can be considered as an important natural antioxidant. However, the low solubility and stability of CA in various solvent systems is a major limiting factor governing the overall application in the lipid industry, so the synthesis of methyl caffeate (MCusing CA and methanol is a feasible way to improve its lipophilicity. Here, the reaction conditions and kinetic parameters for the synthesis of MC using p-toluenesulfonic acid (PTSA as a catalyst were firstly investigated, and the product was confirmed byliquid chromatography-mass spectrometry (LC-MS,Fourier transform infrared spectroscopy (FTIR, nuclear magnetic resonance (NMR, and melting point analysis. The highest yield of MC catalyzed by PTSA reached 84.0% under the optimum conditions as follows: molar ratio of methanol to CA of 20:1, reaction temperature of 65°C, mass ratio of catalyst to substrate of 8 %, and reaction time of 4 h. The esterification kinetics of CA and methanol is described by the pseudo-homogeneous second order reversible model, the relationship between temperature and the forward rate constant is k1 = exp (358.7 - 2111/T, and the activation energy is 17.5 kJ mol-1. These results indicated that the PTSA possesses high catalytic activity in the synthesis of MC, which is an efficient catalyst suitable for MC production in the chemical industry.

  17. Protective Effect of Caffeic Acid Phenethyl Ester in Rat Cerebral Ischemia/Reperfusion Damage

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    Ertuğrul Uzar

    2011-09-01

    Full Text Available OBJECTIVE: Because oxidative stress is related to cerebral ischemia/reperfusion (I/R injury, modulation of oxygen free radical production may represent a new approach to the management of cerebral I/R. Caffeic acid phenethyl ester (CAPE has been determined to have neuroprotective, antioxidant, anti-inflammatory, and anti-apoptotic activities. The aim of this study was to investigate whether CAPE has a protective effect on cerebral I/R damage, and to determine the possible effects of CAPE on total antioxidant/oxidant status. METHODS: A total of 30 rats were randomly divided into three groups as control group, I/R group, and I/R + CAPE. Total oxidant status (TOS, total antioxidant status (TAS and oxidative stress index (OSI levels and histopathological cellular structures were evaluated in cerebral tissues obtained after the experiment procedure in all groups. RESULTS: In the brain tissue, TOS and OSI levels were found to be significantly increased in the I/R group compared to the controls (p= 0.023, p= 0.001, respectively. Significantly decreased TAS levels were found in the I/R group compared to the controls (p= 0.001. CAPE treatment prevented the increase in TOS and OSI that is produced by cerebral I/R (p= 0.041, p= 0.001, respectively. TAS was found to be increased in the CAPE + I/R group compared with the I/R group (p= 0.002. In the I/R group, the brain sections showed findings of cerebral I/R damage including inflammation, vascular congestion and necrosis (for both variables, p= 0.001. These histopathological cerebral damage findings were found to be significantly reduced in the CAPE + I/R group compared to the I/R group (for both parameters, p< 0.05. CONCLUSION: In this study, it was found that oxidative stress had an important role in the pathogenesis of cerebral I/R damage, and histopathological and biochemical evaluations showed significantly decreased I/R damage following CAPE treatment in rats.

  18. Effect of caffeine, caffeic acid and their various combinations on enzymes of cholinergic, monoaminergic and purinergic systems critical to neurodegeneration in rat brain-In vitro.

    Science.gov (United States)

    Akomolafe, S F; Akinyemi, A J; Ogunsuyi, O B; Oyeleye, S I; Oboh, G; Adeoyo, O O; Allismith, Y R

    2017-09-01

    Caffeine and caffeic acid are two bioactive compounds that are present in plant foods and are major constituent of coffee, cocoa, tea, cola drinks and chocolate. Although not structurally related, caffeine and caffeic acid has been reported to elicit neuroprotective properties. However, their different proportional distribution in food sources and possible effect of such interactions are not often taken into consideration. Therefore, in this study, we investigated the effect of caffeine, caffeic acid and their various combinations on activities of some enzymes [acetylcholinesterase (AChE), monoamine oxidase (MAO) ecto-nucleoside triphosphate diphosphohydrolase (E-NTPase), ecto-5 1 -nucleotidase (E-NTDase) and Na + /K + ATPase relevant to neurodegeneration in vitro in rat brain. The stock concentration of caffeine and caffiec acid and their various proportional combinations were prepared and their interactions with the activities of these enzymes were assessed (in vitro) in different brain structures. The Fe 2+ and Cu 2+ chelating abilities of the samples were also investigated. The results revealed that caffeine, caffeic acid and their various combinations exhibited inhibitory effect on activities of AChE, MAO, E-NTPase and E-NTDase, but stimulatory effect on Na + /K + ATPase activity. The combinations also exhibited Fe 2+ and Cu 2+ chelating abilities. Considering the various combinations, a higher caffeine to caffeic acid ratio produced significantly highest enzyme modulatory effects; these were significantly lower to the effect of caffeine alone but significantly higher than the effect of caffeic acid alone. These findings may provide new insight into the effect of proportional combination of these bioactive compounds as obtained in many foods especially with respect to their neuroprotective effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells.

    Science.gov (United States)

    Shin, Hee Soon; Satsu, Hideo; Bae, Min-Jung; Totsuka, Mamoru; Shimizu, Makoto

    2017-02-20

    Chlorogenic acid (CHA) and caffeic acid (CA) are phenolic compounds found in coffee, which inhibit oxidative stress-induced interleukin (IL)-8 production in intestinal epithelial cells, thereby suppressing serious cellular injury and inflammatory intestinal diseases. Therefore, we investigated the anti-inflammatory mechanism of CHA and CA, both of which inhibited hydrogen peroxide (H₂O₂)-induced IL-8 transcriptional activity. They also significantly suppressed nuclear factor kappa-light-chain-enhancer of activated B cells ( NF-κB ) transcriptional activity, nuclear translocation of the p65 subunit, and phosphorylation of IκB kinase (IKK). Additionally, upstream of IKK, protein kinase D (PKD) was also suppressed. Finally, we found that they scavenged H₂O₂-induced reactive oxygen species (ROS) and the functional moiety responsible for the anti-inflammatory effects of CHA and CA was the catechol group. Therefore, we conclude that the presence of catechol groups in CHA and CA allows scavenging of intracellular ROS, thereby inhibiting H₂O₂-induced IL-8 production via suppression of PKD-NF-κB signaling in human intestinal epithelial cells.

  20. Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells

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    Hee Soon Shin

    2017-02-01

    Full Text Available Chlorogenic acid (CHA and caffeic acid (CA are phenolic compounds found in coffee, which inhibit oxidative stress-induced interleukin (IL-8 production in intestinal epithelial cells, thereby suppressing serious cellular injury and inflammatory intestinal diseases. Therefore, we investigated the anti-inflammatory mechanism of CHA and CA, both of which inhibited hydrogen peroxide (H2O2-induced IL-8 transcriptional activity. They also significantly suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB transcriptional activity, nuclear translocation of the p65 subunit, and phosphorylation of IκB kinase (IKK. Additionally, upstream of IKK, protein kinase D (PKD was also suppressed. Finally, we found that they scavenged H2O2-induced reactive oxygen species (ROS and the functional moiety responsible for the anti-inflammatory effects of CHA and CA was the catechol group. Therefore, we conclude that the presence of catechol groups in CHA and CA allows scavenging of intracellular ROS, thereby inhibiting H2O2-induced IL-8 production via suppression of PKD-NF-κB signaling in human intestinal epithelial cells.

  1. Modulation of phenytoin teratogenicity and embryonic covalent binding by acetylsalicylic acid, caffeic acid, and alpha-phenyl-N-t-butylnitrone: implications for bioactivation by prostaglandin synthetase

    International Nuclear Information System (INIS)

    Wells, P.G.; Zubovits, J.T.; Wong, S.T.; Molinari, L.M.; Ali, S.

    1989-01-01

    Teratogenicity of the anticonvulsant drug phenytoin is thought to involve its bioactivation by cytochromes P-450 to a reactive arene oxide intermediate. We hypothesized that phenytoin also may be bioactivated to a teratogenic free radical intermediate by another enzymatic system, prostaglandin synthetase. To evaluate the teratogenic contribution of this latter pathway, an irreversible inhibitor of prostaglandin synthetase, acetylsalicylic acid (ASA), 10 mg/kg intraperitoneally (ip), was administered to pregnant CD-1 mice at 9:00 AM on Gestational Days 12 and 13, 2 hr before phenytoin, 65 mg/kg ip. Other groups were pretreated 2 hr prior to phenytoin administration with either the antioxidant caffeic acid or the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (PBN). Caffeic acid and PBN were given ip in doses that respectively were up to 1.0 to 0.05 molar equivalents to the dose of phenytoin. Dams were killed on Day 19 and the fetuses were assessed for teratologic anomalies. A similar study evaluated the effect of ASA on the in vivo covalent binding of radiolabeled phenytoin administered on Day 12, in which case dams were killed 24 hr later on Day 13. ASA pretreatment produced a 50% reduction in the incidence of fetal cleft palates induced by phenytoin (p less than 0.05), without significantly altering the incidence of resorptions or mean fetal body weight. Pretreatment with either caffeic acid or PBN resulted in dose-related decreases in the incidence of fetal cleft palates produced by phenytoin, with maximal respective reductions of 71 and 82% at the highest doses of caffeic acid and PBN (p less than 0.05)

  2. Enzymatic Browning in Sugar Beet Leaves (Beta vulgaris L.): Influence of Caffeic Acid Derivatives, Oxidative Coupling, and Coupled Oxidation.

    Science.gov (United States)

    Vissers, Anne; Kiskini, Alexandra; Hilgers, Roelant; Marinea, Marina; Wierenga, Peter Alexander; Gruppen, Harry; Vincken, Jean-Paul

    2017-06-21

    Sugar beet (Beta vulgaris L.) leaves of 8 month (8 m ) plants showed more enzymatic browning than those of 3 month (3 m ). Total phenolic content increased from 4.6 to 9.4 mg/g FW in 3 m and 8 m , respectively, quantitated by reverse-phase-ultrahigh-performance liquid chromatography-ultraviolet-mass spectrometry (RP-UHPLC-UV-MS). The PPO activity was 6.7 times higher in extracts from 8 m than from 3 m leaves. Substrate content increased from 0.53 to 2.45 mg/g FW in 3 m and 8 m , respectively, of which caffeic acid glycosyl esters were most important, increasing 10-fold with age. Caffeic acid glycosides and vitexin derivatives were no substrates. In 3 m and 8 m, nonsubstrate-to-substrate ratios were 8:1 and 3:1, respectively. A model system showed browning at 3:1 ratio due to formation of products with extensive conjugated systems through oxidative coupling and coupled oxidation. The 8:1 ratio did not turn brown as oxidative coupling occurred without much coupled oxidation. We postulate that differences in nonsubstrate-to-substrate ratio and therewith extent of coupled oxidation explain browning.

  3. Optimization of lipase-catalyzed synthesis of caffeic acid phenethyl ester in ionic liquids by response surface methodology.

    Science.gov (United States)

    Ha, Sung Ho; Van Anh, Tran; Koo, Yoon-Mo

    2013-06-01

    Lipase-catalyzed caffeic acid phenethyl ester (CAPE) synthesis in ionic liquid, 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([Emim][Tf(2)N]), was investigated in this study. The effects of several reaction conditions, including reaction time, reaction temperature, substrate molar ratio of phenethyl alcohol to caffeic acid (CA), and weight ratio of enzyme to CA, on CAPE yield were examined. In a single parameter study, the highest CAPE yield in [Emim][Tf(2)N] was obtained at 70 °C with a substrate molar ratio of 30:1 and weight ratio of enzyme to CA of 15:1. Based on these results, response surface methodology (RSM) with a 3-level-4-factor central composite rotatable design (CCRD) was adopted to evaluate enzymatic synthesis of CAPE in [Emim][Tf(2)N]. The four major factors were reaction time (36-60 h), reaction temperature (65-75 °C), substrate molar ratio of phenethyl alcohol to CA (20:1-40:1), and weight ratio of enzyme to CA (10:1-20:1). A quadratic equation model was used to analyze the experimental data at a 95 % confidence level (p ratio of phenethyl alcohol to CA (27.1:1), and weight ratio of enzyme to CA (17.8:1)] established by our statistical method, whereas the experimental conversion yield was 96.6 ± 2 %.

  4. Effect of caffeic acid phenethyl ester on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Choi, E-Y; Choe, S-H; Hyeon, J-Y; Choi, J-I; Choi, I S; Kim, S-J

    2015-12-01

    Caffeic acid phenethyl ester (CAPE) has numerous potentially beneficial properties, including antioxidant, immunomodulatory and anti-inflammatory activities. However, the effect of CAPE on periodontal disease has not been studied before. This study was designed to investigate the efficacy of CAPE in ameliorating the production of proinflammatory mediators in macrophages activated by lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in periodontal disease. LPS from P. intermedia ATCC 25611 was isolated by using the standard hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO), interleukin (IL)-1β and IL-6. We used real-time polymerase chain reaction to quantify inducible NO synthase, IL-1β, IL-6, heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS) 1 mRNA expression. HO-1 protein expression and levels of signaling proteins were assessed by immunoblot analysis. DNA-binding activities of NF-κB subunits were analyzed by using the enzyme-linked immunosorbent assay-based kits. CAPE exerted significant inhibitory effects on P. intermedia LPS-induced production of NO, IL-1β and IL-6 as well as their mRNA expression in RAW264.7 cells. CAPE-induced HO-1 expression in cells activated with P. intermedia LPS, and selective inhibition of HO-1 activity by tin protoporphyrin IX attenuated the inhibitory effect of CAPE on LPS-induced NO production. CAPE did not interfere with IκB-α degradation induced by P. intermedia LPS. Instead, CAPE decreased nuclear translocation of NF-κB p65 and p50 subunits induced with LPS, and lessened LPS-induced p50 binding activity. Further, CAPE showed strong inhibitory effects on LPS-induced signal transducer and activator of transcription 1 and 3 phosphorylation. Besides, CAPE significantly elevated SOCS1 mRNA expression in P. intermedia LPS-stimulated cells. Modulation of host response by CAPE may represent an attractive strategy towards the treatment of periodontal disease

  5. The Protective Effects of Caffeic Acid Phenethyl Ester on Acetylsalicylic Acid-induced Lung Injury in Rats.

    Science.gov (United States)

    Taylan, Mahşuk; Kaya, Halide; Demir, Melike; Evliyaoğlu, Osman; Sen, Hadice Selimoglu; Fırat, Ugur; Keles, Aysenur; Yilmaz, Sureyya; Sezgi, Cengizhan

    2016-12-01

    We aimed to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on acetylsalicylic acid (ASA)-induced lung damage in rats in the present study. A total of 40 rats were randomly divided into five groups, with eight rats in each group-group 1: control, not receiving any medication; group 2: ASA (50 mg/kg/day); group 3: ASA (50 mg/kg/day) plus CAPE (20 μg/kg/day); group 4: ASA (100 mg/kg/day); and group 5: ASA (100 mg/kg/day) plus CAPE (20 μg/kg/day). ASA and CAPE were given via orogastric gavage for 5 days. The total oxidant status (TOS), total antioxidant capacity (TAC), oxidant stress index (OSI), and paraoxonase-1 (PON-1) activity of the blood samples and lung tissues were determined. Histopathological examinations of the lung tissues were performed by using light microscopic methods. CAPE treatment significantly increased antioxidant PON-1 level both in the lung tissue and plasma (p < .05). Plasma antioxidant marker (TAC, PON-1) levels significantly increased and oxidant marker (TOS, OSI) levels significantly decreased in CAPE-treated rats (groups 3,5) compared to ASA given no-CAPE groups (group 2,4) (p < .05). Treatment with CAPE improved pulmonary interstitial inflammation and eosinophil accumulation due to ASA histopathologically. Eosinophil-rich inflammation and oxidative stress play important roles in ASA-induced lung toxicity, and CAPE may protect against ASA-induced lung toxicity by reduction of oxidative damage and inflammation in rats.

  6. Amine-modified SBA-15 and MCF mesoporous molecular sieves as promising sorbents for natural antioxidant. Modeling of caffeic acid adsorption.

    Science.gov (United States)

    Moritz, Michał; Geszke-Moritz, Małgorzata

    2016-04-01

    This work presents a detailed study of caffeic acid adsorption on mesoporous SBA-15 and MCF silicas functionalized with (3-aminopropyl)triethoxysilane (APTES) and 3-[2-(aminoethylamino)propyl]trimethoxysilane (AEAPTMS). Synthesized mesoporous adsorbents were characterized using different analytical techniques such as N2 sorption, XRD, TEM, SEM and FT-IR. The adsorption studies of caffeic acid were conducted in various organic solvents. Moreover, the effect of water content in 2-propanol-water mixture on adsorption efficiency was investigated. The experimental data were best fitted to the Langmuir equation, followed by the Temkin, Dubinin-Radushkevich and Freundlich models. The maximum adsorption capacity values calculated from the Langmuir model demonstrated that SBA-15 and MCF silicas modified with AEAPTMS revealed better adsorption properties toward caffeic acid (192.3 and 161.3mg/g, respectively) as compared to the materials modified with APTES (125.0 and 113.6 mg/g, respectively). The obtained results indicate that both SBA-15 and MCF silicas functionalized with AEAPTMS and APTES are promising materials for the entrapment of caffeic acid. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Caffeic Acid Phenethyl Ester as a Protective Agent against Nephrotoxicity and/or Oxidative Kidney Damage: A Detailed Systematic Review

    Directory of Open Access Journals (Sweden)

    Sumeyya Akyol

    2014-01-01

    Full Text Available Caffeic acid phenethyl ester (CAPE, an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R. In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility.

  8. Cooperative Reinforcement of Ionic Liquid and Reactive Solvent on Enzymatic Synthesis of Caffeic Acid Phenethyl Ester as an In Vitro Inhibitor of Plant Pathogenic Bacteria.

    Science.gov (United States)

    Xu, Yan; Sheng, Sheng; Liu, Xi; Wang, Chao; Xiao, Wei; Wang, Jun; Wu, Fu-An

    2017-01-02

    It is widely believed that lipases in ionic liquids (ILs) possess higher enzyme activity, stability and selectivity; however, reaction equilibrium is always limited by product inhibition, and the product is difficult to separate from non-volatile ILs using distillation. To solve this problem, using trialkylphosphine oxide (TOPO) as a complexing agent, a novel biphase of reactive solvent and IL was firstly reported for caffeic acid phenethyl ester (CAPE) production from methyl caffeate (MC) and 2-phenylethanol (PE) catalyzed by lipase via transesterification. The effects of the reaction parameters and their action mechanism were investigated, and the inhibition of CAPE against bacterial wilt pathogen Ralstonia solanacearum was firstly measured. The MC conversion of 98.83% ± 0.76% and CAPE yield of 96.29% ± 0.07% were obtained by response surface methodology in the 25 g/L TOPO-cyclohexane/[Bmim][Tf₂N] (1:1, v / v ); the complex stoichiometry calculation and FTIR spectrum confirmed that the reversible hydrogen-bond complexation between TOPO and caffeates significantly enhances the cooperative effect of two phases on the lipase-catalyzed reaction. The temperature was reduced by 14 °C; the MC concentration increased by 3.33-fold; the ratio of catalyst to donor decreased by 4.5-fold; and K m decreased 1.08-fold. The EC 50 of CAPE against R. solanacearum was 0.17-0.75 mg/mL, suggesting that CAPE is a potential in vitro inhibitor of plant pathogenic bacteria.

  9. Discovery of novel hybrids of diaryl-1,2,4-triazoles and caffeic acid as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase for cancer therapy.

    Science.gov (United States)

    Cai, Hao; Huang, Xiaojing; Xu, Shengtao; Shen, Hao; Zhang, Pengfei; Huang, Yue; Jiang, Jieyun; Sun, Yijun; Jiang, Bo; Wu, Xiaoming; Yao, Hequan; Xu, Jingyi

    2016-01-27

    Inflammation plays a key role in cancer initiation and propagation. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), two important enzymes in inflammatory responses are up-regulated in various tumor types. Dual inhibition of COX-2 and 5-LOX constitutes a rational concept for the design of more efficacious anti-tumor agents with an improved safety profile. We have previously reported a series of diaryl-1,2,4-triazole derivatives as selective COX-2 inhibitors. Herein, we hybridized the diaryl-1,2,4-triazoles with caffeic acid (CA) which was reported to display 5-LOX inhibitory and anti-tumor activities, affording a novel class of COX-2/5-LOX dual inhibitors as anti-tumor drug candidates. Most of these compounds exhibited potent COX-2/5-LOX inhibitory and antiproliferative activities in vitro. And the most potent compound 22b could significantly inhibit tumor growth in vivo. Furthermore, mechanistic investigation showed that the representative compound 15c blocked cell cycle in G2 phase and induced apoptosis in human non-small cell lung cancer A549 cells in a dose-dependent manner. Our preliminary investigation results would provide new clues for the cancer theatment with COX-2/5-LOX dual inhibitors. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Caffeic Acid Phenethyl Ester and Ethanol Extract of Propolis Induce the Complementary Cytotoxic Effect on Triple-Negative Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Anna Rzepecka-Stojko

    2015-05-01

    Full Text Available Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells’ susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP and its derivative caffeic acid phenethyl ester (CAPE towards two triple-negative breast cancer (TNBC cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg∙mL−1 for MDA-MB-23 cells and 33.68 µg∙mL−1 for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs.

  11. Down-Regulation of Caffeic Acid O-Methyltransferase in Maize Revisited Using a Transgenic Approach1

    Science.gov (United States)

    Piquemal, Joel; Chamayou, Simon; Nadaud, Isabelle; Beckert, Michel; Barrière, Yves; Mila, Isabelle; Lapierre, Catherine; Rigau, Joan; Puigdomenech, Pere; Jauneau, Alain; Digonnet, Catherine; Boudet, Alain-Michel; Goffner, Deborah; Pichon, Magalie

    2002-01-01

    Transgenic maize (Zea mays) plants were generated with a construct harboring a maize caffeic acid O-methyltransferase (COMT) cDNA in the antisense (AS) orientation under the control of the maize Adh1 (alcohol dehydrogenase) promoter. Adh1-driven β-glucuronidase expression was localized in vascular tissues and lignifying sclerenchyma, indicating its suitability in transgenic experiments aimed at modifying lignin content and composition. One line of AS plants, COMT-AS, displayed a significant reduction in COMT activity (15%–30% residual activity) and barely detectable amounts of COMT protein as determined by western-blot analysis. In this line, transgenes were shown to be stably integrated in the genome and transmitted to the progeny. Biochemical analysis of COMT-AS showed: (a) a strong decrease in Klason lignin content at the flowering stage, (b) a decrease in syringyl units, (c) a lower p-coumaric acid content, and (d) the occurrence of unusual 5-OH guaiacyl units. These results are reminiscent of some characteristics already observed for the maize bm3 (brown-midrib3) mutant, as well as for COMT down-regulated dicots. However, as compared with bm3, COMT down-regulation in the COMT-AS line is less severe in that it is restricted to sclerenchyma cells. To our knowledge, this is the first time that an AS strategy has been applied to modify lignin biosynthesis in a grass species. PMID:12481050

  12. Constituents of Propolis: Chrysin, Caffeic Acid, p-Coumaric Acid, and Ferulic Acid Induce PRODH/POX-Dependent Apoptosis in Human Tongue Squamous Cell Carcinoma Cell (CAL-27

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    Katarzyna Celińska-Janowicz

    2018-04-01

    Full Text Available Propolis evokes several therapeutic properties, including anticancer activity. These activities are attributed to the action of polyphenols. Previously it has been demonstrated, that one of the most abundant polyphenolic compounds in ethanolic extracts of propolis are chrysin, caffeic acid, p-coumaric acid, and ferulic acid. Although their pro-apoptotic activity on human tongue squamous cell carcinoma cells (CAL-27 was established previously, the detailed mechanism of this process remains unclear. Considering the crucial role of proline metabolism and proline dehydrogenase/proline oxidase (PRODH/POX in the regulation of cancer cell survival/apoptosis, we studied these processes in polyphenol-treated CAL-27 cells. All studied polyphenols evoked anti-proliferative activity, accompanied by increased PRODH/POX, P53, active caspases-3 and -9 expressions and decreased collagen biosynthesis, prolidase activity and proline concentration in CAL-27 cells. These data suggest that polyphenols of propolis induce PRODH/POX-dependent apoptosis through up-regulation of mitochondrial proline degradation and down-regulation of proline utilization for collagen biosynthesis.

  13. Additions of caffeic acid, ascorbyl palmitate or gamma-tocopherol to fish oil-enriched energy bars affect lipid oxidation differently

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte

    2009-01-01

    storage when added at a concentration above 440 mu g/g fish oil. However, the best antioxidative effect was observed when it was added at a concentration of 660 mu g/g fish oil. In contrast, prooxidative effects were observed when using either gamma-tocopherol at concentrations below 220 mu g/g fish oil......The objectives of the study were to investigate the effects of caffeic acid, ascorbyl palmitate and gamma-tocopherol on protection of fish oil-enriched energy bars against lipid oxidation during storage for 10 weeks at room temperature. The lipophilic gamma-tocopherol reduced lipid oxidation during......, or the hydrophilic caffeic acid, or the amphiphilic ascorbyl palmitate at concentrations of 75, 150 and 300 mu g/g fish oil. Prooxidative effects were observed as an increase in the formation of lipid hydroperoxides and volatile secondary oxidation products, as well as the development of rancid off...

  14. Poly(3-hydroxybutyrate)/caffeic acid electrospun fibrous materials coated with polyelectrolyte complex and their antibacterial activity and in vitro antitumor effect against HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Ignatova, Milena G. [Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, Bl. 103A, BG-1113 Sofia (Bulgaria); Manolova, Nevena E., E-mail: manolova@polymer.bas.bg [Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, Bl. 103A, BG-1113 Sofia (Bulgaria); Rashkov, Iliya B. [Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, Bl. 103A, BG-1113 Sofia (Bulgaria); Markova, Nadya D. [Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Bl. 26, BG-1113 Sofia (Bulgaria); Toshkova, Reneta A.; Georgieva, Ani K.; Nikolova, Elena B. [Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev St, bl. 25, BG-1113 Sofia (Bulgaria)

    2016-08-01

    The purpose of this work was to investigate the possibility for the preparation of new poly(3-hydroxybutyrate) (PHB)/poly(ethylene glycol) (PEG)-based fibrous materials containing natural phenolic compound caffeic acid (CA) of diverse architectures, as well as to study the impact of the fiber composition on the in vitro CA release profile and on the biological properties of the fibrous materials. The application of the one-pot electrospinning enabled the fabrication of nanofibrous materials from PHB and PEG loaded with the CA. Materials with targeted design were obtained by coating with polyelectrolyte complex of alginate (Alg) and N,N,N-trimethylchitosan (TMCh). Three different processing paths were used to obtain coated mats: (i) with CA incorporated in the PHB/PEG core; (ii) with CA embedded in the Alg layer; and (iii) with CA included in the TMCh layer. The in vitro release of CA was modulated by controlling the composition and the architecture of the nanofibrous mats. The performed microbiological screening and MTT cell viability studies revealed that in contrast to the bare mats, the CA-containing nanofibrous materials were effective in suppressing the growth of the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli and displayed good cytotoxicity against human cervical HeLa tumor cells. In addition, the proliferation of murine spleen lymphocytes and peritoneal macrophages was increased by the prepared CA-containing nanofibrous materials. The obtained materials are promising for antibacterial wound dressing applications as well as for application in local treatment of cervical tumors. - Highlights: • New caffeic acid-loaded materials from PHB and PEG were prepared by electrospinning. • Different design is achieved by coating and formation of polyelectrolyte complexes. • The control on the architecture of the mats enables modulating caffeic acid release. • The caffeic acid-loaded mats suppress the growth of

  15. Structure-Activity Relationships in the Cytoprotective Effect of Caffeic Acid Phenethyl Ester (CAPE) and Fluorinated Derivatives: Effects on Heme Oxygenase-1 Induction and Antioxidant Activities

    Science.gov (United States)

    2010-03-09

    derivatives than their direct antioxidant activity. © 2010 Published by Elsevier B.V. 1. Introduction Caffeic acid phenethyl ester (CAPE), a polyphenolic ...al., 2006). Fluorine substitution in the design and synthesis of small molecules for potential therapeutic use has become very common (Kirk, 2006...has been suggested that the methylation of polyphenolic compounds may result in the loss of their free radical scavenging ability (Deng et al., 2006

  16. Caffeic acid n-butyl ester-triggered necrosis-like cell death in lung cancer cell line A549 is prompted by ROS mediated alterations in mitochondrial membrane potential.

    Science.gov (United States)

    Zhang, Y-X; Yu, P-F; Gao, Z-M; Yuan, J; Zhang, Z

    2017-04-01

    The aim of the present study was to evaluate the anticancer activity of caffeic acid n-butyl ester against lung cancer cell line A549 and to investigate the underlying mechanism. IC50 was determined by MTT assay. Fluorescent probes DCFH-DA, Indo 1/AM, DiOC6 were used to determine ROS, Ca2+, and mitochondrial membrane potential (ΔΨm). ATP levels were determined by using ATP liteTM kit. DNA damage was investigated by DAPI and comet assays. Protein expression was investigated by Western blotting. Caffeic acid n-butyl ester exhibited lowest IC50 of 25 µM against lung A549 cell line. Caffeic acid n-butyl ester reduced the cell viability of A549 cells concentration and time-dependently. It also augmented the discharge of ROS and Ca2+ and lessened the mitochondrial membrane potential (ΔΨm) and ATP levels in A549 cells. Additionally, caffeic acid n-butyl ester also prompted DNA damage in A549 cell line. Notably, caffeic acid n-butyl ester-stimulated the cytochrome c release only and exhibited no effect on the expression of apoptosis-related protein levels such as caspase-3, caspase-8, and Apaf-1. Caffeic acid n-butyl ester exhibited significant anticancer activity against lung cancer cell line A549. However, the anticancer activity was not due to apoptosis as no significant change was observed in the expression of apoptosis-related proteins. The anticancer activity of caffeic acid n-butyl ester may be attributed to necrosis-like cell death prompted by ROS-mediated alterations in ΔΨm. Taken together, we conclude that caffeic acid n-butyl ester-induced A549 cells death displayed a cellular pattern characteristic of necrotic cell death and not of apoptosis.

  17. Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats

    Directory of Open Access Journals (Sweden)

    Aburrahman Gun

    2016-01-01

    Full Text Available Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS. HFCS (6 weeks, 30% fed with drinking water caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

  18. Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats.

    Science.gov (United States)

    Gun, Aburrahman; Ozer, Mehmet Kaya; Bilgic, Sedat; Kocaman, Nevin; Ozan, Gonca

    2016-01-01

    Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE) has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS). HFCS (6 weeks, 30% fed with drinking water) caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks) effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS) production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

  19. The Effect of Caffeic Acid Phenethyl Ester (CAPE) Fortification on the Liver Element Distribution that Occurs After Exercise.

    Science.gov (United States)

    Akil, Mustafa; Coban, Funda Karabag; Yalcinkaya, Ozcan

    2016-08-01

    The purpose of this study is to examine the effect of the caffeic acid phenethyl ester (CAPE) fortification applied to the rats, which were made to exercise, on the liver elements. The study was conducted on 32 Sprague-Dawley male rats. The experimental animals were divided into 4 groups in equal numbers. Group 1 is the group which was applied 10 μmol/kg/day CAPE as intraperitoneal (IP) for 4 weeks, and they were not made to exercise at the end of the application. Group 2 is the group which was applied 10 μmol/kg/day CAPE as IP for 4 weeks, and they were made to exercise at the end of the 4th week. Group 3 is the general control group. Group 4 is the swimming control group. A 10 mmol/kg CAPE application dissolved in ethyl alcohol of 10 % was applied to the CAPE group. Sodium (Na), zinc (Zn), calcium (Ca), iron (Fe), chrome (Cr), magnesium (Mg), potassium (K), copper (Cu) and cadmium (Cd) levels were identified in the liver samples at the end of the application. The results of the study suggest that exercise and CAPE fortification in rats cause changes in the Na, Zn, Ca, Fe and Cr parameters in liver tissues, and it does not affect Cd, Cu, Mg and K element distribution. It is thought that CAPE fortification would be helpful for preserving those parameters whose levels are known to be changing with exercise.

  20. Synergistic Antibacterial Effects of Chitosan-Caffeic Acid Conjugate against Antibiotic-Resistant Acne-Related Bacteria

    Directory of Open Access Journals (Sweden)

    Ji-Hoon Kim

    2017-06-01

    Full Text Available The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, one of the most common skin diseases. Acne vulgaris is often associated with acne-related bacteria such as Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa. Some of these bacteria exhibit a resistance against commercial antibiotics that have been used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin. In the current study, we tested in vitro antibacterial effect of chitosan-phytochemical conjugates on acne-related bacteria. Three chitosan-phytochemical conjugates used in this study exhibited stronger antibacterial activity than that of chitosan (unmodified control. Chitosan-caffeic acid conjugate (CCA showed the highest antibacterial effect on acne-related bacteria along with minimum inhibitory concentration (MIC; 8 to 256 μg/mL. Additionally, the MIC values of antibiotics against antibiotic-resistant P. acnes and P. aeruginosa strains were dramatically reduced in combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration (FIC indices clearly revealed a synergistic antibacterial effect of CCA with antibiotics. Thus, the median sum of FIC (∑FIC values against the antibiotic-resistant bacterial strains ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics. The results of the present study suggested a potential possibility of chitosan-phytochemical conjugates in the control of infections related to acne vulgaris.

  1. Synergistic Antibacterial Effects of Chitosan-Caffeic Acid Conjugate against Antibiotic-Resistant Acne-Related Bacteria.

    Science.gov (United States)

    Kim, Ji-Hoon; Yu, Daeung; Eom, Sung-Hwan; Kim, Song-Hee; Oh, Junghwan; Jung, Won-Kyo; Kim, Young-Mog

    2017-06-08

    The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, one of the most common skin diseases. Acne vulgaris is often associated with acne-related bacteria such as Propionibacterium acnes , Staphylococcus epidermidis , Staphylococcus aureus , and Pseudomonas aeruginosa . Some of these bacteria exhibit a resistance against commercial antibiotics that have been used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin). In the current study, we tested in vitro antibacterial effect of chitosan-phytochemical conjugates on acne-related bacteria. Three chitosan-phytochemical conjugates used in this study exhibited stronger antibacterial activity than that of chitosan (unmodified control). Chitosan-caffeic acid conjugate (CCA) showed the highest antibacterial effect on acne-related bacteria along with minimum inhibitory concentration (MIC; 8 to 256 μg/mL). Additionally, the MIC values of antibiotics against antibiotic-resistant P. acnes and P. aeruginosa strains were dramatically reduced in combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration (FIC) indices clearly revealed a synergistic antibacterial effect of CCA with antibiotics. Thus, the median sum of FIC (∑FIC) values against the antibiotic-resistant bacterial strains ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics. The results of the present study suggested a potential possibility of chitosan-phytochemical conjugates in the control of infections related to acne vulgaris.

  2. Fibrinolytic Activity and Dose-Dependent Effect of Incubating Human Blood Clots in Caffeic Acid Phenethyl Ester: In Vitro Assays

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    Abuzar Elnager

    2015-01-01

    Full Text Available Background. Caffeic acid phenethyl ester (CAPE has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM. After 3 hours, D-dimer (DD levels and WB clot weights were measured for each concentration. Thromboelastography (TEG parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM. The 50% effective dose (ED50 of CAPE (based on DD was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted.

  3. Novel Antidepressant-Like Activity of Caffeic Acid Phenethyl Ester Is Mediated by Enhanced Glucocorticoid Receptor Function in the Hippocampus

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    Mi-Sook Lee

    2014-01-01

    Full Text Available Caffeic acid phenethyl ester (CAPE is an active component of propolis that has a variety of potential pharmacological effects. Although we previously demonstrated that propolis has antidepressant-like activity, the effect of CAPE on this activity remains unknown. The present study assessed whether treatment with CAPE (5, 10, and 20 µmol/kg for 21 days has an antidepressant-like effect in mice subjected to chronic unpredictable stress via tail suspension (TST and forced swim (FST tests. CAPE administration induced behaviors consistent with an antidepressant effect, evidenced by decreased immobility in the TST and FST independent of any effect on serum corticosterone secretion. Western blots, conducted subsequent to behavioral assessment, revealed that CAPE significantly decreased glucocorticoid receptor phosphorylation at S234 (pGR(S234, resulting in an increased pGR(S220/S234 ratio. We also observed negative correlations between pGR(S220/(S234 and p38 mitogen-activated protein kinase (p38MAPK phosphorylation, which was decreased by CAPE treatment. These findings suggest that CAPE treatment exerts an antidepressant-like effect via downregulation of p38MAPK phosphorylation, thereby contributing to enhanced GR function.

  4. Crystallization and preliminary X-ray diffraction analysis of a Lys49-phospholipase A2 complexed with caffeic acid, a molecule with inhibitory properties against snake venoms

    International Nuclear Information System (INIS)

    Shimabuku, Patrícia S.; Fernandes, Carlos A. H.; Magro, Angelo J.; Costa, Tássia R.; Soares, Andreimar M.; Fontes, Marcos R. M.

    2011-01-01

    Piratoxin I, a noncatalytic and myotoxic Lys49-phospholipase A 2 from B. pirajai venom, was cocrystallized with the inhibitor caffeic acid and a data set was collected to a resolution of 1.65 Å. The electron-density map unambiguously indicated that three inhibitor molecules interact with the C-terminus of the protein. Phospholipases A 2 (PLA 2 s) are one of the main components of bothropic venoms; in addition to their phospholipid hydrolysis action, they are involved in a wide spectrum of pharmacological activities, including neurotoxicity, myotoxicity and cardiotoxicity. Caffeic acid is an inhibitor that is present in several plants and is employed for the treatment of ophidian envenomations in the folk medicine of many developing countries; as bothropic snake bites are not efficiently neutralized by conventional serum therapy, it may be useful as an antivenom. In this work, the cocrystallization and preliminary X-ray diffraction analysis of the Lys49-PLA 2 piratoxin I from Bothrops pirajai venom in the presence of the inhibitor caffeic acid (CA) are reported. The crystals diffracted X-rays to 1.65 Å resolution and the structure was solved by molecular-replacement techniques. The electron-density map unambiguously indicated the presence of three CA molecules that interact with the C-terminus of the protein. This is the first time a ligand has been observed bound to this region and is in agreement with various experiments previously reported in the literature

  5. Cooperative Reinforcement of Ionic Liquid and Reactive Solvent on Enzymatic Synthesis of Caffeic Acid Phenethyl Ester as an In Vitro Inhibitor of Plant Pathogenic Bacteria

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    Yan Xu

    2017-01-01

    Full Text Available It is widely believed that lipases in ionic liquids (ILs possess higher enzyme activity, stability and selectivity; however, reaction equilibrium is always limited by product inhibition, and the product is difficult to separate from non-volatile ILs using distillation. To solve this problem, using trialkylphosphine oxide (TOPO as a complexing agent, a novel biphase of reactive solvent and IL was firstly reported for caffeic acid phenethyl ester (CAPE production from methyl caffeate (MC and 2-phenylethanol (PE catalyzed by lipase via transesterification. The effects of the reaction parameters and their action mechanism were investigated, and the inhibition of CAPE against bacterial wilt pathogen Ralstonia solanacearum was firstly measured. The MC conversion of 98.83% ± 0.76% and CAPE yield of 96.29% ± 0.07% were obtained by response surface methodology in the 25 g/L TOPO-cyclohexane/[Bmim][Tf2N] (1:1, v/v; the complex stoichiometry calculation and FTIR spectrum confirmed that the reversible hydrogen-bond complexation between TOPO and caffeates significantly enhances the cooperative effect of two phases on the lipase-catalyzed reaction. The temperature was reduced by 14 °C; the MC concentration increased by 3.33-fold; the ratio of catalyst to donor decreased by 4.5-fold; and Km decreased 1.08-fold. The EC50 of CAPE against R. solanacearum was 0.17–0.75 mg/mL, suggesting that CAPE is a potential in vitro inhibitor of plant pathogenic bacteria.

  6. Inhibition of the Decrease of Linalool in Muscat Wine by Phenolic Acids

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    Ioannis G. Roussis

    2005-01-01

    Full Text Available Two white wine extracts rich in phenolic acids, caffeic acid and gallic acid were tested as inhibitors of the decrease of linalool in Muscat wine. Each wine extract was added at 60 ppm and each phenolic acid at 40 ppm. Immediately after the addition of each wine extract or phenolic acid, no effect on the concentration of linalool was observed, but it decreased from the initial 470.9 to 223.3 μg/L after storage in open bottles at 20 °C for 4 days. Its decrease was significantly inhibited by each wine extract or phenolic acid.

  7. Immunomodulatory and cellular anti-oxidant activities of caffeic, ferulic, and p-coumaric phenolic acids: a structure-activity relationship study.

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    Kilani-Jaziri, Soumaya; Mokdad-Bzeouich, Imen; Krifa, Mounira; Nasr, Nouha; Ghedira, Kamel; Chekir-Ghedira, Leila

    2017-10-01

    Many studies have been performed to assess the potential utility of natural products as immunomodulatory agents to enhance host responses and to reduce damage to the human body. To determine whether phenolic compounds (caffeic, ferulic, and p-coumaric acids) have immunomodulatory effects and clarify which types of immune effector cells are stimulated in vitro, we evaluated their effect on splenocyte proliferation and lysosomal enzyme activity. We also investigated the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL). In addition, induction of the cellular antioxidant activity in splenocytes, macrophages, and red blood cells was determined by measuring the fluorescence of the DCF product. The study first results indicated that caffeic, ferulic, and p-coumaric acids significantly promote LPS-stimulated splenocyte proliferation, suggesting a potential activation of B cells, and enhanced humoral immune response in hosts treated by the tested natural products. Phenolic acids significantly enhanced the killing activity of isolated NK and CTL cells but had negligible effects on mitogen-induced proliferation of splenic T cells. We showed that caffeic acid enhances lysosomal enzyme activity in murine peritoneal macrophages, suggesting a potential role in activating such cells. Immunomodulatory activity was concomitant with the cellular antioxidant effect in macrophages and splenocytes of caffeic and ferulic acids. We conclude from this study that caffeic, ferulic, and p-coumaric acids exhibited an immunomodulatory effect which could be ascribed, in part, to their cytoprotective effect via their antioxidant capacity. Furthermore, these results suggest that these natural products could be potentially used to modulate immune cell functions in physiological and pathological conditions.

  8. Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.

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    Massimiliano Migliori

    Full Text Available Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF, an active component with known antioxidant activities.The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury.CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

  9. Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.

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    Migliori, Massimiliano; Cantaluppi, Vincenzo; Mannari, Claudio; Bertelli, Alberto A E; Medica, Davide; Quercia, Alessandro Domenico; Navarro, Victor; Scatena, Alessia; Giovannini, Luca; Biancone, Luigi; Panichi, Vincenzo

    2015-01-01

    Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities. The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury. CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration. The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

  10. Acid detergent lignin, lodging resistance index, and expression of the caffeic acid O-methyltransferase gene in brown midrib-12 sudangrass.

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    Li, Yuan; Liu, Guibo; Li, Jun; You, Yongliang; Zhao, Haiming; Liang, Huan; Mao, Peisheng

    2015-09-01

    Understanding the relationship between acid detergent lignin (ADL) and lodging resistance index (LRI) is essential for breeding new varieties of brown midrib (bmr) sudangrass (Sorghum sudanense (Piper) Stapf.). In this study, bmr-12 near isogenic lines and their wild-types obtained by back cross breeding were used to compare relevant forage yield and quality traits, and to analyze expression of the caffeic acid O-methyltransferase (COMT) gene using quantitative real time-PCR. The research showed that the mean ADL content of bmr-12 mutants (20.94 g kg(-1)) was significantly (P bmr-12 mutants (0.29) was significantly (P bmr-12 materials (r = -0.44, P > 0.05). Sequence comparison of the COMT gene revealed two point mutations present in bmr-12 but not in the wild-type, the second mutation changed amino acid 129 of the protein from Gln (CAG) to a stop codon (UAG). The relative expression level of COMT gene was significantly reduced, which likely led to the decreased ADL content observed in the bmr-12 mutant.

  11. Separation of chlorogenic acid and concentration of trace caffeic acid from natural products by pH-zone-refining countercurrent chromatography.

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    Lu, Yuanyuan; Dong, Genlai; Gu, Yanxiang; Ito, Yoichiro; Wei, Yun

    2013-07-01

    Chlorogenic acid and caffeic acid were selected as test samples for separation by the pH-zone-refining countercurrent chromatography (CCC). The separation of these test samples was performed with a two-phase solvent system composed of methyl-tert-butyl-ether/acetonitrile/water at a volume ratio of 4:1:5 v/v/v where trifluoroacetic acid (TFA; 8 mM) was added to the organic stationary phase as a retainer and NH4 OH (10 mM) to the aqueous mobile phase as an eluter. Chlorogenic acid was successfully separated from Flaveria bidentis (L.) Kuntze (F. bidentis) and Lonicerae Flos by pH-zone-refining CCC, a slightly polar two-phase solvent system composed of methyl-tert-butyl-ether/acetonitrile/n-butanol/water at a volume ratio of 4:1:1:5 v/v/v/v was selected where TFA (3 mM) was added to the organic stationary phase as a retainer and NH4 OH (3 mM) to the aqueous mobile phase as an eluter. A 16.2 mg amount of chlorogenic acid with the purity of 92% from 1.4 g of F. bidentis, and 134 mg of chlorogenic acid at the purity of 99% from 1.3 g of crude extract of Lonicerae Flos have been obtained. These results suggest that pH-zone-refining CCC is suitable for the isolation of the chlorogenic acid from the crude extracts of F. bidentis and Lonicerae Flos. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid.

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    Burgos-Morón, Estefanía; Calderón-Montaño, José Manuel; Orta, Manuel Luis; Guillén-Mancina, Emilio; Mateos, Santiago; López-Lázaro, Miguel

    2016-07-08

    Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (γ-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee.

  13. Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid

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    Estefanía Burgos-Morón

    2016-07-01

    Full Text Available Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2 also play an important role in the development of a variety of cancers (e.g., bladder cancer in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay and DNA damage (γ-H2AX and 53BP1 focus assay induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee.

  14. Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells.

    Science.gov (United States)

    Dinc, Erdem; Ayaz, Lokman; Kurt, Akif Hakan

    2017-12-01

    This study aimed to evaluate the protective effects of caffeic acid phenethyl ester (CAPE) and combined CAPE-bevacizumab against oxidative stress induced by hydrogen peroxide (H 2 O 2 ) in human retinal pigment epithelium. ARPE-19 cells were pretreated with 5, 10, and 30 μM CAPE alone and in combination with bevacizumab for 3 h, then exposed to H 2 O 2 for 16 h. Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Vascular endothelial growth factor (VEGF) protein levels in the medium were measured using a human VEGF ELISA kit. Total antioxidant status (TAS) and total oxidant status (TOS) were measured in ARPE-19 cells using the test kit from Rel Assay. Expression levels of VEGF, Bax, Bcl-2, cytochrome c, apoptotic protease activating factor-1 (apaf-1), and caspase-3 were determined using reverse transcription polymerase chain reaction. Pretreatment of ARPE-19 cells with 30 μM CAPE and combined CAPE-bevacizumab reduced H 2 O 2 mediated cell death. H 2 O 2 -induced oxidative stress increased TOS and VEGF production, which was significantly inhibited by CAPE and the CAPE-bevacizumab combination. VEGF, Bax, cytochrome c, apaf-1, and caspase-3 gene expressions were significantly decreased in cells pretreated with 5, 10, and 30 μM CAPE and combined CAPE-bevacizumab compared to the H 2 O 2 group. In addition, Bcl-2 expression was significantly increased in both the CAPE and CAPE-bevacizumab combination groups compared to the H 2 O 2 group. CAPE has a protective effect on ARPE-19 cells against oxidative stress, and VEGF protein level and expression can be decreased by incubation with different concentrations of CAPE. These results demonstrate that CAPE suppresses the mitochondria-mediated apoptosis in ARPE-19 cells under oxidative stress. In addition, the use of CAPE in combination with bevacizumab has an additive effect.

  15. Neuraminidase inhibition of Dietary chlorogenic acids and derivatives - potential antivirals from dietary sources.

    Science.gov (United States)

    Gamaleldin Elsadig Karar, Mohamed; Matei, Marius-Febi; Jaiswal, Rakesh; Illenberger, Susanne; Kuhnert, Nikolai

    2016-04-01

    Plants rich in chlorogenic acids (CGAs), caffeic acids and their derivatives have been found to exert antiviral effects against influenza virus neuroaminidase. In this study several dietary naturally occurring chlorogenic acids, phenolic acids and derivatives were screened for their inhibitory activity against neuroaminidases (NAs) from C. perfringens, H5N1 and recombinant H5N1 (N-His)-Tag using a fluorometric assay. There was no significant difference in inhibition between the different NA enzymes. The enzyme inhibition results indicated that chlorogenic acids and selected derivatives, exhibited high activities against NAs. It seems that the catechol group from caffeic acid was important for the activity. Dietary CGA therefore show promise as potential antiviral agents. However, caffeoyl quinic acids show low bioavailibility and are intensly metabolized by the gut micro flora, only low nM concentrations are observed in plasma and urine, therefore a systemic antiviral effect of these compounds is unlikely. Nevertheless, gut floral metabolites with a catechol moiety or structurally related dietary phenolics with a catechol moiety might serve as interesting compounds for future investigations.

  16. Anti-infective potential of caffeic acid and epicatechin 3-gallate isolated from methanol extract of Euphorbia hirta (L.) against Pseudomonas aeruginosa.

    Science.gov (United States)

    Perumal, S; Mahmud, R; Ramanathan, S

    2015-01-01

    Euphorbia hirta (L.) plant is traditionally used in Malaysia for the treatment of gastrointestinal, bronchial and respiratory ailments caused by nosocomial infectious agents. Bioactivity-guided fractionation of the methanol extract of the aerial parts of E. hirta and analysis using high-performance liquid chromatography have led to the isolation of two antibacterial compounds. These compounds were identified as caffeic acid (CA) and (-)-epicatechin 3-gallate (ECG) based on spectroscopic analyses and comparison with previously published data. Using broth microdilution method, both ECG and CA had demonstrated significant minimum inhibitory concentration of 15.6 and 31.3 μg/mL respectively, against Pseudomonas aeruginosa. Time-kill assessment of ECG and CA displayed bactericidal effect on P. aeruginosa cells.

  17. Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: a review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects.

    Science.gov (United States)

    Tolba, Mai F; Azab, Samar S; Khalifa, Amani E; Abdel-Rahman, Sherif Z; Abdel-Naim, Ashraf B

    2013-08-01

    Caffeic acid phenethyl ester (CAPE) is an important active component of honey bee propolis that possesses a plethora of biological activities. Propolis is used safely in traditional medicine as a dietary supplement for its therapeutic benefits. This review highlights the recently published data about CAPE bioavailability, anti-inflammatory, neuroprotective; hepatoprotective and cardioprotective activities. CAPE showed promising efficacy both in vitro and in vivo studies in animal models with minimum adverse effects. Its effectiveness was demonstrated in multiple target organs. Despite this fact, it has not been yet investigated as a protective agent or a potential therapy in humans. Investigation of CAPE efficacy in clinical trials is strongly encouraged to elucidate its therapeutic benefit for different human diseases after performing full preclinical toxicological studies and gaining more insights into its pharmacokinetics. © 2013 International Union of Biochemistry and Molecular Biology.

  18. Humic substances can modulate the allelopathic potential of caffeic, ferulic, and salicylic acids for seedlings of lettuce (Lactuca sativa L.) and tomato (Lycopersicon esculentum Mill.).

    Science.gov (United States)

    Loffredo, Elisabetta; Monaci, Linda; Senesi, Nicola

    2005-11-30

    The capacity of a leonardite humic acid (LHA), a soil humic acid (SHA), and a soil fulvic acid (SFA) in modulating the allelopathic potential of caffeic acid (CA), ferulic acid (FA), and salicylic acid (SA) on seedlings of lettuce (Lactuca sativa L.) and tomato (Lycopersicon esculentum Mill.) was investigated. Lettuce showed a sensitivity greater than that of tomato to CA, FA, and SA phytotoxicity, which was significantly reduced or even suppressed in the presence of SHA or SFA, especially at the highest dose, but not LHA. In general, SFA was slightly more active than SHA, and the efficiency of the action depended on their concentration, the plant species and the organ examined, and the allelochemical. The daily measured residual concentration of CA and FA decreased drastically and that of SA slightly in the presence of germinating seeds of lettuce, which were thus able to absorb and/or enhance the degradation of CA and FA. The adsorption capacity of SHA for the three allelochemicals was small and decreased in the order FA > CA > SA, thus suggesting that adsorption could be a relevant mechanism, but not the only one, involved in the "antiallelopathic" action.

  19. Activity of chalcones derived from 2,4,5-trimethoxybenzaldehyde against Meloidogyne exigua and in silico interaction of one chalcone with a putative caffeic acid 3-O-methyltransferase from Meloidogyne incognita.

    Science.gov (United States)

    Nunes, Alexandro Silva; Campos, Vicente Paulo; Mascarello, Alessandra; Stumpf, Taisa Regina; Chiaradia-Delatorre, Louise Domenghini; Machado, Alan Rodrigues Teixeira; Santos Júnior, Helvécio Martins; Yunes, Rosendo Augusto; Nunes, Ricardo José; Oliveira, Denilson Ferreira

    2013-12-01

    Meloidogyne exigua is a parasitic nematode of plants that causes great losses to coffee farmers. In an effort to develop parasitic controls, 154 chalcones were synthesized and screened for activity against this nematode. The best results were obtained with (2E)-1-(4'-nitrophenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one (6) with a 50% lethal concentration (LC50) of 171 μg/ml against M. exigua second-stage juveniles, in comparison to the commercially-available nematicide carbofuran which had an LC50 of 260 μg/ml under the same conditions. When coffee plants were used, 6 reduced the nematode population to ~50% of that observed in control plants. To investigate the mechanism of action of 6, an in silico study was carried out, which indicated that 6 may act against M. exigua through inhibition of a putative caffeic acid 3-O-methyltransferase homodimer, the amino acid sequence of which was determined by examining the genome of Meloidogyne incognita. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Oral administration of caffeic acid ameliorates the effect of cisplatin on brush border membrane enzymes and antioxidant system in rat intestine.

    Science.gov (United States)

    Arivarasu, N A; Priyamvada, Shubha; Mahmood, Riaz

    2013-01-01

    Cisplatin (CP) is a widely used antineoplastic drug that exhibits gastrointestinal toxicity. We have previously shown that administration of a single dose of CP results in a decrease in the activities of several brush border membrane (BBM) enzymes, induces oxidative stress and alters the activities of several antioxidant enzymes in the small intestine of rats. In the present study we have investigated the effect of treatment with the dietary antioxidant caffeic acid (CA) on CP induced biochemical changes in the intestine. Administration of a single intraperitoneal dose of CP alone (6 mg/kg body weight) led to a decrease in the activities of the BBM enzymes, increase in lipid peroxidation, decrease in sulfhydryl groups and changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, glucose 6-phosphate dehydrogenase, glutathione reductase, glutathione S-transferase and thioredoxin reductase. Administration of two doses of CA (each of 250 mg/kg body weight), at 15 and 120 min after treatment with CP, significantly attenuated the CP-induced changes in all these parameters but the administration of CA alone had no effect. These results suggest that CA is an effective agent in reducing the effects of CP on the intestine and could prove to be useful in alleviating the gastrointestinal toxicity of this drug. Copyright © 2011 Elsevier GmbH. All rights reserved.

  1. Development of novel antibacterial active, HaCaT biocompatible and biodegradable CA-g-P(3HB-EC biocomposites with caffeic acid as a functional entity

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    H. M. N. Iqbal

    2015-09-01

    Full Text Available We have developed novel composites by grafting caffeic acid (CA onto the P(3HB-EC based material and laccase from Trametes versicolor was used for grafting purposes. The resulting composites were designated as CA-g-P(3HB-EC i.e., P(3HB-EC (control, 5CA-g-P(3HB-EC, 10CA-g-P(3HB-EC, 15CA-g-P(3HB-EC and 20CA-g-P(3HB-EC. FT-IR (Fourier-transform infrared spectroscopy was used to examine the functional and elemental groups of the control and laccase-assisted graft composites. Evidently, 15CA-g-P(3HB-EC composite exhibited resilient antibacterial activity against Gram-positive and Gram-negative bacterial strains. Moreover, a significant level of biocompatibility and biodegradability of the CA-g-P(3HB-EC composites was also achieved with the human keratinocytes-like HaCaT cells and soil burial evaluation, respectively. In conclusion, the newly developed novel composites with multi characteristics could well represent the new wave of biomaterials for medical applications, and more specifically have promising future in the infection free would dressings, burn and/or skin regeneration field due to their sophisticated characteristics.

  2. Caffeic Acid Phenylethyl Ester and MG-132 Have Apoptotic and Antiproliferative Effects on Leukemic Cells But Not on Normal Mononuclear Cells12

    Science.gov (United States)

    Cavaliere, Victoria; Papademetrio, Daniela L; Lorenzetti, Mario; Valva, Pamela; Preciado, María Victoria; Gargallo, Patricia; Larripa, Irene; Monreal, Mariela B; Pardo, María Laura; Hajos, Silvia E; Blanco, Guillermo AC; Álvarez, Élida MC

    2009-01-01

    Chemotherapy aims to limit proliferation and induce apoptotic cell death in tumor cells. Owing to blockade of signaling pathways involved in cell survival and proliferation, nuclear factor κB (NF-κB) inhibitors can induce apoptosis in a number of hematological malignancies. The efficacy of conventional chemotherapeutic drugs, such as vincristine (VCR) and doxorubicine (DOX), may be enhanced with combined therapy based on NF-κB modulation. In this study, we evaluated the effect of caffeic acid phenylethyl ester (CAPE) and MG-132, two nonspecific NF-κB inhibitors, and conventional chemotherapeutics drugs DOX and VCR on cell proliferation and apoptosis induction on a lymphoblastoid B-cell line, PL104, established and characterized in our laboratory. CAPE and MG-132 treatment showed a strong antiproliferative effect accompanied by clear cell cycle deregulation and apoptosis induction. Doxorubicine and VCR showed antiproliferative effects similar to those of CAPE and MG-132, although the latter drugs showed an apoptotic rate two-fold higher than DOX and VCR. None of the four compounds showed cytotoxic effect on peripheral mononuclear cells from healthy volunteers. CAPE- and MG-132-treated bone marrow cells from patients with myeloid and lymphoid leukemias showed 69% (P < .001) and 25% decrease (P < .01) in cell proliferation and 42% and 34% (P < .01) apoptosis induction, respectively. Overall, our results indicate that CAPE and MG-132 had a strong and selective apoptotic effect on tumor cells that may be useful in future treatment of hematological neoplasias. PMID:19252751

  3. Effect of caffeic acid phenethyl ester on oxidant and anti-oxidant status of liver and serum in a rat model with acute methanol intoxication.

    Science.gov (United States)

    Yazgan, Ü C; Elbey, B; Kuş, S; Baykal, B; Keskin, I; Yılmaz, A; Şahin, A

    2017-05-01

    Methanol toxicity is one of the major public health problems because it can cause severe morbidity and mortality. Methanol intoxication causes changes in the balance between the production of free radicals and antioxidant capacity. We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on the total oxidant status, total antioxidant status (TAS), and oxidative stress index (OSI) parameters of the liver and the serum in a rat model of acute methanol intoxication. Rats were treated with intraperitoneal (i.p.) Methotrexate (MTX) for 7 days. On the 8th day, i.p. Methanol was administered in the methanol, ethanol and CAPE groups. Four hours after methanol treatment, ethanol was injected i.p. in the ethanol group; CAPE (i.p.) in the CAPE group; serum physiologic i.p. in other groups. After 8 hours, rats were killed and the serum and the liver samples were obtained for biochemical analyses. The OSI value was significantly higher in the methanol group compared to the ethanol and CAPE groups. Serum TAS levels of the methanol group were significantly different compared to the control group, but not compared to the MTX group. The amelioration of oxidative stress was greater in the CAPE group compared to the ethanol group but was not statistically significant. This study demonstrates that CAPE treatment ameliorates oxidative stress in the serum and liver in a rat model of acute methanol intoxication.

  4. Establishment of Hairy Root Cultures of Rhaponticum carthamoides (Willd. Iljin for the Production of Biomass and Caffeic Acid Derivatives

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    Ewa Skała

    2015-01-01

    Full Text Available The aim of the study was to obtain transformed roots of Rhaponticum carthamoides and evaluate their phytochemical profile. Hairy roots were induced from leaf explants by the transformation of Agrobacterium rhizogenes strains A4 and ATCC 15834. The best response (43% was achieved by infection with A4 strain. The effects of different liquid media (WPM, B5, SH with full and half-strength concentrations of macro- and micronutrients on biomass accumulation of the best grown hairy root line (RC3 at two different lighting conditions (light or dark were investigated. The highest biomass (93 g L−1 of the fresh weight after 35 days was obtained in WPM medium under periodic light. UPLC-PDA-ESI-MS3 and HPLC-PDA analyses of 80% aqueous methanol extracts from the obtained hairy roots revealed the presence of eleven caffeoylquinic acids and their derivatives and five flavonoid glycosides. The production of caffeoylquinic acids and their derivatives was elevated in hairy roots grown in the light. Only light-grown hairy roots demonstrated the capability for the biosynthesis of such flavonoid glycosides as quercetagetin, quercetin, luteolin, and patuletin hexosides. Chlorogenic acid, 3,5-di-O-caffeoylquinic acid and a tentatively identified tricaffeoylquinic acid derivative were detected as the major compounds present in the transformed roots.

  5. Nitrogen Limited Red and Green Leaf Lettuce Accumulate Flavonoid Glycosides, Caffeic Acid Derivatives, and Sucrose while Losing Chlorophylls, Β-Carotene and Xanthophylls.

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    Christine Becker

    Full Text Available Reduction of nitrogen application in crop production is desirable for ecological and health-related reasons. Interestingly, nitrogen deficiency can lead to enhanced concentrations of polyphenols in plants. The reason for this is still under discussion. The plants' response to low nitrogen concentration can interact with other factors, for example radiation intensity. We cultivated red and green leaf lettuce hydroponically in a Mediterranean greenhouse, supplying three different levels of nitrogen (12 mM, 3 mM, 0.75 mM, either in full or reduced (-50% radiation intensity. In both red and green lettuce, we found clear effects of the nitrogen treatments on growth characteristics, phenolic and photosynthetic compounds, nitrogen, nitrate and carbon concentration of the plants. Interestingly, the concentrations of all main flavonoid glycosides, caffeic acid derivatives, and sucrose increased with decreasing nitrogen concentration, whereas those of chlorophylls, β-carotene, neoxanthin, lactucaxanthin, all trans- and cis-violaxanthin decreased. The constitutive concentrations of polyphenols were lower in the green cultivar, but their relative increase was more pronounced than in the red cultivar. The constitutive concentrations of chlorophylls, β-carotene, neoxanthin, all trans- and cis-violaxanthin were similar in red and green lettuce and with decreasing nitrogen concentration they declined to a similar extent in both cultivars. We only detected little influence of the radiation treatments, e.g. on anthocyanin concentration, and hardly any interaction between radiation and nitrogen concentration. Our results imply a greater physiological plasticity of green compared to the red lettuce regarding its phenolic compounds. They support the photoprotection theory regarding anthocyanins as well as the theory that the deamination activity of phenylalanine ammonia-lyase drives phenylpropanoid synthesis.

  6. Chloroplast overexpression of rice caffeic acid O-methyltransferase increases melatonin production in chloroplasts via the 5-methoxytryptamine pathway in transgenic rice plants.

    Science.gov (United States)

    Choi, Geun-Hee; Lee, Hyoung Yool; Back, Kyoungwhan

    2017-08-01

    Recent analyses of the enzymatic features of various melatonin biosynthetic genes from bacteria, animals, and plants have led to the hypothesis that melatonin could be synthesized via the 5-methoxytryptamine (5-MT) pathway. 5-MT is known to be synthesized in vitro from serotonin by the enzymatic action of O-methyltransferases, including N-acetylserotonin methyltransferase (ASMT) and caffeic acid O-methyltransferase (COMT), leading to melatonin synthesis by the subsequent enzymatic reaction with serotonin N-acetyltransferase (SNAT). Here, we show that 5-MT was produced and served as a precursor for melatonin synthesis in plants. When rice seedlings were challenged with senescence treatment, 5-MT levels and melatonin production were increased in transgenic rice seedlings overexpressing the rice COMT in chloroplasts, while no such increases were observed in wild-type or transgenic seedlings overexpressing the rice COMT in the cytosol, suggesting a 5-MT transport limitation from the cytosol to chloroplasts. In contrast, cadmium treatment led to results different from those in senescence. The enhanced melatonin production was not observed in the chloroplast COMT lines relative over the cytosol COMT lines although 5-MT levels were equally induced in all genotypes upon cadmium treatment. The transgenic seedlings with enhanced melatonin in their chloroplasts exhibited improved seedling growth vs the wild type under continuous light conditions. This is the first report describing enhanced melatonin production in chloroplasts via the 5-MT pathway with the ectopic overexpression of COMT in chloroplasts in plants. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Spectroscopic (FT-IR, FT-Raman, UV absorption, 1H and 13C NMR) and theoretical (in B3LYP/6-311++G** level) studies on alkali metal salts of caffeic acid.

    Science.gov (United States)

    Świsłocka, Renata

    2013-01-01

    The effect of some metals on the electronic system of benzoic and nicotinic acids has recently been investigated by IR, Raman and UV spectroscopy [1-3]. Benzoic and nicotinic acids are regarded model systems representing a wide group of aromatic ligands which are incorporated into enzymes. In this work the FT-IR (in solid state and in solution), FT-Raman, UV absorption and (1)H and (13)C NMR spectra of caffeic acid (3,4-dihydroxycinnamic acid) and its salts with lithium, sodium, potassium, rubidium and caesium were registered, assigned and analyzed. The effect of alkali metals on the electronic system of ligands was discussed. Studies of differences in the number and position of bands from the IR, Raman, UV absorption spectra and chemical shifts from NMR spectra allowed to conclude on the distribution of electronic charge in the molecules, the delocalization energy of π electrons and the reactivity of ligands in metal complexes. Optimized geometrical structures of studied compounds were calculated by B3LYP method using 6-311++G** basis set. Bond lengths, angles and dipole moments for the optimized structures of caffeic acid and lithium, sodium, potassium caffeinates were also calculated. The theoretical wavenumbers and intensities of IR spectra were obtained. The calculated parameters were compared to the experimental characteristics of investigated compounds. Microbial activity of studied compounds was tested against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Proteus vulgaris. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Ilex paraguariensis crude extract acts on protection and reversion from damage induced by t-butyl hydroperoxide in human erythrocytes: a comparative study with isolated caffeic and/or chlorogenic acids.

    Science.gov (United States)

    Portela, José Luiz; Soares, Deividi; Rosa, Hemerson; Roos, Daniel Henrique; Pinton, Simone; Ávila, Daiana Silva; Puntel, Robson L

    2017-05-01

    Studies comparing the effects of phytochemicals under different regimens of exposure are necessary to give a better indication about their mechanism(s) of protection. Hence, in the present study, we investigated the preventive (pre-incubation), protective (co-incubation) and/or remediative (post-incubation) activity of chlorogenic acid and caffeic acids, in comparison with Ilex paraguariensis crude extract, against t-butyl hydroperoxide (t-BHP)-induced damage to human erythrocytes. We found that both caffeic and chlorogenic acids were able to prevent and revert the hemolysis associated with t-BHP exposure. By contrast, isolated compounds (alone or in combination) presented no effect on basal and/or t-BHP-induced non-protein thiol (NPSH) oxidation or production of thiobarbituric acid reactive substances (TBBARS). In turn, I. paraguariensis extract was effective to prevent, protect and revert the hemolysis associated with t-BHP exposure. Moreover, I. paraguariensis significantly protects and reverts t-BHP-induced NPSH oxidation and TBARS production. We have found that I. paraguariensis extract acts better with respect to the protection and reversion of t-BHP-associated changes, whereas isolated compounds are more active in preventing and reverting t-BHP pro-hemolytic action. Moreover, our data suggest that the pro-hemolytic activity of t-BHP may occur via mechanism(s) other(s) than lipid peroxidation and/or NPSH oxidation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  9. Ameliorating Role of Caffeic Acid Phenethyl Ester (CAPE Against Methotrexate-Induced Oxidative Stress in the Sciatic Nerve, Spinal Cord and Brain Stem Tissues of Rats

    Directory of Open Access Journals (Sweden)

    Ertuğrul Uzar

    2010-03-01

    Full Text Available OBJECTIVE: Methotrexate (MTX-associated neurotoxicity is an important clinical problem in cancer patients, but the mechanisms of MTX-induced neurotoxicity are not yet known exactly. The aims of this study were (1 to investigate the possible role of malondialdehyde (MDA, superoxide dismutase (SOD enzyme, glutathione peroxidase (GSH-Px and catalase (CAT in the pathogenesis of MTX-induced neurotoxicity and (2 to determine whether there is a putative protective effect of caffeic acid phenethyl ester (CAPE on MTX-induced neurotoxicity in the spinal cord, brainstem and sciatic nerve of rats. METHODS: A total of 19 adult Wistar male rats were divided into three experimental groups. Group I, control group; Group II, MTX-treated group; and Group III, MTX + CAPE-treated group. MTX was administered to the MTX and MTX + CAPE groups intraperitoneally (IP with a single dose of 20 mg/kg on the second day of the experiment. CAPE was administered to the MTX + CAPE group IP with a dose of 10 μmol/kg for 7 days. RESULTS: In the sciatic nerve and spinal cord tissue, CAT and GSH-Px activities were increased in the MTX group in comparison with the control group. CAPE treatment with MTX significantly decreased CAT and GSH-Px activities in the neuronal tissues of rats in comparison with the MTX group. In the spinal cord and brainstem tissues, SOD activity in the MTX group was decreased in comparison with the control group, but in the sciatic nerve, there was no significant difference. In the spinal cord and brainstem of rats, SOD activity was increased in the CAPE + MTX group when compared with the MTX group. The level of MDA was higher in the MTX group than in the control group. CAPE administration with MTX injection caused a significant decrease in MDA level when compared with the MTX group. CONCLUSION: These results reveal that MTX increases oxidative stress in the sciatic nerve, spinal cord and brainstem of rats and that CAPE has a preventive effect on the

  10. Reuse of Organomineral Substrate Waste from Hydroponic Systems as Fertilizer in Open-Field Production Increases Yields, Flavonoid Glycosides, and Caffeic Acid Derivatives of Red Oak Leaf Lettuce (Lactuca sativa L.) Much More than Synthetic Fertilizer.

    Science.gov (United States)

    Dannehl, Dennis; Becker, Christine; Suhl, Johanna; Josuttis, Melanie; Schmidt, Uwe

    2016-09-28

    Effects of organic waste from a hydroponic system added with minerals (organomineral fertilizer) and synthetic fertilizer on major polyphenols of red oak leaf lettuce using HPLC-DAD-ESI-MS(3) were investigated. Interestingly, contents of the main flavonoid glycosides and caffeic acid derivatives of lettuce treated with organomineral fertilizer were equal to those synthesized without soil additives. This was found although soil nutrient concentrations, including that of nitrogen, were much lower without additives. However, lettuce treated with synthetic fertilizer showed a significant decrease in contents of caffeic acid derivatives and flavonoid glycosides up to 78.3 and 54.2%, respectively. It is assumed that a negative effect of a high yield on polyphenols as described in the growth-differentiation balance hypothesis can be counteracted by (i) a higher concentration of Mg or (ii) optimal physical properties of the soil structure. Finally, the organomineral substrate waste reused as fertilizer and soil improver resulted in the highest yield (+78.7%), a total fertilizer saving of 322 kg ha(-1) and waste reduction in greenhouses.

  11. Nickel Inhibits Mitochondrial Fatty Acid Oxidation

    Science.gov (United States)

    Uppala, Radha; McKinney, Richard W.; Brant, Kelly A.; Fabisiak, James P.; Goetzman, Eric S.

    2015-01-01

    Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation—the pathway by which fatty acids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273

  12. Phytic Acid Inhibits Lipid Peroxidation In Vitro

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    Alicja Zajdel

    2013-01-01

    Full Text Available Phytic acid (PA has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II/ascorbate-induced peroxidation, as well as Fe(II/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II/ascorbate. The observed inhibitory effect of PA on Fe(II/ascorbate-induced lipid peroxidation was lower (10–20% compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II/ascorbate-induced peroxidation. In the absence of Fe(II/ascorbate, PA at 100 μM and 500 μM significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100 μM and 500 μM significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products.

  13. Undecylenic Acid Inhibits Morphogenesis of Candida albicans

    OpenAIRE

    McLain, Nealoo; Ascanio, Rhoda; Baker, Carol; Strohaver, Robert A.; Dolan, Joseph W.

    2000-01-01

    Resilient liners are frequently used to treat denture stomatitis, a condition often associated with Candida albicans infections. Of 10 liners tested, 2 were found to inhibit the switch from the yeast form to hyphae and a third was found to stimulate this switch. The inhibitor was determined to be undecylenic acid.

  14. Undecylenic acid inhibits morphogenesis of Candida albicans.

    Science.gov (United States)

    McLain, N; Ascanio, R; Baker, C; Strohaver, R A; Dolan, J W

    2000-10-01

    Resilient liners are frequently used to treat denture stomatitis, a condition often associated with Candida albicans infections. Of 10 liners tested, 2 were found to inhibit the switch from the yeast form to hyphae and a third was found to stimulate this switch. The inhibitor was determined to be undecylenic acid.

  15. Enhanced lignin monomer production caused by cinnamic Acid and its hydroxylated derivatives inhibits soybean root growth.

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    Rogério Barbosa Lima

    Full Text Available Cinnamic acid and its hydroxylated derivatives (p-coumaric, caffeic, ferulic and sinapic acids are known allelochemicals that affect the seed germination and root growth of many plant species. Recent studies have indicated that the reduction of root growth by these allelochemicals is associated with premature cell wall lignification. We hypothesized that an influx of these compounds into the phenylpropanoid pathway increases the lignin monomer content and reduces the root growth. To confirm this hypothesis, we evaluated the effects of cinnamic, p-coumaric, caffeic, ferulic and sinapic acids on soybean root growth, lignin and the composition of p-hydroxyphenyl (H, guaiacyl (G and syringyl (S monomers. To this end, three-day-old seedlings were cultivated in nutrient solution with or without allelochemical (or selective enzymatic inhibitors of the phenylpropanoid pathway in a growth chamber for 24 h. In general, the results showed that 1 cinnamic, p-coumaric, caffeic and ferulic acids reduced root growth and increased lignin content; 2 cinnamic and p-coumaric acids increased p-hydroxyphenyl (H monomer content, whereas p-coumaric, caffeic and ferulic acids increased guaiacyl (G content, and sinapic acid increased sinapyl (S content; 3 when applied in conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4-hydroxylase, C4H, cinnamic acid reduced H, G and S contents; and 4 when applied in conjunction with 3,4-(methylenedioxycinnamic acid (MDCA, an inhibitor of the 4-coumarate:CoA ligase, 4CL, p-coumaric acid reduced H, G and S contents, whereas caffeic, ferulic and sinapic acids reduced G and S contents. These results confirm our hypothesis that exogenously applied allelochemicals are channeled into the phenylpropanoid pathway causing excessive production of lignin and its main monomers. By consequence, an enhanced stiffening of the cell wall restricts soybean root growth.

  16. Synthesis and characterization of MnO2/NiO nanocomposites for photocatalysis of tetracycline antibiotic and modification with guanidine for carriers of Caffeic acid phenethyl ester-an anticancer drug.

    Science.gov (United States)

    Gupta, Vinod Kumar; Fakhri, Ali; Agarwal, Shilpi; Ahmadi, Elham; Nejad, Pedram Afshar

    2017-09-01

    In the present studies, modified NiO nanoparticles and MnO 2 /NiO nanocomposites with guanidine were synthesized by anchoring method for carriers of anticancer drug "Caffeic acid phenethyl ester". The prepared nanocomposites were characterized by using Scanning Electron Microscopy, Raman and Fourier transform infrared spectroscopy, X-ray diffraction, Vibrating sample magnetometer. The results from XRD indicated that the crystalline size of NiO nanoparticles and MnO 2 /NiO nanocomposites are 12 and 15nm, respectively. Saturation magnetization (Ms) for NiO NPs and MnO 2 /NiO nanocomposites was to be 0.60, and 0.68emu/g indicating that these are superparamagnetic and ferromagnetic properties in nature. The prepared nanocomposites were evaluated as catalyst for degradation of antibiotics in photocatalysis process. Particularly, the MnO 2 /NiO composite demonstrated the higher degradation rate (89.55%) of tetracycline antibiotic under UV light irradiation than the NiO (67.80%). Drug load on and release from nanopowders was investigated by using UV-Vis spectroscopy method. Time of drug loading was 100min and the drug release in 1-10h with 20-80% drug release were found, and then, it's applicable to in-vivo drug delivery. Therefore, the NiO nanoparticles and MnO 2 /NiO nanocomposites are promising for targeted Caffeic acid phenethyl ester anticancer drug delivery applications. The anticancer drug loaded on guanidine-NiO and guanidine-MnO 2 /NiO in high concentration has an antioxidant property. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. From the X-rays to a reliable “low cost” computational structure of caffeic acid: DFT, MP2, HF and integrated molecular dynamics-X-ray diffraction approach to condensed phases

    Science.gov (United States)

    Lombardo, Giuseppe M.; Portalone, Gustavo; Colapietro, Marcello; Rescifina, Antonio; Punzo, Francesco

    2011-05-01

    The ability of caffeic acid to act as antioxidant against hyperoxo-radicals as well as its recently found therapeutic properties in the treatment of hepatocarcinoma, still make this compound, more than 20 years later the refinement of its crystal structure, object of study. It belongs to the vast family of humic substances, which play a key role in the biodegradation processes and easily form complexes with ions widely diffused in the environment. This class of compounds is therefore interesting for potential environmental chemistry applications concerning the possible complexation of heavy metals. Our study focused on the characterization of caffeic acid as a starting necessary step, which will be followed in the future by the application of our findings on the study of the properties of caffeate anion interaction with heavy metal ions. To reach this goal, we applied a low cost approach - in terms of computational time and resources - aimed at the achievement of a high resolution, robust and trustable structure using the X-ray single crystal data, recollected with a higher resolution, as touchstone for a detailed check. A comparison between the calculations carried out with density functional theory (DFT), Hartree-Fock (HF) method and post SCF second order Møller-Plesset perturbation method (MP2), at the 6-31G ** level of the theory, molecular mechanics (MM) and molecular dynamics (MD) was performed. As a consequence we explained on one hand the possible reasons for the pitfalls of the DFT approach and on the other the benefits of using a good and robust force field developed for condensed phases, as AMBER, with MM and MD. The reliability of the latter, highlighted by the overall agreement extended up to the anisotropic displacement parameters calculated by means of MD and the ones gathered by X-ray measurements, makes it very promising for the above-mentioned goals.

  18. Boswellic acid inhibits expression of acid sphingomyelinase in intestinal cells

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    Duan Rui-Dong

    2009-12-01

    Full Text Available Abstract Background Boswellic acid is a type of triterpenoids with antiinflammatory and antiproliferative properties. Sphingomyelin metabolism generates multiple lipid signals affecting cell proliferation, inflammation, and apoptosis. Upregulation of acid sphingomyelinase (SMase has been found in several inflammation-related diseases such as inflammatory bowel diseases, atherosclerosis, and diabetes. Methods The present study is to examine the effect of 3-acetyl-11-keto-β-boswellic acids (AKBA, a potent boswellic acid, on acid SMase activity and expression in intestinal cells. Both transformed Caco-2 cells and non-transformed Int407 cells were incubated with AKBA. After incubation, the change of acid SMase activity was assayed biochemically, the enzyme protein was examined by Western blot, and acid SMase mRNA was quantified by qPCR. Results We found that AKBA decreased acid SMase activity in both intestinal cell lines in dose and time dependent manners without affecting the secretion of the enzyme to the cell culture medium. The effect of AKBA was more effective in the fetal bovine serum-free culture medium. Among different types of boswellic acid, AKBA was the most potent one. The inhibitory effect on acid SMase activity occurred only in the intact cells but not in cell-free extract in the test tubes. At low concentration, AKBA only decreased the acid SMase activity but not the quantity of the enzyme protein. However, at high concentration, AKBA decreased both the mass of acid SMase protein and the mRNA levels of acid SMase in the cells, as demonstrated by Western blot and qPCR, respectively. Under the concentrations decreasing acid SMase activity, AKBA significantly inhibited cell proliferation. Conclusion We identified a novel inhibitory effect of boswellic acids on acid SMase expression, which may have implications in human diseases and health.

  19. Verbascoside is not genotoxic in the ST and HB crosses of the Drosophila wing spot test, and its constituent, caffeic acid, decreases the spontaneous mutation rate in the ST cross.

    Science.gov (United States)

    Santos-Cruz, Luis Felipe; Ávila-Acevedo, José Guillermo; Ortega-Capitaine, Diego; Ojeda-Duplancher, Jesús Clemente; Perdigón-Moya, Juana Laura; Hernández-Portilla, Luis Barbo; López-Dionicio, Héctor; Durán-Díaz, Angel; Dueñas-García, Irma Elena; Castañeda-Partida, Laura; García-Bores, Ana María; Heres-Pulido, María Eugenia

    2012-03-01

    Verbascoside (VB) is a phenylpropanoid isolated from Buddleja species, some of which originate in Mexico, and was first described in the sixteenth century in the codices of Mexican traditional medicine. VB is present in alcohol extracts and is widely used in the north of Mexico as a sunscreen. VB absorbs UV-A and UV-B radiation and has high antioxidant and anti-inflammatory capacities. VB and its constituent caffeic acid (CA) were screened to determine their genotoxic activity using the Drosophila wing spot test. Third instar larvae (72±4 h) of the standard (ST) and high bioactivation (HB) crosses, with regulated and high levels of cytochrome P450s (Cyp450s), respectively, were exposed to VB or CA (0, 27, 57, 81, 135, and 173 mM). VB was not genotoxic at any of the concentrations tested in both crosses. The amount of VB residue as determined by HPLC in the adult flies that were fed with VB indicated a low metabolism of this compound, which explains the absence of genotoxicity. CA decreased the spontaneous frequencies of small and total spots and showed putative toxicity in the ST cross. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Carbon nanotube reinforced hollow fiber solid/liquid phase microextraction: a novel extraction technique for the measurement of caffeic acid in Echinacea purpurea herbal extracts combined with high-performance liquid chromatography.

    Science.gov (United States)

    Es'haghi, Zarrin; Golsefidi, Mazyar Ahmadi; Saify, Ali; Tanha, Ali Akbar; Rezaeifar, Zohre; Alian-Nezhadi, Zahra

    2010-04-23

    A new design of hollow fiber solid-liquid phase microextraction (HF-SLPME) was developed for the determination of caffeic acid in medicinal plants samples as Echinacea purpure. The membrane extraction with sorbent interface used in this research is a three-phase supported liquid membrane consisting of an aqueous (donor phase), organic solvent/nano sorbent (membrane) and aqueous (acceptor phase) system operated in direct immersion sampling mode. The multi-walled carbon nanotube dispersed in the organic solvent is held in the pores of a porous membrane supported by capillary forces and sonification. It is in contact with two aqueous phases: the donor phase, which is the aqueous sample, and the acceptor phase, usually an aqueous buffer. All microextraction experiments were supported using an Accurel Q3/2 polypropylene hollow fiber membrane (600 microm I.D., 200 microm wall thicknesses, and 0.2 microm pore size). The experimental setup is very simple and highly affordable. The hollow fiber is disposable, so single use of the fiber reduces the risk of cross-contamination and carry-over problems. The proposed method allows the very effective and enriched recuperation of an acidic analyte into one single extract. In order to obtain high enrichment and extraction efficiency of the analyte using this novel technique, the main parameters were optimized. Under the optimized extraction conditions, the method showed good linearity (0.0001-50 microg/L), repeatability, low limits of detection (0.00005 microg/L) and excellent enrichment (EF=2108). Copyright 2010 Elsevier B.V. All rights reserved.

  1. Ilex paraguariensis and its main component chlorogenic acid inhibit fructose formation of advanced glycation endproducts with amino acids at conditions compatible with those in the digestive system.

    Science.gov (United States)

    Bains, Yasmin; Gugliucci, Alejandro

    2017-03-01

    We have previously shown that Ilex paraguariensis extracts have potent antiglycation actions. Associations of excess free fructose consumption with inflammatory diseases have been proposed to be mediated through in situ enteral formation of fructose AGEs, which, after being absorbed may contribute to inflammatory diseases via engagement of RAGE. In this proof of principle investigation we show fluorescent AGE formation between amino acids (Arg, Lys, Gly at 10-50mM) and fructose (10-50mM) under time, temperature, pH and concentrations compatible with the digestive system lumen and its inhibition by Ilex paraguariensis extracts. Incubation of amino acids with fructose (but not glucose) leads to a time dependent formation of AGE fluorescence, already apparent after just 1h incubation, a time frame well compatible with the digestive process. Ilex paraguariensis (mate tea) inhibited AGE formation by 83% at 50μl/ml (pacid and cholorogenic acid were as potent as aminoguanidine-a specific antiglycation agent: IC50 of 0.9mM (pacids at times and concentrations plausibly found in the intestines. The reaction is inhibited by mate tea and its individual phenolics (caffeic acid and chlorogenic acids). The study provides the first evidence for the proposed mechanism to explain epidemiological correlations between excess fructose consumption and inflammatory diseases. Enteral fructose-AGE formation would be inhibited by co-intake of Ilex paraguariensis, and potentially other beverages, fruits and vegetables that contain comparable concentrations of phenolics as in IP (mate tea). Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Corrosion inhibition of aqueous solutions of inorganic mineral acids

    Energy Technology Data Exchange (ETDEWEB)

    Stanford, J.R.

    1971-06-15

    A particularly corrosive use of mineral acids is the employment of 15% solutions and, in some instances, even more concentrated solutions of hydrochloric acid in oil well acidizing applications. It has been found that aqueous solutions of inorganic mineral acids, particularly hydrochloric acid solutions, may be inhibited against their corrosive tendencies toward ferrous metals by adding novel compositions of the invention whereby inhibited mineral acid aqueous solutions are provided. In its simplest embodiment the invention comprises using in combination the Mannich reaction products of a hydroabietyl amine, formaldehyde, and certain aliphatic aldehydes in combination with an acetylenic alcohol which contains from 3 to 12 carbon atoms. (7 claims)

  3. Caffeic acid phenethylester increases stress resistance and enhances lifespan in Caenorhabditis elegans by modulation of the insulin-like DAF-16 signalling pathway.

    Science.gov (United States)

    Havermann, Susannah; Chovolou, Yvonni; Humpf, Hans-Ulrich; Wätjen, Wim

    2014-01-01

    CAPE is an active constituent of propolis which is widely used in traditional medicine. This hydroxycinnamic acid derivate is a known activator of the redox-active Nrf2 signalling pathway in mammalian cells. We used C. elegans to investigate the effects of this compound on accumulation of reactive oxygen species and the modulation of the pivotal redox-active pathways SKN-1 and DAF-16 (homologues of Nrf2 and FoxO, respectively) in this model organism; these results were compared to the effects in Hct116 human colon carcinoma cells. CAPE exerts a strong antioxidative effect in C. elegans: The increase of reactive oxygen species induced by thermal stress was diminished by about 50%. CAPE caused a nuclear translocation of DAF-16, but not SKN-1. CAPE increased stress resistance of the nematode against thermal stress and finally a prolongation of the median and maximum lifespan by 9 and 17%, respectively. This increase in stress resistance and lifespan was dependent on DAF-16 as shown in experiments using a DAF-16 loss of function mutant strain. Life prolongation was retained under SKN-1 RNAi conditions showing that the effect is SKN-1 independent. The results of CAPE obtained in C. elegans differed from the results obtained in Hct116 colon carcinoma cells: CAPE also caused strong antioxidative effects in the mammalian cells, but no activation of the FoxO4 signalling pathway was detectable. Instead, an activation of the Nrf2 signalling pathway was shown by luciferase assay and western blots. CAPE activates the insulin-like DAF-16, but not the SKN-1 signalling pathway in C. elegans and therefore enhances the stress resistance and lifespan of this organism. Since modulation of the DAF-16 pathway was found to be a pivotal effect of CAPE in C. elegans, this has to be taken into account for the investigation of the molecular mechanisms of the traditional use of propolis.

  4. Neuroprotection comparison of chlorogenic acid and its metabolites against mechanistically distinct cell death-inducing agents in cultured cerebellar granule neurons.

    Science.gov (United States)

    Taram, Faten; Winter, Aimee N; Linseman, Daniel A

    2016-10-01

    While the number of patients diagnosed with neurodegenerative disorders like Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease is increasing, there are currently no effective treatments that significantly limit the neuronal cell death underlying these diseases. Chlorogenic acid (CGA), a polyphenolic compound found in high concentration in coffee, is known to possess antioxidant and free radical scavenging activity. In this study, we investigated the neuroprotective effects of CGA and its major metabolites in primary cultures of rat cerebellar granule neurons. We show that CGA and caffeic acid displayed a dramatic protective effect against the nitric oxide donor, sodium nitroprusside. In marked contrast, ferulic acid and quinic acid had no protective effect against this nitrosative stress. While CGA and quinic acid had no protective effect against glutamate-induced cell death, caffeic acid and ferulic acid significantly protected neurons from excitotoxicity. Finally, caffeic acid was the only compound to display significant protective activity against hydrogen peroxide, proteasome inhibition, caspase-dependent intrinsic apoptosis, and endoplasmic reticulum stress. These results indicate that caffeic acid displays a much broader profile of neuroprotection against a diverse range of stressors than its parent polyphenol, CGA, or the other major metabolites, ferulic acid and quinic acid. We conclude that caffeic acid is a promising candidate for testing in pre-clinical models of neurodegeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Thyroid peroxidase activity is inhibited by amino acids

    Directory of Open Access Journals (Sweden)

    D.P. Carvalho

    2000-03-01

    Full Text Available Normal in vitro thyroid peroxidase (TPO iodide oxidation activity was completely inhibited by a hydrolyzed TPO preparation (0.15 mg/ml or hydrolyzed bovine serum albumin (BSA, 0.2 mg/ml. A pancreatic hydrolysate of casein (trypticase peptone, 0.1 mg/ml and some amino acids (cysteine, tryptophan and methionine, 50 µM each also inhibited the TPO iodide oxidation reaction completely, whereas casamino acids (0.1 mg/ml, and tyrosine, phenylalanine and histidine (50 µM each inhibited the TPO reaction by 54% or less. A pancreatic digest of gelatin (0.1 mg/ml or any other amino acid (50 µM tested did not significantly decrease TPO activity. The amino acids that impair iodide oxidation also inhibit the TPO albumin iodination activity. The inhibitory amino acids contain side chains with either sulfur atoms (cysteine and methionine or aromatic rings (tyrosine, tryptophan, histidine and phenylalanine. Among the amino acids tested, only cysteine affected the TPO guaiacol oxidation reaction, producing a transient inhibition at 25 or 50 µM. The iodide oxidation inhibitory activity of cysteine, methionine and tryptophan was reversed by increasing iodide concentrations from 12 to 18 mM, while no such effect was observed when the cofactor (H2O2 concentration was increased. The inhibitory substances might interfere with the enzyme activity by competing with its normal substrates for their binding sites, binding to the free substrates or reducing their oxidized form.

  6. Corrosion inhibition of carbon steel by an amine- fatty acid in acidic ...

    African Journals Online (AJOL)

    The corrosion inhibition of carbon steel in 3% de-aerated NaCl acidic solution with amine–fatty acid corrosion inhibitor, KI384, was investigated at different temperatures using potentiodynamic polarization technique. The Corrosion rate was calculated in the presence and absence of inhibitor. The inhibition increased with ...

  7. Omeprazole Inhibits Acetylsalicylic Acid-Modified Histamine Stimulation of Acid Secretion in Rabbit Gastric Glands

    Directory of Open Access Journals (Sweden)

    Daniel T Brosseuk

    1994-01-01

    Full Text Available The effects of misoprostol and omeprazole on basal-, histamine- and acetylsalicylic acid (ASA-induced gastric acid secretion by isolated rabbit gastric glands were studied. The authors found that ASA at a concentration of 2.4×10-3 M significantly inhibited acid secretion in the isolated gastric glands to 65% of basal levels, and that ASA at a concentration of 2.4×l0-2 M significantly inhibited the histamine stimulation of acid secretion to 78% of maximal. Misoprostol inhibited acid secretion to 76% of basal acid secretion, while omeprazole inhibited secretion to 58% of basal values. Misoprostol inhibited the ASA-modified histamine stimulation to 82% of maximal stimulation. In contrast, omeprazole was able to inhibit the ASA-modified histamine stimulation to 48% of maximal. This omeprazole inhibition of secretagogue-induced acid production reduced acid secretion to levels below basal secretion, indicating that neither histamine nor ASA (at the concentrations used, alone or in combination, had any stimulatory effect in the presence of omeprazole. Misoprostol is the recommended drug of choice for prevention and treatment of nonsteroidal anti-inflammatory drug (NSAID-induced gastrointestinal mucosal injury. In vitro results suggest that omeprazole appears to treat this condition more effectively if gastric acid secretion is a necessary prerequisite for NSAID-induced mucosal injury.

  8. Mechanism of acid corrosion inhibition using magnetic nanofluid

    Science.gov (United States)

    Parekh, Kinnari; Jauhari, Smita; Upadhyay, R. V.

    2016-12-01

    The inhibition effect of magnetic nanofluid on carbon steel in acid solutions was investigated using gravimetric, potentiodynamic and SEM measurement. The inhibition efficiency increases up to 95% and 75% for 51.7 mM concentration, respectively, in 1 M HCl and 1 M H2SO4 medium. The adsorption of nanoparticles to the steel surface forms a barrier between the metal and the aggressive environment, which is responsible for observed inhibition action. The adsorption of nanoparticles on steel surface is supported by the Langmuir and Freundlich adsorption isotherm and surface morphology scanned through SEM.

  9. Inhibiting Effect of Nicotinic Acid Hydrazide on Corrosion of Aluminum and Mild Steel in Acidic Medium

    International Nuclear Information System (INIS)

    Bhat, J. Ishwara; Alva, Vijaya D. P.

    2014-01-01

    The corrosion behavior of aluminum and mild steel in hydrochloric acid medium was studied using a nicotinic acid hydrazide as inhibitor by potentiodynamic polarization, electrochemical impedance spectroscopy technique and gravimetric methods. The effects of inhibitor concentration and temperature were investigated. The experimental results suggested, nicotinic acid hydrazide is a good corrosion inhibitor for both aluminum and mild steel in hydrochloric acid medium and the inhibition efficiency increased with increase in the inhibitor concentration. The polarization studies revealed that nicotinic acid hydrazide exhibits mixed type of inhibition. The inhibition was assumed to occur via adsorption of the inhibitor molecules on the aluminum and mild steel surface and inhibits corrosion by blocking the reaction sites on the surface of aluminum

  10. Glycation inhibits trichloroacetic acid (TCA)-induced whey protein precipitation

    Science.gov (United States)

    Four different WPI saccharide conjugates were successfully prepared to test whether glycation could inhibit WPI precipitation induced by trichloroacetic acid (TCA). Conjugates molecular weights after glycation were analyzed with SDS-PAGE. No significant secondary structure change due to glycation wa...

  11. Inhibition of nuclear T3 binding by fatty acids

    NARCIS (Netherlands)

    Wiersinga, W. M.; Chopra, I. J.; Teco, G. N.

    1988-01-01

    Studies were performed to evaluate a possible modulatory role of lipids on the binding of T3 to rat liver nuclear receptors in vitro. Unsaturated fatty acids were potent inhibitors of the binding of [125I] T3 to isolated rat liver nuclei. Doses (in mumol/L) causing a 50% inhibition of nuclear T3

  12. Phosphatidic acid inhibits ceramide 1-phosphate-stimulated macrophage migration.

    Science.gov (United States)

    Ouro, Alberto; Arana, Lide; Rivera, Io-Guané; Ordoñez, Marta; Gomez-Larrauri, Ana; Presa, Natalia; Simón, Jorge; Trueba, Miguel; Gangoiti, Patricia; Bittman, Robert; Gomez-Muñoz, Antonio

    2014-12-15

    Ceramide 1-phosphate (C1P) was recently demonstrated to potently induce cell migration. This action could only be observed when C1P was applied exogenously to cells in culture, and was inhibited by pertussis toxin. However, the mechanisms involved in this process are poorly understood. In this work, we found that phosphatidic acid (PA), which is structurally related to C1P, displaced radiolabeled C1P from its membrane-binding site and inhibited C1P-stimulated macrophage migration. This effect was independent of the saturated fatty acid chain length or the presence of a double bond in each of the fatty acyl chains of PA. Treatment of RAW264.7 macrophages with exogenous phospholipase D (PLD), an enzyme that produces PA from membrane phospholipids, also inhibited C1P-stimulated cell migration. Likewise, PA or exogenous PLD inhibited C1P-stimulated extracellularly regulated kinases (ERK) 1 and 2 phosphorylation, leading to inhibition of cell migration. However, PA did not inhibit C1P-stimulated Akt phosphorylation. It is concluded that PA is a physiological regulator of C1P-stimulated macrophage migration. These actions of PA may have important implications in the control of pathophysiological functions that are regulated by C1P, including inflammation and various cellular processes associated with cell migration such as organogenesis or tumor metastasis. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The pro-fibrotic properties of transforming growth factor on human fibroblasts are counteracted by caffeic acid by inhibiting myofibroblast formation and collagen synthesis

    NARCIS (Netherlands)

    Mia, Masum M.; Bank, Ruud A.

    Fibrosis is a chronic disorder affecting many organs. A universal process in fibrosis is the formation of myofibroblasts and the subsequent collagen deposition by these cells. Transforming growth factor beta1 (TGF beta 1) plays a major role in the formation of myofibroblasts, e.g. by activating

  14. Theobromine inhibits uric acid crystallization. A potential application in the treatment of uric acid nephrolithiasis.

    Science.gov (United States)

    Grases, Felix; Rodriguez, Adrian; Costa-Bauza, Antonia

    2014-01-01

    To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system. The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments. Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis.

  15. Theobromine inhibits uric acid crystallization. A potential application in the treatment of uric acid nephrolithiasis.

    Directory of Open Access Journals (Sweden)

    Felix Grases

    Full Text Available To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis.The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM. The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL was evaluated using a flow system.The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments.Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis.

  16. Theobromine Inhibits Uric Acid Crystallization. A Potential Application in the Treatment of Uric Acid Nephrolithiasis

    Science.gov (United States)

    Grases, Felix; Rodriguez, Adrian; Costa-Bauza, Antonia

    2014-01-01

    Purpose To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. Materials and Methods The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system. Results The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments. Conclusions Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis. PMID:25333633

  17. Chlorogenic Acid Inhibits Human Platelet Activation and Thrombus Formation

    Science.gov (United States)

    Fuentes, Eduardo; Caballero, Julio; Alarcón, Marcelo; Rojas, Armando; Palomo, Iván

    2014-01-01

    Background Chlorogenic acid is a potent phenolic antioxidant. However, its effect on platelet aggregation, a critical factor in arterial thrombosis, remains unclear. Consequently, chlorogenic acid-action mechanisms in preventing platelet activation and thrombus formation were examined. Methods and Results Chlorogenic acid in a dose-dependent manner (0.1 to 1 mmol/L) inhibited platelet secretion and aggregation induced by ADP, collagen, arachidonic acid and TRAP-6, and diminished platelet firm adhesion/aggregation and platelet-leukocyte interactions under flow conditions. At these concentrations chlorogenic acid significantly decreased platelet inflammatory mediators (sP-selectin, sCD40L, CCL5 and IL-1β) and increased intraplatelet cAMP levels/PKA activation. Interestingly, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent A2A receptor antagonist) attenuated the antiplatelet effect of chlorogenic acid. Chlorogenic acid is compatible to the active site of the adenosine A2A receptor as revealed through molecular modeling. In addition, chlorogenic acid had a significantly lower effect on mouse bleeding time when compared to the same dose of aspirin. Conclusions Antiplatelet and antithrombotic effects of chlorogenic acid are associated with the A2A receptor/adenylate cyclase/cAMP/PKA signaling pathway. PMID:24598787

  18. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  19. Muricholic acids inhibit Clostridium difficile spore germination and growth.

    Directory of Open Access Journals (Sweden)

    Michael B Francis

    Full Text Available Infections caused by Clostridium difficile have increased steadily over the past several years. While studies on C. difficile virulence and physiology have been hindered, in the past, by lack of genetic approaches and suitable animal models, newly developed technologies and animal models allow these processes to be studied in detail. One such advance is the generation of a mouse-model of C. difficile infection. The development of this system is a major step forward in analyzing the genetic requirements for colonization and infection. While important, it is equally as important in understanding what differences exist between mice and humans. One of these differences is the natural bile acid composition. Bile acid-mediated spore germination is an important step in C. difficile colonization. Mice produce several different bile acids that are not found in humans. These muricholic acids have the potential to impact C. difficile spore germination. Here we find that the three muricholic acids (α-muricholic acid, β-muricholic acid and ω-muricholic acid inhibit C. difficile spore germination and can impact the growth of vegetative cells. These results highlight an important difference between humans and mice and may have an impact on C. difficile virulence in the mouse-model of C. difficile infection.

  20. Inhibition of tyrosinase by fumaric acid: Integration of inhibition kinetics with computational docking simulations.

    Science.gov (United States)

    Gou, Lin; Lee, Jinhyuk; Yang, Jun-Mo; Park, Yong-Doo; Zhou, Hai-Meng; Zhan, Yi; Lü, Zhi-Rong

    2017-12-01

    Fumaric acid (FA), which is naturally found in organisms, is a well known intermediate of the citric acid cycle. We evaluated the effects of FA on tyrosinase activity and structure via enzyme kinetics and computational simulations. FA was found to be a reversible inhibitor of tyrosinase and its induced mechanism was the parabolic non-competitive inhibition type with IC 50 =13.7±0.25mM and K i slope =12.64±0.75mM. We newly established the equation for the dissociation constant (K islope ) for the parabolic inhibition type in this study. Kinetic measurements and spectrofluorimetry studies showed that FA induced regional changes in the active site of tyrosinase. One possible binding site for FA was identified under the condition without L-DOPA. The computational docking simulations further revealed that FA can interact with HIS263 and HIS85 at the active site. Furthermore, four important hydrogen bonds were found to be involved with the docking of FA on tyrosinase. Our study provides insight into the mechanism by which dicarboxylic acids such as FA inhibit tyrosinase. By inhibiting tyrosinase and its central role in pigment production, FA is a potential natural antipigmentation agent. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Inhibition studies of soybean (Glycine max) urease with heavy metals, sodium salts of mineral acids, boric acid, and boronic acids.

    Science.gov (United States)

    Kumar, Sandeep; Kayastha, Arvind M

    2010-10-01

    Various inhibitors were tested for their inhibitory effects on soybean urease. The K(i) values for boric acid, 4-bromophenylboronic acid, butylboronic acid, and phenylboronic acid were 0.20 +/- 0.05 mM, 0.22 +/- 0.04 mM, 1.50 +/- 0.10 mM, and 2.00 +/- 0.11 mM, respectively. The inhibition was competitive type with boric acid and boronic acids. Heavy metal ions including Ag(+), Hg(2+), and Cu(2+) showed strong inhibition on soybean urease, with the silver ion being a potent inhibitor (IC(50) = 2.3 x 10(-8) mM). Time-dependent inhibition studies exhibited biphasic kinetics with all heavy metal ions. Furthermore, inhibition studies with sodium salts of mineral acids (NaF, NaCl, NaNO(3), and Na(2)SO(4)) showed that only F(-) inhibited soybean urease significantly (IC(50) = 2.9 mM). Competitive type of inhibition was observed for this anion with a K(i) value of 1.30 mM.

  2. Macrokinetics of magnesium sulfite oxidation inhibited by ascorbic acid.

    Science.gov (United States)

    Lidong, Wang; Yongliang, Ma; Wendi, Zhang; Qiangwei, Li; Yi, Zhao; Zhanchao, Zhang

    2013-08-15

    Magnesia flue gas desulfurization is a promising process for small to medium scale industrial coal-fired boilers in order to reduce sulfur dioxide emissions, in which oxidation control of magnesium sulfite is of great importance for the recycling of products. Effects of four inhibitors were compared by kinetic experiments indicating that ascorbic acid is the best additive, which retards the oxidation process of magnesium sulfite in trace presence. The macrokinetics of magnesium sulfite oxidation inhibited by ascorbic acid were studied. Effects of the factors, including ascorbic acid concentration, magnesium sulfite concentration, oxygen partial pressure, pH, and temperature, were investigated in a stirred reactor with bubbling. The results show that the reaction rate is -0.55 order in ascorbic acid, 0.77 in oxygen partial pressure, and zero in magnesium sulfite concentration, respectively. The apparent activation energy is 88.0 kJ mol(-1). Integrated with the kinetic model, it is concluded that the oxidation rate of magnesium sulfite inhibited by ascorbic acid is controlled by the intrinsic chemical reaction. The result provides a useful reference for sulfite recovery in magnesia desulfurization. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Lactobacillus plantarum lipoteichoic acid inhibits biofilm formation of Streptococcus mutans

    Science.gov (United States)

    Ahn, Ki Bum; Baik, Jung Eun; Park, Ok-Jin; Yun, Cheol-Heui

    2018-01-01

    Dental caries is a biofilm-dependent oral disease and Streptococcus mutans is the known primary etiologic agent of dental caries that initiates biofilm formation on tooth surfaces. Although some Lactobacillus strains inhibit biofilm formation of oral pathogenic bacteria, the molecular mechanisms by which lactobacilli inhibit bacterial biofilm formation are not clearly understood. In this study, we demonstrated that Lactobacillus plantarum lipoteichoic acid (Lp.LTA) inhibited the biofilm formation of S. mutans on polystyrene plates, hydroxyapatite discs, and dentin slices without affecting the bacterial growth. Lp.LTA interferes with sucrose decomposition of S. mutans required for the production of exopolysaccharide, which is a main component of biofilm. Lp.LTA also attenuated the biding of fluorescein isothiocyanate-conjugated dextran to S. mutans, which is known to have a high affinity to exopolysaccharide on S. mutans. Dealanylated Lp.LTA did not inhibit biofilm formation of S. mutans implying that D-alanine moieties in the Lp.LTA structure were crucial for inhibition. Collectively, these results suggest that Lp.LTA attenuates S. mutans biofilm formation and could be used to develop effective anticaries agents. PMID:29420616

  4. Cadmium inhibits acid secretion in stimulated frog gastric mucosa

    International Nuclear Information System (INIS)

    Gerbino, Andrea; Debellis, Lucantonio; Caroppo, Rosa; Curci, Silvana; Colella, Matilde

    2010-01-01

    Cadmium, a toxic environmental pollutant, affects the function of different organs such as lungs, liver and kidney. Less is known about its toxic effects on the gastric mucosa. The aim of this study was to investigate the mechanisms by which cadmium impacts on the physiology of gastric mucosa. To this end, intact amphibian mucosae were mounted in Ussing chambers and the rate of acid secretion, short circuit current (I sc ), transepithelial potential (V t ) and resistance (R t ) were recorded in the continuous presence of cadmium. Addition of cadmium (20 μM to 1 mM) on the serosal but not luminal side of the mucosae resulted in inhibition of acid secretion and increase in NPPB-sensitive, chloride-dependent short circuit current. Remarkably, cadmium exerted its effects only on histamine-stimulated tissues. Experiments with TPEN, a cell-permeant chelator for heavy metals, showed that cadmium acts from the intracellular side of the acid secreting cells. Furthermore, cadmium-induced inhibition of acid secretion and increase in I sc cannot be explained by an action on: 1) H 2 histamine receptor, 2) Ca 2+ signalling 3) adenylyl cyclase or 4) carbonic anhydrase. Conversely, cadmium was ineffective in the presence of the H + /K + -ATPase blocker omeprazole suggesting that the two compounds likely act on the same target. Our findings suggest that cadmium affects the functionality of histamine-stimulated gastric mucosa by inhibiting the H + /K + -ATPase from the intracellular side. These data shed new light on the toxic effect of this dangerous environmental pollutant and may result in new avenues for therapeutic intervention in acute and chronic intoxication.

  5. Effect of fatty acids on arenavirus replication: inhibition of virus production by lauric acid.

    Science.gov (United States)

    Bartolotta, S; García, C C; Candurra, N A; Damonte, E B

    2001-01-01

    To study the functional involvement of cellular membrane properties on arenavirus infection, saturated fatty acids of variable chain length (C10-C18) were evaluated for their inhibitory activity against the multiplication of Junin virus (JUNV). The most active inhibitor was lauric acid (C12), which reduced virus yields of several attenuated and pathogenic strains of JUNV in a dose dependent manner, without affecting cell viability. Fatty acids with shorter or longer chain length had a reduced or negligible anti-JUNV activity. Lauric acid did not inactivate virion infectivity neither interacted with the cell to induce a state refractory to virus infection. From mechanistic studies, it can be concluded that lauric acid inhibited a late maturation stage in the replicative cycle of JUNV. Viral protein synthesis was not affected by the compound, but the expression of glycoproteins in the plasma membrane was diminished. A direct correlation between the inhibition of JUNV production and the stimulation of triacylglycerol cell content was demonstrated, and both lauric-acid induced effects were dependent on the continued presence of the fatty acid. Thus, the decreased insertion of viral glycoproteins into the plasma membrane, apparently due to the increased incorporation of triacylglycerols, seems to cause an inhibition of JUNV maturation and release.

  6. Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation.

    Science.gov (United States)

    Yamaguchi, Yoshie; Yamamoto, Katsunori; Sato, Yoshinori; Inoue, Shinjiro; Morinaga, Tetsuo; Hirano, Eiichi

    2016-01-01

    Placental extract contains several biologically active compounds, and pharmacological induction of placental extract has therapeutic effects, such as improving liver function in patients with hepatitis or cirrhosis. Here, we searched for novel molecules with an anti-tumor activity in placental extracts. Active molecules were separated by chromatographic analysis, and their antiproliferative activities were determined by a colorimetric assay. We identified aspartic acid and glutamic acid to possess the antiproliferative activity against human hepatoma cells. Furthermore, we showed that the combination of aspartic acid and glutamic acid exhibited enhanced antiproliferative activity, and inhibited Akt phosphorylation. We also examined in vivo tumor inhibition activity using the rabbit VX2 liver tumor model. The treatment mixture (emulsion of the amino acids with Lipiodol) administered by hepatic artery injection inhibited tumor cell growth of the rabbit VX2 liver. These results suggest that the combination of aspartic acid and glutamic acid may be useful for induction of tumor cell death, and has the potential for clinical use as a cancer therapeutic agent.

  7. Inhibition of histone deacetylase activity by valproic acid blocks adipogenesis.

    Science.gov (United States)

    Lagace, Diane C; Nachtigal, Mark W

    2004-04-30

    Adipogenesis is dependent on the sequential activation of transcription factors including the CCAAT/enhancer-binding proteins (C/EBP), peroxisome proliferator-activated receptor gamma (PPARgamma), and steroid regulatory element-binding protein (SREBP). We show that the mood stabilizing drug valproic acid (VPA; 0.5-2 mm) inhibits mouse 3T3 L1 and human preadipocyte differentiation, likely through its histone deacetylase (HDAC) inhibitory properties. The HDAC inhibitor trichostatin A (TSA) also inhibited adipogenesis, whereas the VPA analog valpromide, which does not possess HDAC inhibitory effects, did not prevent adipogenesis. Acute or chronic VPA treatment inhibited differentiation yet did not affect mitotic clonal expansion. VPA (1 mm) inhibited PPARgamma induced differentiation but does not activate a PPARgamma reporter gene, suggesting that it is not a PPARgamma ligand. VPA or TSA treatment reduced mRNA and protein levels of PPARgamma and SREBP1a. TSA reduced C/EBPalpha mRNA and protein levels, whereas VPA only produced a decrease in C/EBPalpha protein expression. Overall our results highlight a role for HDAC activity in adipogenesis that can be blocked by treatment with VPA.

  8. Inhibition of Listeria monocytogenes by fatty acids and monoglycerides.

    Science.gov (United States)

    Wang, L L; Johnson, E A

    1992-01-01

    Fatty acids and monoglycerides were evaluated in brain heart infusion broth and in milk for antimicrobial activity against the Scott A strain of Listeria monocytogenes. C12:0, C18:3, and glyceryl monolaurate (monolaurin) had the strongest activity in brain heart infusion broth and were bactericidal at 10 to 20 micrograms/ml, whereas potassium (K)-conjugated linoleic acids and C18:2 were bactericidal at 50 to 200 micrograms/ml. C14:0, C16:0, C18:0, C18:1, glyceryl monomyristate, and glyceryl monopalmitate were not inhibitory at 200 micrograms/ml. The bactericidal activity in brain heart infusion broth was higher at pH 5 than at pH 6. In whole milk and skim milk, K-conjugated linoleic acid was bacteriostatic and prolonged the lag phase especially at 4 degrees C. Monolaurin inactivated L. monocytogenes in skim milk at 4 degrees C, but was less inhibitory at 23 degrees C. Monolaurin did not inhibit L. monocytogenes in whole milk because of the higher fat content. Other fatty acids tested were not effective in whole or skim milk. Our results suggest that K-conjugated linoleic acids or monolaurin could be used as an inhibitory agent against L. monocytogenes in dairy foods. Images PMID:1610184

  9. 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.

  10. Unusal pattern of product inhibition: batch acetic acid fermentation

    Energy Technology Data Exchange (ETDEWEB)

    Bar, R.; Gainer, J.L.; Kirwan, D.J.

    1987-04-20

    The limited tolerance of microorganisms to their metabolic products results in inhibited growth and product formation. The relationship between the specific growth rate, micro, and the concentration of an inhibitory product has been described by a number of mathematical models. In most cases, micro was found to be inversely proportional to the product concentration and invariably the rate of substrate utilization followed the same pattern. In this communication, the authors report a rather unusual case in which the formation rate of a product, acetic acid, increased with a decreasing growth rate of the microorganism, Acetobacter aceti. Apparently, a similar behavior was mentioned in a review report with respect to Clostridium thermocellum in a batch culture but was not published in the freely circulating literature. The fermentation of ethanol to acetic acid, C/sub 2/H/sub 5/OH + O/sub 2/ = CH/sub 3/COOH + H/sub 2/O is clearly one of the oldest known fermentations. Because of its association with the commercial production of vinegar it has been a subject of extensive but rather technically oriented studies. Suprisingly, the uncommon uncoupling between the inhibited microbial growth and the product formation appears to have been unnoticed. 13 references.

  11. Proteolytic Pathways Induced by Herbicides That Inhibit Amino Acid Biosynthesis

    Science.gov (United States)

    Zulet, Amaia; Gil-Monreal, Miriam; Villamor, Joji Grace; Zabalza, Ana; van der Hoorn, Renier A. L.; Royuela, Mercedes

    2013-01-01

    Background The herbicides glyphosate (Gly) and imazamox (Imx) inhibit the biosynthesis of aromatic and branched-chain amino acids, respectively. Although these herbicides inhibit different pathways, they have been reported to show several common physiological effects in their modes of action, such as increasing free amino acid contents and decreasing soluble protein contents. To investigate proteolytic activities upon treatment with Gly and Imx, pea plants grown in hydroponic culture were treated with Imx or Gly, and the proteolytic profile of the roots was evaluated through fluorogenic kinetic assays and activity-based protein profiling. Results Several common changes in proteolytic activity were detected following Gly and Imx treatment. Both herbicides induced the ubiquitin-26 S proteasome system and papain-like cysteine proteases. In contrast, the activities of vacuolar processing enzymes, cysteine proteases and metacaspase 9 were reduced following treatment with both herbicides. Moreover, the activities of several putative serine protease were similarly increased or decreased following treatment with both herbicides. In contrast, an increase in YVADase activity was observed under Imx treatment versus a decrease under Gly treatment. Conclusion These results suggest that several proteolytic pathways are responsible for protein degradation upon herbicide treatment, although the specific role of each proteolytic activity remains to be determined. PMID:24040092

  12. Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons

    Directory of Open Access Journals (Sweden)

    Nadine eBeckmann

    2014-09-01

    Full Text Available Amitriptyline, a tricyclic antidepressant, has been used in the clinic to treat a number of disorders, in particular major depression and neuropathic pain. In the 1970s the ability of tricyclic antidepressants to inhibit acid sphingomyelinase (ASM was discovered. The enzyme ASM catalyzes the hydrolysis of sphingomyelin to ceramide. ASM and ceramide were shown to play a crucial role in a wide range of diseases, including cancer, cystic fibrosis, diabetes, Alzheimer’s disease and major depression, as well as viral (e.g. measles virus and bacterial (e.g. Staphylococcus aureus, Pseudomonas aeruginosa infections. Ceramide molecules may act in these diseases by the alteration of membrane biophysics, the self-association of ceramide molecules within the cell membrane and the ultimate formation of larger ceramide-enriched membrane domains/platforms. These domains were shown to serve the clustering of certain receptors such as CD95 and may also act in the above named diseases. The potential to block the generation of ceramide by inhibiting the ASM has opened up new therapeutic approaches for the treatment of these conditions. Since amitriptyline is one of the longest used clinical drugs and side effects are well studied, it could potentially become a cheap and easily accessible medication for patients suffering from these diseases. In this review, we aim to provide an overview of current in vitro and in vivo studies and clinical trials utilizing amitriptyline to inhibit ASM and contemplate possible future applications of the drug.

  13. Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression.

    Science.gov (United States)

    Chen, Nian-Hong; Liu, Jian-Wen; Zhong, Jian-Jiang

    2010-01-01

    The traditional Chinese medicinal mushroom, Ganoderma lucidum, has been used in Asia for several thousand years for the prevention and treatment of a variety of diseases, including cancer. In previous work, we purified ganoderic acid T (GA-T) from G. lucidum [28]. In the present study, we investigate the functions of GA-T in terms of its effects on invasion in vitro and metastasis in vivo. A trypan blue dye exclusion assay indicates that GA-T inhibits proliferation of HCT-116 cells, a human colon carcinoma cell line. Cell aggregation and adhesion assays show that GA-T promotes homotypic aggregation and simultaneously inhibits the adhesion of HCT-116 cells to the extracellular matrix (ECM) in a dose-dependent manner.Wound healing assays indicate that GA-T also inhibits the migration of HCT-116 cells in a dose-dependent manner, and it suppresses the migration of 95-D cells, a highly metastatic human lung tumor cell line, in a dose- and time-dependent manner. In addition, GA-T inhibits the nuclear translocation of nuclear factor-kappaB (NF-kappaB) and the degradation of inhibitor of kappaB-alpha (IkappaBalpha), which leads to down-regulated expression of matrix metalloproteinase-9 (MMP-9), inducible nitric oxide synthase (iNOS), and urokinase-type plasminogen activator (uPA). Animal and Lewis Lung Carcinoma (LLC) model experiments demonstrate that GA-T suppresses tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo. Taken together, these results demonstrate that GA-T effectively inhibits cancer cell invasion in vitro and metastasis in vivo, and thus it may act as a potential drug for treating cancer.

  14. Boric acid inhibits embryonic histone deacetylases: A suggested mechanism to explain boric acid-related teratogenicity

    International Nuclear Information System (INIS)

    Di Renzo, Francesca; Cappelletti, Graziella; Broccia, Maria L.; Giavini, Erminio; Menegola, Elena

    2007-01-01

    Histone deacetylases (HDAC) control gene expression by changing histonic as well as non histonic protein conformation. HDAC inhibitors (HDACi) are considered to be among the most promising drugs for epigenetic treatment for cancer. Recently a strict relationship between histone hyperacetylation in specific tissues of mouse embryos exposed to two HDACi (valproic acid and trichostatin A) and specific axial skeleton malformations has been demonstrated. The aim of this study is to verify if boric acid (BA), that induces in rodents malformations similar to those valproic acid and trichostatin A-related, acts through similar mechanisms: HDAC inhibition and histone hyperacetylation. Pregnant mice were treated intraperitoneally with a teratogenic dose of BA (1000 mg/kg, day 8 of gestation). Western blot analysis and immunostaining were performed with anti hyperacetylated histone 4 (H4) antibody on embryos explanted 1, 3 or 4 h after treatment and revealed H4 hyperacetylation at the level of somites. HDAC enzyme assay was performed on embryonic nuclear extracts. A significant HDAC inhibition activity (compatible with a mixed type partial inhibition mechanism) was evident with BA. Kinetic analyses indicate that BA modifies substrate affinity by a factor α = 0.51 and maximum velocity by a factor β = 0.70. This work provides the first evidence for HDAC inhibition by BA and suggests such a molecular mechanism for the induction of BA-related malformations

  15. Inhibition of xanthine oxidase by phytic acid and its antioxidative action.

    Science.gov (United States)

    Muraoka, Sanae; Miura, Toshiaki

    2004-02-13

    We examined if phytic acid inhibits the enzymatic superoxide source xanthine oxidase (XO). Half inhibition of XO by phytic acid (IC50) was about 30 mM in the formation of uric acid from xanthine, but generation of the superoxide was greatly affected by phytic acid; the IC50 was about 6 mM, indicating that the superoxide generating domain of XO is more sensitive to phytic acid. The XO activity in intestinal homogenate was also inhibited by phytic acid. However, it was not observed with intestinal homogenate that superoxide generation was more sensitive to phytic acid compared with the formation of uric acid as observed with XO from butter milk. XO-induced superoxide-dependent lipid peroxidation was inhibited by phytic acid, but not by myo-inositol. Reduction of ADP-Fe3+ caused by XO was inhibited by superoxide dismutase, but not phytic acid. The results suggest that phytic acid interferes with the formation of ADP-iron-oxygen complexes that initiate lipid peroxidation. Both phytic acid and myo-inositol inhibited XO-induced superoxide-dependent DNA damage. Mannitol inhibited the DNA strand break. Myo-inositol may act as a hydroxyl radical scavenger. The antioxidative action of phytic acid may be due to not only inhibiting XO, but also preventing formation of ADP-iron-oxygen complexes.

  16. Lichen-derived caperatic acid and physodic acid inhibit Wnt signaling in colorectal cancer cells.

    Science.gov (United States)

    Paluszczak, Jarosław; Kleszcz, Robert; Studzińska-Sroka, Elżbieta; Krajka-Kuźniak, Violetta

    2018-04-01

    Lichens are a source of secondary metabolites which possess important biological activities, including antioxidant, antibacterial, anti-inflammatory, and cytotoxic effects. The anticancer activity of lichens was shown in many types of tumors, including colorectal cancers (CRC). Several studies revealed that the application of lichen extracts diminished the proliferation of CRC cells and induced apoptosis. Colon carcinogenesis is associated with aberrations in Wnt signaling. Elevated transcriptional activity of β-catenin induces cell survival, proliferation, and migration. Thus, the inhibition of Wnt signaling is a promising therapeutic strategy in colorectal cancer. The aim of this study was the evaluation of the effects of lichen-derived depsides (atranorin, lecanoric acid, squamatic acid) and depsidones (physodic acid, salazinic acid) and a poly-carboxylic fatty acid-caperatic acid, on Wnt signaling in HCT116 and DLD-1 colorectal cancer cell lines. HCT116 cells were more sensitive to the modulatory effects of the compounds. PKF118-310, which was used as a reference β-catenin inhibitor, dose-dependently reduced the expression of the classical β-catenin target gene-Axin2 in both cell lines. Lecanoric acid slightly reduced Axin2 expression in HCT116 cells while caperatic acid tended to reduce Axin2 expression in both cell lines. Physodic acid much more potently decreased Axin2 expression in HCT116 cells than in DLD-1 cells. Physodic acid and caperatic acid also diminished the expression of survivin and MMP7 in a cell line and time-dependent manner. None of the compounds affected the nuclear translocation of β-catenin. This is the first report showing the ability of caperatic acid and physodic acid to modulate β-catenin-dependent transcription.

  17. Docosahexaenoic Acid Inhibits Cerulein-Induced Acute Pancreatitis in Rats

    Directory of Open Access Journals (Sweden)

    Yoo Kyung Jeong

    2017-07-01

    Full Text Available Oxidative stress is an important regulator in the pathogenesis of acute pancreatitis (AP. Reactive oxygen species induce activation of inflammatory cascades, inflammatory cell recruitment, and tissue damage. NF-κB regulates inflammatory cytokine gene expression, which induces an acute, edematous form of pancreatitis. Protein kinase C δ (PKCδ activates NF-κB as shown in a mouse model of cerulein-induced AP. Docosahexaenoic acid (DHA, an ω-3 fatty acid, exerts anti-inflammatory and antioxidant effects in various cells and tissues. This study investigated whether DHA inhibits cerulein-induced AP in rats by assessing pancreatic edema, myeloperoxidase activity, levels of lipid peroxide and IL-6, activation of NF-κB and PKCδ, and by histologic observation. AP was induced by intraperitoneal injection (i.p. of cerulein (50 μg/kg every hour for 7 h. DHA (13 mg/kg was administered i.p. for three days before AP induction. Pretreatment with DHA reduced cerulein-induced activation of NF-κB, PKCδ, and IL-6 in pancreatic tissues of rats. DHA suppressed pancreatic edema and decreased the abundance of lipid peroxide, myeloperoxidase activity, and inflammatory cell infiltration into the pancreatic tissues of cerulein-stimulated rats. Therefore, DHA may help prevent the development of pancreatitis by suppressing the activation of NF-κB and PKCδ, expression of IL-6, and oxidative damage to the pancreas.

  18. Characterization of Protein Tyrosine Phosphatase 1B Inhibition by Chlorogenic Acid and Cichoric Acid.

    Science.gov (United States)

    Lipchock, James M; Hendrickson, Heidi P; Douglas, Bonnie B; Bird, Kelly E; Ginther, Patrick S; Rivalta, Ivan; Ten, Nicholas S; Batista, Victor S; Loria, J Patrick

    2017-01-10

    Protein tyrosine phosphatase 1B (PTP1B) is a known regulator of the insulin and leptin signaling pathways and is an active target for the design of inhibitors for the treatment of type II diabetes and obesity. Recently, cichoric acid (CHA) and chlorogenic acid (CGA) were predicted by docking methods to be allosteric inhibitors that bind distal to the active site. However, using a combination of steady-state inhibition kinetics, solution nuclear magnetic resonance experiments, and molecular dynamics simulations, we show that CHA is a competitive inhibitor that binds in the active site of PTP1B. CGA, while a noncompetitive inhibitor, binds in the second aryl phosphate binding site, rather than the predicted benzfuran binding pocket. The molecular dynamics simulations of the apo enzyme and cysteine-phosphoryl intermediate states with and without bound CGA suggest CGA binding inhibits PTP1B by altering hydrogen bonding patterns at the active site. This study provides a mechanistic understanding of the allosteric inhibition of PTP1B.

  19. CYCLOSPORINE-A BLOCKS BILE-ACID SYNTHESIS IN CULTURED-HEPATOCYTES BY SPECIFIC-INHIBITION OF CHENODEOXYCHOLIC ACID SYNTHESIS

    NARCIS (Netherlands)

    PRINCEN, HMG; WOLTHERS, BG; VONK, RJ; KUIPERS, F

    1991-01-01

    Bile acid synthesis, determined by conversion of [4-C-14]cholesterol into bile acids in rat and human hepatocytes and by measurement of mass production of bile acids in rat hepatocytes, was dose-dependently decreased by cyclosporin A, with 52% (rat) and 45% (human) inhibition at 10-mu-M. The

  20. Inhibition of carbon steel corrosion by 11-aminoundecanoic acid

    Directory of Open Access Journals (Sweden)

    Saad Ghareba

    2015-12-01

    Full Text Available The current study reports results on the investigation of the possibility of using 11-aminoundecanoic acid (AA as an inhibitor of general corrosion of carbon steel (CS in HCl under a range of experimental conditions: inhibitor concentration, exposure time, electrolyte temperature and pH and CS surface roughness. It was found that AA acts as a mixed-type inhibitor, yielding maximum inhibition efficiency of 97 %. The adsorption of AA onto the CS surface was described by the Langmuir adsorption isotherm. The corresponding apparent Gibbs free energy of AA adsorption on CS at 295 K was calculated to be −30.2 kJ mol–1. The adsorption process was found to be driven by a positive change in entropy of the system. PM-IRRAS measurements revealed that the adsorbed AA layer is amorphous, which can be attributed to the repulsion between the neighboring positively charged amine groups and a high heterogeneity of the CS surface. It was also found that the AA provides very good corrosion protection of CS of various surface roughness, and over a prolonged time.

  1. Inhibition of fatty acid synthase prevents preadipocyte differentiation

    International Nuclear Information System (INIS)

    Schmid, Bernhard; Rippmann, Joerg F.; Tadayyon, Moh; Hamilton, Bradford S.

    2005-01-01

    Inhibition of fatty acid synthase (FAS) reduces food intake in rodents. As adipose tissue expresses FAS, we sought to investigate the effect of reduced FAS activity on adipocyte differentiation. FAS activity was suppressed either pharmacologically or by siRNA during differentiation of 3T3-L1 cells. Cerulenin (10 μM), triclosan (50 μM), and C75 (50 μM) reduced dramatically visible lipid droplet accumulation, while incorporation of [1- 14 C]acetate into lipids was reduced by 75%, 70%, and 90%, respectively. Additionally, the substances reduced FAS, CEBPα, and PPARγ mRNA by up to 85% compared to that of control differentiated cells. Transient transfection with FAS siRNA suppressed FAS mRNA and FAS activity, and this was accompanied by reduction of CEBPα and PPARγ mRNA levels, and complete prevention of lipid accumulation. CD36, a late marker of differentiation, was also reduced. Together, these results suggest that FAS generated signals may be essential to support preadipocyte differentiation

  2. Inhibition of Corrosion of Zinc in (HNO 3 + HCl) acid mixture by ...

    African Journals Online (AJOL)

    Corrosion of Zinc metal in (HNO3 + HCl) binary acid mixture and inhibition efficiency of aniline has been studied by weight loss method and polarization technique. Corrosion rate increases with the concentration of acid mixture and the temperature. Inhibition efficiency (I.E.) of aniline increases with the concentration of ...

  3. Furanyl Fatty Acid Inhibition of FABP5 as a Mechanism for Treatment and Prevention of Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0699 TITLE: Furanyl Fatty Acid Inhibition of FABP5 as a Mechanism for Treatment and Prevention of Cancer PRINCIPAL...pharmacologic inhibition will prevent the oncogenic effects of FABP5 overexpression in highly relevant breast cancer models that display a high ratio of...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Furanyl Fatty Acid Inhibition of FABP5 as a Mechanism for Treatment and Prevention of

  4. Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Garcinia speciosa.

    Science.gov (United States)

    Okudaira, C; Ikeda, Y; Kondo, S; Furuya, S; Hirabayashi, Y; Koyano, T; Saito, Y; Umezawa, K

    2000-01-01

    Sphingomyelinase is considered to be involved in the regulation of apoptosis and cell growth. In the course of our screening for acidic sphingomyelinase inhibitors we isolated three xanthone compounds, alpha-mangostin, cowanin, and cowanol, from the bark of Garcinia speciosa. These compounds competitively inhibited bovine brain-derived acidic sphingomyelinase with IC(50) values of 14.1, 19.2, and 10.9 microM, respectively and inhibited the acidic sphingomyelinase more effectively than the neutral sphingomyelinase of bovine brain. alpha-Mangostin inhibited the acidic sphingomyelinase in the most selective manner. alpha-Mangostin was chemically modified and its structure-activity relationships are discussed.

  5. Effects of the Aqueous Extract from Tabebuia roseoalba and Phenolic Acids on Hyperuricemia and Inflammation

    Directory of Open Access Journals (Sweden)

    Zilma Schimith Ferraz-Filha

    2017-01-01

    Full Text Available Tabebuia species (Bignoniaceae have long been used in folk medicine as anti-inflammatory, antirheumatic, antimicrobial, and antitumor. The aim of this study was to investigate if aqueous extract from the leaves (AEL of Tabebuia roseoalba (Ridl. Sandwith, Bignoniaceae, and its constituents could be useful to decrease serum uric acid levels and restrain the gout inflammatory process. HPLC analysis identified caffeic acid and chlorogenic acid in AEL. Antihyperuricemic effects and inhibition of liver XOD (xanthine oxidoreductase by AEL and identified compounds were evaluated in hyperuricemic mice. Anti-inflammatory activity was evaluated on MSU (monosodium urate crystal-induced paw edema. In addition, AEL antioxidant activity in vitro was evaluated. AEL, caffeic, and chlorogenic acids were able to reduce serum uric acid levels in hyperuricemic mice probably through inhibition of liver xanthine oxidase activity and significantly decreased the paw edema induced by MSU crystals. AEL showed significant antioxidant activity in all evaluated assays. The results show that the AEL of Tabebuia roseoalba can be a promising agent for treatment for gout and inflammatory diseases. We suggest that caffeic and chlorogenic acids may be responsible for the activities demonstrated by the species.

  6. Effects of the Aqueous Extract from Tabebuia roseoalba and Phenolic Acids on Hyperuricemia and Inflammation

    Science.gov (United States)

    Ferraz-Filha, Zilma Schimith; Ferrari, Fernanda Cristina; Araújo, Marcela Carolina de Paula Michel; Bernardes, Ana Catharina Fernandes P. F.

    2017-01-01

    Tabebuia species (Bignoniaceae) have long been used in folk medicine as anti-inflammatory, antirheumatic, antimicrobial, and antitumor. The aim of this study was to investigate if aqueous extract from the leaves (AEL) of Tabebuia roseoalba (Ridl.) Sandwith, Bignoniaceae, and its constituents could be useful to decrease serum uric acid levels and restrain the gout inflammatory process. HPLC analysis identified caffeic acid and chlorogenic acid in AEL. Antihyperuricemic effects and inhibition of liver XOD (xanthine oxidoreductase) by AEL and identified compounds were evaluated in hyperuricemic mice. Anti-inflammatory activity was evaluated on MSU (monosodium urate) crystal-induced paw edema. In addition, AEL antioxidant activity in vitro was evaluated. AEL, caffeic, and chlorogenic acids were able to reduce serum uric acid levels in hyperuricemic mice probably through inhibition of liver xanthine oxidase activity and significantly decreased the paw edema induced by MSU crystals. AEL showed significant antioxidant activity in all evaluated assays. The results show that the AEL of Tabebuia roseoalba can be a promising agent for treatment for gout and inflammatory diseases. We suggest that caffeic and chlorogenic acids may be responsible for the activities demonstrated by the species. PMID:29375639

  7. Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids.

    Science.gov (United States)

    Liang, T; Liao, S

    1992-01-01

    Human or rat microsomal 5 alpha-reductase activity, as measured by enzymic conversion of testosterone into 5 alpha-dihydrotestosterone or by binding of a competitive inhibitor, [3H]17 beta-NN-diethulcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([3H]4-MA) to the reductase, is inhibited by low concentrations (less than 10 microM) of certain polyunsaturated fatty acids. The relative inhibitory potencies of unsaturated fatty acids are, in decreasing order: gamma-linolenic acid greater than cis-4,7,10,13,16,19-docosahexaenoic acid = cis-6,9,12,15-octatetraenoic acid = arachidonic acid = alpha-linolenic acid greater than linoleic acid greater than palmitoleic acid greater than oleic acid greater than myristoleic acid. Other unsaturated fatty acids such as undecylenic acid, erucic acid and nervonic acid, are inactive. The methyl esters and alcohol analogues of these compounds, glycerols, phospholipids, saturated fatty acids, retinoids and carotenes were inactive even at 0.2 mM. The results of the binding assay and the enzymic assay correlated well except for elaidic acid and linolelaidic acid, the trans isomers of oleic acid and linoleic acid respectively, which were much less active than their cis isomers in the binding assay but were as potent in the enzymic assay. gamma-Linolenic acid had no effect on the activities of two other rat liver microsomal enzymes: NADH:menadione reductase and glucuronosyl transferase. gamma-Linolenic acid, the most potent inhibitor tested, decreased the Vmax. and increased Km values of substrates, NADPH and testosterone, and promoted dissociation of [3H]4-MA from the microsomal reductase. gamma-Linolenic acid, but not the corresponding saturated fatty acid (stearic acid), inhibited the 5 alpha-reductase activity, but not the 17 beta-dehydrogenase activity, of human prostate cancer cells in culture. These results suggest that unsaturated fatty acids may play an important role in regulating androgen action in target cells. PMID:1637346

  8. Simultaneous determination of chlorogenic acid, caffeic acid and caffeine in hydroalcoholic and aqueous extracts of Ilex paraguariensis by HPLC and correlation with antioxidant capacity of the extracts by DPPH· reduction Determinação simultânea de ácido clorogênico, ácido caféico e cafeína, no extrato aquoso e hidroalcoólico de Ilex paraguariensis por CLAE e correlação com a capacidade antioxidante dos extratos por redução do DPPH·

    Directory of Open Access Journals (Sweden)

    Diogo Pineda Rivelli

    2007-06-01

    Full Text Available A new high performance liquid chromatographic method has been established for simultaneous determination of chlorogenic acid, caffeic acid and caffeine in hydroalcoholic and aqueous extracts of Ilex paraguariensis. Analytical curves showed good linear regression in the concentration ranges 0.49-7.8 µg/mL for chlorogenic acid, 0.25-3.9 µg/mL for caffeic acid and 0.244-7.8 µg/mL for caffeine. Reduction of the DPPH· radical was used to determine the antioxidant capacity of the extracts. Our method for the simultaneous determination of chlorogenic acid, caffeic acid and caffeine was highly sensitive, having lower detection and quantitation limits than other papers that used similar methodology.Um novo método de cromatografia líquida de alta eficiência foi desenvolvido para a determinação simultânea de ácido clorogênico, ácido caféico e cafeína no extrato hidroalcoólico e aquoso de Ilex paraguariensis. As curvas de calibração mostraram boa regressão linear nas faixas de concentração 0,49-7,8 µg/mL para o ácido clorogênico, 0,25-3,9 µg/mL para ácido caféico e 0,244-7,8 µg/mL para cafeína. A redução do radical DPPH· foi usada para determinar a capacidade antioxidante dos extratos. Nosso método para a determinação simultânea de ácido caféico, ácido clorogênico e cafeína foi altamente sensível, possuindo limites de detecção e de quantificação menores do que em outros trabalhos que empregaram metodologias semelhantes.

  9. Eicosapentaenoic acid inhibits oxidation of high density lipoprotein particles in a manner distinct from docosahexaenoic acid.

    Science.gov (United States)

    Sherratt, Samuel C R; Mason, R Preston

    2018-02-05

    The omega-3 fatty acid eicosapentaenoic acid (EPA) reduces oxidation of ApoB-containing particles in vitro and in patients with hypertriglyceridemia. EPA may produce these effects through a potent antioxidant mechanism, which may facilitate LDL clearance and slow plaque progression. We hypothesize that EPA antioxidant effects may extend to ApoA-containing particles like HDL, potentially preserving certain atheroprotective functions. HDL was isolated from human plasma and incubated at 37 °C in the absence (vehicle) or presence of EPA and/or DHA; 5.0 or 10.0 μM each. Samples were then subjected to copper-induced oxidation (10 μM). HDL oxidation was inhibited similarly by EPA and DHA up to 1 h. EPA (10 μM) maintained significant HDL oxidation inhibition of 89% (0.622 ± 0.066 μM MDA; p < .001) at 4 h, with continued inhibition of 64% at 14 h, vs. vehicle (5.65 ± 0.06 to 2.01 ± 0.10 μM MDA; p < .001). Conversely, DHA (10 μM) antioxidant benefit was lost by 4 h. At a lower concentration (5 μM), EPA antioxidant activity remained at 81% (5.53 ± 0.15 to 1.03 ± 0.10 μM MDA; p < .001) at 6 h, while DHA lost all antioxidant activity by 4 h. The antioxidant activity of EPA was preserved when combined with an equimolar concentration of DHA (5 μM each). EPA pretreatment prevented HDL oxidation in a dose-dependent manner that was preserved over time. These results suggest unique lipophilic and electron stabilization properties for EPA as compared to DHA with respect to inhibition of HDL oxidation. These antioxidant effects of EPA may enhance certain atheroprotective functions for HDL. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Humic Acid-Like and Fulvic Acid-Like Inhibition on the Hydrolysis of Cellulose and Tributyrin

    NARCIS (Netherlands)

    Fernandes, Tania V.; van Lier, Jules B.; Zeeman, Grietje

    2015-01-01

    Enzymatic hydrolysis of complex wastes is a critical step for efficient biogas production in anaerobic digesters. Inhibition of this hydrolytic step was studied by addition of humic acid-like (HAL) and fulvic acid-like (FAL) substances, extracted from maize silage and fresh cow manure, to batch

  11. Humic Acid-Like and Fulvic Acid-Like Inhibition on the Hydrolysis of Cellulose and Tributyrin

    NARCIS (Netherlands)

    Fernandes, T.V.; Lier, van J.B.; Zeeman, Grietje

    2015-01-01

    Enzymatic hydrolysis of complex wastes is a critical step for efficient biogas production in anaerobic digesters. Inhibition of this hydrolytic step was studied by addition of humic acid-like (HAL) and fulvic acid-like (FAL) substances, extracted from maize silage and fresh cow manure, to batch

  12. Corrosion and Inhibition Effects of Mild Steel in Hydrochloric Acid Solutions Containing Organophosphonic Acid

    Directory of Open Access Journals (Sweden)

    Manish Gupta

    2013-01-01

    Full Text Available A study has been made on the mechanism of corrosion of mild steel and the effect of nitrilo trimethylene phosphonic (NTMP acid as a corrosion inhibitor in acidic medium, that is, 10% HC1 using the weight loss method and electrochemical techniques, that is, potentiodynamic and galvanostatic polarization measurements. Although corrosion is a long-time process, but it takes place at a faster rate in the beginning which goes on decreasing with due course of time. The above-mentioned methods of corrosion rate determination furnish an average value for a long-time interval. Looking at the versatility and minimum detection limit of the voltammetric method, the authors have developed a new voltammetric method for the determination of corrosion rate at short-time intervals. The results of corrosion of mild steel in 10% HC1 solution with and without NTMP inhibitor at short-time intervals have been reported. The corrosion inhibition efficiency of NTMP is 93% after 24 h.

  13. Inhibition of cholinesterases by phenolic acids detected in beer: A ...

    African Journals Online (AJOL)

    ... and the interactive index of combination. These results support the idea that simple phenolic acids from beer can play a role in neuroprotection, but further studies need to be conducted. Keywords: Acetylcholinesterase, Alzheimer's disease, beer, butyrylcholinesterase, phenolic acids. African Journal of Biotechnology Vol.

  14. Inhibition of platelet aggregation by diterpene acids from Pinus massoniana resin.

    Science.gov (United States)

    Cheung, H T; Fu, S L; Smal, M A

    1994-01-01

    The acidic fraction of the resin of Pinus massoniana Lamb. from China was converted to the p-nitrophenyl esters, and the esters separated by chromatography. The separated p-nitrophenyl esters were individually hydrolysed by potassium hydroxide in acetone-water at room temperature to 8 diterpene acids of the pimarane and abietane groups: pimaric acid (8(14),15-pimaradien-18-oic acid) (1), levopimaric acid (8(14),12-abietadien-18-oic acid) (2), palustric acid (8,13-abietadien-18-oic acid) (3), neobietic acid (8(14),13(15)-abietadien-18-oic acid) (4), abietic acid (7,13-abietadien-18-oic acid) (5), dehydroabietic acid (8,11,13-abietatrien-18-oic acid) (6), 7-oxodehydroabietic acid (7-oxo-8,11,13-abietatrien-18-oic acid) (7) and 7 alpha-hydroxydehydroabietic acid (7 alpha-hydroxy-8,11,13-abietatrien-18-oic acid) (8). The structure (and stereochemistry) of the diterpene acids were substantiated by nuclear magnetic resonance spectroscopy (proton and carbon-13, one and two dimensional), by mass spectrometry (electron impact and methane chemical ionization) and by rotation measurements. The 8 diterpene acids were tested for their ability to inhibit the aggregation of washed rabbit platelets induced by platelet activating factor (PAF), adenosine diphosphate (ADP) and by calcium ionophore A23187. With platelet aggregation induced by the latter two agonists, activities comparable with or higher than linolenic acid were given by the first 4 acids. With aggregation induced by PAF, the first 3 acids show activity, but at a level significantly lower than that of linolenic acid. Levopimaric acid has the highest activity among the diterpene acids tested. It is proposed that this activity is related to the folded shape of the molecule.

  15. A role for AMPK in the inhibition of glucose-6-phosphate dehydrogenase by polyunsaturated fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Kohan, Alison B.; Talukdar, Indrani; Walsh, Callee M. [Department of Biochemistry, West Virginia University, Morgantown, WV (United States); Salati, Lisa M., E-mail: lsalati@hsc.wvu.edu [Department of Biochemistry, West Virginia University, Morgantown, WV (United States)

    2009-10-09

    Both polyunsaturated fatty acids and AMPK promote energy partitioning away from energy consuming processes, such as fatty acid synthesis, towards energy generating processes, such as {beta}-oxidation. In this report, we demonstrate that arachidonic acid activates AMPK in primary rat hepatocytes, and that this effect is p38 MAPK-dependent. Activation of AMPK mimics the inhibition by arachidonic acid of the insulin-mediated induction of G6PD. Similar to intracellular signaling by arachidonic acid, AMPK decreases insulin signal transduction, increasing Ser{sup 307} phosphorylation of IRS-1 and a subsequent decrease in AKT phosphorylation. Overexpression of dominant-negative AMPK abolishes the effect of arachidonic acid on G6PD expression. These data suggest a role for AMPK in the inhibition of G6PD by polyunsaturated fatty acids.

  16. Galacturonic acid inhibits the growth of Saccharomyces cerevisiae on galactose, xylose, and arabinose.

    Science.gov (United States)

    Huisjes, Eline H; de Hulster, Erik; van Dam, Jan C; Pronk, Jack T; van Maris, Antonius J A

    2012-08-01

    The efficient fermentation of mixed substrates is essential for the microbial conversion of second-generation feedstocks, including pectin-rich waste streams such as citrus peel and sugar beet pulp. Galacturonic acid is a major constituent of hydrolysates of these pectin-rich materials. The yeast Saccharomyces cerevisiae, the main producer of bioethanol, cannot use this sugar acid. The impact of galacturonic acid on alcoholic fermentation by S. cerevisiae was investigated with anaerobic batch cultures grown on mixtures of glucose and galactose at various galacturonic acid concentrations and on a mixture of glucose, xylose, and arabinose. In cultures grown at pH 5.0, which is well above the pK(a) value of galacturonic acid (3.51), the addition of 10 g · liter(-1) galacturonic acid did not affect galactose fermentation kinetics and growth. In cultures grown at pH 3.5, the addition of 10 g · liter(-1) galacturonic acid did not significantly affect glucose consumption. However, at this lower pH, galacturonic acid completely inhibited growth on galactose and reduced galactose consumption rates by 87%. Additionally, it was shown that galacturonic acid strongly inhibits the fermentation of xylose and arabinose by the engineered pentose-fermenting S. cerevisiae strain IMS0010. The data indicate that inhibition occurs when nondissociated galacturonic acid is present extracellularly and corroborate the hypothesis that a combination of a decreased substrate uptake rate due to competitive inhibition on Gal2p, an increased energy requirement to maintain cellular homeostasis, and/or an accumulation of galacturonic acid 1-phosphate contributes to the inhibition. The role of galacturonic acid as an inhibitor of sugar fermentation should be considered in the design of yeast fermentation processes based on pectin-rich feedstocks.

  17. Wall teichoic acid protects Staphylococcus aureus from inhibition by Congo red and other dyes.

    Science.gov (United States)

    Suzuki, Takashi; Campbell, Jennifer; Kim, Younghoon; Swoboda, Jonathan G; Mylonakis, Eleftherios; Walker, Suzanne; Gilmore, Michael S

    2012-09-01

    Polyanionic polymers, including lipoteichoic acid and wall teichoic acid, are important determinants of the charged character of the staphylococcal cell wall. This study was designed to investigate the extent to which teichoic acid contributes to protection from anionic azo dyes and to identify barriers to drug penetration for development of new antibiotics for multidrug-resistant Staphylococcus aureus infection. We studied antimicrobial activity of azo dyes against S. aureus strains with or without inhibition of teichoic acid in vitro and in vivo. We observed that inhibition of wall teichoic acid expression resulted in an ∼1000-fold increase in susceptibility to azo dyes such as Congo red, reducing its MIC from >1024 to Congo red susceptibility. Based on this finding, combination therapy was tested using the highly synergistic combination of Congo red plus tunicamycin at sub-MIC concentrations (to inhibit wall teichoic acid biosynthesis). The combination rescued Caenorhabditis elegans from a lethal challenge of S. aureus. Our studies show that wall teichoic acid confers protection to S. aureus from anionic azo dyes and related compounds, and its inhibition raises the prospect of development of new combination therapies based on this inhibition.

  18. Nucleoside phosphonic acids in thymidine phosphorylase inhibition: Structure - activity relationship

    Czech Academy of Sciences Publication Activity Database

    Panova, Natalya; Kóšiová, Ivana; Petrová, Magdalena; Vaněk, Václav; Liboska, Radek; Kovačková, Soňa; Kočalka, Petr; Králíková, Šárka; Točík, Zdeněk; Páv, Ondřej; Pačes, Ondřej; Rejman, Dominik; Rosenberg, Ivan

    -, č. 52 (2008), s. 665-666 ISSN 0261-3166. [Joint Symposium of the International Roundtable on Nucleosides, Nucleotides and Nucleic Acids /18./ and the International Symposium on Nucleic Acid Chemistry /35./. Kyoto, 08.09.2008-12.09.2008] R&D Projects: GA MŠk(CZ) LC06061; GA MŠk(CZ) LC06077; GA MŠk LC512 Institutional research plan: CEZ:AV0Z40550506 Keywords : thymidine phosphorylase * inhibitors * phosphonic acids Subject RIV: CC - Organic Chemistry

  19. Corrosion inhibition behavior of Ketosulfone for Zinc in acidic medium

    African Journals Online (AJOL)

    The corrosion inhibition behavior of Ketosulfone for zinc is investigated by polarization and AC-impedance techniques at 303-333K. The Tafel plots indicates that the Ketosulfone is a mixed type inhibitor. The interaction between metal and inhibitor is explained by Langmuir adsorption isotherm. DG0ads andDH0ads value ...

  20. trans-Cinnamic and Chlorogenic Acids Affect the Secondary Metabolic Profiles and Ergosterol Biosynthesis by Fusarium culmorum and F. graminearum Sensu Stricto.

    Science.gov (United States)

    Kulik, Tomasz; Stuper-Szablewska, Kinga; Bilska, Katarzyna; Buśko, Maciej; Ostrowska-Kołodziejczak, Anna; Załuski, Dariusz; Perkowski, Juliusz

    2017-06-22

    Plant-derived compounds limiting mycotoxin contamination are currently of major interest in food and feed production. However, their potential application requires an evaluation of their effects on fungal secondary metabolism and membrane effects. In this study, different strains of Fusarium culmorum and F. graminearum sensu stricto were exposed to trans -cinnamic and chlorogenic acids on solid YES media. Fusaria produced phenolic acids, whose accumulation was lowered by exogenous phenolic compounds. In addition, fungi reduced exogenous phenolic acids, leading either to their conversion or degradation. trans -Cinnamic acid was converted to caffeic and ferulic acids, while chlorogenic acid was degraded to caffeic acid. The latter underwent further degradation to protocatechuic acid. Fungal-derived trans -cinnamic acid, as the first intermediate of the shikimate pathway, increased after chlorogenic acid treatment, presumably due to the further inhibition of the conversion of trans -cinnamic acid. Exogenous trans -cinnamic and chlorogenic acid displayed the inhibition of mycotoxin production by Fusaria, which appeared to be largely dependent on the phenolic compound and its concentration and the assayed strain. Exogenous phenolic acids showed different effects on ergosterol biosynthesis by fungi. It was found that the production of this membrane sterol was stimulated by trans -cinnamic acid, while chlorogenic acid negatively impacted ergosterol biosynthesis, suggesting that phenolic acids with stronger antifungal activities may upregulate ergosterol biosynthesis by Fusaria. This paper reports on the production of phenolic acids by Fusaria for the first time.

  1. Inhibition kinetics and molecular simulation of p-substituted cinnamic acid derivatives on tyrosinase.

    Science.gov (United States)

    Cui, Yi; Hu, Yong-Hua; Yu, Feng; Zheng, Jing; Chen, Lin-Shan; Chen, Qing-Xi; Wang, Qin

    2017-02-01

    This study was to investigate the inhibition effects of para-substituted cinnamic acid derivatives (4-chlorocinnamic acid, 4-ethoxycinnamic acid and 4-nitrocinnamic acid) on tyrosinase catalyzing the substrates, with the purpose of elucidating the inhibition mechanism of the tested derivatives on tyrosinase by the UV-vis spectrum, fluorescence spectroscopy, copper interacting and molecular docking, respectively. The native-PAGE results showed that 4-chlorocinnamic acid (4-CCA), 4-ethoxycinnamic acid (4-ECA) and 4-nitrocinnamic acid (4-NCA) had inhibitory effects on tyrosinase. Spectrophotometric analysis used to determine the inhibition capabilities of these compounds on tyrosinase catalyzing L-tyrosine (L-Tyr) and L-3,4-Dihydroxyphenylalanine (L-DOPA) as well. The IC 50 values and inhibition constants were further determined. Moreover, quenching mechanisms of tested compounds to tyrosinase belonged to static type and a red shift on fluorescence emission peak occurred when 4-NCA added. Copper interacting and molecular docking demonstrated that 4-CCA could not bind directly to the copper, but it could interact with residues in the active center of tyrosinase. Meanwhile, 4-ECA and 4-NCA could chelate a copper ion of tyrosinase. Anti-tyrosinase activities of para-substituted cinnamic acid derivatives would lay scientific foundation for their utilization in designing of novel tyrosinase inhibitors. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Corrosion Inhibition of Titanium in Acidic Media Containing Fluoride with Bixin

    OpenAIRE

    Jinendra Singh Chauhan; D. K. Gupta

    2009-01-01

    The bixin in acidic media were tested for corrosion inhibition of Ti in 0.5 N sulphuric acid and 0.1 N HCl solution at 30 to 40 °C temperature range by electrochemical methods. It reveals that bixin works as a corrosion inhibitor in halide media and protect the metals from the corrosion with great efficiency

  3. Corrosion Inhibition of Titanium in Acidic Media Containing Fluoride with Bixin

    Directory of Open Access Journals (Sweden)

    Jinendra Singh Chauhan

    2009-01-01

    Full Text Available The bixin in acidic media were tested for corrosion inhibition of Ti in 0.5 N sulphuric acid and 0.1 N HCl solution at 30 to 40 °C temperature range by electrochemical methods. It reveals that bixin works as a corrosion inhibitor in halide media and protect the metals from the corrosion with great efficiency

  4. Growth inhibition by nitrocompounds of selected uric acid-utilizing microorganisms isolated from poultry manure.

    Science.gov (United States)

    Kim, W K; Anderson, R C; Ratliff, A L; Nisbet, D J; Ricke, S C

    2006-01-01

    The overall objective of this study was to evaluate the potential ability of nitrocompounds to reduce ammonia volatilization by inhibiting uric acid-utilizing microorganisms. Experiment I was conducted to evaluate the effects of nitrocompounds on the growth of uric acid-utilizing microorganisms isolated from poultry manure during six-hour incubation. There were five treatments: (1) control, (2) 50 mM nitroethane, (3) 50 mM nitroethanol, (4) 50 mM nitropropanol, and (5) 50 mM nitropropionic acid. Optical density values of nitrocompounds were significantly lower than that of control at two, four, and six hours. Plate counts of uric acid-utilizing microorganisms after six-hour incubation exhibited that nitrocompounds greatly reduced the growth of these microorganisms except for the nitroethane (P nitrocompounds on growth of uric acid-utilizing microorganisms compared to non-nitrocompounds such as ethanol, propanol, and propionic acid. Experiments II and III consisted of seven treatments: (1) control, (2) nitroethanol, (3) nitropropanol, (4) nitropropionic acid, (5) ethanol, (6) propanol, and (7) propionic acid. The incubation times of Experiments II and III were 6 and 24 h, respectively. The nitrocompounds were significantly more successful in inhibiting growth of uric acid-utilizing microorganisms compared to those non-nitrocompounds. These results suggest that nitrocompounds exhibit potential to reduce ammonia volatilization in poultry manure by inhibiting growth of uric acid-utilizing microorganisms.

  5. Corrosion inhibition of mild steel in 1 M HCl solution by henna extract: A comparative study of the inhibition by henna and its constituents (Lawsone, Gallic acid, {alpha}-D-Glucose and Tannic acid)

    Energy Technology Data Exchange (ETDEWEB)

    Ostovari, A. [Technical Inspection Engineering Department, Petroleum University of Technology, Abadan (Iran, Islamic Republic of)], E-mail: A.Ostovari@gmail.com; Hoseinieh, S.M.; Peikari, M. [Technical Inspection Engineering Department, Petroleum University of Technology, Abadan (Iran, Islamic Republic of); Shadizadeh, S.R. [Petroleum Engineering Department, Petroleum University of Technology, Abadan (Iran, Islamic Republic of); Hashemi, S.J. [Technical Inspection Engineering Department, Petroleum University of Technology, Abadan (Iran, Islamic Republic of)

    2009-09-15

    The inhibitive action of henna extract (Lawsonia inermis) and its main constituents (lawsone, gallic acid, {alpha}-D-Glucose and tannic acid) on corrosion of mild steel in 1 M HCl solution was investigated through electrochemical techniques and surface analysis (SEM/EDS). Polarization measurements indicate that all the examined compounds act as a mixed inhibitor and inhibition efficiency increases with inhibitor concentration. Maximum inhibition efficiency (92.06%) is obtained at 1.2 g/l henna extract. Inhibition efficiency increases in the order: lawsone > henna extract > gallic acid > {alpha}-D-Glucose > tannic acid. Also, inhibition mechanism and thermodynamic parameters are discussed.

  6. Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type1) diabetic rats

    Science.gov (United States)

    Nagai, Ryoji; Nagai, Mime; Shimasaki, Satoko; Baynes, John W.; Fujiwara, Yukio

    2010-01-01

    Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end products (AGEs) such as Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis . We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes. PMID:20117096

  7. A Fluorescent Assay for Plant Caffeic Acid O-methyltransferases

    Science.gov (United States)

    We have developed a facile, sensitive and continuous assay to measure the activities of plant COMTs using s-adenosyl homocysteine hydrolase as a coupling enzyme and and adeonsine a thiol-specific fluor, Thioglo1, as the detecting reagent. This assay was validated using recombinant sorghum COMT (BMR-...

  8. Inhibition of Listeria monocytogenes by fatty acids and monoglycerides.

    OpenAIRE

    Wang, L L; Johnson, E A

    1992-01-01

    Fatty acids and monoglycerides were evaluated in brain heart infusion broth and in milk for antimicrobial activity against the Scott A strain of Listeria monocytogenes. C12:0, C18:3, and glyceryl monolaurate (monolaurin) had the strongest activity in brain heart infusion broth and were bactericidal at 10 to 20 micrograms/ml, whereas potassium (K)-conjugated linoleic acids and C18:2 were bactericidal at 50 to 200 micrograms/ml. C14:0, C16:0, C18:0, C18:1, glyceryl monomyristate, and glyceryl m...

  9. Sugar fatty acid esters inhibit biofilm formation by food-borne pathogenic bacteria

    Science.gov (United States)

    Furukawa, Soichi; Akiyoshi, Yuko; O’Toole, George A.; Ogihara, Hirokazu; Morinaga, Yasushi

    2010-01-01

    Effects of food additives on biofilm formation by food-borne pathogenic bacteria were investigated. Thirty-three potential food additives and 3 related compounds were added to the culture medium at concentrations from 0.001 to 0.1% (w/w), followed by inoculation and cultivation of five biofilm-forming bacterial strains for the evaluation of biofilm formation. Among the tested food additives, 21 showed inhibitory effects of biofilm formation by Staphylococcus aureus and Escherichia coli, and in particular, sugar fatty acid esters showed significant anti-biofilm activity. Sugar fatty acid esters with long chain fatty acid residues (C14-16) exerted their inhibitory effect at the concentration of 0.001%(w/w), but bacterial growth was not affected at this low concentration. Activities of the sugar fatty acid esters positively correlated with the increase of the chain length of the fatty acid residues. Sugar fatty acid esters inhibited the initial attachment of the Staphylococcus aureus cells to the abiotic surface. Sugar fatty acid esters with long chain fatty acid residues (C14-16) also inhibited biofilm formation by Streptococcus mutans and Listeria monocytogenes at 0.01%(w/w), while the inhibition of biofilm formation by Pseudomonas aeruginosa required the addition of a far higher concentration (0.1%(w/w)) of the sugar fatty acid esters. PMID:20089325

  10. Auxin-Induced Ethylene Triggers Abscisic Acid Biosynthesis and Growth Inhibition1

    Science.gov (United States)

    Hansen, Hauke; Grossmann, Klaus

    2000-01-01

    The growth-inhibiting effects of indole-3-acetic acid (IAA) at high concentration and the synthetic auxins 7-chloro-3-methyl-8-quinolinecarboxylic acid (quinmerac), 2-methoxy-3,6-dichlorobenzoic acid (dicamba), 4-amino-3,6,6-trichloropicolinic acid (picloram), and naphthalene acetic acid, were investigated in cleavers (Galium aparine). When plants were root treated with 0.5 mm IAA, shoot epinasty and inhibition of root and shoot growth developed during 24 h. Concomitantly, 1-aminocyclopropane-1-carboxylic acid (ACC) synthase activity, and ACC and ethylene production were transiently stimulated in the shoot tissue within 2 h, followed by increases in immunoreactive (+)-abscisic acid (ABA) and its precursor xanthoxal (xanthoxin) after 5 h. After 24 h of treatment, levels of xanthoxal and ABA were elevated up to 2- and 24-fold, relative to control, respectively. In plants treated with IAA, 7-chloro-3-methyl-8-quinolinecarboxylic acid, naphthalene acetic acid, 2-methoxy-3,6-dichlorobenzoic acid, and 4-amino-3,6,6-trichloropicolinic acid, levels of ethylene, ACC, and ABA increased in close correlation with inhibition of shoot growth. Aminoethoxyvinyl-glycine and cobalt ions, which inhibit ethylene synthesis, decreased ABA accumulation and growth inhibition, whereas the ethylene-releasing ethephon promoted ABA levels and growth inhibition. In accordance, tomato mutants defective in ethylene perception (never ripe) did not produce the xanthoxal and ABA increases and growth inhibition induced by auxins in wild-type plants. This suggests that auxin-stimulated ethylene triggers ABA accumulation and the consequent growth inhibition. Reduced catabolism most probably did not contribute to ABA increase, as indicated by immunoanalyses of ABA degradation and conjugation products in shoot tissue and by pulse experiments with [3H]-ABA in cell suspensions of G. aparine. In contrast, studies using inhibitors of ABA biosynthesis (fluridone, naproxen, and tungstate), ABA

  11. Comparison of the inhibition capability of oleanolic acid and ...

    African Journals Online (AJOL)

    Background: Human UDP-glucuronosyltransferases (UGTs) are important membrane proteins located in endoplasmic reticulum, and play important roles in metabolism of a variety of endogenous and exogenous compounds. Aims: To determine the influence of subtle difference in the structure of oleanolic acid and betulinic ...

  12. Inhibition of aflatoxin-producing aspergilli by lactic acid bacteria ...

    African Journals Online (AJOL)

    A total of six lactic acid bacteria (LAB) isolates were selected from five indigenously fermented cereal gruels and identified as Lactobacillus fermentum OYB, Lb. fermentum RS2, Lb. plantarum MW, Lb. plantarum YO, Lb. brevis WS3, and Lactococcus spp. RS3. Six aflatoxin-producing aspergilli were also selected from the ...

  13. INHIBITION OF CORROSION OF ZINC IN (HNO3 + HCl) ACID ...

    African Journals Online (AJOL)

    2015-05-01

    May 1, 2015 ... the present work, the role of aniline as inhibitor for corrosion of zinc in (HNO3 + HCl) binary acid mixture ... and without inhibitor containing 230 ml test solution at 301 + 1 K for 24 h immersion period. After the ... rate was determined at various temperatures e.g.at 303, 313, 323 and 333 K for an immersion.

  14. Comparison of the inhibition capability of oleanolic acid and ...

    African Journals Online (AJOL)

    reticulum, and play important roles in metabolism of a variety of endogenous and exogenous compounds. Aims: To determine the influence of subtle difference in the structure of oleanolic acid ... immune deficiency syndrome (HIV/AIDS) is defined as a disease spectrum of the human immune system caused by infection with ...

  15. Growth inhibition of Monodus subterraneus by free fatty acids

    NARCIS (Netherlands)

    Bosma, R.; Miazek, K.; Willemsen, S.M.; Vermuë, M.H.; Wijffels, R.H.

    2008-01-01

    Monodus subterraneus is a microalga, which is known for its high eicosapentaenoic acid (EPA; 20:5omega3) content. To produce EPA commercially, high volumetric productivities of microalgae are required. These high productivities can be reached in flat panel photobioreactors with small optical paths

  16. Sphingoid bases inhibit acid-induced demineralization of hydroxyapatite

    NARCIS (Netherlands)

    Valentijn-Benz, M.; van 't Hof, W.; Bikker, F.J.; Nazmi, K.; Brand, H.S.; Sotres, J.; Lindh, L.; Arnebrant, T.; Veerman, E.C.I.

    2015-01-01

    Calcium hydroxyapatite (HAp), the main constituent of dental enamel, is inherently susceptible to the etching and dissolving action of acids, resulting in tooth decay such as dental caries and dental erosion. Since the prevalence of erosive wear is gradually increasing, there is urgent need for

  17. Ursolic Acid Florotriazole Treatment Causes Inhibition of Squamous ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of ursolic acid florotriazole (UFT), on SCC-15 oral squamous cancer cells. Methods: Confocal laser microscope with a 490 nm argon laser was used to record the fluorescence of the cells and capture the images. Flow cytometry and Cell Quest program were used to analyze the DNA content ...

  18. Inhibition of aldo-keto reductase family 1 member B10 by unsaturated fatty acids.

    Science.gov (United States)

    Hara, Akira; Endo, Satoshi; Matsunaga, Toshiyuki; Soda, Midori; El-Kabbani, Ossama; Yashiro, Koji

    2016-11-01

    A human member of the aldo-keto reductase (AKR) superfamily, AKR1B10, is a cytosolic NADPH-dependent reductase toward various carbonyl compounds including reactive aldehydes, and is normally expressed in intestines. The enzyme is overexpressed in several extraintestinal cancers, and suggested as a potential target for cancer treatment. We found that saturated and cis-unsaturated fatty acids inhibit AKR1B10. Among the saturated fatty acids, myristic acid was the most potent, showing the IC 50 value of 4.2 μM cis-Unsaturated fatty acids inhibited AKR1B10 more potently, and linoleic, arachidonic, and docosahexaenoic acids showed the lowest IC 50 values of 1.1 μM. The inhibition by these fatty acids was reversible and kinetically competitive with respect to the substrate, showing the K i values of 0.24-1.1 μM. These fatty acids, except for α-linoleic acid, were much less inhibitory to structurally similar aldose reductase. Site-directed mutagenesis study suggested that the fatty acids interact with several active site residues of AKR1B10, of which Gln114, Val301 and Gln303 are responsible for the inhibitory selectivity. Linoleic and arachidonic acids also effectively inhibited AKR1B10-mediated 4-oxo-2-nonenal metabolism in HCT-15 cells. Thus, the cis-unsaturated fatty acids may be used as an adjuvant therapy for treatment of cancers that up-regulate AKR1B10. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Esomeprazole inhibits the pentagastrin-stimulated secretion of gastric acid in healthy Japanese volunteers.

    Science.gov (United States)

    Maejima, Ryuhei; Koike, Tomoyuki; Nakagawa, Kenichiro; Iijima, Katsunori; Shimosegawa, Tooru

    2015-03-01

    Gastroesophageal reflux disease (GERD) is a common disease, in which the reflux of gastric acid causes mucosal damage of the esophagus and/or troublesome symptoms. Esomeprazole, a proton pump inhibitor, has been used for treatment of GERD in Japan since 2011; namely, only little is known about its effect on gastric acid secretion in Japanese. We, therefore, assessed the relationship between dose and timing of esomeprazole administration and gastric acid inhibition in 11 healthy male Japanese volunteers by directly examining gastric acid secretion capacity. In this randomized, open-label, three-way crossover study, the subjects were dosed with esomeprazole 10 mg or 20 mg once a day (q.d.), or 20 mg twice a day (b.i.d.) for 14 days, and pentagastrin-stimulated gastric acid secretion was measured by endoscopic gastrin test. At steady states, gastric acid inhibition rates were significantly higher in esomeprazole 20 mg b.i.d. (median 100.0%, interquartile range [IQR] 99.4-100%, P = 0.027) or 20 mg q.d. (100.0%, IQR 99.7-100%, P = 0.016), compared with 10 mg q.d. (98.4%, IQR 84.4-100%). At trough states, esomeprazole 20 mg b.i.d. showed significantly higher gastric acid inhibition (99.6%, IQR 99.0-100%) than did 20 mg q.d. (84.2%, IQR 76.4-88.8%, P = 0.002) or 10 mg q.d. (64.9%, IQR 59.1-76.7%, P = 0.001). Thus, esomeprazole 20 mg b.i.d. was sufficient to inhibit > 99% gastric acid secretion in healthy subjects. We propose that esomeprazole 20 mg b.i.d. is effective for treating Japanese patients with refractory GERD who require long-lasting gastric acid inhibition.

  20. Corrosion Inhibition Activities of Chemical Compound for Mild Steel in Hydrochloric Acid

    Directory of Open Access Journals (Sweden)

    Ahmed Khaleel Al-Okbi

    2017-11-01

    Full Text Available Corrosive solution (Hydrochloric acid has been over and over utilized in manufacturing processes, covering cleaning pickling, acid descaling by acids and oil fully acidize. Inhibition effect of the inhibitor named "2-(((1H-benzo[d]imidazol-2-yl iminomethylphenol" [BIMP] on mild steel in 1 M hydrochloric acid has been scanned employing a technique named weight loss. The results of the study reveal that the inhibition efficiency of BIMP depends on its concentration and attains approximately 81.4% at 0.5 g/L. It is found that the BIMP shows significant action as an inhibitor for mild steel corrosion in corrosive media. BIMP has efficiency raised regarding to temperature decreasing and raising BIMP concentrations.  

  1. Quinic acid derivatives inhibit dengue virus replication in vitro.

    Science.gov (United States)

    Zanello, Paula Rodrigues; Koishi, Andrea Cristine; Rezende Júnior, Celso de Oliveira; Oliveira, Larissa Albuquerque; Pereira, Adriane Antonia; de Almeida, Mauro Vieira; Duarte dos Santos, Claudia Nunes; Bordignon, Juliano

    2015-12-22

    Dengue is the most prevalent arboviral disease in tropical and sub-tropical areas of the world. The incidence of infection is estimated to be 390 million cases and 25,000 deaths per year. Despite these numbers, neither a specific treatment nor a preventive vaccine is available to protect people living in areas of high risk. With the aim of seeking a treatment that can mitigate dengue infection, we demonstrated that the quinic acid derivatives known as compound 2 and compound 10 were effective against all four dengue virus serotypes and safe for use in a human hepatoma cell line (Huh7.5). Both compounds were non-virucidal to dengue virus particles and did not interfere with early steps of the dengue virus life cycle, including binding and internalization. Experiments using a replicon system demonstrated that compounds 2 and 10 impaired dengue virus replication in Huh7.5 cells. Additionally, the anti-dengue virus effects of the quinic acid derivatives were preserved in human peripheral blood mononuclear cells. Taken together, these data suggest that quinic acid derivatives represent a novel chemical class of active compounds that could be used to combat dengue virus infection.

  2. AMP-activated kinase restricts Rift Valley fever virus infection by inhibiting fatty acid synthesis.

    Directory of Open Access Journals (Sweden)

    Theresa S Moser

    Full Text Available The cell intrinsic innate immune responses provide a first line of defense against viral infection, and often function by targeting cellular pathways usurped by the virus during infection. In particular, many viruses manipulate cellular lipids to form complex structures required for viral replication, many of which are dependent on de novo fatty acid synthesis. We found that the energy regulator AMPK, which potently inhibits fatty acid synthesis, restricts infection of the Bunyavirus, Rift Valley Fever Virus (RVFV, an important re-emerging arthropod-borne human pathogen for which there are no effective vaccines or therapeutics. We show restriction of RVFV both by AMPK and its upstream activator LKB1, indicating an antiviral role for this signaling pathway. Furthermore, we found that AMPK is activated during RVFV infection, leading to the phosphorylation and inhibition of acetyl-CoA carboxylase, the first rate-limiting enzyme in fatty acid synthesis. Activating AMPK pharmacologically both restricted infection and reduced lipid levels. This restriction could be bypassed by treatment with the fatty acid palmitate, demonstrating that AMPK restricts RVFV infection through its inhibition of fatty acid biosynthesis. Lastly, we found that this pathway plays a broad role in antiviral defense since additional viruses from disparate families were also restricted by AMPK and LKB1. Therefore, AMPK is an important component of the cell intrinsic immune response that restricts infection through a novel mechanism involving the inhibition of fatty acid metabolism.

  3. The bisphosphonate zoledronic acid effectively targets lung cancer cells by inhibition of protein prenylation

    International Nuclear Information System (INIS)

    Xie, Fan; Li, Pengcheng; Gong, Jianhua; Zhang, Jiahong; Ma, Jingping

    2015-01-01

    Aberrant activation of oncoproteins such as members of the Ras family is common in human lung cancers. The proper function of Ras largely depends on a post-translational modification termed prenylation. Bisphosphonates have been shown to inhibit prenylation in cancer cells. In this study, we show that zoledronic acid, a third generation bisphosphonate, is effective in targeting lung cancer cells. This is achieved by the induction of apoptosis and inhibition of proliferation, through suppressing the activation of downstream Ras and EGFR signalling by zoledronic acid. The combination of zoledronic acid and paclitaxel or cisplatin (commonly used chemotherapeutic drugs for lung cancer) augmented the activity of either drug alone in in vitro lung cancer cellular system and in vivo lung xenograft mouse model. Importantly, zoledronic acid inhibits protein prenylation as shown by the increased levels of unprenylated Ras and Rap1A. In addition, the effects of zoledronic acid were reversed in the presence of geranylgeraniol and farnesol, further confirming that mechanism of zoledroinc acid's action in lung cancer cells is through prenylation inhibition. Since zoledronic acid is already available for clinic use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of lung cancer. - Highlights: • Zoledronic acid (ZA) is effectively against lung cancer cells in vitro and in vivo. • ZA acts on lung cancer cells through inhibition of protein prenylation. • ZA suppresses global downstream phosphorylation of Ras signalling. • ZA enhances the effects of chemotherapeutic drugs in lung cancer cells.

  4. The bisphosphonate zoledronic acid effectively targets lung cancer cells by inhibition of protein prenylation

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Fan [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China); Li, Pengcheng [Department of Oncology, Wuhan Union Hospital Affiliated to Huazhong University of Science and Technology, Wuhan (China); Gong, Jianhua; Zhang, Jiahong [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China); Ma, Jingping, E-mail: mjpjzhospital@hotmail.com [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China)

    2015-11-27

    Aberrant activation of oncoproteins such as members of the Ras family is common in human lung cancers. The proper function of Ras largely depends on a post-translational modification termed prenylation. Bisphosphonates have been shown to inhibit prenylation in cancer cells. In this study, we show that zoledronic acid, a third generation bisphosphonate, is effective in targeting lung cancer cells. This is achieved by the induction of apoptosis and inhibition of proliferation, through suppressing the activation of downstream Ras and EGFR signalling by zoledronic acid. The combination of zoledronic acid and paclitaxel or cisplatin (commonly used chemotherapeutic drugs for lung cancer) augmented the activity of either drug alone in in vitro lung cancer cellular system and in vivo lung xenograft mouse model. Importantly, zoledronic acid inhibits protein prenylation as shown by the increased levels of unprenylated Ras and Rap1A. In addition, the effects of zoledronic acid were reversed in the presence of geranylgeraniol and farnesol, further confirming that mechanism of zoledroinc acid's action in lung cancer cells is through prenylation inhibition. Since zoledronic acid is already available for clinic use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of lung cancer. - Highlights: • Zoledronic acid (ZA) is effectively against lung cancer cells in vitro and in vivo. • ZA acts on lung cancer cells through inhibition of protein prenylation. • ZA suppresses global downstream phosphorylation of Ras signalling. • ZA enhances the effects of chemotherapeutic drugs in lung cancer cells.

  5. Extracts of Edible Plants Inhibit Pancreatic Lipase, Cholesterol Esterase and Cholesterol Micellization, and Bind Bile Acids

    Directory of Open Access Journals (Sweden)

    Julnaryn Intrawangso

    2012-01-01

    Full Text Available The application of edible plants with more effective ability to inhibit fat digestion and absorption has recently been explored for possible treatment of hyperlipidaemia. The aim of the present study is to investigate the effect of nine edible plants on the inhibition of pancreatic lipase and pancreatic cholesterol esterase activities, as well as the inhibition of cholesterol micelle formation, and bile acid binding. Our findings have shown strong pancreatic lipase inhibitory activity and the inhibition of cholesterol micellization by mulberry leaf extract. Safflower extract was the most potent inhibitor of pancreatic cholesterol esterase. In addition, cat’s whiskers and safflower extracts had a potent bile acid binding activity. It is suggested that a daily intake of these edible plants may delay postprandial hypertriacylglycerolaemia and hypercholesterolaemia, and therefore may be applied for the prevention and treatment of hyperlipidaemia.

  6. Docosahexaenoic acid antagonizes the boosting effect of palmitic acid on LPS inflammatory signaling by inhibiting gene transcription and ceramide synthesis.

    Science.gov (United States)

    Jin, Junfei; Lu, Zhongyang; Li, Yanchun; Cowart, L Ashley; Lopes-Virella, Maria F; Huang, Yan

    2018-01-01

    It is well known that saturated fatty acids (SFAs) and unsaturated fatty acid, in particular omega-3 polyunsaturated fatty acids (n-3 PUFAs), have different effects on inflammatory signaling: SFAs are pro-inflammatory but n-3 PUFAs have strong anti-inflammatory properties. We have reported that palmitic acid (PA), a saturated fatty acid, robustly amplifies lipopolysaccharide (LPS) signaling to upregulate proinflammatory gene expression in macrophages. We also reported that the increased production of ceramide (CER) via sphingomyelin (SM) hydrolysis and CER de novo synthesis plays a key role in the synergistic effect of LPS and PA on proinflammatory gene expression. However, it remains unclear if n-3 PUFAs are capable of antagonizing the synergistic effect of LPS and PA on gene expression and CER production. In this study, we employed the above macrophage culture system and lipidomical analysis to assess the effect of n-3 PUFAs on proinflammatory gene expression and CER production stimulated by LPS and PA. Results showed that DHA strongly inhibited the synergistic effect of LPS and PA on proinflammatory gene expression by targeting nuclear factor kappa B (NFκB)-dependent gene transcription. Results also showed that DHA inhibited the cooperative effect of LPS and PA on CER production by targeting CER de novo synthesis, but not SM hydrolysis. Furthermore, results showed that myriocin, a specific inhibitor of serine palmitoyltransferase, strongly inhibited both LPS-PA-stimulated CER synthesis and proinflammatory gene expression, indicating that CER synthesis is associated with proinflammatory gene expression and that inhibition of CER synthesis contributes to DHA-inhibited proinflammatory gene expression. Taken together, this study demonstrates that DHA antagonizes the boosting effect of PA on LPS signaling on proinflammatory gene expression by targeting both NFκB-dependent transcription and CER de novo synthesis in macrophages.

  7. Root exudates from grafted-root watermelon showed a certain contribution in inhibiting Fusarium oxysporum f. sp. niveum.

    Directory of Open Access Journals (Sweden)

    Ning Ling

    Full Text Available Grafting watermelon onto bottle gourd rootstock is commonly used method to generate resistance to Fusarium oxysporum f. sp. niveum (FON, but knowledge of the effect of the root exudates of grafted watermelon on this soil-borne pathogen in rhizosphere remains limited. To investigate the root exudate profiles of the own-root bottle gourd, grafted-root watermelon and own-root watermelon, recirculating hydroponic culture system was developed to continuously trap these root exudates. Both conidial germination and growth of FON were significantly decreased in the presence of root exudates from the grafted-root watermelon compared with the own-root watermelon. HPLC analysis revealed that the composition of the root exudates released by the grafted-root watermelon differed not only from the own-root watermelon but also from the bottle gourd rootstock plants. We identified salicylic acid in all 3 root exudates, chlorogenic acid and caffeic acid in root exudates from own-root bottle gourd and grafted-root watermelon but not own-root watermelon, and abundant cinnamic acid only in own-root watermelon root exudates. The chlorogenic and caffeic acid were candidates for potentiating the enhanced resistance of the grafted watermelon to FON, therefore we tested the effects of the two compounds on the conidial germination and growth of FON. Both phenolic acids inhibited FON conidial germination and growth in a dose-dependent manner, and FON was much more susceptible to chlorogenic acid than to caffeic acid. In conclusion, the key factor in attaining the resistance to Fusarium wilt is grafting on the non-host root stock, however, the root exudates profile also showed some contribution in inhibiting FON. These results will help to better clarify the disease resistance mechanisms of grafted-root watermelon based on plant-microbe communication and will guide the improvement of strategies against Fusarium-mediated wilt of watermelon plants.

  8. Corrosion Inhibition of Mild Steel in Citric Acid by Aqueous Extract of Piper Nigrum L.

    Directory of Open Access Journals (Sweden)

    P. Matheswaran

    2012-01-01

    Full Text Available The inhibition efficiency (IE of an aqueous extract of Piper Nigrum L. in controlling corrosion of mild steel at pH 12 has been evaluated by weight loss method in the absence and presence of inhibitor in citric acid medium at different concentration. The result showed that the corrosion inhibition efficiency of these compounds was found to vary with the different concentration at two hour time interval at room temperature. Also, it was found that the corrosion inhibition behaviour of Piper Nigrum L. is greater in 2 N Citric acid than 1 N Citric acid medium. So Piper Nigrum L. can be used has a good inhibitor for preventing mild steel material which is used in many construction purpose.

  9. Inhibition of the corrosion of mild steel in hydrochloric acid by isatin ...

    African Journals Online (AJOL)

    The inhibition of corrosion of mild steel in hydrochloric acid by isatin glycine (ING) and isatin (IN) at 30-60 oC and concentrations of 0.0001 M to 0.0005 M was studied via weight loss method. At the highest inhibitor concentration studied ING exhibited inhibition efficiency of 87% while IN exhibited 84% at 60 oC. A chemical ...

  10. Ginkgolic acid inhibits the invasiveness of colon cancer cells through AMPK activation.

    Science.gov (United States)

    Qiao, Lina; Zheng, Jianbao; Jin, Xianzhen; Wei, Guangbing; Wang, Guanghui; Sun, Xuejun; Li, Xuqi

    2017-11-01

    Tumor cell invasion and metastasis are important processes in colorectal cancer that exert negative effects on patient outcomes; consequently, a prominent topic in the field of colorectal cancer study is the identification of safe and affordable anticancer drugs against cell invasion and metastasis, with limited side effects. Ginkgolic acid is a phenolic acid extracted from ginkgo fruit, ginkgo exotesta and ginkgo leaves. Previous studies have indicated that ginkgolic acid inhibits tumor growth and invasion in a number of types of cancer; however, limited studies have considered the effects of ginkgolic acid on colon cancer. In the present study, SW480 colon cancer cells were treated with a range of concentrations of ginkgolic acid; tetrazolium dye-based MTT, wound-scratch and transwell migration assays were performed to investigate the effects on the proliferation, migration and invasion of colon cancer cells, and potential mechanisms for the effects were explored. The results indicated that ginkgolic acid reduced the proliferation and significantly inhibited the migration and invasion of SW480 cells in a concentration-dependent manner. Additional experiments indicated that ginkgolic acid significantly decreased the expression of invasion-associated proteins, including matrix metalloproteinase (MMP)-2, MMP-9, urinary-type plasminogen activator and C-X-C chemokine receptor type 4, and activated adenosine monophosphate activated protein kinase (AMPK) in SW480 cells. Small interfering RNA silencing of AMPK expression reversed the effect of ginkgolic acid on the expression of invasion-associated proteins. This result suggested that ginkgolic acid inhibited the proliferation, migration and invasion of SW480 colon cancer cells by inducing AMPK activation and inhibiting the expression of invasion-associated proteins.

  11. Synthesis, characterization and corrosion inhibition properties of benzamide-2-chloro-4-nitrobenzoic acid and anthranilic acid-2-chloro-4-nitrobenzoic acid for mild steel corrosion in acidic medium

    Science.gov (United States)

    Pandey, Archana; Verma, Chandrabhan; Singh, B.; Ebenso, Eno E.

    2018-03-01

    The present study deals with the synthesis of two new compounds namely, benzamide - 2-chloro-4-nitrobenzoic acid (BENCNBA) and anthranilic acid-2-chloro-4-nitrobenzoic acid (AACNBA) using solid phase reactions. The phase diagram studies revealed that formation of the investigated compounds occurs in 1:1 molar ratio. The synthesized compounds were characterized using several spectral techniques such as FT-IR, 1H and 13C NMR, UV-Vis, powder X-ray diffraction (PXRD). Single crystal XRD (SCXRD) study showed that both BENCNBA and AACNBA compounds crystallize in triclinic crystal system with P-1 space group. Further, the presence of intermolecular hydrogen bonding between the constituent components was also supported by single crystal X-ray diffraction (SCXRD) method. Heat of mixing, entropy of fusion, roughness parameter, interfacial energy and excess thermodynamic functions have also been computed using the enthalpy of fusion values derived from differential scanning calorimeter (DSC) study. The inhibition effect of BENCNBA and AACNBA on the mild steel corrosion in hydrochloric acid solution was tested using electrochemical methods. Electrochemical impedance spectroscopy (EIS) study revealed that both BENCNBA and AACNBA behaved as interface corrosion inhibitors and showed maximum inhibition efficiencies of 95.71% and 96.42%, respectively at 400 ppm (1.23 × 10-3 M) concentration. Potentiodynamic polarization (PDP) measurements suggested that BENCNBA and AACNBA acted as mixed type corrosion inhibitors. EIS and PDP results showed that BENCNBA and AACNBA act as efficient corrosion inhibitors for mild steel and their inhibition efficiencies enhances on increasing their concentrations.

  12. Inhibition Effect of Miconazole Nitrate on the Corrosion of Mild Steel in Hydrochloric Acid Medium

    Directory of Open Access Journals (Sweden)

    J. Ishwara Bhat

    2011-01-01

    Full Text Available The corrosion inhibition of mild steel by miconazole nitrate, an antifungal drug has been investigated using potentiodynamic polarization, electrochemical impedance spectroscopy technique, and weight loss methods. The experimental results suggested miconazole nitrate is a good corrosion inhibitor for mild steel in 1 M hydrochloric acid medium. The inhibition efficiency increased with increase in inhibitor concentration. The thermodynamic parameters were determined and discussed. The inhibition was assumed to occur via adsorption of the inhibitor molecule on the surface of mild steel following Langmuir adsorption isotherm.

  13. [Inhibition of Candida mycelia growth by a medium chain fatty acids, capric acid in vitro and its therapeutic efficacy in murine oral candidiasis].

    Science.gov (United States)

    Takahashi, Miki; Inoue, Shigeharu; Hayama, Kazumi; Ninomiya, Kentaro; Abe, Shigeru

    2012-01-01

    We assessed anti-C. albicans activities of the 4 fatty acids : caproic acid, caprylic acid, capric acid and lauric acid in vitro. All four inhibited not only the mycelial but also the yeast-form growth of Candida albicans. In particular, capric acid and caprylic acid inhibited Candida mycelia growth at very low concentrations. The effects of treatment of these two fatty acids on oral candidiasis were examined using a murine model. When 50 µl of capric acid (more than 48.8 µM) was administered three times into the oral cavity of Candida-infected mice, symptom scores of tongues of the mice were significantly improved. Histological studies of the capric acid-treated animals indicated that the fatty acid suppressed mycelial growth of the fungus on the tongue surface. These results suggest that all four fatty acids, and especially capric acid, have potential as substances supporting anti-Candida treatment.

  14. The Dietary Food Components Capric Acid and Caprylic Acid Inhibit Virulence Factors in Candida albicans Through Multitargeting.

    Science.gov (United States)

    Jadhav, Ashwini; Mortale, Supriya; Halbandge, Shivkrupa; Jangid, Priyanka; Patil, Rajendra; Gade, Wasudev; Kharat, Kiran; Karuppayil, Sankunny Mohan

    2017-11-01

    Capric acid and caprylic acid are the dietary food components. They are found to inhibit the virulence factors like morphogenesis, adhesion, and biofilm formation in the human pathogenic yeast Candida albicans. Our study demonstrated that yeast-to-hyphal signal transduction pathways were affected by capric acid and caprylic acid. The expression profile of genes associated with serum-induced morphogenesis showed reduced expressions of Cdc35, Hwp1, Hst7, and Cph1 by the treatment with both the fatty acids. Cell elongation gene, Ece1, was surprisingly downregulated by 5208-fold by the treatment of caprylic acid. Nrg1 and Tup1, negative regulators of hyphal formation, were overexpressed in presence of capric or caprylic acid. Cell cycle studies revealed that capric and caprylic acids arrested cell cycle at G2/M and S phase. Targeting the virulence factors like yeast-to-hyphal transition is efficacious for treatment of opportunistic fungal infections. This research suggests that both capric and caprylic acid may be effective interventions for treating C. albicans yeast infections.

  15. Oleic acid and linoleic acid from Tenebrio molitor larvae inhibit BACE1 activity in vitro: molecular docking studies.

    Science.gov (United States)

    Youn, Kumju; Yun, Eun-Young; Lee, Jinhyuk; Kim, Ji-Young; Hwang, Jae-Sam; Jeong, Woo-Sik; Jun, Mira

    2014-02-01

    In our ongoing research to find therapeutic compounds for Alzheimer's disease (AD) from natural resources, the inhibitory activity of the BACE1 enzyme by Tenebrio molitor larvae and its major compounds were evaluated. The T. molitor larvae extract and its fractions exhibited strong BACE1 suppression. The major components of hexane fraction possessing both high yield and strong BACE1 inhibition were determined by thin layer chromatography, gas chromatography, and nuclear magnetic resonance analysis. A remarkable composition of unsaturated long chain fatty acids, including oleic acid and linoleic acid, were identified. Oleic acid, in particular, noncompetitively attenuated BACE1 activity with a half-maximal inhibitory concentration (IC₅₀) value of 61.31 μM and Ki value of 34.3 μM. Furthermore, the fatty acids were stably interacted with BACE1 at different allosteric sites of the enzyme bound with the OH of CYS319 and the NH₃ of TYR320 for oleic acid and with the C=O group of GLN304 for linoleic acid. Here, we first revealed novel pharmacophore features of oleic acids and linoleic acid to BACE1 by in silico docking studies. The present findings would clearly suggest potential guidelines for designing novel BACE1 selective inhibitors.

  16. Identification of self-growth-inhibiting compounds lauric acid and 7-(Z)-tetradecenoic acid from Helicobacter pylori.

    Science.gov (United States)

    Yamashita, Shinpei; Igarashi, Masayuki; Hayashi, Chigusa; Shitara, Tetsuo; Nomoto, Akio; Mizote, Tomoko; Shibasaki, Masakatsu

    2015-06-01

    Helicobacter pylori growth medium is usually supplemented with horse serum (HS) or FCS. However, cyclodextrin derivatives or activated charcoal can replace serum. In this study, we purified self-growth-inhibiting (SGI) compounds from H. pylori growth medium. The compounds were recovered from porous resin, Diaion HP-20, which was added to the H. pylori growth medium instead of known supplements. These SGI compounds were also identified from 2,6-di-O-methyl-β-cyclodextrin, which was supplemented in a pleuropneumonia-like organisms broth. The growth-inhibiting compounds were identified as lauric acid (LA) and 7-(Z)-tetradecenoic acid [7-(Z)-TDA]. Although several fatty acids had been identified in H. pylori, these specific compounds were not previously found in this species. However, we confirmed that these fatty acids were universally present in the cultivation medium of the H. pylori strains examined in this study. A live/dead assay carried out without HS indicated that these compounds were bacteriostatic; however, no significant growth-inhibiting effect was observed against other tested bacterial species that constituted the indigenous bacterial flora. These findings suggested that LA and 7-(Z)-TDA might play important roles in the survival of H. pylori in human stomach epithelial cells.

  17. Antibiotics influence on lactic acid bacteria inhibiting gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Andreja Čanžek Majhenič

    2001-04-01

    Full Text Available Lactic acid bacteria (LAB are common inhabitants of the gastrointestinal (GI tract and have important role in maintaining the equilibrium of GI flora, which can be influenced by various factors like diets, antimicrobials and stress. Minimal inhibitory concentrations (MIC and minimal bactericidal concentrations (MBC of 6 antibiotics, commonly used in human medicine for 8 selected lactobacilli strains were determined by macrodilution and microdilution methods in liquid media and by diffusion method on agar plates. The effects of Penicillin G and Ampicillin on intestinal LAB were tested in vivoon mice as well. Lactobacilli were sensitive to Penicillin G, (penicillines and their derivatives and Erythromycin (macrolides by in vitro testing. Clyndamycin (pyranosid showed moderate inhibitory effect. All lactobacilli strains were resistant to Kanamycin and Neomycin (aminoglycosides, while L. salivarius IM 124 has shown extra resistance to Erythromycin and Clyndamycin. The influence of orally administered Ampicillin showed no significant influence on LAB count in mice faeces. The effect of Penicillin G on mice LAB total count was significant, while no effect of orally administered lactobacilli was determined.

  18. Uses of Nucleic Acid Analogues in the Inhibition of Nucleic Acid Amplification

    DEFF Research Database (Denmark)

    1999-01-01

    The present invention relates to the use of nucleic acid analogues in blocking nucleic acid ampli?cation procedures and to diagnostic and analytical techniques based thereon. Also included are kits for use in the conduct of nucleic acid ampli?cation reactions....

  19. Autoxidated linolenic acid inhibits aflatoxin biosynthesis in Aspergillus flavus via oxylipin species.

    Science.gov (United States)

    Yan, Shijuan; Liang, Yating; Zhang, Jindan; Chen, Zhuang; Liu, Chun-Ming

    2015-08-01

    Aflatoxins produced by Aspergillus species are among the most toxic and carcinogenic compounds in nature. Although it has been known for a long time that seeds with high oil content are more susceptible to aflatoxin contamination, the role of fatty acids in aflatoxin biosynthesis remains controversial. Here we demonstrate in A. flavus that both the saturated stearic acid (C18:0) and the polyunsaturated linolenic acid (C18:3) promoted aflatoxin production, while C18:3, but not C18:0, inhibited aflatoxin biosynthesis after exposure to air for several hours. Further experiments showed that autoxidated C18:3 promoted mycelial growth, sporulation, and kojic acid production, but inhibited the expression of genes in the AF biosynthetic gene cluster. Mass spectrometry analyses of autoxidated C18:3 fractions that were able to inhibit aflatoxin biosynthesis led to the identification of multiple oxylipin species. These results may help to clarify the role of fatty acids in aflatoxin biosynthesis, and may explain why controversial results have been obtained for fatty acids in the past. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Mitigation of Humic Acid Inhibition in Anaerobic Digestion of Cellulose by Addition of Various Salts

    Directory of Open Access Journals (Sweden)

    Samet Azman

    2015-03-01

    Full Text Available Humic compounds are inhibitory to the anaerobic hydrolysis of cellulosic biomass. In this study, the impact of salt addition to mitigate the inhibitory effects of humic compounds was investigated. The experiment was conducted using batch tests to monitor the anaerobic hydrolysis of cellulose in the presence of humic acid. Sodium, potassium, calcium, magnesium and iron salts were tested separately for their efficiency to mitigate humic acid inhibition. All experiments were done under mesophilic conditions (30 °C and at pH 7. Methane production was monitored online, using the Automatic Methane Potential Test System. Methane production, soluble chemical oxygen demand and volatile fatty acid content of the samples were measured to calculate the hydrolysis efficiencies. Addition of magnesium, calcium and iron salts clearly mitigated the inhibitory effects of humic acid and hydrolysis efficiencies reached up to 75%, 65% and 72%, respectively, which were similar to control experiments. Conversely, potassium and sodium salts addition did not mitigate the inhibition and hydrolysis efficiencies were found to be less than 40%. Mitigation of humic acid inhibition via salt addition was also validated by inductively coupled plasma atomic emission spectroscopy analyses, which showed the binding capacity of different cations to humic acid.

  1. Inhibition of prostaglandin D₂ production by trihydroxy fatty acids isolated from Ulmus davidiana var. japonica.

    Science.gov (United States)

    Choi, Hyun Gyu; Park, Yu Mi; Lu, Yue; Chang, Hyeun Wook; Na, Minkyun; Lee, Seung Ho

    2013-09-01

    The stem and root barks of Ulmus davidiana var. japonica (Ulmaceae) have been used to treat inflammatory diseases including mastitis, rhinitis, sinusitis, and enteritis. In an ongoing study focused on the discovery of natural anti-inflammatory compounds from natural products, a methanol extract of the stem and root barks of U. davidiana var. japonica showed anti-inflammatory activities. Activity-guided fractionation of the methanol extract yielded a new trihydroxy fatty acid, 9,12,13-trihydroxyoctadeca-10(Z),15(Z)-dienoic acid (1), and a known compound, pinellic acid (2). These two trihydroxy fatty acids 1 and 2 inhibited prostaglandin D₂ production with IC₅₀ values of 25.8 and 40.8 μM, respectively. These results suggest that 9,12,13-trihydroxyoctadeca-10(Z),15(Z)-dienoic acid (1) and pinellic acid (2) are among the anti-inflammatory principles in this medicinal plant. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine.

    Science.gov (United States)

    Edelsbrunner, Martin E; Nakano, Motoko; Holzer, Peter

    2009-06-02

    Lafutidine is a histamine H2 receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg/kg) modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge. Adult rats were treated with vehicle, lafutidine (10 - 30 mg/kg) or cimetidine (10 mg/kg), and 30 min later their stomachs were exposed to exogenous HCl (0.25 M). During the period of 2 h post-HCl, intragastric pH, gastric volume, gastric acidity and extent of macroscopic gastric mucosal injury were determined and the activation of neurons in the brainstem was visualized by c-Fos immunocytochemistry. Gastric acid challenge enhanced the expression of c-Fos in the nucleus tractus solitarii but caused only minimal damage to the gastric mucosa. Lafutidine reduced the HCl-evoked expression of c-Fos in the NTS and elevated the intragastric pH following intragastric administration of excess HCl. Further analysis showed that the gastroprotective effect of lafutidine against excess acid was delayed and went in parallel with facilitation of gastric emptying, measured indirectly via gastric volume changes, and a reduction of gastric acidity. The H2 receptor antagonist cimetidine had similar but weaker effects. These observations indicate that lafutidine inhibits the vagal afferent signalling of a gastric acid insult, which may reflect an inhibitory action on acid-induced gastric pain. The ability of lafutidine to decrease intragastric acidity following exposure to excess HCl cannot be explained by its antisecretory activity but appears to reflect dilution and/or emptying of the acid load into the duodenum. This profile of actions emphasizes the notion that H2 receptor antagonists can protect the gastric mucosa from acid injury independently of their

  3. Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine

    Directory of Open Access Journals (Sweden)

    Holzer Peter

    2009-06-01

    Full Text Available Abstract Background Lafutidine is a histamine H2 receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg/kg modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge. Methods Adult rats were treated with vehicle, lafutidine (10 – 30 mg/kg or cimetidine (10 mg/kg, and 30 min later their stomachs were exposed to exogenous HCl (0.25 M. During the period of 2 h post-HCl, intragastric pH, gastric volume, gastric acidity and extent of macroscopic gastric mucosal injury were determined and the activation of neurons in the brainstem was visualized by c-Fos immunocytochemistry. Results Gastric acid challenge enhanced the expression of c-Fos in the nucleus tractus solitarii but caused only minimal damage to the gastric mucosa. Lafutidine reduced the HCl-evoked expression of c-Fos in the NTS and elevated the intragastric pH following intragastric administration of excess HCl. Further analysis showed that the gastroprotective effect of lafutidine against excess acid was delayed and went in parallel with facilitation of gastric emptying, measured indirectly via gastric volume changes, and a reduction of gastric acidity. The H2 receptor antagonist cimetidine had similar but weaker effects. Conclusion These observations indicate that lafutidine inhibits the vagal afferent signalling of a gastric acid insult, which may reflect an inhibitory action on acid-induced gastric pain. The ability of lafutidine to decrease intragastric acidity following exposure to excess HCl cannot be explained by its antisecretory activity but appears to reflect dilution and/or emptying of the acid load into the duodenum. This profile of actions emphasizes the notion that H2 receptor antagonists can protect

  4. Quantitative analysis of the modes of growth inhibition by weak organic acids in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ullah, Azmat; Orij, Rick; Brul, Stanley; Smits, Gertien J

    2012-12-01

    Weak organic acids are naturally occurring compounds that are commercially used as preservatives in the food and beverage industries. They extend the shelf life of food products by inhibiting microbial growth. There are a number of theories that explain the antifungal properties of these weak acids, but the exact mechanism is still unknown. We set out to quantitatively determine the contributions of various mechanisms of antifungal activity of these weak acids, as well as the mechanisms that yeast uses to counteract their effects. We analyzed the effects of four weak organic acids differing in lipophilicity (sorbic, benzoic, propionic, and acetic acids) on growth and intracellular pH (pH(i)) in Saccharomyces cerevisiae. Although lipophilicity of the acids correlated with the rate of acidification of the cytosol, our data confirmed that not initial acidification, but rather the cell's ability to restore pH(i), was a determinant for growth inhibition. This pH(i) recovery in turn depended on the nature of the organic anion. We identified long-term acidification as the major cause of growth inhibition under acetic acid stress. Restoration of pH(i), and consequently growth rate, in the presence of this weak acid required the full activity of the plasma membrane ATPase Pma1p. Surprisingly, the proposed anion export pump Pdr12p was shown to play an important role in the ability of yeast cells to restore the pH(i) upon lipophilic (sorbic and benzoic) acid stress, probably through a charge interaction of anion and proton transport.

  5. Sequence-specific inhibition of duck hepatitis B virus reverse transcription by peptide nucleic acids (PNA)

    DEFF Research Database (Denmark)

    Robaczewska, Magdalena; Narayan, Ramamurthy; Seigneres, Beatrice

    2005-01-01

    BACKGROUND/AIMS: Peptide nucleic acids (PNAs) appear as promising new antisense agents, that have not yet been examined as hepatitis B virus (HBV) inhibitors. Our aim was to study the ability of PNAs targeting the duck HBV (DHBV) encapsidation signal epsilon to inhibit reverse transcription (RT...

  6. Acetylsalicylic acid inhibits platelet PAI-1 antigen release without affecting circulating PAI-1 antigen in plasma

    NARCIS (Netherlands)

    Cogo, A.; Ling, E.; Sturk, A.; ten Cate, J. W.; Prandoni, P.

    1990-01-01

    An important plasminogen activator-inhibitor (PAI-1) is present in plasma and concentrated in alpha-granules of platelets. PAI-1 is released during platelet stimulation in vitro. It is presently unknown to what extent the treatment with acetylsalicylic acid (ASA) inhibits platelet PAI-1 release and

  7. Inhibition of class IIa histone deacetylase activity by gallic acid, sulforaphane, TMP269, and panobinostat.

    Science.gov (United States)

    Choi, Sin Young; Kee, Hae Jin; Jin, Li; Ryu, Yuhee; Sun, Simei; Kim, Gwi Ran; Jeong, Myung Ho

    2018-02-23

    Histone deacetylase (HDAC) inhibitors are gaining increasing attention as potential therapeutics for cardiovascular diseases as well as cancer. We recently reported that the class II HDAC inhibitor, MC1568, and the phytochemical, gallic acid, lowered high blood pressure in mouse models of hypertension. We hypothesized that class II HDACs may be involved in the regulation of hypertension. The aim of this study was to determine and compare the effects of well-known HDAC inhibitors (TMP269, panobinostat, and MC1568), phytochemicals (gallic acid, sulforaphane, and piceatannol), and anti-hypertensive drugs (losartan, carvedilol, and furosemide) on activities of class IIa HDACs (HDAC4, 5, 7, and 9). The selective class IIa HDAC inhibitor, TMP269, and the pan-HDAC inhibitor, panobinostat, but not MC1568, clearly inhibited class IIa HDAC activities. Among the three phytochemicals, gallic acid showed remarkable inhibition, whereas sulforaphane presented mild inhibition of class IIa HDACs. Piceatannol inhibited only HDAC7 activity. As expected, the anti-hypertensive drugs losartan, carvedilol, and furosemide did not affect the activity of any class IIa HDAC. In addition, we evaluated the inhibitory effect of several compounds on the activity of class l HDACs (HDAC1, 2, 3, and 8) and class IIb HDAC (HDAC6). MC1568 did not affect the activities of HDAC1, HDAC2, and HDAC3, but it reduced the activity of HDAC8 at concentrations of 1 and 10 μM. Gallic acid weakly inhibited HDAC1 and HDAC6 activities, but strongly inhibited HDAC8 activity with effectiveness comparable to that of trichostatin A. Inhibition of HDAC2 activity by sulforaphane was stronger than that by piceatnnaol. These results indicated that gallic acid is a powerful dietary inhibitor of HDAC8 and class IIa/b HDAC activities. Sulforaphane may also be used as a dietary inhibitor of HDAC2 and class IIa HDAC. Our findings suggest that the class II HDAC inhibitor, MC1568, does not inhibit class IIa HDAC, but inhibits

  8. Cytochrome P450 4A11 inhibition assays based on characterization of lauric acid metabolites.

    Science.gov (United States)

    Choi, Yeon Jung; Zhou, Yuanyuan; Lee, Ji-Yoon; Ryu, Chang Seon; Kim, Young Ho; Lee, Kiho; Kim, Sang Kyum

    2018-02-01

    This study was designed to characterize lauric acid metabolism to facilitate the establishment of cytochrome P450 4A11 (CYP4A11) inhibition assay. Three metabolites (2-, 11-, and 12-hydroxylauric acids) were identified in pooled human liver microsomes based on comparisons with authentic standards. Reaction phenotyping using 14 recombinant CYPs showed that ω-hydroxylation was mediated dominantly by CYP4A11 and marginally by CYP4F3B. CYP2B6 played an exclusive role in the formation of 2-hydroxylauric acid. The production of 11-hydroxylauric acid was mediated by CYP2E1, CYP2C9, CYP2B6, CYP1A2, CYP3A4, and CYP4A11. The IC 50 values of HET0016, a well-known pan-CYP4 inhibitor, against the formation of 12-, 11-, and 2-hydroxylauric acid were 1.0, 1.0, and 0.009 μM, respectively. Among the 50 natural compounds examined, plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) inhibited the formation of 12-, 11-, and 2-hydroxylauric acid with IC 50 values of 1.7, 2.3, and 2.7 μM, respectively. In the selectivity study, HET0016 inhibited CYP2B6 with an IC 50 of 9.2 nM, as well as CYP1A2, CYP2C19, and CYP2E1 with IC 50 values of 1-2 μM. Plumbagin inhibited all CYP enzymes tested with IC 50 values of 1.7-3.0 μM. These methods can be used as tools to develop CYP4A11 inhibitors; simultaneous determination of the hydroxylauric acid metabolites provides further information on selectivity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

    Directory of Open Access Journals (Sweden)

    Naganna Narra

    2017-01-01

    Full Text Available The synthesis of five novel methyl 10-undecenoate-based lipoconjugates of phenolic acids from undecenoic acid was carried out. Undecenoic acid was methylated to methyl 10-undecenoate which was subjected to a thiol–ene reaction with cysteamine hydrochloride. Further amidation of the amine was carried out with different phenolic acids such as caffeic, ferulic, sinapic, coumaric and cinnamic acid. All synthesized compounds were fully characterized and their structures were confirmed by spectral data. The anti-oxidant activity of the synthesized lipoconjugates of phenolic acids was studied by the 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging assay and also by the inhibition of linoleic acid oxidation in micellar medium by differential scanning calorimetry (DSC. The prepared compounds were also screened for their cytotoxic activity against five cell lines. It was observed that the lipoconjugates of caffeic acid, sinapic acid, ferulic acid, and coumaric acid displayed anticancer and anti-oxidant properties. The anticancer properties of these derivatives have been assessed by their IC50 inhibitory values in the proliferation of MDA-MB231, SKOV3, MCF7, DU 145 and HepG2 cancer cell lines.

  10. Adsorption and corrosion inhibition of mild steel in acidic media by expired pharmaceutical drug

    Directory of Open Access Journals (Sweden)

    P. Geethamani

    2015-12-01

    Full Text Available The inhibitive action of an examined expired Ambroxol drug on the corrosion of mild steel in 1 M HCl and 1 M H2SO4 acid medium has been studied by weight loss and electrochemical techniques. The weight loss techniques result was discussed. The inhibition efficiency increases with increasing the concentration of the inhibitor. Electrochemical studies data support that examined expired drug is an efficient inhibitor for mild steel corrosion. The adsorption of the examined drug obeys Langmuir’s adsorption isotherm. Polarization studies indicate that this inhibitor acts as a mixed type inhibition. The various thermodynamic parameters were calculated and discussed. The protective film formed on the surface was confirmed by SEM. The data collected from the studied techniques are in good agreement to confirm the ability of using expired Ambroxol drug as corrosion inhibitor for mild steel in both acid media.

  11. Nalidixic acid inhibition of post-ultraviolet recovery by nalidixic acid sensitive and resistant strains of Candida albicans

    International Nuclear Information System (INIS)

    Sarachek, A.; Lee, S.C.

    1980-01-01

    Nalidixic acid (Nal) can kill Candida albicans directly or suppress the organism's recovery from ultraviolet irradiation. Mutants selected for resistance to inactivation by Nal alone have generally enhanced DNA repair proficiencies evidenced by their coincident increased resistances to ultraviolet radiation, ethylmethane sulfonate, and nitrous acid. The effects of Nal, erythromycin, and inhibitors of oxidative phosphorylation on survivals of mutant and wild type strains following ultraviolet exposure indicate that different mechanisms underly the direct lethality of Nal and its ability to inhibit post-irradiation recovery. (author)

  12. Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.

    Science.gov (United States)

    Huang, Ya; Chen, Huaguo; Zhou, Xin; Wu, Xingdong; Hu, Enming; Jiang, Zhengmeng

    2017-08-15

    This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (Pchlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity. Copyright © 2017. Published by Elsevier B.V.

  13. Corrosion Inhibition Studies of Mild Steel in Acid Medium Using Musa Acuminata Fruit Peel Extract

    Directory of Open Access Journals (Sweden)

    N. Gunavathy

    2012-01-01

    Full Text Available The inhibition effect of unripe fruit peel extract of Musa acuminata (Cultivar variety – Nendran (MNP on corrosion of mild steel in 1 N HCl has been investigated by weight loss and electrochemical impedance spectroscopy (EIS with various concentrations of the extract. The effect of temperature on the corrosion inhibition of mild steel in the temperature range of 30°C – 80°C was carried out. The results indicate that MNP extract act as an effective inhibitor in the acid environment and is of mixed type inhibitor having efficiency as high as 96% at 2% inhibitor concentration. The inhibition efficiency of MNP extract increases with the increase of concentration but decreases with the increase in temperature. The inhibitor achieves its inhibition by physical adsorption of nutrients of the peel extract on the surface of the mild steel. The experimental data revealed that the adsorption occurred according to the Langmuir and Temkin adsorption isotherm.

  14. Inhibition of ornithine decarboxylase and glutamic acid decarboxylase activities by phosphorylethanolamine and phosphorylcholine.

    Science.gov (United States)

    Gilad, G M; Gilad, V H

    1984-07-18

    Ornithine decarboxylase, which catalyzes the first step in polyamine biosynthesis, is rapidly and transiently increased in various tissues during growth and after various hormonal or noxious stimuli, prior to an elevation in choline kinase activity. Polyamines themselves have been demonstrated to activate choline kinase. The present study sought to determine the effect of phosphorylcholine, the product of the reaction catalyzed by choline kinase, on ornithine decarboxylase activity. The data demonstrate that ornithine decarboxylase activity. The data demonstrate that ornithine decarboxylase activity is inhibited by phosphorylcholine and more potently by the related compound phosphorylethanolamine. The inhibition by both compounds led to decreased affinity of partially purified ornithine decarboxylase for ornithine. The inhibition is not time dependent and reversible. Both compounds also inhibit glutamic acid decarboxylase activity. The results suggest that high intracellular levels of phosphorylethanolamine and phosphorylcholine can serve as natural inhibitors of decarboxylases.

  15. Fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C.

    Science.gov (United States)

    Lin, Zhaoyu; Liu, Fei; Shi, Peiliang; Song, Anying; Huang, Zan; Zou, Dayuan; Chen, Qin; Li, Jianxin; Gao, Xiang

    2018-02-26

    Changes in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in fatty acid oxidation, was significantly upregulated in the early stage of the reprogramming process. Mouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various fatty acid oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty acid oxidation-related metabolites were measured by liquid chromatography-mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation. We found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated fatty acid oxidation, also promoted reprogramming. In the early reprogramming process, fatty acid oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming. We demonstrated that fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that fatty acid oxidation is crucial for the reprogramming efficiency.

  16. Comparison of inhibition effects of some benzoic acid derivatives on sheep heart carbonic anhydrase

    Science.gov (United States)

    Kiliç, Deryanur; Yildiz, Melike; Şentürk, Murat; Erdoǧan, Orhan; Küfrevioǧlu, Ömer Irfan

    2016-04-01

    Carbonic anhydrase (CA) is a family of metalloenzymes that requires Zn as a cofactor and catalyze the quick conversion of CO2 to HCO3- and H+. Inhibitors of the carbonic anhydrases (CAs) have medical usage of significant diseases such as glaucoma, epilepsy, gastroduodenal ulcers, acid-base disequilibria and neurological disorders. In the present study, inhibition of CA with some benzoic derivatives (1-6) were investigated. Sheep heart CA (shCA) enzyme was isolated by means of designed affinity chromatography gel (cellulose-benzyl-sulfanylamide) 42.45-fold in a yield of 44 % with 564.65 EU/mg. Purified shCA enzyme was used in vitro studies. In the studies, IC50 values were calculated for 3-aminobenzoic acid (1), 4-aminobenzoic acid (2), 2-hydroxybenzoic acid (3), 2-benzoylbenzoic acid (4), 2,3-dimethoxybenzoic acid (5), and 3,4,5-trimethoxybenzoic acid (6), showing the inhibition effects on the purified enzyme. Such molecules can be used as pioneer for discovery of novel effective CA inhibitors for medicinal chemistry applications.

  17. Formulation, Characterization, and In Vitro Evaluation of Transdermal Patches for Inhibiting Crystallization of Mefenamic Acid

    Directory of Open Access Journals (Sweden)

    Jirapornchai Suksaeree

    2017-01-01

    Full Text Available The crystallization of mefenamic acid in transdermal patch is a major problem that makes the patch unstable and decreases the drug release. The additive was used to inhibit crystallization of a mefenamic acid. Among the different types of additives, polyvinylpyrrolidone (PVP K30 and PVP K90 were studied and found to be highly effective in inhibiting the crystallization of the drug. The PVP presented as a solubilizer agent for mefenamic acid in matrix patches at the different ratio between drug : PVP, 1 : 2 and 1 : 2.5 for using PVP K30 and 1 : 1.5 and 1 : 2 for using PVP K90. The characterizations showed the homogeneous patches without the crystal form of the mefenamic acid in matrix patches. The release profiles of the mefenamic acid from the patches were investigated by Franz diffusion cells. Over the first 1 h, the release behavior of mefenamic acid from the patches obviously increased when PVP was used as a crystallization inhibitor. However, the ratio between drug : PVP K90 at 1 : 2 was found to be the most effective in increasing the drug release from patch. Thus, the PVP could be used as a crystallization inhibitor for mefenamic acid in matrix patches which will increase the drug release.

  18. Propolis Extracted from the Stingless Bee Trigona sirindhornae Inhibited S. mutans Activity In Vitro.

    Science.gov (United States)

    Utispan, Kusumawadee; Chitkul, Bordin; Monthanapisut, Paopanga; Meesuk, Ladda; Pugdee, Kamolparn; Koontongkaew, Sittichai

    The aim of this study was to determine the antimicrobial effects of propolis extracted from an endemic species of stingless bee, T. sirindhornae, on the cariogenic bacterium Streptococcus mutans. Dichloromethane extracts (DME) of propolis (DMEP) were prepared and analysed by reverse-phase high-performance liquid chromatography. The antibacterial growth and antibiofilm formation effects of DMEP on S. mutans were compared with those of apigenin, a commercial propolis product. The effects of DMEP and apigenin on glucosyltransferase (gtf) B expression in S. mutans were investigated using real-time polymerase chain reaction. Chlorhexidine (CHX) was used as a positive control in the experiments. Apigenin, pinocembrin, p-coumaric acid, and caffeic acid were not detected in the propolis extracts. DMEP and apigenin significantly inhibited S. mutans growth (IC50 = 43.5 and 17.36 mg/ml, respectively). DMEP and apigenin also exhibited antiadherence effects on S. mutans as shown by reduced biofilm formation. Furthermore, a significant inhibition in gtfB expression was observed in DMEP and apigenin treated S. mutans. Propolis produced by T. sirindhornae demonstrated antibacterial and antibiofilm effects, and reduced gtfB expression in S. mutans. The antibacterial activities of propolis observed were not due to apigenin, pinocembrin, p-coumaric acid, or caffeic acid.

  19. Evaluation of the inhibitive effect of some plant extracts on the acid corrosion of mild steel

    International Nuclear Information System (INIS)

    Oguzie, Emeka E.

    2008-01-01

    Corrosion inhibition of mild steel in 2 M HCl and 1 M H 2 SO 4 by extracts of selected plants was investigated using a gasometric technique at temperatures of 30 and 60 deg. C. The studied plants materials include leaf extracts Occimum viridis (OV), Telferia occidentalis (TO), Azadirachta indica (AI) and Hibiscus sabdariffa (HS) as well as extracts from the seeds of Garcinia kola (GK). The results indicate that all the extracts inhibited the corrosion process in both acid media by virtue of adsorption and inhibition efficiency improved with concentration. Synergistic effects increased the inhibition efficiency in the presence of halide additives. Inhibition mechanisms were deduced from the temperature dependence of the inhibition efficiency as well as from assessment of kinetic and activation parameters that govern the processes. Comparative analysis of the inhibitor adsorption behaviour in 2 M HCl and 1 M H 2 SO 4 as well as the effects of temperature and halide additives suggest that both protonated and molecular species could be responsible for the inhibiting action of the extracts

  20. Evaluation of the inhibitive effect of some plant extracts on the acid corrosion of mild steel

    Energy Technology Data Exchange (ETDEWEB)

    Oguzie, Emeka E. [Electrochemistry and Materials Science Research Laboratory, Department of Chemistry, Federal University of Technology, PMB 1526, Owerri (Nigeria)], E-mail: oguziemeka@yahoo.com

    2008-11-15

    Corrosion inhibition of mild steel in 2 M HCl and 1 M H{sub 2}SO{sub 4} by extracts of selected plants was investigated using a gasometric technique at temperatures of 30 and 60 deg. C. The studied plants materials include leaf extracts Occimum viridis (OV), Telferia occidentalis (TO), Azadirachta indica (AI) and Hibiscus sabdariffa (HS) as well as extracts from the seeds of Garcinia kola (GK). The results indicate that all the extracts inhibited the corrosion process in both acid media by virtue of adsorption and inhibition efficiency improved with concentration. Synergistic effects increased the inhibition efficiency in the presence of halide additives. Inhibition mechanisms were deduced from the temperature dependence of the inhibition efficiency as well as from assessment of kinetic and activation parameters that govern the processes. Comparative analysis of the inhibitor adsorption behaviour in 2 M HCl and 1 M H{sub 2}SO{sub 4} as well as the effects of temperature and halide additives suggest that both protonated and molecular species could be responsible for the inhibiting action of the extracts.

  1. Inhibition of Host Cell Ribosomal Ribonucleic Acid Methylation by Foot-and-Mouth Disease Virus

    Science.gov (United States)

    Ascione, Richard; Vande Woude, George F.

    1969-01-01

    A study of protein and ribonucleic acid (RNA) synthesis in cells infected by foot-and-mouth disease virus has indicated possible mechanisms of viral control over host cell metabolism. Foot-and-mouth disease virus infection of baby hamster kidney cells resulted in 50% inhibition of host cell protein synthesis at 180 min postinfection. A viral-induced interference with host cell RNA methylation was observed to be more rapidly inhibited than protein synthesis. To determine the nature of methylation inhibition, the kinetics of several host cell methylated RNA species were examined subsequent to virus infection. Data from sucrose zonal centrifugation and methylated albumin kieselguhr chromatography showed that methylation of nuclear RNA was inhibited 50% at 60 min postinfection. Inhibition of nuclear ribosomal RNA precursors and formation of nascent ribosomes correlated with inhibition kinetics of nuclear RNA methylation. It is suggested that the viral interference with the host nuclear RNA methylation is directly responsible for the observed loss of nascent ribosome formation. Moreover, early in the infectious cycle, methylation inhibition of host cell RNA could, in part, account for the cessation of host protein synthesis. PMID:4311801

  2. Use of jasmonic acid and salicylic acid to inhibit growth of sugarbeet storage rot pathogens

    Science.gov (United States)

    Jasmonic acid (JA) and salicylic acid (SA) are endogenous plant hormones that induce native plant defense responses and provide protection against a wide range of diseases. Previously, JA, applied after harvest, was shown to protect sugarbeet roots against the storage pathogens, Botrytis cinerea, P...

  3. Amelioration of bleomycin-induced pulmonary fibrosis by chlorogenic acid through endoplasmic reticulum stress inhibition.

    Science.gov (United States)

    Wang, Yi-Chun; Dong, Jing; Nie, Jing; Zhu, Ji-Xiang; Wang, Hui; Chen, Qiong; Chen, Jun-Yi; Xia, Jia-Mei; Shuai, Wei

    2017-09-01

    To investigate the inhibitory effects of chlorogenic acid on pulmonary fibrosis and the internal mechanisms in vivo and in vitro. 30 male BALB/C mice were randomized into 5 groups: control group, pulmonary fibrosis model group, low, middle and high dose of chlorogenic acid groups. Mice in pulmonary fibrosis model group were administered 5.0 mg/kg bleomycin with intracheal instillation and mice in 3 chlorogenic acid groups were treated with chlorogenic acid every day for 28 days after bleomycin administration. Lung tissue histology was observed using HE staining. Primary pulmonary fibroblasts were isolated and cultured. The expressions of fibrosis related factors (α-SMA and collagen I), as well as ER stress markers (CHOP and GRP78) were determined by both real-time PCR assay and Western blotting, while the expressions of other ER stress signaling pathway factors PERK, IRE-1, ATF-6 and protein levels of caspase-12, caspase-9, caspase-3, PARP were determined by Western blotting. RLE-6TN cell line induced by TGF-β1 was also used to verify the amelioration effects in vitro study. In both in vivo and in vitro studies, TUNEL staining was used to evaluate cell apoptosis. Expressions of collagen I, α-SMA, GRP78, and CHOP were significantly inhibited by chlorogenic acid in dose-dependent manner. Similarly, decreasing levels of cleaved caspase-12, caspase-9, caspase-3 and increasing level of uncleaved PARP were observed in chlorogenic acid groups compared with those in the fibrosis group both in vivo and in vitro. Chlorogenic acid could also significantly down-regulate the level of phosphorylation of PERK and cleaved ATF-6 in vivo study. Moreover, MTT assay demonstrated chlorogenic acid could enhance proliferation of RLE-6TN cells induced by TGFβ1 in vitro. And the apoptosis assays indicated that chlorogenic acid could significantly inhibit cell apoptosis both in vivo and in vitro studies. Chlorogenic acid could inhibit the pulmonary fibrosis through endoplasmic

  4. Adsorption and corrosion inhibiting effect of riboflavin on Q235 mild steel corrosion in acidic environments

    Energy Technology Data Exchange (ETDEWEB)

    Chidiebere, Maduabuchi A. [Institute of Metal Research, Chinese Academy of Sciences, 62 Wencui Rd, Shenyang 110016 (China); Electrochemistry and Materials Science Research Laboratory, Department of Chemistry, Federal University of Technology Owerri, PMB 1526 Owerri (Nigeria); Oguzie, Emeka E. [Electrochemistry and Materials Science Research Laboratory, Department of Chemistry, Federal University of Technology Owerri, PMB 1526 Owerri (Nigeria); Liu, Li [Institute of Metal Research, Chinese Academy of Sciences, 62 Wencui Rd, Shenyang 110016 (China); Li, Ying, E-mail: liying@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, 62 Wencui Rd, Shenyang 110016 (China); Wang, Fuhui [Institute of Metal Research, Chinese Academy of Sciences, 62 Wencui Rd, Shenyang 110016 (China)

    2015-04-15

    The inhibiting effect of Riboflavin (RF) on Q235 mild steel corrosion in 1 M HCl and 0.5 M H{sub 2}SO{sub 4} at 30 °C temperature was investigated using electrochemical techniques (electrochemical impedance spectroscopy and potentiodynamic polarization). The obtained results revealed that RF inhibited the corrosion reaction in both acidic solutions. Maximum inhibition efficiency values in 1 M HCl and 0.5 M H{sub 2}SO{sub 4} were 83.9% and 71.4%, respectively, obtained for 0.0012 M RF. Polarization data showed RF to be a mixed-type inhibitor, while EIS results revealed that the RF species adsorbed on the metal surface. The adsorption of RF followed Langmuir adsorption isotherm. Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) studies confirmed the formation of a protective layer adsorbed on the steel surface. Quantum chemical calculations were used to correlate the inhibition ability of RF with its electronic structural parameters. - Highlights: • The inhibitory mechanism was influenced by the nature of acid anions. • RF has reasonable inhibition effect especially in 1 M HCl solution. • Polarization studies showed that RF functioned as a mixed type inhibitor. • Improved surface morphology was observed in the presence of RF.

  5. Cinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition.

    Science.gov (United States)

    Song, Yeong Hun; Kim, Dae Wook; Curtis-Long, Marcus J; Park, Chanin; Son, Minky; Kim, Jeong Yoon; Yuk, Heung Joo; Lee, Keun Woo; Park, Ki Hun

    2016-05-23

    The α-glucosidase inhibitory potential of Tribulus terrestris extracts has been reported but as yet the active ingredients are unknown. This study attempted to isolate the responsible metabolites and elucidate their inhibition mechanism of α-glucosidase. By fractionating T. terristris extracts, three cinnamic acid amide derivatives (1-3) were ascertained to be active components against α-glucosidase. The lead structure, N-trans-coumaroyltyramine 1, showed significant inhibition of α-glucosidase (IC50 = 0.42 μM). Moreover, all active compounds displayed uncompetitive inhibition mechanisms that have rarely been reported for α-glucosidase inhibitors. This kinetic behavior was fully demonstrated by showing a decrease of both Km and Vmax, and Kik/Kiv ratio ranging between 1.029 and 1.053. We progressed to study how chemical modifications to the lead structure 1 may impact inhibition. An α, β-unsaturation carbonyl group and hydroxyl group in A-ring of cinnamic acid amide emerged to be critical functionalities for α-glucosidase inhibition. The molecular modeling study revealed that the inhibitory activities are tightly related to π-π interaction as well as hydrogen bond interaction between enzyme and inhibitors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid.

    Science.gov (United States)

    Uwai, Yuichi; Nakashima, Yuta; Honjo, Emi; Kawasaki, Tatsuya; Nabekura, Tomohiro

    2014-01-01

    The conjugates with sulfate and glucoside of xanthurenic acid, a tryptophan metabolite, were reported to show natriuresis. Sulfotransferase for xanthurenic acid works in the renal proximal tubule to produce the sulfate of xanthurenic acid as well as the liver, and we recently found that xanthurenic acid is a substrate of renal organic anion transporter OAT1. The purpose of this study was to examine relationship between the transport by OAT1 and diuresis related with xanthurenic acid. Drug transport experiment using Xenopus laevis oocytes represented that probenecid inhibited xanthurenic acid uptake by rat OAT1 (rOAT1). Although no diuresis was recognized by the intravenous injection of xanthurenic acid as a bolus in rats, the addition of its infusion exhibited natriuresis. Simultaneous administration of probenecid significantly decreased the urine volume and excreted amounts of sodium into urine. These findings showed the diuresis by the xanthurenic acid administration, and it was probenecid-sensitive. The rOAT1-mediated transport of xanthurenic acid might, at least in part, contribute to its diuretic effect.

  7. Pterodontic Acid Isolated from Laggera pterodonta Inhibits Viral Replication and Inflammation Induced by Influenza A Virus

    Directory of Open Access Journals (Sweden)

    Wenda Guan

    2017-10-01

    Full Text Available Laggera pterodonta (DC. Benth. is a traditional Chinese medicine. The previous study revealed that the crude extracts of this herb could inhibit influenza virus infection, but its anti-influenza components and underlying mechanism of action remain unknown. Column chromatography was performed to isolate components from the plant. Activity against influenza virus of the compound was determined by CPE inhibition assay. Neuraminidase (NA inhibition was measured by chemiluminescence assay. The anti-virus and anti-inflammation effects were determined using dual-luciferase reporter assay, immunofluorescence, quantitative real-time PCR and luminex assay. Pterodontic acid was isolated from L. pterodonta, which showed selective anti-viral activities to H1 subtype of human influenza A virus. Meanwhile, the NA activity was not obviously inhibited by the compound. Further experiments exhibited that the compound can suppress the activation of NF-κB signal pathway and export of viral RNP complexes from the nucleus. In addition, it can significantly attenuate expression of the pro-inflammatory molecules IL-6, MIP-1β, MCP-1, and IP-10 induced by human influenza A virus (H1N1 and similarly downregulate expression of cytokines and chemokines induced by avian influenza A virus (H9N2. This study showed that in vitro antiviral activity of pterodontic acid is most probably associated with inhibiting the replication of influenza A virus by blocking nuclear export of viral RNP complexes, and attenuating the inflammatory response by inhibiting activation of the NF-κB pathway. Pterodontic acid might be a potential antiviral agent against influenza A virus.

  8. [Shikimic acid inhibits the degranulation and histamine release in RBL-2H3 cells].

    Science.gov (United States)

    Chen, Xianyong; Zheng, Qianqian; Liu, Wei; Yu, Lingling; Wang, Jinling; Li, Shigang

    2017-05-01

    Objective To study the effects of shikimic acid on the proliferation of rat RBL-2H3 cells and the degranulation of the cells induced by C48/80 and its mechanism. Methods MTT assay was performed to measure the proliferation of RBL-2H3 cells treated with 3, 10, 30 μg/mL shikimic acid. Toluidine blue staining was used to observe the degranulation of RBL-2H3 cells. The release of β-hexosaminidase from RBL-2H3 cells treated with 0, 12.5, 25, 50, 80, 100 μg/mL C48/80 was determined by substrate assay. ELISA was used to detect the histamine content in the supernatant of each treated group. Results Shikimic acid at 3, 10, 300 μg/mL had no obvious inhibitory effect on the proliferation of RBL-2H3 cells. There was a dose-effect relationship between the degranulation of RBL-2H3 cells and C48/80 concentration. Shikimic acid inhibited the degranulation of RBL-2H3 cells compared with the positive control group, the β-hexosaminidase release rate and histamine release were significantly reduced in RBL-2H3 cells treated with shikimic acid and C48/80. Conclusion Shikimic acid can inhibit the degranulation of RBL-2H3 cells and reduce histamine release.

  9. Interfacial (o/w) properties of naphthetic acids and metal naphthenates, naphtenic acid characterization and metal naphthenate inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Brandal, Oeystein

    2005-07-01

    Deposition of metal naphthenates in process facilities is becoming a huge problem for petroleum companies producing highly acidic crudes. In this thesis, the main focus has been towards the oil-water (o/w) interfacial properties of naphthenic acids and their ability to react with different divalent cations across the interface to form metal naphthenates. The pendant drop technique was utilized to determine dynamic interfacial tensions (IFT) between model oil containing naphthenic acid, synthetic as well as indigenous acid mixtures, and pH adjusted water upon addition of different divalent cations. Changes in IFT caused by the divalent cations were correlated to reaction mechanisms by considering two reaction steps with subsequent binding of acid monomers to the divalent cation. The results were discussed in light of degree of cation hydration and naphthenic acid conformation, which affect the interfacial conditions and thus the rate of formation of 2:1 complexes of acid and cations. Moreover, addition of non-ionic oil-soluble surfactants used as basis compounds in naphthenate inhibitors was found to hinder a completion of the reaction through interfacial dilution of the acid monomers. Formation and stability of metal naphthenate films at o/w interfaces were studied by means of Langmuir technique with a trough designed for liquid-liquid systems. The effects of different naphthenic acids, divalent cations, and pH of the subphase were investigated. The results were correlated to acid structure, cation hydration, and degree of dissociation, which all affect the film stability against compression. Naphthenic acids acquired from a metal naphthenate deposit were characterized by different spectroscopic techniques. The sample was found to consist of a narrow family of 4-protic naphthenic acids with molecular weights around 1230 g/mol. These acids were found to be very o/w interfacially active compared to normal crude acids, and to form Langmuir monolayers with stability

  10. Oleanolic acid and ursolic acid inhibit peptidoglycan biosynthesis in Streptococcus mutans UA159

    Directory of Open Access Journals (Sweden)

    Soon-Nang Park

    2015-06-01

    Full Text Available In this study, we revealed that OA and UA significantly inhibited the expression of most genes related to peptidoglycan biosynthesis in S. mutans UA159. To the best of our knowledge, this is the first report to introduce the antimicrobial mechanism of OA and UA against S. mutans.

  11. Retinoic Acid Inhibits Adipogenesis Modulating C/EBPβ Phosphorylation and Down Regulating Srebf1a Expression.

    Science.gov (United States)

    Ayala-Sumuano, Jorge-Tonatiuh; Vélez-DelValle, Cristina; Marsch-Moreno, Meytha; Beltrán-Langarica, Alicia; Hernández-Mosqueira, Claudia; Kuri-Harcuch, Walid

    2016-03-01

    Adipogenesis comprises a complex network of signaling pathways and transcriptional cascades; the GSK3β-C/EBPβ-srebf1a axis is a critical signaling pathway at early stages leading to the expression of PPARγ2, the master regulator of adipose differentiation. Previous work has demonstrated that retinoic acid inhibits adipogenesis affecting different signaling pathways. Here, we evaluated the anti-adipogenic effect of retinoic acid on the adipogenic transcriptional cascade, and the expression of adipogenic genes cebpb, srebf1a, srebf1c, pparg2, and cebpa. Our results demonstrate that retinoic acid blocks adipose differentiation during commitment, returning cells to an apparent non-committed state, since they have to be newly induced to adipose conversion after the retinoid is removed from the culture medium. Retinoic acid down regulates the expression of the adipogenic genes, srebf1a, srebf1c, pparg2, and cebpa; however, it did not down regulate the expression of cebpb, but it inhibited C/EBPβ phosphorylation at Thr188, a critical step for the progression of the adipogenic program. We also found that RA inhibition of adipogenesis did not increase the expression of dlk1, the gene encoding for Pref1, a well-known anti-adipogenic factor. © 2015 Wiley Periodicals, Inc.

  12. The corrosion inhibition of iron and aluminum by various naturally occurring biological molecules

    Energy Technology Data Exchange (ETDEWEB)

    McCafferty, E.; Hansen, D.C. [Naval Research Lab., Washington, DC (United States)

    1995-12-31

    Biological polymers that exhibit a strong affinity for metal surfaces are increasingly becoming the focus of research toward the development of environmentally friendly corrosion inhibitors. This paper deals with the use of various naturally occurring organic molecules as corrosion inhibitors for iron or aluminum. Among the organic molecules considered are catecholate and hydroxamate siderophores isolated from bacteria, the adhesive protein from the blue mussel Mytilus edulis L, and caffeic acid and chlorogenic acid. FTIR analysis, anodic polarization curves, and AC impedance measurements were used to determine the adsorption and effectiveness of the various organic molecules as corrosion inhibitors. Parabactin, a catecholate siderophore, was effective in inhibiting both the corrosion of iron in hydrochloric acid and the pitting of aluminum in 0.1 M sodium chloride. The adhesive protein from the blue mussel was also effective in inhibiting the pitting of aluminum.

  13. Injury-induced inhibition of small intestinal protein and nucleic acid synthesis

    International Nuclear Information System (INIS)

    Carter, E.A.; Hatz, R.A.; Yarmush, M.L.; Tompkins, R.G.

    1990-01-01

    Small intestinal mucosal weight and nutrient absorption are significantly diminished early after cutaneous thermal injuries. Because these intestinal properties are highly dependent on rates of nucleic acid and protein synthesis, in vivo incorporation of thymidine, uridine, and leucine into small intestinal deoxyribonucleic acid, ribonucleic acid, and proteins were measured. Deoxyribonucleic acid synthesis was markedly decreased with the lowest thymidine incorporation in the jejunum (p less than 0.01); these findings were confirmed by autoradiographic identification of radiolabeled nuclei in the intestinal crypts. Protein synthesis was decreased by 6 h postinjury (p less than 0.01) but had returned to normal by 48 h. Consistent with a decreased rate of protein synthesis, ribonucleic acid synthesis was also decreased 18 h postinjury (p less than 0.01). These decreased deoxyribonucleic acid, ribonucleic acid, and protein synthesis rates are not likely a result of ischemia because in other studies of this injury model, intestinal blood flow was not significantly changed by the burn injury. Potentially, factors initiating the acute inflammatory reaction may directly inhibit nucleic acid and protein synthesis and lead to alterations in nutrient absorption and intestinal barrier function after injury

  14. Ascorbic acid inhibits human insulin aggregation and protects against amyloid induced cytotoxicity.

    Science.gov (United States)

    Alam, Parvez; Beg, Ayesha Zainab; Siddiqi, Mohammad Khursheed; Chaturvedi, Sumit Kumar; Rajpoot, Ravi Kant; Ajmal, Mohd Rehan; Zaman, Masihuz; Abdelhameed, Ali S; Khan, Rizwan Hasan

    2017-05-01

    Protein aggregation into oligomers and fibrils are associated with many human pathophysiologies. Compounds that modulate protein aggregation and interact with preformed fibrils and convert them to less toxic species, expect to serve as promising drug candidates and aid to the drug development efforts against aggregation diseases. In present study, the kinetics of amyloid fibril formation by human insulin (HI) and the anti-amyloidogenic activity of ascorbic acid (AA) were investigated by employing various spectroscopic, imaging and computational approaches. We demonstrate that ascorbic acid significantly inhibits the fibrillation of HI in a dose-dependent manner. Interestingly ascorbic acid destabilise the preformed amyloid fibrils and protects human neuroblastoma cell line (SH- SY5Y) against amyloid induced cytotoxicity. The present data signifies the role of ascorbic acid that can serve as potential molecule in preventing human insulin aggregation and associated pathophysiologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Free Fatty Acids Inhibit Protein Tyrosine Phosphatase 1B and Activate Akt

    Directory of Open Access Journals (Sweden)

    Eisuke Shibata

    2013-09-01

    Full Text Available Background/Aims: Accumulating evidence has suggested that free fatty acids (FFAs interact with protein kinases and protein phosphatases. The present study examined the effect of FFAs on protein phosphatases and Akt. Methods: Activities of protein phosphatase 1 (PP1, protein phosphatase 2A (PP2A, and protein tyrosine phosphatase 1B (PTP1B were assayed under the cell-free conditions. Phosphorylation of Akt was monitored in MSTO-211H human malignant pleural mesothelioma cells without and with knocking-down phosphatidylinositol 3 kinase (PI3K or 3-phosphoinositide-dependent protein kinase-1 (PDK1. Results: In the cell-free assay, unsaturated FFAs (uFFAs such as oleic, linoleic and linolenic acid and saturated FFAs (sFFAs such as stearic, palmitic, myristic, and behenic acid markedly reduced PTP1B activity, with the potential for uFFAs greater than that for sFFAs. All the investigated sFFAs inhibited PP2A activity, but otherwise no inhibition was obtained with uFFAs. Both uFFAs and sFFAs had no effect on PP1 activity. Oleic acid phosphorylated Akt both on Thr308 and Ser473, while stearic acid phosphorylated Akt on Thr308 alone. The effects of oleic and stearic acid on Akt phosphorylation were abrogated by the PI3K inhibitor wortmannin or the PDK1 inhibitor BX912 and also by knocking-down PI3K or PDK1. Conclusion: The results of the present study indicate that uFFAs and sFFAs could activate Akt through a pathway along a PI3K/PDK1/Akt axis in association with PTP1B inhibition.

  16. Effect of inhibition on tyrosinase and melanogenesis of Agastache rugosa Kuntze by lactic acid bacteria fermentation.

    Science.gov (United States)

    Kim, Nam Young; Kwon, Hee Souk; Lee, Hyeon Yong

    2017-09-01

    This work presents the first report that A. rugosa could have tyrosinase and melanogenesis inhibition and that its activities also be improved by fermentation with Lactobacillus rhamnosus and Lactobacillus paracasei. It was found that the tyrosinase and melanogenesis inhibition was correlated with antioxidant activity of acacetin, the major biologically active substances in A. rugosa. we pursued an improvement in tyrosinase and melanogenesis inhibition of A. rugosa extract by fermentation process. A. rugosa was extracted by lactic acid fermentation process; we measured antioxidant activities and tyrosinase and melanogenesis inhibition of A. rugosa extracts. In particular, reducing power of the extract from fermentation process (FE) was measured as 0.562 (O.D.), whereas reducing power of the extracts from 70% ethanol extraction (EE) was lower than the FE as 0.496 (O.D.). Polyphenols and flavonoids in the FE were higher than the EE: 69.3 mg/g vs. 60.5 mg/g, and 187 mg/g vs. 138 mg/g. The FE was estimated as 51.04% tyrosinase inhibition and 41.88% for the EE. Similarly, melanin inhibition in melanocyte B16F10 was observed as 66.60% vs. 42.23% for the FE and EE. The increase in tyrosinase and melanogenesis inhibition activity was confirmed by high elution of acacetin through fermentation process such as 289.97 mg/100 g vs. 198.04 mg/100 g in the FE and EE. These results indicate that tyrosinase and melanogenesis inhibition activities of the extracts should be associated with antioxidant activity because acacetin is known to have strong antioxidant activity, which can also positively affect whitening activities. © 2016 Wiley Periodicals, Inc.

  17. Corrosion inhibition of iron in acidic solution by a green formulation derived from Nigella sativa L

    International Nuclear Information System (INIS)

    Chellouli, M.; Chebabe, D.; Dermaj, A.; Erramli, H.; Bettach, N.; Hajjaji, N.; Casaletto, M.P.; Cirrincione, C.; Privitera, A.; Srhiri, A.

    2016-01-01

    In this work the corrosion inhibition of iron in acidic solution by a formulation based on the oil extracted from the seeds of Nigella Sativa L. (labeled as FBN) was investigated by means of potentiodynamic polarization, electrochemical impedance spectroscopy and weight loss measurements. Results showed that the formulation acts as a good mixed type (cathodic/anodic) inhibitor. The dissolution rate decreased with the increase of the FBN concentration and the immersion time. An inhibition efficiency of 99% was reached for FBN concentration at 2500 ppm. Surface analysis of the samples was performed by Scanning Electron Microscopy coupled with chemical analysis (SEM-EDS) and X-ray Photoemission Spectroscopy (XPS). Results confirmed a good protective action of the FBN film on the iron substrate in acidic solution. The FBN formulation is a not toxic and environmentally safe product, as determined by acute toxicity tests, and can be fruitfully used for a sustainable conservation of iron-based artifacts.

  18. Adsorption and inhibitive properties of Tryptophan on low alloy steel corrosion in acidic media

    Directory of Open Access Journals (Sweden)

    Hesham T.M. Abdel-Fatah

    2017-02-01

    Corrosion inhibition was studied using electrochemical methods (electrochemical impedance spectroscopy; EIS and the new technique electrochemical frequency modulation; EFM and weight loss measurements. The influence of inhibitor concentration, solution temperature, and immersion time on the corrosion resistance of low alloy steel (LAS has been investigated. Trp proved to be a very good inhibitor for low alloy steel acid corrosion. EFM measurements showed that Trp is a mixed type inhibitor. Trp behaved better in 0.6 M HCl than in 0.6 M HSO3NH2. Moreover, it was found that the inhibition efficiency increased with increasing inhibitor concentration, while a decrease was detected with the rise of temperature and immersion time. The associated activation energy (Ea has been determined. The values of Ea indicate that the type of adsorption of Trp on the steel surface in both acids belongs to physical adsorption. The adsorption process was tested using Temkin adsorption isotherm.

  19. Inhibition of Listeria monocytogenes in Fresh Cheese Using Chitosan-Grafted Lactic Acid Packaging

    Directory of Open Access Journals (Sweden)

    Laura N. Sandoval

    2016-04-01

    Full Text Available A chitosan from biologically obtained chitin was successfully grafted with d,l-lactic acid (LA in aqueous media using p-toluenesulfonic acid as catalyst to obtain a non-toxic, biodegradable packaging material that was characterized using scanning electron microscopy, water vapor permeability, and relative humidity (RH losses. Additionally, the grafting in chitosan with LA produced films with improved mechanical properties. This material successfully extended the shelf life of fresh cheese and inhibited the growth of Listeria monocytogenes during 14 days at 4 °C and 22% RH, whereby inoculated samples with chitosan-g-LA packaging presented full bacterial inhibition. The results were compared to control samples and commercial low-density polyethylene packaging.

  20. Inhibition of Listeria monocytogenes in Fresh Cheese Using Chitosan-Grafted Lactic Acid Packaging.

    Science.gov (United States)

    Sandoval, Laura N; López, Monserrat; Montes-Díaz, Elizabeth; Espadín, Andres; Tecante, Alberto; Gimeno, Miquel; Shirai, Keiko

    2016-04-08

    A chitosan from biologically obtained chitin was successfully grafted with d,l-lactic acid (LA) in aqueous media using p-toluenesulfonic acid as catalyst to obtain a non-toxic, biodegradable packaging material that was characterized using scanning electron microscopy, water vapor permeability, and relative humidity (RH) losses. Additionally, the grafting in chitosan with LA produced films with improved mechanical properties. This material successfully extended the shelf life of fresh cheese and inhibited the growth of Listeria monocytogenes during 14 days at 4 °C and 22% RH, whereby inoculated samples with chitosan-g-LA packaging presented full bacterial inhibition. The results were compared to control samples and commercial low-density polyethylene packaging.

  1. Agents that increase phosphatidic acid inhibit the LH-induced testosterone production

    DEFF Research Database (Denmark)

    Lauritzen, L.; Nielsen, L.-L.A.; Vinggaard, Anne Marie

    1994-01-01

    The results of the present study point to phosphatidic acid (PtdOH) as a possible intracellular messenger, which might be involved in local modulation of testicular testosterone production in vivo. Propranolol (27-266 µM) induced an increased level of [H]PtdOH in isolated rat Leydig cells......, prelabeled with [H]myristate, and at the same time a strong dose-dependent inhibition of the acute testosterone production stimulated by luteinizing hormone (LH). The inhibition was not bypassed by the addition of dibutyryl-cAMP but was overcome, when 22(R)-hydroxycholesterol was added as a direct substrate...... for cytochrome P-450 side chain cleavage enzyme. Thus, the inhibition appears to be exerted at a point distal to cAMP-generation but before the first enzyme in the testosterone synthetic pathway. Treatment with other agents (4ß-phorbol 12-myristate 13-acetate (PMA), A23187, and sphingosine) giving rise...

  2. The inhibition of anti-DNA binding to DNA by nucleic acid binding polymers.

    Directory of Open Access Journals (Sweden)

    Nancy A Stearns

    Full Text Available Antibodies to DNA (anti-DNA are the serological hallmark of systemic lupus erythematosus (SLE and can mediate disease pathogenesis by the formation of immune complexes. Since blocking immune complex formation can attenuate disease manifestations, the effects of nucleic acid binding polymers (NABPs on anti-DNA binding in vitro were investigated. The compounds tested included polyamidoamine dendrimer, 1,4-diaminobutane core, generation 3.0 (PAMAM-G3, hexadimethrine bromide, and a β-cylodextrin-containing polycation. As shown with plasma from patients with SLE, NABPs can inhibit anti-DNA antibody binding in ELISA assays. The inhibition was specific since the NABPs did not affect binding to tetanus toxoid or the Sm protein, another lupus autoantigen. Furthermore, the polymers could displace antibody from preformed complexes. Together, these results indicate that NABPs can inhibit the formation of immune complexes and may represent a new approach to treatment.

  3. Theoretical study of inhibition efficiencies of some amino acids on corrosion of carbon steel in acidic media: green corrosion inhibitors.

    Science.gov (United States)

    Dehdab, Maryam; Shahraki, Mehdi; Habibi-Khorassani, Sayyed Mostafa

    2016-01-01

    Inhibition efficiencies of three amino acids [tryptophan (B), tyrosine (c), and serine (A)] have been studied as green corrosion inhibitors on corrosion of carbon steel using density functional theory (DFT) method in gas and aqueous phases. Quantum chemical parameters such as EH OMO (highest occupied molecular orbital energy), E LUMO (lowest unoccupied molecular orbital energy), hardness (η), polarizability ([Formula: see text]), total negative charges on atoms (TNC), molecular volume (MV) and total energy (TE) have been calculated at the B3LYP level of theory with 6-311++G** basis set. Consistent with experimental data, theoretical results showed that the order of inhibition efficiency is tryptophan (B) > tyrosine (C) > serine (A). In order to determine the possible sites of nucleophilic and electrophilic attacks, local reactivity has been evaluated through Fukui indices.

  4. In vitro effect of ursolic acid on the inhibition of Mycobacterium tuberculosis and its cell wall mycolic acid.

    Science.gov (United States)

    Jyoti, Md Anirban; Zerin, Tamanna; Kim, Tae-Hyun; Hwang, Tae-Seon; Jang, Woong Sik; Nam, Kung-Woo; Song, Ho-Yeon

    2015-08-01

    Mycobacterium tuberculosis is a dangerous intracellular pathogen. In order to protect against mycobacterium infection, novel agents with anti-mycobacterial activity should be given emergency priority for evaluation. Ursolic acid (UA), a plant triterpenoid, shows promising bioactivities, including anti-mycobacterial potency. In this study, the action of UA against Mycobacterium tuberculosis H37Ra was evaluated, and the inhibitory concentration was found to range between 10 and 20 μg/ml in a resazurin assay and MGIT 960 instrument. The total mycolic acid in UA-treated H37Ra was detected and compared with INH-treated and non-treated bacterium by LC-MS/MS. Quantitative LC-MS/MS data confirmed that both UA and INH decreased mycolic acid biosynthesis in a dose-dependent manner. Thin-layer chromatogram (TLC) analysis showed that all mycolic acid subtypes were affected by UA treatment in the wild type but not in strains resistant to UA. Electron microscopy images also confirmed that UA treatment affected both H37Ra cell and intracellular content of H37Ra. Altogether, these data confirmed the promise of the inhibitory action of UA in mycolic acid, which might further delineate the mechanistic pathway of mycobacterial inhibition by UA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Ethacrynic acid inhibition of histamine release from rat mast cells: effect on cellular ATP levels and thiol groups

    DEFF Research Database (Denmark)

    Johansen, Torben

    1983-01-01

    The experiments concerned the effect of ethacrynic acid (0.5 mM) on the adenosine triphosphate (ATP) content of rat mast cells and the effect on histamine release induced by the ionophore A23187 (10 microM). Ethacrynic acid decreased the ATP level of the cells in presence of antimycin A and glucose....... Furthermore, the inhibition of histamine release occurred mainly through interaction with thiol groups, although inhibition of cellular energy production may have been an additional mechanism....... as well as in presence of 2-deoxyglucose. A23187-induced histamine release was inhibited by ethacrynic acid, and this inhibition was completely reversed by dithiothreitol. These observations may indicate that ethacrynic acid inhibits glycolytic and respiratory energy production in rat mast cells...

  6. Potent Gastric Acid Inhibition Over 24 Hours by 4-Times Daily Dosing of Esomeprazole 20 mg.

    Science.gov (United States)

    Sahara, Shu; Sugimoto, Mitsushige; Uotani, Takahiro; Ichikawa, Hitomi; Yamade, Mihoko; Kagami, Takuma; Hamaya, Yasushi; Iwaizumi, Moriya; Osawa, Satoshi; Sugimoto, Ken; Miyajima, Hiroaki; Furuta, Takahisa

    2015-01-01

    When administered at a standard dose, proton pump inhibitors (PPIs) do not always provide sufficient acid inhibition for all subjects, particularly in extensive metabolizers (EMs) of CYP2C19. Whether esomeprazole at a dose of 20 mg four times daily dosing (q.i.d.) can attain sufficient acid inhibition throughout 24 h in EMs remains unclear. We therefore investigated the efficacy of esomeprazole q.i.d. for acid inhibition. In a randomized cross-over design, 30 Helicobacter pylori-negative healthy young Japanese volunteers received esomeprazole at a dose of 20 mg two times a day (b.i.d.) or q.i.d. for 7 days. A pH monitoring was conducted before the trial as a control and on day 7 of both regimens. Median pH values in the q.i.d. regimen were significantly higher than those with the b.i.d. regimen in EMs (b.i.d.: 5.3, q.i.d.: 6.6, p = 0.022), intermediate metabolizer (IM) (b.i.d.: 5.5, q.i.d.: 6.8, p = 0.005) and poor metabolizer (PM) (b.i.d.: 6.2, q.i.d.: 7.0, p = 0.047), respectively. Median pH with the b.i.d. regimen differed significantly by CYP2C19 genotypes (p = 0.004), but not the q.i.d. regimen (p = 0.384). Esomeprazole q.i.d. achieved potent acid inhibition in all Helicobacter pylori-negative subjects, irrespective of CYP2C19 genotype, which might be one of the rescue regimens for patients' refractory to PPI treatment.

  7. Corrosion Inhibition of Mild Steel in Hydrochloric Acid by Sodium Lauryl Sulfate (SLS

    Directory of Open Access Journals (Sweden)

    Atul Kumar

    2008-01-01

    Full Text Available Effect of Sodium Lauryl Sulfate (SLS, a surfactant on corrosion of mild steel in 1 M hydrochloric acid was studied using three techniques namely: weight loss, electrochemical polarization and metallurgical research microscopy. Results obtained reveal that SLS is good inhibitor and shows very good corrosion inhibition efficiency (IE. The IE was found to vary with concentration of inhibitor and temperature. The electrochemical polarization result revealed that SLS is anodic in nature.

  8. Inhibition of fatty acid binding proteins elevates brain anandamide levels and produces analgesia.

    Directory of Open Access Journals (Sweden)

    Martin Kaczocha

    Full Text Available The endocannabinoid anandamide (AEA is an antinociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by fatty acid amide hydrolase (FAAH. Fatty acid binding proteins (FABPs are intracellular carriers that deliver AEA and related N-acylethanolamines (NAEs to FAAH for hydrolysis. The mammalian brain expresses three FABP subtypes: FABP3, FABP5, and FABP7. Recent work from our group has revealed that pharmacological inhibition of FABPs reduces inflammatory pain in mice. The goal of the current work was to explore the effects of FABP inhibition upon nociception in diverse models of pain. We developed inhibitors with differential affinities for FABPs to elucidate the subtype(s that contributes to the antinociceptive effects of FABP inhibitors. Inhibition of FABPs reduced nociception associated with inflammatory, visceral, and neuropathic pain. The antinociceptive effects of FABP inhibitors mirrored their affinities for FABP5, while binding to FABP3 and FABP7 was not a predictor of in vivo efficacy. The antinociceptive effects of FABP inhibitors were mediated by cannabinoid receptor 1 (CB1 and peroxisome proliferator-activated receptor alpha (PPARα and FABP inhibition elevated brain levels of AEA, providing the first direct evidence that FABPs regulate brain endocannabinoid tone. These results highlight FABPs as novel targets for the development of analgesic and anti-inflammatory therapeutics.

  9. Inhibition of hydrogen fermentation of organic wastes by lactic acid bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Noike, Tatsuya; Takabatake, Hiroo [Tohoku Univ., Sendai (Japan). Dept. of Civil Engineering; Japan Science and Technology Corporation, Saitama (Japan). CREST; Mizuno, Osama [Ataka Construction and Engineering Co., Osaka (Japan); Ohba, Mika [Japan Science and Technology Corporation, Saitama (Japan). CREST

    2002-12-01

    The effects of lactic acid bacteria (LAB) on hydrogen fermentation of organic waste were investigated. For this three hydrogen producing strains of Clostridium were cultured with two lactic acid bacteria, i.e. Lactobacillus paracasei and Enterococcus durans, which were isolated from the wastes generated in the bean curd manufacturing. The decrease or cessation of hydrogen production by Clostridium was caused by the addition of LAB. The supernatants of L. paracasei and E. durans suspensions also inhibited hydrogen production by Clostridium. This inhibition was partially destroyed in the presence of trypsin, which is a protease inactivating a bacteriocin. These results suggest that the inhibitory effect of lactic acid bacteria on hydrogen production was caused by bacteriocins excreted from LAB which have a deleterious effect on other bacteria. To suppress any effect by LAB, heat treatment of this waste was investigated as a possible pretreatment step. The inhibition of hydrogen production was reduced by heat treatment for 30 min at temperatures ranging from 50{sup o}C to 90{sup o}C. This means that a temperature of 50{sup o}C is already adequate to prevent growth of LAB. (Author)

  10. Immobilization of Tyrosinase from Avocado Crude Extract in Polypyrrole Films for Inhibitive Detection of Benzoic Acid

    Directory of Open Access Journals (Sweden)

    André Brisolari

    2014-07-01

    Full Text Available Inhibition-based biosensors were developed by immobilizing tyrosinase (Tyr, polyphenol oxidase from the crude extract of avocado fruit on electrochemically prepared polypyrrole (PPy films. The biosensors were prepared during the electropolymerization of pyrrole in a solution containing a fixed volume of the crude extract of avocado. The dependence of the biosensor responses on the volume used from the crude extract, values of pH and temperature was studied, and a substrate, catechol, at different concentrations, was amperometrically detected by these biosensors. Benzoic acid, a competitive inhibitor of Try, was added to the catechol solutions at specific concentrations aimed at obtaining the inhibition constant, K’m, which ranged from 1.7 to 4.6 mmol∙L−1 for 0.0 and 60 µmol∙L−1 of benzoic acid, respectively. Studies on the inhibition caused by benzoic acid by using PPy/Try films, and catechol as a substrate, allowed us propose how to develop, under optimized conditions, simple and low-cost biosensors based on the use of avocado fruit.

  11. Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G

    Directory of Open Access Journals (Sweden)

    Andreas Koeberle

    2018-02-01

    Full Text Available Age-related diseases, such as osteoarthritis, Alzheimer’s disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO pathway. Boswellic acids (BAs are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging.

  12. Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G.

    Science.gov (United States)

    Koeberle, Andreas; Henkel, Arne; Verhoff, Moritz; Tausch, Lars; König, Stefanie; Fischer, Dagmar; Kather, Nicole; Seitz, Stefanie; Paul, Michael; Jauch, Johann; Werz, Oliver

    2018-02-24

    Age-related diseases, such as osteoarthritis, Alzheimer's disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging.

  13. In vitro lactic acid inhibition and alterations in volatile fatty acid production by antimicrobial feed additives.

    Science.gov (United States)

    Nagaraja, T G; Taylor, M B; Harmon, D L; Boyer, J E

    1987-10-01

    Batch culture fermentations were used to determine the effects of avoparcin, lasalocid, monensin, narasin, salinomycin, thiopeptin, tylosin, virginiamycin, monensin + tylosin combination, and two new ionophore compounds (RO22-6924/004 and RO21-6447/009) on lactic acid and volatile fatty acid (VFA) production. Ruminal fluid from cattle fed a high alfalfa hay diet was incubated with glucose for 12 h in a buffered medium to determine the effect of antimicrobial compounds on lactic acid concentration. Fermentations treated with antimicrobial compounds had higher final pH and lower L(+) lactic acid concentration. Narasin and salinomycin were more inhibitory than other ionophore compounds. Monensin and tylosin in combination was more effective than monensin alone. Among the nonionophore compounds, avoparcin was the least effective and thiopeptin, tylosin and virginiamycin were extremely effective in reducing lactic acid concentration. Ruminal fluid from cattle fed a diet of alfalfa hay and grain (50:50) was incubated with a mixture of sugars, casein and urea for 12 h in a buffered medium to determine the effect of antimicrobial compounds on VFA production. Generally, total VFA concentration was not affected by antimicrobial compounds except RO22-6924/004, tylosin and virginiamycin, which caused a reduction at high concentrations. Tylosin, monensin and tylosin mixture, thiopeptin and virginiamycin at high concentrations (greater than 6.0 micrograms/ml) increased the acetate proportion. All compounds increased the molar proportion of propionate. Tylosin and virginiamycin at high concentrations (greater than 6.0 micrograms/ml) decreased the proportion of propionate. Monensin and tylosin in combination had no effect on propionate proportion. Among the compounds tested, narasin and salinomycin were the most effective in enhancing propionate proportion. Ionophore compounds were more inhibitory to butyrate production than the nonionophore compounds. Batch culture fermentations

  14. Correlating enzymatic browning inhibition and antioxidant ability of Maillard reaction products derived from different amino acids.

    Science.gov (United States)

    Xu, Haining; Zhang, Xiaoming; Karangwa, Eric; Xia, Shuqin

    2017-09-01

    Up to now, only limited research on enzymatic browning inhibition capacity (BIC) of Maillard reaction products (MRPs) has been reported and there are still no overall and systematic researches on MRPs derived from different amino acids. In the present study, BIC and antioxidant capacity, including 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and Fe 2+ reducing power activity, of the MRPs derived from 12 different amino acids and three reducing sugars were investigated. The MRPs of cysteine (Cys), cystine, arginine (Arg) and histidine (His) showed higher BIC compared to other amino acids. Lysine (Lys)-MRPs showed the highest absorbance value at 420 nm (A 420 ) but very limited BIC, whereas Cys-MRPs, showed the highest BIC and the lowest A 420 . The A 420 can roughly reflect the trend of BIC of MRPs from different amino acids, except Cys and Lys. MRPs from tyrosine (Tyr) showed the most potent antioxidant capacity but very limited BIC, whereas Cys-MRPs showed both higher antioxidant capacity and BIC compared to other amino acids. Partial least squares regression analysis showed positive and significant correlation between BIC and Fe 2+ reducing power of MRPs from 12 amino acids with glucose or fructose, except Lys, Cys and Tyr. The suitable pH for generating efficient browning inhibition compounds varies depending on different amino acids: acidic pH was favorable for Cys, whereas neutral and alkaline pH were suitable for His and Arg, respectively. Increasing both heating temperature and time over a certain range could improve the BIC of MRPs of Cys, His and Arg, whereas any further increase deteriorates their browning inhibition efficiencies. The types of amino acid, initial pH, temperature and time of the Maillard reaction were found to greatly influence the BIC and antioxidant capacity of the resulting MRPs. There is no clear relationship between BIC and the antioxidant capacity of MRPs when reactant type and processing parameters of the Maillard

  15. Synergistic effects of sodium lauroyl sarcosinate and glutamic acid in inhibition assembly against copper corrosion in acidic solution

    Science.gov (United States)

    Yu, Yinzhe; Zhang, Daquan; Zeng, Huijing; Xie, Bin; Gao, Lixin; Lin, Tong

    2015-11-01

    A self-assembled multilayer (SAM) from sodium lauroyl sarcosinate (SLS) and glutamic acid (GLU) is formed on copper surface. Its inhibition ability against copper corrosion is examined by electrochemical analysis and weight loss test. In comparison to SAM formed by just SLS or GLU, a synergistic effect is observed when the coexistence of SLS and GLU in SAM. The SLS/GLU SAM has an acicular multilayer structure, and SAM prepared under the condition of 5 mM SLS and 1 mM GLU shows the best protection efficiency. PM6 calculation reveals that the synergistic effect stems from interactions between SLS, GLU and cupric ions.

  16. Alpha-lipoic acid protects cardiomyocytes against hypoxia/reoxygenation injury by inhibiting autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Xueming; Chen, Aihua, E-mail: aihuachen2012@sina.com; Yang, Pingzhen; Song, Xudong; Liu, Yingfeng; Li, Zhiliang; Wang, Xianbao; Wang, Lizi; Li, Yunpeng

    2013-11-29

    Highlights: •We observed the cell viability and death subjected to H/R in H9c2 cardiomyocytes. •We observed the degree of autophagy subjected to H/R in H9c2 cardiomyocytes. •LA inhibited the degree of autophagy in parallel to the enhanced cell survival. •LA inhibited the autophagy in parallel to the decreased total cell death. •We concluded that LA protected cardiomyocytes against H/R by inhibiting autophagy. -- Abstract: Hypoxia/reoxygenation (H/R) is an important in vitro model for exploring the molecular mechanisms and functions of autophagy during myocardial ischemia/reperfusion (I/R). Alpha-lipoic acid (LA) plays an important role in the etiology of cardiovascular disease. Autophagy is widely implicated in myocardial I/R injury. We assessed the degree of autophagy by pretreatment with LA exposed to H/R in H9c2 cell based on the expression levels of Beclin-1, LC3II/LC3I, and green fluorescent protein-labeled LC3 fusion proteins. Autophagic vacuoles were confirmed in H9c2 cells exposed to H/R using transmission electron microscopy. Our findings indicated that pretreatment with LA inhibited the degree of autophagy in parallel to the enhanced cell survival and decreased total cell death in H9c2 cells exposed to H/R. We conclude that LA protects cardiomyocytes against H/R injury by inhibiting autophagy.

  17. Inhibition Behaviour of Some Isonicotinic Acid Hydrazides on the Corrosion of Mild Steel in Hydrochloric Acid Solution

    Directory of Open Access Journals (Sweden)

    M. P. Chakravarthy

    2013-01-01

    Full Text Available New corrosion inhibitors, namely, isonicotinic acid (1H-indol-3-yl-methylenehydrazide (INIMH and isonicotinic acid (1H-pyrrol-2-yl-methylenehydrazide (INPMH, have been synthesized, and their inhibitive characteristics for the corrosion of mild steel in 0.5 M HCl were investigated by mass loss and electrochemical techniques. The structures of the synthesized compounds were confirmed using spectral studies. Potentiodynamic polarization studies revealed that the investigated inhibitors are of mixed type. Various thermodynamic parameters were evaluated. Langmuir adsorption isotherm was found to be the best description for both inhibitors. FTIR spectra, energy dispersive X-ray spectroscopy (EDX, and scanning electron microscopy (SEM were performed to characterize the passive film on the metal surface.

  18. Carnosic Acid Inhibits the Epithelial-Mesenchymal Transition in B16F10 Melanoma Cells: A Possible Mechanism for the Inhibition of Cell Migration

    Directory of Open Access Journals (Sweden)

    So Young Park

    2014-07-01

    Full Text Available Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an in vitro Transwell system, carnosic acid inhibited cell migration in a dose-dependent manner. Carnosic acid suppressed the adhesion of B16F10 cells, as well as the secretion of matrix metalloproteinase (MMP-9, tissue inhibitor of metalloproteinase (TIMP-1, urokinase plasminogen activator (uPA, and vascular cell adhesion molecule (VCAM-1. Interestingly, secretion of TIMP-2 increased significantly in B16F10 cells treated with 10 μmol/L carnosic acid. Additionally, carnosic acid suppressed the mesenchymal markers snail, slug, vimentin, and N-cadherin and induced epithelial marker E-cadherin. Furthermore, carnosic acid suppressed phosphorylation of Src, FAK, and AKT. These results indicate that inhibition of the epithelial-mesenchymal transition may be important for the carnosic acid-induced inhibition of B16F10 cell migration.

  19. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

    Science.gov (United States)

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2015-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.

  20. Reduction of linoleic acid inhibition in production of conjugated linoleic acid by Propionibacterium freudenreichii ssp. shermanii.

    Science.gov (United States)

    Rainio, A; Vahvaselkä, M; Suomalainen, T; Laakso, S

    2001-08-01

    A method for the production of conjugated linoleic acid (CLA) from linoleic acid (LA) using growing cultures of Propionibacterium freudenreichii ssp. shermanii JS was developed. The growth inhibitory effect of LA was eliminated by dispersing it in a sufficient concentration of polyoxyethylene sorbitan monooleate detergent. For the whey permeate medium used, the optimum LA:detergent ratio was 1:15 (w/w). As a result, the cultures tolerated at least 1000 microg x mL(-1) LA, which was converted to CLA with 57%-87% efficiency. The cis-9, trans-11 and trans-9, cis-11 isomers constituted 85%-90% of the CLA produced. The feasibility of the method was demonstrated also in de Man Rogosa-Sharpe (MRS) broth.

  1. Ricinoleic acid inhibits methanogenesis and fatty acid biohydrogenation in ruminal digesta from sheep and in bacterial cultures.

    Science.gov (United States)

    Ramos Morales, E; Mata Espinosa, M A; McKain, N; Wallace, R J

    2012-12-01

    Ricinoleic acid (RA; 12-hydroxy-cis-9-18:1) is the main fatty acid component of castor oil. Although a precursor for CLA synthesis in lactic acid bacteria, RA was found previously not to form CLA in ruminal digesta but to have some inhibitory properties. The present study was undertaken to evaluate the potential of RA to modulate ruminal biohydrogenation and methanogenesis. Ruminal digesta from 4 sheep receiving a mixed hay-concentrate diet was incubated in vitro with 0.167 g/L of linoleic acid (LA; cis-9,cis-12-18:2) or with a combination of LA and RA or LA and castor oil (LA, RA, and castor oil added to a final concentration of 0.167 g/L) in the presence and absence of lipase. The CLA rumenic acid (cis-9,trans-11-18:2) accumulated when either RA or castor oil and lipase was present. Vaccenic acid (VA; trans-11-18:1) also accumulated, and a decrease of the rate of production of stearic acid (SA; 18:0) was observed. When LA was incubated with castor oil in the absence of lipase, no effects on biohydrogenation were observed. Ricinoleic acid at 0.02 g/L did not affect growth of Butyrivibrio fibrisolvens but it inhibited growth of Butyrivibrio proteoclasticus. Butyrivibrio proteoclasticus but not B. fibrisolvens metabolized RA to 12-hydroxystearate. Linoleic acid metabolism by B. proteoclasticus appeared to be unaffected by RA addition whereas rumenic acid accumulation increased (P = 0.015 at 12 h) when RA was added. A 28% decrease (P = 0.004) in methane was obtained in 24 h in vitro incubations of diluted buffered ruminal fluid with added 0.2 g RA/L. There was no effect on the total concentration of VFA after 24 h as a result of RA addition, but the molar proportions of acetate and butyrate were decreased (P = 0.041 and P methane emissions. In vivo studies are now required to confirm the potential of these additives.

  2. Ferulic acid inhibits proliferation and promotes apoptosis via blockage of PI3K/Akt pathway in osteosarcoma cell.

    Science.gov (United States)

    Wang, Ting; Gong, Xia; Jiang, Rong; Li, Hongzhong; Du, Weimin; Kuang, Ge

    2016-01-01

    Ferulic acid, a ubiquitous phenolic acid abundant in corn, wheat and flax, has potent anti-tumor effect in various cancer cell lines. However, the anti-tumor effect of ferulic acid on osteosarcoma remains unclear. Therefore, we conduct current study to examine the effect of ferulic acid on osteosarcoma cells and explore the underlying mechanisms. In present study, ferulic acid inhibited proliferation and induced apoptosis in both 143B and MG63 osteosarcoma cells dose-dependently, indicated by MTT assay and Annexin V-FITC apoptosis detection. Additionally, ferulic acid induced G0/G1 phase arrest and down-regulated the expression of cell cycle-related protein, CDK 2, CDK 4, CDK 6, confirmed by flow cytometry assay and western blotting. Moreover, ferulic acid upregulated Bax, downregulated Bcl-2, and subsequently enhanced caspase-3 activity. More importantly, ferulic acid dose-dependently inhibited PI3K/Akt activation. Using adenoviruses expressing active Akt, the anti-proliferation and pro-apoptosis of ferulic acid were reverted. Our results demonstrated that ferulic acid might inhibit proliferation and induce apoptosis via inhibiting PI3K/Akt pathway in osteosarcoma cells. Ferulic acid is a novel therapeutic agent for osteosarcoma.

  3. Evidence that Speciation of Oxovanadium Complexes does not Solely Account for Inhibition of Leishmania Acid Phosphatases

    Science.gov (United States)

    Dorsey, Benjamin M.; McLauchlan, Craig C.; Jones, Marjorie A.

    2018-04-01

    Leishmaniasis is an endemic disease affecting a diverse spectra of populations, with 1.6 million new cases reported each year. Current treatment options are costly and have harsh side effects. New therapeutic options that have been previously identified, but still underappreciated as potential pharmaceutical targets, are Leishmania secreted acid phosphatases (SAP). These acid phosphatases, which are reported to play a role in the survival of the parasite in the sand fly vector, and in homing to the host macrophage, are inhibited by orthovanadate and decavanadate. Here, we use L. tarentolae to further evaluate these inhibitors. Using enzyme assays, and UV-visible spectroscopy, we investigate which oxovanadium starting material (orthovanadate or decavanadate) is a better inhibitor of L. tarentolae secreted acid phosphatase activity in vitro at the same total moles of vanadium. Considering speciation and total vanadium concentration, decavanadate is a consistently better inhibitor of SAP in our conditions, especially at low substrate:inhibitor ratios.

  4. Structural basis of the inhibition of class C acid phosphatases by adenosine 5;#8242;-phosphorothioate

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Harkewal; Reilly, Thomas J.; Tanner, John J. (UMC)

    2012-01-20

    The inhibition of phosphatases by adenosine 5'-phosphorothioate (AMPS) was first reported in the late 1960s; however, the structural basis for the inhibition has remained unknown. Here, it is shown that AMPS is a submicromolar inhibitor of class C acid phosphatases, a group of bacterial outer membrane enzymes belonging to the haloacid dehalogenase structural superfamily. Furthermore, the 1.35-{angstrom} resolution crystal structure of the inhibited recombinant Haemophilus influenzae class C acid phosphatase was determined; this is the first structure of a phosphatase complexed with AMPS. The conformation of AMPS is identical to that of the substrate 5'-AMP, except that steric factors force a rotation of the thiophosphoryl out of the normal phosphoryl-binding pocket. This conformation is catalytically nonproductive, because the P atom is not positioned optimally for nucleophilic attack by Asp64, and the O atom of the scissile O-P bond is too far from the Asp (Asp66) that protonates the leaving group. The structure of 5'-AMP complexed with the Asp64 {yields} Asn mutant enzyme was also determined at 1.35-{angstrom} resolution. This mutation induces the substrate to adopt the same nonproductive binding mode that is observed in the AMPS complex. In this case, electrostatic considerations, rather than steric factors, underlie the movement of the phosphoryl. The structures not only provide an explanation for the inhibition by AMPS, but also highlight the precise steric and electrostatic requirements of phosphoryl recognition by class C acid phosphatases. Moreover, the structure of the Asp64 {yields} Asn mutant illustrates how a seemingly innocuous mutation can cause an unexpected structural change.

  5. Omega 3 Fatty Acid inhibition of inflammatory cytokine-mediated Connexin43 regulation in the heart

    Directory of Open Access Journals (Sweden)

    Jennifer R Baum

    2012-07-01

    Full Text Available Background: The proinflammatory cytokine Interleukin-1β (IL-1β, which increases in the heart post myocardial infarction (MI, has been shown to cause loss of Connexin43 (Cx43 function, an event known to underlie formation of the arrhythmogenic substrate. Omega 3 Fatty acids exhibit antiarrhythmic properties and impact IL-1β signaling. We hypothesize that Omega-3 fatty acids prevent arrhythmias in part, by inhibiting IL-1β signaling thus maintaining functional Cx43 channels. Methods: Rat neonatal myocytes or Madin-Darby Canine Kidney Epithelial (MDCK cells grown in media in the absence (Ctr or presence of 30μM docosahexaenoic acid (DHA, an Omega-3 Fatty acid were treated with 0.1μM activated IL-1β. We determined Cx43 channel function using a dye spread assay. Western blot and immunostaining were used to examine Cx43 levels/localization and downstream effectors of IL-1 β. In addition we used a murine model of myocardial infarction (MI for 24 hours to determine the impact of an Omega-3 fatty acid enriched diet on Cx43 levels/localization post myocardial infarction.Results: IL-1β significantly inhibited Cx43 function in Ctr cells (200.9 +/- 17.7 μm [Ctr] vs. 112.8 +/- 14.9 μm [0.1uM IL-1β], p<0.05. However, DHA-treated cells remained highly coupled in the presence of IL-1β [167.9 +/- 21.9 μm [DHA] vs. 164.4 +/- 22.3 μm [DHA+0.1uM IL-1β], p<0.05, n=4. Additionally, western blot showed that IL-1β treatment caused a 38.5% downregulation of Cx43 [1.00au [Ctr] vs 0.615au (0.1μM IL-1β which was completely abolished in DHA treated cells (0.935au [DHA] vs. 1.02au [DHA+0.1μM IL-1β, p<0.05, n=3]. Examination of the downstream modulator of IL-1β, NFκβ showed that while hypoxia caused translocation of NFκβ to the nucleus, this was inhibited by DHA. Additionally we found that a diet enriched in Omega-3 Fatty acids inhibited lateralization of Cx43 in the post-myocardial infarction murine heart as well as limited activation of fibroblasts

  6. The induction of apoptosis in pre-malignant keratinocytes by omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is inhibited by albumin.

    Science.gov (United States)

    Nikolakopoulou, Zacharoula; Shaikh, Mushfiq Hassan; Dehlawi, Hebah; Michael-Titus, Adina Teodora; Parkinson, Eric Kenneth

    2013-04-12

    The long chain omega-3 polyunsaturated fatty acids (PUFA) have been reported to exert anti-cancer effects. At this study we tested the effect of the omega-3 PUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on pre-malignant keratinocytes growth in the well-characterised human pre-malignant epidermal cell line, HaCaT and attempted to identify a PUFA serum antagonist. Both EPA and DHA inhibited HaCaT growth and induced apoptosis. At the 10% (v/v) foetal bovine serum (FBS) medium, limited growth inhibition (3-20% for 50μM DHA and EPA respectively) and negligible apoptosis were observed with PUFA use. However, at 3% (v/v) FBS medium, 30-50μM of PUFA caused impressive levels of growth inhibition (82-83% for 50μM DHA and EPA respectively) and increase of apoptosis (8-19% increase in 72h). None of the numerous serum growth factors present in FBS or the antioxidant n-tert-butyl-α-phenylnitrone could inhibit the PUFA-induced cytotoxicity. In contrast, bovine and human albumin (0.1-0.3%, w/v) significantly antagonized the growth inhibitory and apoptosis-inducing effects of PUFA. In conclusion, we have shown for the first time that omega-3 PUFA inhibit the growth and induce apoptosis of pre-malignant keratinocytes and identified albumin as a major antagonistic factor in serum that could limit their effectiveness at pharmacologically-achievable doses. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Pharmacological inhibition of fatty acid amide hydrolase attenuates social behavioural deficits in male rats prenatally exposed to valproic acid.

    Science.gov (United States)

    Kerr, Daniel M; Gilmartin, Aoife; Roche, Michelle

    2016-11-01

    Autism spectrum disorders are a group of neurodevelopmental disorders characterised by impaired social interaction, deficits in communication and repetitive stereotyped behaviours. The endocannabinoid system plays an important role in modulating emotionality and social responding, however there have been a paucity of studies investigating this system in autistic animal models. This study investigated the effect of inhibiting fatty acid amide hydrolyase (FAAH), the anandamide catabolic enzyme, on behavioural responding in the valproic acid (VPA) rat model of autism. Male rats prenatally exposed to VPA exhibit an autistic-like behavioural phenotype exemplified as thermal hypoalgesia, reduced social and exploratory behaviour, and enhanced repetitive behaviour. Systemic administration of the FAAH inhibitor PF3845 (10mg/kg) attenuated the deficit in social behaviour observed in VPA exposed male animals without altering nociceptive, repetitive or exploratory behaviour. In comparison, female VPA exposed rats displayed enhanced repetitive and reduced exploratory behaviour, but no change in social behaviour or thermal nociceptive responding. PF3845 did not alter social, repetitive or thermal nociceptive responding, but reduced exploratory behaviour in a social context in VPA-, but not saline-, exposed females. These data indicate that FAAH inhibition elicits sexual dimorphic effects on behavioural responding in VPA exposed rodents, and support an important role for FAAH in the regulation of social behavioural deficits in autistic males. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Capric acid secreted by S. boulardii inhibits C. albicans filamentous growth, adhesion and biofilm formation.

    Directory of Open Access Journals (Sweden)

    Anna Murzyn

    Full Text Available Candidiasis are life-threatening systemic fungal diseases, especially of gastro intestinal track, skin and mucous membranes lining various body cavities like the nostrils, the mouth, the lips, the eyelids, the ears or the genital area. Due to increasing resistance of candidiasis to existing drugs, it is very important to look for new strategies helping the treatment of such fungal diseases. One promising strategy is the use of the probiotic microorganisms, which when administered in adequate amounts confer a health benefit. Such a probiotic microorganism is yeast Saccharomyces boulardii, a close relative of baker yeast. Saccharomyces boulardii cells and their extract affect the virulence factors of the important human fungal pathogen C. albicans, its hyphae formation, adhesion and biofilm development. Extract prepared from S. boulardii culture filtrate was fractionated and GC-MS analysis showed that the active fraction contained, apart from 2-phenylethanol, caproic, caprylic and capric acid whose presence was confirmed by ESI-MS analysis. Biological activity was tested on C. albicans using extract and pure identified compounds. Our study demonstrated that this probiotic yeast secretes into the medium active compounds reducing candidal virulence factors. The chief compound inhibiting filamentous C. albicans growth comparably to S. boulardii extract was capric acid, which is thus responsible for inhibition of hyphae formation. It also reduced candidal adhesion and biofilm formation, though three times less than the extract, which thus contains other factors suppressing C. albicans adherence. The expression profile of selected genes associated with C. albicans virulence by real-time PCR showed a reduced expression of HWP1, INO1 and CSH1 genes in C. albicans cells treated with capric acid and S. boulardii extract. Hence capric acid secreted by S. boulardii is responsible for inhibition of C. albicans filamentation and partially also adhesion and

  9. Signal Transducer and Activator of Transcription 3 (STAT3) Mediates Amino Acid Inhibition of Insulin Signaling through Serine 727 Phosphorylation*

    OpenAIRE

    Kim, Jeong-Ho; Yoon, Mee-Sup; Chen, Jie

    2009-01-01

    Nutrient overload is associated with the development of obesity, insulin resistance, and type II diabetes. High plasma concentrations of amino acids have been found to correlate with insulin resistance. At the cellular level, excess amino acids impair insulin signaling, the mechanisms of which are not fully understood. Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells. Excess amino acids inhibited insulin-stimulated Akt phosphorylation a...

  10. Monomethylarsonous acid (MMA+3) Inhibits IL-7 Signaling in Mouse Pre-B Cells.

    Science.gov (United States)

    Ezeh, Peace C; Xu, Huan; Lauer, Fredine T; Liu, Ke Jian; Hudson, Laurie G; Burchiel, Scott W

    2016-02-01

    Our previously published data show that As(+3) in vivo and in vitro, at very low concentrations, inhibits lymphoid, but not myeloid stem cell development in mouse bone marrow. We also showed that the As(+3) metabolite, monomethylarsonous acid (MMA(+3)), was responsible for the observed pre-B cell toxicity caused by As(+3). Interleukin-7 (IL-7) is the primary growth factor responsible for pre-lymphoid development in mouse and human bone marrow, and Signal Transducer and Activator of Transcription 5 (STAT5) is a transcriptional factor in the IL-7 signaling pathway. We found that MMA(+3) inhibited STAT5 phosphorylation at a concentration as low as 50 nM in mouse bone marrow pre-B cells. Inhibition of STAT5 phosphorylation by As(+3) occurred only at a concentration of 500 nM. In the IL-7 dependent mouse pre-B 2E8 cell line, we also found selective inhibition of STAT5 phosphorylation by MMA(+3), and this inhibition was dependent on effects on JAK3 phosphorylation. IL-7 receptor expression on 2E8 cell surface was also suppressed by 50 nM MMA(+3) at 18 h. As further evidence for the inhibition of STAT5, we found that the induction of several genes required in B cell development, cyclin D1, E2A, EBF1, and PAX5, were selectively inhibited by MMA(+3). Since 2E8 cells lack the enzymes responsible for the conversion of As(+3) to MMA(+3) in vitro, the results of these studies suggest that As(+3) induced inhibition of pre-B cell formation in vivo is likely dependent on the formation of MMA(+3) which in turn inhibits IL-7 signaling at several steps in mouse pre-B cells. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. High uric acid directly inhibits insulin signalling and induces insulin resistance.

    Science.gov (United States)

    Zhu, Yuzhang; Hu, Yaqiu; Huang, Tianliang; Zhang, Yongneng; Li, Zhi; Luo, Chaohuan; Luo, Yinfeng; Yuan, Huier; Hisatome, Ichiro; Yamamoto, Tetsuya; Cheng, Jidong

    2014-05-16

    Accumulating clinical evidence suggests that hyperuricemia is strongly associated with abnormal glucose metabolism and insulin resistance. However, how high uric acid (HUA) level causes insulin resistance remains unclear. We aimed to determine the direct role of HUA in insulin resistance in vitro and in vivo in mice. An acute hyperuricemia mouse model was created by potassium oxonate treatment, and the impact of HUA level on insulin resistance was investigated by glucose tolerance test, insulin tolerance test and insulin signalling, including phosphorylation of insulin receptor substrate 1 (IRS1) and Akt. HepG2 cells were exposed to HUA treatment and N-acetylcysteine (NAC), reactive oxygen species scavenger; IRS1 and Akt phosphorylation was detected by Western blot analysis after insulin treatment. Hyperuricemic mice showed impaired glucose tolerance with insulin resistance. Hyperuricemia inhibited phospho-Akt (Ser473) response to insulin and increased phosphor-IRS1 (Ser307) in liver, muscle and fat tissues. HUA induced oxidative stress, and the antioxidant NAC blocked HUA-induced IRS1 activation and Akt inhibition in HepG2 cells. This study supplies the first evidence of HUA directly inducing insulin resistance in vivo and in vitro. Increased uric acid level may inhibit IRS1 and Akt insulin signalling and induce insulin resistance. The reactive oxygen species pathway plays a key role in HUA-induced insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Inhibition of Collagenase by Mycosporine-like Amino Acids from Marine Sources.

    Science.gov (United States)

    Hartmann, Anja; Gostner, Johanna; Fuchs, Julian E; Chaita, Eliza; Aligiannis, Nektarios; Skaltsounis, Leandros; Ganzera, Markus

    2015-07-01

    Matrix metalloproteinases play an important role in extracellular matrix remodeling. Excessive activity of these enzymes can be induced by UV light and leads to skin damage, a process known as photoaging. In this study, we investigated the collagenase inhibition potential of mycosporine-like amino acids, compounds that have been isolated from marine organisms and are known photoprotectants against UV-A and UV-B. For this purpose, the commonly used collagenase assay was optimized and for the first time validated in terms of relationships between enzyme-substrate concentrations, temperature, incubation time, and enzyme stability. Three compounds were isolated from the marine red algae Porphyra sp. and Palmaria palmata, and evaluated for their inhibitory properties against Chlostridium histolyticum collagenase. A dose-dependent, but very moderate, inhibition was observed for all substances and IC50 values of 104.0 µM for shinorine, 105.9 µM for porphyra, and 158.9 µM for palythine were determined. Additionally, computer-aided docking models suggested that the mycosporine-like amino acids binding to the active site of the enzyme is a competitive inhibition. Georg Thieme Verlag KG Stuttgart · New York.

  13. Do pH and flavonoids influence hypochlorous acid-induced catalase inhibition and heme modification?

    Science.gov (United States)

    Krych-Madej, Justyna; Gebicka, Lidia

    2015-09-01

    Hypochlorous acid (HOCl), highly reactive oxidizing and chlorinating species, is formed in the immune response to invading pathogens by the reaction of hydrogen peroxide with chloride catalyzed by the enzyme myeloperoxidase. Catalase, an important antioxidant enzyme, catalyzing decomposition of hydrogen peroxide to water and molecular oxygen, hampers in vitro HOCl formation, but is also one of the main targets for HOCl. In this work we have investigated HOCl-induced catalase inhibition at different pH, and the influence of flavonoids (catechin, epigallocatechin gallate and quercetin) on this process. It has been shown that HOCl-induced catalase inhibition is independent on pH in the range 6.0-7.4. Preincubation of catalase with epigallocatechin gallate and quercetin before HOCl treatment enhances the degree of catalase inhibition, whereas catechin does not affect this process. Our rapid kinetic measurements of absorption changes around the heme group have revealed that heme modification by HOCl is mainly due to secondary, intramolecular processes. The presence of flavonoids, which reduce active catalase intermediate, Compound I to inactive Compound II have not influenced the kinetics of HOCl-induced heme modification. Possible mechanisms of the reaction of hypochlorous acid with catalase are proposed and the biological consequences are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Inhibitive action of some plant extracts on the corrosion of steel in acidic media

    International Nuclear Information System (INIS)

    Abdel-Gaber, A.M.; Abd-El-Nabey, B.A.; Sidahmed, I.M.; El-Zayady, A.M.; Saadawy, M.

    2006-01-01

    The effect of extracts of Chamomile (Chamaemelum mixtum L.), Halfabar (Cymbopogon proximus), Black cumin (Nigella sativa L.), and Kidney bean (Phaseolus vulgaris L.) plants on the corrosion of steel in aqueous 1 M sulphuric acid were investigated by electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization techniques. EIS measurements showed that the dissolution process of steel occurs under activation control. Potentiodynamic polarization curves indicated that the plant extracts behave as mixed-type inhibitors. The corrosion rates of steel and the inhibition efficiencies of the extracts were calculated. The results obtained show that the extract solution of the plant could serve as an effective inhibitor for the corrosion of steel in sulphuric acid media. Inhibition was found to increase with increasing concentration of the plant extract up to a critical concentration. The inhibitive actions of plant extracts are discussed on the basis of adsorption of stable complex at the steel surface. Theoretical fitting of different isotherms, Langmuir, Flory-Huggins, and the kinetic-thermodynamic model, were tested to clarify the nature of adsorption

  15. Inhibitive action of some plant extracts on the corrosion of steel in acidic media

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Gaber, A.M. [Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, P.O. Box 426, Alexandria 21321 (Egypt)]. E-mail: ashrafmoustafa@yahoo.com; Abd-El-Nabey, B.A. [Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, P.O. Box 426, Alexandria 21321 (Egypt); Sidahmed, I.M. [Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, P.O. Box 426, Alexandria 21321 (Egypt); El-Zayady, A.M. [Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, P.O. Box 426, Alexandria 21321 (Egypt); Saadawy, M. [Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, P.O. Box 426, Alexandria 21321 (Egypt)

    2006-09-15

    The effect of extracts of Chamomile (Chamaemelum mixtum L.), Halfabar (Cymbopogon proximus), Black cumin (Nigella sativa L.), and Kidney bean (Phaseolus vulgaris L.) plants on the corrosion of steel in aqueous 1 M sulphuric acid were investigated by electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization techniques. EIS measurements showed that the dissolution process of steel occurs under activation control. Potentiodynamic polarization curves indicated that the plant extracts behave as mixed-type inhibitors. The corrosion rates of steel and the inhibition efficiencies of the extracts were calculated. The results obtained show that the extract solution of the plant could serve as an effective inhibitor for the corrosion of steel in sulphuric acid media. Inhibition was found to increase with increasing concentration of the plant extract up to a critical concentration. The inhibitive actions of plant extracts are discussed on the basis of adsorption of stable complex at the steel surface. Theoretical fitting of different isotherms, Langmuir, Flory-Huggins, and the kinetic-thermodynamic model, were tested to clarify the nature of adsorption.

  16. Dafachronic acid inhibits C. elegans germ cell proliferation in a DAF-12-dependent manner.

    Science.gov (United States)

    Mukherjee, Madhumati; Chaudhari, Snehal N; Balachandran, Riju S; Vagasi, Alexandra S; Kipreos, Edward T

    2017-12-15

    Dafachronic acid (DA) is a bile acid-like steroid hormone that regulates dauer formation, heterochrony, and lifespan in C. elegans. Here, we describe that DA is an inhibitor of C. elegans germ stem cell proliferation in adult hermaphrodites. Using a C. elegans germ cell primary culture system, we show that DA inhibits the proliferation of germ cells in vitro. Exogenous DA reduces the frequency of large tumors in adult tumorous germline mutants and decreases the proliferation of wild-type germ stem cells in adult hermaphrodites. In contrast, DA has no appreciable effect on the proliferation of larval-stage germ cells in wild type. The inhibition of adult germ cell proliferation by DA requires its canonical receptor DAF-12. Blocking DA production by inactivating the cytochrome P450 DAF-9 increases germ cell proliferation in wild-type adult hermaphrodites and the frequency of large tumors in germline tumorous mutants, suggesting that DA inhibits the rate of germ cell proliferation under normal growth conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Ursolic acid inhibits superoxide production in activated neutrophils and attenuates trauma-hemorrhage shock-induced organ injury in rats.

    Directory of Open Access Journals (Sweden)

    Tsong-Long Hwang

    Full Text Available Neutrophil activation is associated with the development of organ injury after trauma-hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma-hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma-hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma-hemorrhagic shock-induced organ injury in rats.

  18. [Inhibition of oxidation of unsaturated fatty acid methyl esters by essential oils].

    Science.gov (United States)

    Misharina, T A; Alinkina, E S; Vorobjeva, A K; Terenina, M B; Krikunova, N I

    2016-01-01

    The essential oils from 16 various spice plants were studied as natural antioxidants for the inhibition of autooxidation of polyunsaturated fatty acids methyl esters isolated from linseed oil. The content of methyl oleate, methyl linoleate, and methyl linolenoate after 1, 2, and 4 months of autooxidation were used as criteria to estimate the antioxidant efficiencies of essential oils. In 4 months, 92% of the methyl linolenoate and 79% of the methyl linoleate were oxidized in a control sample of a model system. It was found that the most effective antioxidants were essential oils from clove bud, cinnamon leaves, and oregano. They inhibited autooxidation of methyl linolenoate by 76–85%. The antioxidant properties of these essential oils were due to phenols— eugenol, carvacrol, and thymol. Essential oil from coriander did not contain phenols, but it inhibited methyl linolenoate oxidation by 38%. Essential oils from thyme, savory, mace, lemon, and tea tree inhibited methyl linolenoate oxidation by 17–24%. The other essential oils had no antioxidant properties.

  19. Acid sphingomyelinase inhibition protects mice from lung edema and lethal Staphylococcus aureus sepsis.

    Science.gov (United States)

    Peng, Huiming; Li, Cao; Kadow, Stephanie; Henry, Brian D; Steinmann, Jörg; Becker, Katrin Anne; Riehle, Andrea; Beckmann, Natalie; Wilker, Barbara; Li, Pin-Lan; Pritts, Timothy; Edwards, Michael J; Zhang, Yang; Gulbins, Erich; Grassmé, Heike

    2015-06-01

    Pulmonary edema associated with increased vascular permeability is a severe complication of Staphylococcus aureus-induced sepsis and an important cause of human pathology and death. We investigated the role of the mammalian acid sphingomyelinase (Asm)/ceramide system in the development of lung edema caused by S. aureus. Our findings demonstrate that genetic deficiency or pharmacologic inhibition of Asm reduced lung edema in mice infected with S. aureus. The Asm/ceramide system triggered the formation of superoxide, resulting in degradation of tight junction proteins followed by lung edema. Treatment of infected mice with amitriptyline, a potent inhibitor of Asm, protected mice from lung edema caused by S. aureus, but did not reduce systemic bacterial numbers. In turn, treatment with antibiotics reduced bacterial numbers but did not protect mice from lung edema. In contrast, only the combination of antibiotics and amitriptyline inhibited both pulmonary edema and bacteremia protecting mice from lethal sepsis and lung dysfunction suggesting the combination of both drugs as novel treatment option for sepsis. Antibiotics are often insufficient to cure S. aureus-induced sepsis. S. aureus induces lung edema via the Asm/ceramide system. Genetic deficiency of Asm inhibits lung dysfunction upon infection with S. aureus. Pharmacologic inhibition of Asm reduces lung edema induced by S. aureus. Antibiotics plus amitriptyline protect mice from lung edema and lethal S. aureus sepsis.

  20. Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters.

    Science.gov (United States)

    Lin, Yuguang; Vermeer, Mario A; Trautwein, Elke A

    2011-01-01

    Hawthorn (Crataegus pinnatifida) is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT) activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA) and ursolic acid (UA)) contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE) were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w) cholesterol (control) or the same diet supplemented with (i) 0.37% hawthorn dichloromethane extract, (ii) 0.24% PSE, (iii) hawthorn dichloromethane extract (0.37%) plus PSE (0.24%) or (iv) OA/UA mixture (0.01%) for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL) cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA) enhanced the cholesterol lowering effect of plant sterols.

  1. Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters

    Directory of Open Access Journals (Sweden)

    Yuguang Lin

    2011-01-01

    Full Text Available Hawthorn (Crataegus pinnatifida is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA and ursolic acid (UA contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w cholesterol (control or the same diet supplemented with (i 0.37% hawthorn dichloromethane extract, (ii 0.24% PSE, (iii hawthorn dichloromethane extract (0.37% plus PSE (0.24% or (iv OA/UA mixture (0.01% for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA enhanced the cholesterol lowering effect of plant sterols.

  2. Flower inhibition in Kalanchoe blossfeldiana. Bioassay of an endogenous long-day inhibitor and inhibition by (±) abscisic acid and xanthoxin.

    Science.gov (United States)

    Schwabe, W W

    1972-03-01

    The inhibition of flowering in Kalanchoe by crude sap expressed from leaves held in non-inductive long-day conditions is described, using a bioassay technique of leaf injection, which confirms the existence of a transferable inhibitor.This technique has also revealed that ± abscisic acid and Xanthoxin are inhibitory to flowering at 50 and 100 ppm respectively. The previously known inhibitory effects of gibberellic acid on flowering have also been confirmed.

  3. Effects of gamma-aminobutyric acid on the Hering-Breuer inspiration-inhibiting reflex.

    Science.gov (United States)

    Aleksandrova, N P; Aleksandrov, V G; Ivanova, T G

    2010-02-01

    Acute experiments on rats were performed to study the effects of intraventricular microinjections of gamma-aminobutyric acid (GABA) on the volume-time parameters of external respiration and the inspiration-inhibiting Hering-Breuer reflex. The state of this reflex before and after GABA administration was assessed in terms of the extent of changes in the duration and amplitude of inspiratory oscillations in intrathoracic pressure in response to end-expiratory occlusion of the trachea. Administration of 20 microM GABA into the lateral ventricles of the brain decreased the minute ventilation (due to reductions in the respiratory frequency and respiratory volume), weakened respiratory muscle contractions, and decreased the peak airflow rate on inspiration and expiration. The response to end-expiratory occlusion decreased significantly after administration of GABA, demonstrating the involvement of GABAergic mechanisms in mediating the inspiration-inhibiting Hering-Breuer reflex.

  4. Inhibition of natural killer cell activity by eicosapentaenoic acid in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, N.; Sugiyama, E.; Hamazaki, T.; Yano, S.

    1988-01-15

    To examine the effects of in vivo eicosapentaenoic acid (EPA) on natural killer (NK) cell activity, C3H/He mice each received a single intraperitoneal bolus of an emulsion of trieicosapentaenoyl-glycerol (EPA-TG). Spleen cells were tested for NK activity using /sup 51/Chromium-release assays against YAC-1 target cells. Forty eight hours after injection, NK activity was inhibited in a dose-dependent manner. EPA-TG emulsion also inhibited the NK activity of NK-enriched effector cells. Decreased cytotoxicity was first noted 24 hr after injection; it resumed the baseline by 7 days. The addition of EPA-TG emulsion to a cytotoxicity assay system resulted in moderate depression of NK activity. These results demonstrate that EPA has significant immunomodulatory effects on NK activity.

  5. Molecular Basis for Allosteric Inhibition of Acid-Sensing Ion Channel 1a by Ibuprofen

    DEFF Research Database (Denmark)

    Lynagh, Timothy; Romero-Rojo, José Luis; Lund, Camilla

    2017-01-01

    A growing body of evidence links certain aspects of nonsteroidal anti-inflammatory drug (NSAID) pharmacology with acid-sensing ion channels (ASICs), a small family of excitatory neurotransmitter receptors implicated in pain and neuroinflammation. The molecular basis of NSAID inhibition of ASICs has......-clamp fluorometry. Our results show that ibuprofen is an allosteric inhibitor of ASIC1a, which binds to a crucial site in the agonist transduction pathway and causes conformational changes that oppose channel activation. Ibuprofen inhibits several ASIC subtypes, but certain ibuprofen derivatives show some...... selectivity for ASIC1a over ASIC2a and vice versa. These results thus define the NSAID/ASIC interaction and pave the way for small-molecule drug design targeting pain and inflammation....

  6. INHIBITION OF FATTY ACID DESATURASES IN Drosophila melanogaster LARVAE BLOCKS FEEDING AND DEVELOPMENTAL PROGRESSION.

    Science.gov (United States)

    Wang, Yiwen; da Cruz, Tina Correia; Pulfemuller, Alicia; Grégoire, Stéphane; Ferveur, Jean-François; Moussian, Bernard

    2016-05-01

    Fatty acid desaturases are metabolic setscrews. To study their systemic impact on growth in Drosophila melanogaster, we inhibited fatty acid desaturases using the inhibitor CAY10566. As expected, the amount of desaturated lipids is reduced in larvae fed with CAY10566. These animals cease feeding soon after hatching, and their growth is strongly attenuated. A starvation program is not launched, but the expression of distinct metabolic genes is activated, possibly to mobilize storage material. Without attaining the normal size, inhibitor-fed larvae molt to the next stage indicating that the steroid hormone ecdysone triggers molting correctly. Nevertheless, after molting, expression of ecdysone-dependent regulators is not induced. While control larvae molt a second time, these larvae fail to do so and die after few days of straying. These effects are similar to those observed in experiments using larvae deficient for the fatty acid desaturase1 gene. Based on these data, we propose that the ratio of saturated to unsaturated fatty acids adjusts a sensor system that directs feeding behavior. We also hypothesize that loss of fatty acid desaturase activity leads to a block of the genetic program of development progression indirectly by switching on a metabolic compensation program. © 2016 Wiley Periodicals, Inc.

  7. [Cyclooxygenase inhibitors in some dietary vegetables inhibit platelet aggregation function induced by arachidonic acid].

    Science.gov (United States)

    Wang, Xin-Hua; Shao, Dong-Hua; Liang, Guo-Wei; Zhang, Ru; Xin, Qin; Zhang, Tao; Cao, Qing-Yun

    2011-10-01

    The study was purposed to investigate whether the cyclooxygenase inhibitors from some dietary vegetables can inhibit platelet aggregation function by the arachidonic acid (AA). The vegetable juice was mixed with platelet rich plasma (PRP), and asprin was used as positive control. The maximum ratio of platelet aggregation induced by AA was measured on the aggregometer; heme and cyclooxygenase-1 (COX(1)) or cyclooxygenase-2 (COX(2)) were added to test tubes containing COX reaction buffer, the mixture was vortex-mixed and exposed to aspirin or vegetable juice, followed by addition of AA and then hydrochloric acid (1 mol/L) was added to stop the COX reaction, followed by chemical reduction with stannous chloride solution. The concentration of COX inhibitors was detected by the enzyme immunoassay kit; vegetable juice (aspirin as positive control) was mixed with whole blood, which was followed by the addition of AA, and then the reaction was stopped by adding indomethacin, centrifuged, then the supernatant was collected, and the plasma thromboxane B(2) (TXB(2)) was measured by radioimmunoassay. The results showed that spinach juice, garlic bolt juice, blanched garlic leave juice and Chinese leek juice could inhibit by 80% human platelet aggregation induced by AA. 4 kinds of vegetables were all found a certain amount of cyclooxygenase inhibitors, which COX(1) and COX(2) inhibitor concentrations of spinach were higher than that of aspirin; 4 vegetable juice could significantly reduce the human plasma concentrations of TXB(2) induced by AA (p < 0.05). It is concluded that 4 kinds of raw vegetables containing cyclooxygenase inhibitors inhibit the production of TXA(2) and thus hinder platelet aggregation. Raw spinach, garlic bolt, blanched garlic and chinese leek inhibit significantly AA-induced human platelet aggregation in vitro. 4 kinds of vegetables may have a good potential perspective of anti-platelet aggregation therapy or prevention of thrombosis.

  8. Oxymetazoline inhibits proinflammatory reactions: effect on arachidonic acid-derived metabolites.

    Science.gov (United States)

    Beck-Speier, Ingrid; Dayal, Niru; Karg, Erwin; Maier, Konrad L; Schumann, Gabriele; Semmler, Manuela; Koelsch, Stephan M

    2006-02-01

    The nasal decongestant oxymetazoline effectively reduces rhinitis symptoms. We hypothesized that oxymetazoline affects arachidonic acid-derived metabolites concerning inflammatory and oxidative stress-dependent reactions. The ability of oxymetazoline to model pro- and anti-inflammatory and oxidative stress responses was evaluated in cell-free systems, including 5-lipoxygenase (5-LO) as proinflammatory, 15-lipoxygenase (15-LO) as anti-inflammatory enzymes, and oxidation of methionine by agglomerates of ultrafine carbon particles (UCPs), indicating oxidative stress. In a cellular approach using canine alveolar macrophages (AMs), the impact of oxymetazoline on phospholipase A(2) (PLA(2)) activity, respiratory burst and synthesis of prostaglandin E(2) (PGE(2)), 15(S)-hydroxy-eicosatetraenoic acid (15-HETE), leukotriene B(4) (LTB(4)), and 8-isoprostane was measured in the absence and presence of UCP or opsonized zymosan as particulate stimulants. In cell-free systems, oxymetazoline (0.4-1 mM) inhibited 5-LO but not 15-LO activity and did not alter UCP-induced oxidation of methionine. In AMs, oxymetazoline induced PLA(2) activity and 15-HETE at 1 mM, enhanced PGE(2) at 0.1 mM, strongly inhibited LTB(4) and respiratory burst at 0.4/0.1 mM (p oxymetazoline did not alter UCP-induced PLA(2) activity and PGE(2) and 15-HETE formation in AMs but inhibited UCP-induced LTB(4) formation and respiratory burst at 0.1 mM and 8-isoprostane formation at 0.001 mM (p oxymetazoline inhibited LTB(4) formation and respiratory burst at 0.1 mM (p oxymetazoline suppressed proinflammatory reactions including 5-LO activity, LTB(4) formation, and respiratory burst and prevented particle-induced oxidative stress, whereas PLA(2) activity and synthesis of immune-modulating PGE(2) and 15-HETE were not affected.

  9. Strategies for improving production performance of probiotic Pediococcus acidilactici viable cell by overcoming lactic acid inhibition.

    Science.gov (United States)

    Othman, Majdiah; Ariff, Arbakariya B; Wasoh, Helmi; Kapri, Mohd Rizal; Halim, Murni

    2017-11-27

    Lactic acid bacteria are industrially important microorganisms recognized for fermentative ability mostly in their probiotic benefits as well as lactic acid production for various applications. Fermentation conditions such as concentration of initial glucose in the culture, concentration of lactic acid accumulated in the culture, types of pH control strategy, types of aeration mode and different agitation speed had influenced the cultivation performance of batch fermentation of Pediococcus acidilactici. The maximum viable cell concentration obtained in constant fed-batch fermentation at a feeding rate of 0.015 L/h was 6.1 times higher with 1.6 times reduction in lactic acid accumulation compared to batch fermentation. Anion exchange resin, IRA 67 was found to have the highest selectivity towards lactic acid compared to other components studied. Fed-batch fermentation of P. acidilactici coupled with lactic acid removal system using IRA 67 resin showed 55.5 and 9.1 times of improvement in maximum viable cell concentration compared to fermentation without resin for batch and fed-batch mode respectively. The improvement of the P. acidilactici growth in the constant fed-batch fermentation indicated the use of minimal and simple process control equipment is an effective approach for reducing by-product inhibition. Further improvement in the cultivation performance of P. acidilactici in fed-bath fermentation with in situ addition of anion-exchange resin significantly helped to enhance the growth of P. acidilactici by reducing the inhibitory effect of lactic acid and thus increasing probiotic production.

  10. Corrosion Inhibition and Adsorption Behavior of Clove Oil on Iron in Acidic Medium

    Directory of Open Access Journals (Sweden)

    Archana Saxena

    2012-01-01

    Full Text Available Corrosion behavior of iron in hydrochloric acid solution was studied using weight loss as well Scanning electron microscopy study without and with clove oil. The percentage inhibition efficiency increases with increasing clove oil concentration. All the data revel that the oil acts as an excellent inhibitor for the corrosion of iron in HCl solution. Thermodynamic, kinetic parameters and equilibrium constant for adsorption process were calculated from the experimental data. The adsorption of clove oil on experimental metals was found to follow the Langmuir adsorption isotherm at all the concentration studies. Scanning electron microscope (SEM, investigations also indicate that clove oil greatly lowers the dissolution currents.

  11. Influence of poly(aminoquinone) on corrosion inhibition of iron in acid media

    Science.gov (United States)

    Jeyaprabha, C.; Sathiyanarayanan, S.; Phani, K. L. N.; Venkatachari, G.

    2005-11-01

    The inhibitor performance of chemically synthesized water soluble poly(aminoquinone) (PAQ) on iron corrosion in 0.5 M sulphuric acid was studied in relation to inhibitor concentration using potentiodynamic polarization and electrochemical impedance spectroscopy measurements. On comparing the inhibition performance of PAQ with that of the monomer o-phenylenediamine (OPD), the OPD gave an efficiency of 80% for 1000 ppm while it was 90% for 100 ppm of PAQ. PAQ was found to be a mixed inhibitor. Besides, PAQ was able to improve the passivation tendency of iron in 0.5 M H 2SO 4 markedly.

  12. Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells

    OpenAIRE

    Li, Ping; Tian, Weixi; Ma, Xiaofeng

    2014-01-01

    Background Fatty acid synthase (FAS) has been proven over-expressed in human breast cancer cells and consequently, has been recognized as a target for breast cancer treatment. Alpha-mangostin, a natural xanthone found in mangosteen pericarp, has a variety of biological activities, including anti-cancer effect. In our previous study, alpha-mangostin had been found both fast-binding and slow-binding inhibitions to FAS in vitro. This study was designed to investigate the activity of alpha-mangos...

  13. Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium

    Directory of Open Access Journals (Sweden)

    María R. Alberto

    2012-03-01

    Full Text Available The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC, found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arginine. Arginine consumption decreased in presence of protocatechuic and gallic acids (31 and 17%, respectively and increased in presence of quercetin, rutin, catechin and the caffeic and vanillic phenolic acids (between 10 and 13%, respectively. ADI enzyme activities varied in presence of phenolic compounds. Rutin, quercetin and caffeic and vanillic acids stimulated the enzyme arginine deiminase about 37-40%. Amounts of 200 mg/L gallic and protocatechuic acids inhibited the arginine deiminase enzyme between 53 and 100%, respectively. Ornithine transcarbamylase activity was not modified at all concentrations of phenolic compounds. As gallic and protocatechuic acids inhibited the arginine deiminase enzyme that produces citrulline, precursor of EC, these results are important considering the formation of toxic compounds.

  14. Inhibition of GABAA receptor chloride channel by quinolones and norfloxacin-biphenylacetic acid hybrid compounds.

    Science.gov (United States)

    Ito, Y; Miyasaka, T; Fukuda, H; Akahane, K; Kimura, Y

    1996-01-01

    Receptor binding studies have shown that the combination of some new quinolone antibacterial agents with 4-biphenylacetic acid (BPAA), a metabolite of fenbufen, inhibits GABAA receptors. In order to elucidate further the mechanism of these drug interactions, the effect of quinolone antibacterial agents on muscimol-stimulated 36Cl- uptake in rat cerebral cortical synaptoneurosomes was investigated in the absence or presence of BPAA. In the absence of BPAA, quinolones such as norfloxacin (NFLX) and enoxacin attenuated muscimol-stimulated 36Cl- uptake at 10 microM and above. In combination with 10 microM BPAA, the inhibitory effect of these drugs was potentiated and there was a parallel shift of the inhibition curves to the left for these drugs. BPAA alone (1 and 10 microM) did not affect basal or muscimol-stimulated 36Cl- uptake. Hybrid molecules of NFLX and BPAA were synthesized and their inhibitory potency was also investigated. Inhibition curves of muscimol-stimulated 36Cl- uptake revealed that a hybrid with a -CONH(CH2)3- chain between NFLX and BPAA (flexible structure) (1 nM-20 microM) inhibited muscimol-stimulated 36Cl- uptake more potently than did the combination of NFLX (10 nm-100 microM) and 10 microM BPAA. In contrast, another hybrid linked by -CONH-(stretched structure) exhibited a weak inhibitory effect at 10 microM. These results suggest that quinolones in combination with BPAA bind to GABAA receptors, thus inhibiting Cl- channel activity, and that the inhibitory potency of quinolones may be enhanced by an intermolecular interaction with BPAA.

  15. Inhibition of mutagenicity of N-methyl-N-nitrosourea by ellagic acid

    International Nuclear Information System (INIS)

    Dixit, R.; Gold, B.

    1986-01-01

    Ellagic acid (EA), a plant phenol present in a variety of soft fruits and vegetables, has been shown to possess antimutagenic and anticarcinogenic properties against bay region diol epoxide of polycyclic aromatic hydrocarbons. It is suggested that EA forms an adduct with diol epoxide of benzo (α) pyrene and thus prevents its binding to DNA. To better understand the mechanism of reactivity and inhibition properties of EA, we studied the effect of EA on mutagenicity and DNA alkylation of carcinogenic N-nitroso compounds, including N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-Nnitrosoguanidine (MNNG). MNU and MNNG are direct-acting mutagens requiring no metabolic activation. MNU showed a linear dose response between the concentration range of 50 to 400 nmole in an Ames/Salmonella mammalian mutagenicity test. EA at concentrations of 100, 250, 500, and 1,000 nmole inhibited the mutagenicity of MNU (400 nmole) by 3, 13, 45,and 60%, respectively. MNNG produced a nonlinear dose response in mutagenicity between the concentrations of 0.5 to 4 nmole. EA showed no appreciable inhibition of MNNG mutagenicity. Inhibition of DNA alkylation by MNU and MNNG by EA was studied by preincubating 50 to 200 nmole of EA with 200 nmole of ( 3 H)-MNU or ( 3 H)-MNNG for 10 min at 37 0 c, followed by incubation of polymer deoxyguanosine: deoxycytosine (poly dG:dC) (1 unit) overnight. EA caused no inhibitory effect on MNNG alkylation of poly dG:dC. Experiments on the effect of EA on alkylation of DNA and formation of nucleoside adducts by MNU are in progress, and results will be discussed with reference to MNU and MNNG mutagenicity and EA inhibition

  16. Investigation of adsorption and inhibitive effect of acid red GRE (183 dye on the corrosion of carbon steel in hydrochloric acid media

    Directory of Open Access Journals (Sweden)

    M. Abd El-raouf

    2015-09-01

    Full Text Available The adsorption and corrosion inhibitive effect of acid red GRE (183 dye on carbon steel alloy in 1 M HCl solutions was studied using various techniques. Results of weight loss, Tafel polarization measurements and electrochemical impedance spectroscopy (EIS techniques show that this compound has fairly good inhibiting properties for steel corrosion in acidic bath; with efficiency around 96% at a concentration of 50 ppm. The inhibition is of a mixed anodic–cathodic nature. Factors affecting the corrosion process have been calculated and discussed. Acid red GRE (183 dye was shown to be an inhibitor in the acidic corrosion. Inhibition efficiency increased with acid red GRE (183 dye concentration but decreased with rise in temperature, corrosion inhibition is attributed to the adsorption of acid red GRE (183 dye on the carbon steel surface via a physical adsorption mechanism. Langmuir isotherm is found to provide an accurate description of the adsorption behavior of the investigated azo compound. The nature of the protective film was investigated using SEM and EDX techniques.

  17. Changes in composition and enamel demineralization inhibition activities of gallic acid at different pH values

    NARCIS (Netherlands)

    Zhang, J.; Huang, X.; Huang, S.; Deng, M.; Xie, X.; Liu, M.; Liu, H.; Zhou, X.; Li, J.; ten Cate, J.M.

    2015-01-01

    Background. Gallic acid (GA) has been shown to inhibit demineralization and enhance remineralization of enamel; however, GA solution is highly acidic. This study was to investigate the stability of GA solutions at various pH and to examine the resultant effects on enamel demineralization. Methods.

  18. Factors that inhibit growth of Listeria monocytogenes in nature-ripened Gouda cheese: A major role for undissociated lactic acid

    NARCIS (Netherlands)

    Wemmenhove, E.; Valenberg, van H.J.F.; Hooijdonk, van A.C.M.; Wells-Bennik, M.H.J.; Zwietering, M.H.

    2018-01-01

    In this study, factors relevant to nature-ripened Gouda cheese were evaluated for their potential to inhibit growth of Listeria monocytogenes. Factors included water activity, pH, undissociated acetic and lactic acid, diacetyl, free fatty acids, lactoferrin, nitrate, nitrite and nisin. In addition,

  19. The pattern recognition molecule deleted in malignant brain tumors 1 (DMBT1) and synthetic mimics inhibit liposomal nucleic acid delivery

    DEFF Research Database (Denmark)

    Lund Hansen, Pernille; Blaich, Stephanie; End, Caroline

    2011-01-01

    Liposomal nucleic acid delivery is a preferred option for therapeutic settings. The cellular pattern recognition molecule DMBT1, secreted at high levels in various diseases, and synthetic mimics efficiently inhibit liposomal nucleic acid delivery to human cells. These findings may have relevance ...

  20. NOVEL HYDROXAMIC ACIDS HAVING HISTONE DEACETYLASE INHIBITING ACTIVITY AND ANTI-CANCER COMPOSITION COMPRISING THE SAME AS AN ACTIVE INGREDIENT

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to a pharmaceutical composition for anticancer including novel hydroxamic acid with histone deacetylase inhibiting activity as an active ingredient. Hydroxamic acid compound of the present invention has inhibitory activity of histone deacetylase (HDAC) and shows...... cytotoxicity to a variety of cancer cells, being useful in strong anti-cancer drug....

  1. Inhibition of ice crystallisation in highly viscous aqueous organic acid droplets

    Directory of Open Access Journals (Sweden)

    B. J. Murray

    2008-09-01

    Full Text Available Homogeneous nucleation of ice within aqueous solution droplets and their subsequent crystallisation is thought to play a significant role in upper tropospheric ice cloud formation. It is normally assumed that homogeneous nucleation will take place at a threshold supersaturation, irrespective of the identity of the solute, and that rapid growth of ice particles will follow immediately after nucleation. However, it is shown here through laboratory experiments that droplets may not readily freeze in the very cold tropical tropopause layer (TTL, typical temperatures of 186–200 K. In these experiments ice crystal growth in citric acid solution droplets did not occur when ice nucleated below 197±6 K. Citric acid, 2-hydroxypropane-1,2,3-tricarboxyllic acid, is a molecule with similar functionality to oxygenated organic compounds which are ubiquitous in atmospheric aerosol. It is therefore thought to be a sensible proxy for atmospheric organic material. Evidence is presented that suggests citric acid solution droplets become ultra-viscous and form glassy solids under atmospherically relevant conditions. Diffusion of liquid water molecules to ice nuclei is expected to be very slow in ultra-viscous solution droplets and nucleation is negligible in glassy droplets; this most likely provides an explanation for the experimentally observed inhibition of ice crystallisation. The implications of ultra-viscous and glassy solution droplets for ice cloud formation and supersaturations in the TTL are discussed.

  2. Evaluation of human D-amino acid oxidase inhibition by anti-psychotic drugs in vitro.

    Science.gov (United States)

    Shishikura, Miho; Hakariya, Hitomi; Iwasa, Sumiko; Yoshio, Takashi; Ichiba, Hideaki; Yorita, Kazuko; Fukui, Kiyoshi; Fukushima, Takeshi

    2014-06-01

    It is of importance to determine whether antipsychotic drugs currently prescribed for schizophrenia exert D-amino acid oxidase (DAO)-inhibitory effects. We first investigated whether human (h)DAO can metabolize D-kynurenine (D-KYN) to produce the fluorescent compound kynurenic acid (KYNA) by using high-performance liquid chromatography with mass spectrometry, and fluorescence spectrometry. After confirmation of KYNA production from D-KYN by hDAO, 8 first- and second-generation antipsychotic drugs, and 6 drugs often prescribed concomitantly, were assayed for hDAO-inhibitory effects by using in vitro fluorometric methods with D-KYN as the substrate. DAO inhibitors 3-methylpyrazole-5-carboxylic acid and 4H-thieno[3,2-b]pyrrole-5-carboxylic acid inhibited KYNA production in a dose-dependent manner. Similarly, the second-generation antipsychotics blonanserin and risperidone were found to possess relatively strong hDAO-inhibitory effects in vitro (5.29 ± 0.47 μM and 4.70 ± 0.17 μM, respectively). With regard to blonanserin and risperidone, DAO-inhibitory effects should be taken into consideration in the context of their in vivo pharmacotherapeutic efficacy.

  3. Corrosion inhibition of carbon steel in acidic medium by orange peel extract and its main antioxidant compounds

    International Nuclear Information System (INIS)

    M’hiri, Nouha; Veys-Renaux, Delphine; Rocca, Emmanuel; Ioannou, Irina; Boudhrioua, Nourhéne Mihoubi; Ghoul, Mohamed

    2016-01-01

    Highlights: • Catechol and derived functions are responsible for flavonoids antioxidant activity. • Antioxidant activity of adsorbed molecules explains cathodic inhibition. • Orange peel extract inhibition is enhanced by the precipitation of a covering film. - Abstract: Chemical compounds of orange peel extracts were identified and their antioxidant activities were determined. The inhibiting effect on acidic steel corrosion brought by the extract and selected antioxidant compounds (neohesperidin, naringin, ascorbic acid) was evaluated separately by electrochemical methods. Whatever the extract concentration, a significant inhibition is observed, whereas selected antioxidant compounds show only a slight effect. Both electrochemical impedance spectroscopy results and scanning electron microscopy observations after immersion reveal that the inhibiting efficiency of orange peel extract is not only due to the antioxidant activity of its compounds but also to the precipitation of a surface film.

  4. Mechanism of inhibition of N-methyl-N-nitrosourea-induced mutagenicity and DNA binding by ellagic acid.

    Science.gov (United States)

    Dixit, R; Gold, B

    1987-01-01

    Ellagic acid (EA) is a dilactone derivative of shikimic acid, which is found in a variety of soft fruits and vegetables. EA inhibits mutagenesis and carcinogenesis induced by benzo[a]pyrene and its bay-region dihydrodiol epoxide derivative by preventing their covalent binding to DNA. EA at concentrations of 100, 250, 500 and 1000 nmol/plate inhibited the mutagenicity of N-methyl-N-nitrosourea (MNU) (400 nmol/plate) in Salmonella typhimurium TA100 by 3, 13, 45 and 60%, respectively. A study of inhibition of 3H-MNU-mediated DNA methylation by EA showed that it inhibited only the formation of O6-methylguanine, while attack at the N7 and N3 positions of guanine and adenine, respectively, was not altered. This inhibition was observed only in double-stranded DNA. Ultraviolet and equilibrium dialysis studies show that EA has a definite affinity for DNA, but that an intercalating process is not involved.

  5. Inhibition of epidermal growth factor receptor by ferulic acid and 4-vinylguaiacol in human breast cancer cells.

    Science.gov (United States)

    Sudhagar, S; Sathya, S; Anuradha, R; Gokulapriya, G; Geetharani, Y; Lakshmi, B S

    2018-02-01

    To examine the potential of ferulic acid and 4-vinylguaiacol for inhibiting epidermal growth factor receptor (EGFR) in human breast cancer cells in vitro. Ferulic acid and 4-vinylguaiacol limit the EGF (epidermal growth factor)-induced breast cancer proliferation and new DNA synthesis. Western blot analysis revealed both ferulic acid and 4-vinylguaiacol exhibit sustained inhibition of EGFR activation through down-regulation of Tyr 1068 autophosphorylation. Molecular docking analysis shows ferulic acid forming hydrogen bond interaction with Lys 745 and Met 793 whereas, 4-vinylguaiacol forms two hydrogen bonds with Phe 856 and exhibits stronger hydrophobic interactions with multiple amino acid residues at the EGFR kinase domain. Ferulic acid and 4-vinylguaiacol could serve as a potential structure for the development of new small molecule therapeutics against EGFR.

  6. Identification of organic acids in Cichorium intybus inhibiting virulence-related properties of oral pathogenic bacteria.

    Science.gov (United States)

    Papetti, Adele; Mascherpa, Dora; Carazzone, Chiara; Stauder, Monica; Spratt, David A; Wilson, Michael; Pratten, Jonathan; Ciric, Lena; Lingström, Peter; Zaura, Egija; Weiss, Ervin; Ofek, Itzak; Signoretto, Caterina; Pruzzo, Carla; Gazzani, Gabriella

    2013-06-01

    The low molecular mass (LMM) extract of Cichorium intybus var. silvestre (red chicory) has been shown to inhibit virulence-linked properties of oral pathogens including Streptococcus mutans, Actinomyces naeslundii and Prevotella intermedia. In the present study HPLC-DAD-ESI/MS(2) was used to investigate the compounds contained in this extract for their anti-virulence activity. The extract contained a number of components, including oxalic, succinic, shikimic and quinic acids, which interfere with the growth and virulence traits (i.e., biofilm formation, adherence to epithelial cells and hydroxyapatite) of oral pathogens involved in gingivitis and tooth decay. Succinic and quinic acid seem to be the most potent, mainly by interfering with the ability of oral pathogens to form biofilms (either through inhibition of their development or promotion of their disruption). Our findings suggest that one or more of these compounds may modulate plaque formation in vivo, which is a prerequisite for the development of both caries and gingivitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Docosahexaenoic acid inhibits Helicobacter pylori growth in vitro and mice gastric mucosa colonization.

    Directory of Open Access Journals (Sweden)

    Marta Correia

    Full Text Available H. pylori drug-resistant strains and non-compliance to therapy are the major causes of H. pylori eradication failure. For some bacterial species it has been demonstrated that fatty acids have a growth inhibitory effect. Our main aim was to assess the ability of docosahexaenoic acid (DHA to inhibit H. pylori growth both in vitro and in a mouse model. The effectiveness of standard therapy (ST in combination with DHA on H. pylori eradication and recurrence prevention success was also investigated. The effects of DHA on H. pylori growth were analyzed in an in vitro dose-response study and n in vivo model. We analized the ability of H. pylori to colonize mice gastric mucosa following DHA, ST or a combination of both treatments. Our data demonstrate that DHA decreases H. pylori growth in vitro in a dose-dependent manner. Furthermore, DHA inhibits H. pylori gastric colonization in vivo as well as decreases mouse gastric mucosa inflammation. Addition of DHA to ST was also associated with lower H. pylori infection recurrence in the mouse model. In conclusion, DHA is an inhibitor of H. pylori growth and its ability to colonize mouse stomach. DHA treatment is also associated with a lower recurrence of H. pylori infection in combination with ST. These observations pave the way to consider DHA as an adjunct agent in H. pylori eradication treatment.

  8. Neuroprotective effect of undecylenic acid extracted from Ricinus communis L. through inhibition of μ-calpain.

    Science.gov (United States)

    Lee, Eunyoung; Eom, Ji-Eun; Kim, Hye-Lin; Kang, Da-Hye; Jun, Kyu-Yeon; Jung, Duk Sang; Kwon, Youngjoo

    2012-05-12

    The key neuropathological features of Alzheimer's disease are abnormal deposition of Aβ plaques and insoluble Aβ peptides in extracellular brain and intracellular neurofibril tangles induced by abnormal tau hyperphosphorylation. μ-Calpain is one of the factors that bridge these Aβ- and hyperphosphorylated tau-mediated pathological pathways. Undecylenic acid (UDA), a naturally occurring unsaturated fatty acid, was discovered as a μ-calpain inhibitor by screening a chemical library using a substrate specific μ-calpain assay method. UDA inhibited Aβ oligomerization and Aβ fibrillation and reversed Aβ-induced neuronal cell death. In addition, UDA scavenged ROS and reversed the levels of proapoptotic proteins induced by ROS in SH-SY5Y cells. UDA inhibited μ-calpain activity with better potency than the known peptide-like μ-calpain inhibitor, MDL28170, in SH-SY5Y and HEK293T cells transfected with the catalytic subunit of μ-calpain. These results suggest that UDA is a novel non-peptide-like μ-calpain inhibitor with good cell permeability and potent neuroprotective effect. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Oxidative stress-induced apoptosis and matrix loss of chondrocytes is inhibited by eicosapentaenoic acid.

    Science.gov (United States)

    Sakata, Shuhei; Hayashi, Shinya; Fujishiro, Takaaki; Kawakita, Kohei; Kanzaki, Noriyuki; Hashimoto, Shingo; Iwasa, Kenjiro; Chinzei, Nobuaki; Kihara, Shinsuke; Haneda, Masahiko; Ueha, Takeshi; Nishiyama, Takayuki; Kuroda, Ryosuke; Kurosaka, Masahiro

    2015-03-01

    Eicosapentaenoic acid (EPA) is an antioxidant and n-3 polyunsaturated fatty acid that reduces the production of inflammatory cytokines. We evaluated the role of EPA in chondrocyte apoptosis and degeneration. Normal human chondrocytes were treated with EPA and sodium nitroprusside (SNP). Expression of metalloproteinases (MMPs) was detected by real-time polymerase chain reaction (PCR) and that of apoptosis-related proteins was detected by western blotting. Chondrocyte apoptosis was detected by flow cytometry. C57BL/6J mice were used for the detection of MMP expression by immunohistochemistry and for investigation of chondrocyte apoptosis. EPA inhibited SNP-induced chondrocyte apoptosis, caspase 3 and poly(ADP-ribose) polymerase cleavage, phosphorylation of p38 MAPK and p53, and expression of MMP3 and MMP13. Intra-articular injection of EPA prevented the progression of osteoarthritis (OA) by inhibiting MMP13 expression and chondrocyte apoptosis. EPA treatment can control oxidative stress-induced OA progression, and thus may be a new approach for OA therapy. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  10. Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus.

    Science.gov (United States)

    Soto-Acosta, Rubén; Bautista-Carbajal, Patricia; Syed, Gulam H; Siddiqui, Aleem; Del Angel, Rosa M

    2014-09-01

    Dengue is the most common mosquito borne viral disease in humans. The infection with any of the 4 dengue virus serotypes (DENV) can either be asymptomatic or manifest in two clinical forms, the mild dengue fever or the more severe dengue hemorrhagic fever that may progress into dengue shock syndrome. A DENV replicative cycle relies on host lipid metabolism; specifically, DENV infection modulates cholesterol and fatty acid synthesis, generating a lipid-enriched cellular environment necessary for viral replication. Thus, the aim of this work was to evaluate the anti-DENV effect of the Nordihydroguaiaretic acid (NDGA), a hypolipidemic agent with antioxidant and anti-inflammatory properties. A dose-dependent inhibition in viral yield and NS1 secretion was observed in supernatants of infected cells treated for 24 and 48 h with different concentrations of NDGA. To evaluate the effect of NDGA in DENV replication, a DENV4 replicon transfected Vero cells were treated with different concentrations of NDGA. NDGA treatment significantly reduced DENV replication, reiterating the importance of lipids in viral replication. NDGA treatment also led to reduction in number of lipid droplets (LDs), the neutral lipid storage organelles involved in DENV morphogenesis that are known to increase in number during DENV infection. Furthermore, NDGA treatment resulted in dissociation of the C protein from LDs. Overall our results suggest that NDGA inhibits DENV infection by targeting genome replication and viral assembly. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. α 1-acid glycoprotein inhibits lipogenesis in neonatal swine adipose tissue.

    Science.gov (United States)

    Ramsay, T G; Blomberg, L; Caperna, T J

    2016-05-01

    Serum α1-acid glycoprotein (AGP) is elevated during late gestation and at birth in the pig and rapidly declines postnatally. In contrast, the pig is born with minimal lipid stores in the adipose tissue, but rapidly accumulates lipid during the first week. The present study examined if AGP can affect adipose tissue metabolism in the neonatal pig. Isolated cell cultures or tissue explants were prepared from dorsal subcutaneous adipose tissue of preweaning piglets. Porcine AGP was used at concentrations of 0, 100, 1000 and 5000 ng/ml medium in 24 h incubations. AGP reduced the messenger RNA (mRNA) abundance of the lipogenic enzymes, malic enzyme (ME), fatty acid synthase and acetyl coA carboxylase by at least 40% (Plipogenesis due to AGP inhibition of lipogenic gene expression in vitro, which the metabolic data and SREBP, ChREBP and IRS1 gene expression analysis suggest is through an inhibition in insulin-mediated events. Second, these data suggest that AGP may contribute to limiting lipogenesis within adipose tissue during the perinatal period, as AGP levels are highest for any serum protein at birth.

  12. Prolongation of bleeding time and inhibition of platelet aggregation by low-dose acetylsalicylic acid in patients with cerebrovascular disease

    DEFF Research Database (Denmark)

    Boysen, G; Boss, A H; Ødum, Niels

    1984-01-01

    the bleeding time averaged 11.2 minutes in contrast to 7.0 minutes in the placebo group, p less than 0.001. This study confirms our previous findings of platelet inhibition by low-dose acetylsalicylic acid in patients with cerebrovascular disease. The prolongation of the bleeding time demonstrates that we......Platelet aggregation and bleeding time was measured in 43 cerebrovascular patients participating in a controlled double-blind study of low-dose acetylsalicylic acid. In 19 patients with satisfactory inhibition of the platelet aggregation obtained by 50 to 70 mg acetylsalicylic acid per day...

  13. Inhibition of Collagenase by Mycosporine-like Amino Acids from Marine Sources

    Science.gov (United States)

    Hartmann, Anja; Gostner, Johanna; Fuchs, Julian E.; Chaita, Eliza; Aligiannis, Nektarios; Skaltsounis, Leandros; Ganzera, Markus

    2015-01-01

    Matrix metalloproteinases (MMP) play an important role in extracellular matrix remodeling. Excessive activity of these enzymes can be induced by UV light and leads to skin damage, a process known as photoaging. In this study we investigated the collagenase inhibition potential of mycosporine-like amino acids (MAA), compounds that have been isolated from marine organisms and are known photoprotectants against UV-A and UV-B. For this purpose the commonly used collagenase assay was optimized and for the first time validated in terms of relationships between enzyme-substrate concentrations, temperature, incubation time and enzyme stability. Three compounds were isolated from the marine red algae Porphyra sp. and Palmaria palmata, and evaluated for their inhibitory properties against Chlostridium histolyticum collagenase (Chc). A dose-dependent, but very moderate inhibition was observed for all substances and IC50 values of 104.0 μM for shinorine, 105.9 μM for porphyra and 158.9 μM for palythine were determined. Additionally, computer-aided docking models suggested that the MAA binding to the active site of the enzyme is a competitive inhibition. PMID:26039265

  14. Chicoric acid suppresses BAFF expression in B lymphocytes by inhibiting NF-κB activity.

    Science.gov (United States)

    Chen, Lingxi; Huang, Gang; Gao, Min; Shen, Xiaodong; Gong, Wei; Xu, Zhizhen; Zeng, Yijun; He, Fengtian

    2017-03-01

    B cell activating factor belonging to the TNF family (BAFF) plays a critical role in the pathogenesis of autoimmune diseases. The inhibition of BAFF expression is an emerging therapeutic approach for these disorders. Chicoric acid (CA), a bioactive phytochemical found in several widely used traditional medicinal plants, has significant anti-inflammatory activity and anti-arthritic effects. However, the role of CA in modulation of BAFF expression remains unknown. In this study, we demonstrated that CA reduced BAFF expression in human B lymphocyte cell lines and decreased the DNA-binding activity of nuclear factor-κB (NF-κB) in the BAFF promoter region. Furthermore, CA inhibited both the nuclear translocation of p65 (the subunit of NF-κB) and the phosphorylation of IκBα (inhibitor of NF-κB). These results suggest that CA suppresses BAFF expression by inhibiting NF-κB activity, and CA may serve as a novel therapeutic agent to down-regulate excessive BAFF expression in autoimmune diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Tributyltin and triphenyltin inhibit osteoclast differentiation through a retinoic acid receptor-dependent signaling pathway

    International Nuclear Information System (INIS)

    Yonezawa, Takayuki; Hasegawa, Shin-ichi; Ahn, Jae-Yong; Cha, Byung-Yoon; Teruya, Toshiaki; Hagiwara, Hiromi; Nagai, Kazuo; Woo, Je-Tae

    2007-01-01

    Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), have been widely used in agriculture and industry. Although these compounds are known to have many toxic effects, including endocrine-disrupting effects, their effects on bone resorption are unknown. In this study, we investigated the effects of organotin compounds, such as monobutyltin (MBT), dibutyltin (DBT), TBT, and TPT, on osteoclast differentiation using mouse monocytic RAW264.7 cells. MBT and DBT had no effects, whereas TBT and TPT dose-dependently inhibited osteoclast differentiation at concentrations of 3-30 nM. Treatment with a retinoic acid receptor (RAR)-specific antagonist, Ro41-5253, restored the inhibition of osteoclastogenesis by TBT and TPT. TBT and TPT reduced receptor activator of nuclear factor-κB ligand (RANKL) induced nuclear factor of activated T cells (NFAT) c1 expression, and the reduction in NFATc1 expression was recovered by Ro41-5253. Our results suggest that TBT and TPT suppress osteoclastogenesis by inhibiting RANKL-induced NFATc1 expression via an RAR-dependent signaling pathway

  16. Biodegradable Kojic Acid-Based Polymers: Controlled Delivery of Bioactives for Melanogenesis Inhibition.

    Science.gov (United States)

    Faig, Jonathan J; Moretti, Alysha; Joseph, Laurie B; Zhang, Yingyue; Nova, Mary Joy; Smith, Kervin; Uhrich, Kathryn E

    2017-02-13

    Kojic acid (KA) is a naturally occurring fungal metabolite that is utilized as a skin-lightener and antibrowning agent owing to its potent tyrosinase inhibition activity. While efficacious, KA's inclination to undergo pH-mediated, thermal-, and photodegradation reduces its efficacy, necessitating stabilizing vehicles. To minimize degradation, poly(carbonate-esters) and polyesters comprised of KA and natural diacids were prepared via solution polymerization methods. In vitro hydrolytic degradation analyses revealed KA release was drastically influenced by polymer backbone composition (e.g., poly(carbonate-ester) vs polyester), linker molecule (aliphatic vs heteroatom-containing), and release conditions (physiological vs skin). Tyrosinase inhibition assays demonstrated that aliphatic KA dienols, the major degradation product under skin conditions, were more potent then KA itself. All dienols were found to be less toxic than KA at all tested concentrations. Additionally, the most lipophilic dienols were statistically more effective than KA at inhibiting melanin biosynthesis in cells. These KA-based polymer systems deliver KA analogues with improved efficacy and cytocompatible profiles, making them ideal candidates for sustained topical treatments in both medical and personal care products.

  17. Inhibition of fatty acid amide hydrolase by kaempferol and related naturally occurring flavonoids

    Science.gov (United States)

    Thors, L; Belghiti, M; Fowler, C J

    2008-01-01

    Background and purpose: Recent studies have demonstrated that the naturally occurring isoflavone compounds genistein and daidzein inhibit the hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) in the low micromolar concentration range. The purpose of the present study was to determine whether this property is shared by flavonoids. Experimental approach: The hydrolysis of anandamide in homogenates and intact cells was measured using the substrate labelled in the ethanolamine part of the molecule. Key results: Twenty compounds were tested. Among the commonly occurring flavonoids, kaempferol was the most potent, inhibiting FAAH in a competitive manner with a Ki value of 5 μM. Among flavonoids with a more restricted distribution in nature, the two most active toward FAAH were 7-hydroxyflavone (IC50 value of 0.5–1 μM depending on the solvent used) and 3,7-dihydroxyflavone (IC50 value 2.2 μM). All three compounds reduced the FAAH-dependent uptake of anandamide and its metabolism by intact RBL2H3 basophilic leukaemia cells. Conclusions and implications: Inhibition of FAAH is an additional in vitro biochemical property of flavonoids. Kaempferol, 7-hydroxyflavone and 3,7-dihydroxyflavone may be useful as templates for the synthesis of novel compounds, which target several systems that are involved in the control of inflammation and cancer. PMID:18552875

  18. Intracellular ascorbic acid inhibits transport of glucose by neurons, but not by astrocytes.

    Science.gov (United States)

    Castro, Maite A; Pozo, Miguel; Cortés, Christian; García, María de Los Angeles; Concha, Ilona I; Nualart, Francisco

    2007-08-01

    It has been demonstrated that glutamatergic activity induces ascorbic acid (AA) depletion in astrocytes. Additionally, different data indicate that AA may inhibit glucose accumulation in primary cultures of rat hippocampal neurons. Thus, our hypothesis postulates that AA released from the astrocytes during glutamatergic synaptic activity may inhibit glucose uptake by neurons. We observed that cultured neurons express the sodium-vitamin C cotransporter 2 and the facilitative glucose transporters (GLUT) 1 and 3, however, in hippocampal brain slices GLUT3 was the main transporter detected. Functional activity of GLUTs was confirmed by means of kinetic analysis using 2-deoxy-d-glucose. Therefore, we showed that AA, once accumulated inside the cell, inhibits glucose transport in both cortical and hippocampal neurons in culture. Additionally, we showed that astrocytes are not affected by AA. Using hippocampal slices, we observed that upon blockade of monocarboxylate utilization by alpha-cyano-4-hydroxycinnamate and after glucose deprivation, glucose could rescue neuronal response to electrical stimulation only if AA uptake is prevented. Finally, using a transwell system of separated neuronal and astrocytic cultures, we observed that glutamate can reduce glucose transport in neurons only in presence of AA-loaded astrocytes, suggesting the essential role of astrocyte-released AA in this effect.

  19. Syringic Acid Extracted from Herba dendrobii Prevents Diabetic Cataract Pathogenesis by Inhibiting Aldose Reductase Activity

    Directory of Open Access Journals (Sweden)

    Xiaoyong Wei

    2012-01-01

    Full Text Available Objective. Effects of Syringic acid (SA extracted from dendrobii on diabetic cataract (DC pathogenesis were explored. Methods. Both in vitro and in vivo DC lens models were established using D-gal, and proliferation of HLEC exposed to SA was determined by MMT assay. After 60-day treatment with SA, rat lens transparency was observed by anatomical microscopy using a slit lamp. SA protein targets were extracted and isolated using 2-DE and MALDI TOF/TOF. AR gene expression was investigated using qRT-PCR. Interaction sites and binding characteristics were determined by molecule-docking techniques and dynamic models. Results. Targeting AR, SA provided protection from D-gal-induced damage by consistently maintaining lens transparency and delaying lens turbidity development. Inhibition of AR gene expression by SA was confirmed by qRT-PCR. IC50 of SA for inhibition of AR activity was 213.17 μg/mL. AR-SA binding sites were Trp111, His110, Tyr48, Trp20, Trp79, Leu300, and Phe122. The main binding modes involved hydrophobic interactions and hydrogen bonding. The stoichiometric ratio of non-covalent bonding between SA and AR was 1.0 to 13.3. Conclusion. SA acts to prevent DC in rat lenses by inhibiting AR activity and gene expression, which has potential to be developed into a novel drug for therapeutic management of DC.

  20. Phenylbutyric acid inhibits epithelial-mesenchymal transition during bleomycin-induced lung fibrosis.

    Science.gov (United States)

    Zhao, Hui; Qin, Hou-Ying; Cao, Lin-Feng; Chen, Yuan-Hua; Tan, Zhu-Xia; Zhang, Cheng; Xu, De-Xiang

    2015-01-05

    A recent report showed that unfolded protein response (UPR) signaling was activated during bleomycin (BLM)-induced pulmonary fibrosis. Phenylbutyric acid (PBA) is an endoplasmic reticulum (ER) chemical chaperone that inhibits the UPR signaling. The present study investigated the effects of PBA on BLM-induced epithelial-mesenchymal transition (EMT) and pulmonary fibrosis. For induction of pulmonary fibrosis, all mice except controls were intratracheally injected with a single dose of BLM (3.0mg/kg). In PBA+BLM group, mice were intraperitoneally injected with PBA (150mg/kg) daily. Three weeks after BLM injection, EMT was measured and pulmonary fibrosis was evaluated. BLM-induced pulmonary UPR activation was inhibited by PBA. Moreover, BLM-induced pulmonary nuclear factor kappa B (NF-κB) p65 activation was blocked by PBA. In addition, BLM-induced up-regulation of pulmonary inflammatory cytokines was repressed by PBA. Further analysis showed that BLM-induced α-smooth muscle actin (α-SMA), a marker for EMT, was significantly attenuated by PBA. Moreover, BLM-induced pulmonary collagen (Col1α1 and Col1α2) was obviously inhibited by PBA. Importantly, BLM-induced pulmonary fibrosis, as determined using Sirius red staining, was obviously alleviated by PBA. Taken together, these results suggest that PBA alleviates ER stress-mediated EMT in the pathogenesis of BLM-induced pulmonary fibrosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during experimental colon obstruction in dogs.

    Science.gov (United States)

    Kaszaki, J; Palásthy, Z; Erczes, D; Rácz, A; Torday, C; Varga, G; Vécsei, L; Boros, M

    2008-01-01

    Kynurenic acid (KynA), an endogenous antagonist of N-methyl-d-aspartate (NMDA) glutamate receptors, protects the central nervous system in excitotoxic neurological diseases. We hypothesized that the inhibition of enteric glutamate receptors by KynA may influence dysmotility in the gastrointestinal tract. Group 1 of healthy dogs served as the sham-operated control, in group 2, the animals were treated with KynA, while in groups 3 and 4 mechanical colon obstruction was maintained for 7 h. Group 4 was treated with KynA at the onset of ileus. Hemodynamics and motility changes were monitored, and the activities of xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) were determined from tissue samples. Colon obstruction induced a hyperdynamic circulatory reaction, significantly elevated the motility index and increased the mucosal leucocyte accumulation and the XOR activity. The KynA treatment augmented the tone of the colon, permanently decreased the motility index of the giant colonic contractions and reduced the increases in XOR and MPO activities. These effects were concomitant with the in vitro inhibition of XOR activity. In conclusion, KynA antagonizes the obstruction-induced motility responses and XOR activation in the colon. Inhibition of enteric NMDA receptors may provide an option to influence intestinal hypermotility and inflammatory changes.

  2. Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells.

    Science.gov (United States)

    Li, Ping; Tian, Weixi; Ma, Xiaofeng

    2014-06-03

    Fatty acid synthase (FAS) has been proven over-expressed in human breast cancer cells and consequently, has been recognized as a target for breast cancer treatment. Alpha-mangostin, a natural xanthone found in mangosteen pericarp, has a variety of biological activities, including anti-cancer effect. In our previous study, alpha-mangostin had been found both fast-binding and slow-binding inhibitions to FAS in vitro. This study was designed to investigate the activity of alpha-mangostin on intracellular FAS activity in FAS over-expressed human breast cancer cells, and to testify whether the anti-cancer activity of alpha-mangostin may be related to its inhibitory effect on FAS. We evaluated the cytotoxicity of alpha-mangostin in human breast cancer MCF-7 and MDA-MB-231 cells. Intracellular FAS activity was measured by a spectrophotometer at 340 nm of NADPH absorption. Cell Counting Kit assay was used to test the cell viability. Immunoblot analysis was performed to detect FAS expression level, intracellular fatty acid accumulation and cell signaling (FAK, ERK1/2 and AKT). Apoptotic effects were detected by flow cytometry and immunoblot analysis of PARP, Bax and Bcl-2. Small interfering RNA was used to down-regulate FAS expression and/or activity. Alpha-mangostin could effectively suppress FAS expression and inhibit intracellular FAS activity, and result in decrease of intracellular fatty acid accumulation. It could also reduce cell viability, induce apoptosis in human breast cancer cells, increase in the levels of the PARP cleavage product, and attenuate the balance between anti-apoptotic and pro-apoptotic proteins of the Bcl-2 family. Moreover, alpha-mangostin inhibited the phosphorylation of FAK. However, the active forms of AKT, and ERK1/2 proteins were not involved in the changes of FAS expression induced by alpha-mangostin. Alpha-mangostin induced breast cancer cell apoptosis by inhibiting FAS, which provide a basis for the development of xanthone as an agent for

  3. The in vitro study of ursolic acid and oleanolic acid inhibiting cariogenic microorganisms as well as biofilm.

    Science.gov (United States)

    Zhou, L; Ding, Y; Chen, W; Zhang, P; Chen, Y; Lv, X

    2013-07-01

    The aim of this study was to examine the effect of ursolic acid (UA) and oleanolic acid (OA), triterpenoid compounds that are isolated from many edible and medicinal plants, on cariogenic microorganisms and biofilms. A microtitre plate dilution assay was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of UA and OA against two Actinomyces spp. and four Streptococcus spp. The antibacterial activity of UA and OA was assessed by crystal violet staining, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). UA and OA displayed differential antibacterial activities against the six tested bacteria, with UA showing greater antibacterial activity than OA. Furthermore, the two drugs had greater antibacterial activity against Actinomyces spp. than Streptococcus spp. UA and OA at 1/4 MIC can reduce bacterial biofilm formation, whereas higher UA concentrations displayed antibacterial activity against Actinomyces viscosus and Streptococcus mutans in mature biofilms. For instance, 2.0 mg ml(-1) UA was sufficient to kill an A. viscosus biofilm. UA and OA inhibit the growth of cariogenic microorganisms, which suggests that UA and OA have considerable potential as antibacterial agents for dental caries prevention. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun, E-mail: biochelab@yuhs.ac; Chung, Won-Yoon, E-mail: wychung@yuhs.ac

    2014-03-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  5. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    International Nuclear Information System (INIS)

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun; Chung, Won-Yoon

    2014-01-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  6. Uric acid inhibition of dipeptidyl peptidase IV in vitro is dependent on the intracellular formation of triuret.

    Science.gov (United States)

    Mohandas, Rajesh; Sautina, Laura; Beem, Elaine; Schuler, Anna; Chan, Wai-Yan; Domsic, John; McKenna, Robert; Johnson, Richard J; Segal, Mark S

    2014-08-01

    Uric acid affects endothelial and adipose cell function and has been linked to diseases such as hypertension, metabolic syndrome, and cardiovascular disease. Interestingly uric acid has been shown to increase endothelial progenitor cell (EPC) mobilization, a potential mechanism to repair endothelial injury. Since EPC mobilization is dependent on activity of the enzyme CD26/dipeptidyl peptidase (DPP)IV, we examined the effect uric acid will have on CD26/DPPIV activity. Uric acid inhibited the CD26/DPPIV associated with human umbilical vein endothelial cells but not human recombinant (hr) CD26/DPPIV. However, triuret, a product of uric acid and peroxynitrite, could inhibit cell associated and hrCD26/DPPIV. Increasing or decreasing intracellular peroxynitrite levels enhanced or decreased the ability of uric acid to inhibit cell associated CD26/DPPIV, respectively. Finally, protein modeling demonstrates how triuret can act as a small molecule inhibitor of CD26/DPPIV activity. This is the first time that uric acid or a uric acid reaction product has been shown to affect enzymatic activity and suggests a novel avenue of research in the role of uric acid in the development of clinically important diseases. Published by Elsevier Inc.

  7. Uric Acid Inhibition of Dipeptidyl Peptidase IV In Vitro is Dependent on the Intracellular Formation of Triuret

    Science.gov (United States)

    Mohandas, Rajesh; Sautina, Laura; Beem, Elaine; Schuler, Anna; Chan, Wai-Yan; Domsic, John; McKenna, Robert; Johnson, Richard J.; Segal, Mark S.

    2014-01-01

    Uric acid affects endothelial and adipose cell function and has been linked to diseases such as hypertension, metabolic syndrome, and cardiovascular disease. Interestingly uric acid has been shown to increase endothelial progenitor cell (EPC) mobilization, a potential mechanism to repair endothelial injury. Since EPC mobilization is dependent on activity of the enzyme CD26/dipeptidyl peptidase (DPP)IV, we examined the effect uric acid has on CD26/DPPIV activity. Uric acid inhibited the CD26/DPPIV associated with human umbilical vein endothelial cells but not human recombinant (hr)CD26/DPPIV. However, triuret, a product of uric acid and peroxynitrite, could inhibit cell associated and hrCD26/DPPIV. Increasing or decreasing intracellular peroxynitrite levels enhanced or decreased the ability of uric acid to inhibit cell associated CD26/DPPIV respectively. Last, protein modeling demonstrates how triuret can act as a small molecule inhibitor of CD26/DPPIV activity. This is the first time that uric acid or a uric acid reaction product has been shown to affect enzymatic activity and suggests a novel avenue of research in the role of uric acid in the development of clinically important diseases. PMID:24925478

  8. Antiobesity potential of ursolic acid stearoyl glucoside by inhibiting pancreatic lipase.

    Science.gov (United States)

    Kazmi, Imran; Afzal, Muhammad; Rahman, Shakilur; Iqbal, Muzaffar; Imam, Faisal; Anwar, Firoz

    2013-06-05

    The present study was designed to evaluate the hypolipidemic effect of ursolic acid stearoyl glucoside (UASG) in high-fat diet-induced obesity. Two in vivo experiments such as high-fat diet-induced obesity mice model and lipid emulsion tolerance test in normal rats were performed. In vitro inhibition of pancreatic lipase activity was further measured to substantiate the results. In high-fat diet-induced obesity mice model, female Swiss mice were fed a high fat diet (HFD; 40% fat) with or without 1 or 2% of UASG or 0.012% orlistat for nine weeks. In lipid emulsion tolerance test male Wister rats were orally administered, lipid emulsion with or without 500 or 1000 mg/kg of UASG and the plasma triglycerides were measured from 0.5 to 5 h. Consumption of HFD containing UASG to mice for nine weeks exhibited significant reduction in lipid parameters, body weight, parametrial adipose tissue weight, liver triglyceride (TG) and different organ weight compared to HFD fed control. Further it was noted the improvement in insulin resistance induced by the HFD alone group. Furthermore, consumption of an HFD containing 1 or 2% of UASG significantly increased the fecal content and fecal triglyceride compared with the HFD group. Pre-treatment with UASG inhibited the elevated plasma triglyceride level after the oral administration of the lipid emulsion to rats. Further, UASG significantly inhibits activity of pancreatic lipase at a concentration of 2.5 mg/ml. Data obtained from the results indicated that UASG prevent high-fat diet-induced obesity in mice possibly by inhibiting pancreatic lipase activity. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  9. Gut Microbiota Conversion of Dietary Ellagic Acid into Bioactive Phytoceutical Urolithin A Inhibits Heme Peroxidases.

    Directory of Open Access Journals (Sweden)

    Piu Saha

    Full Text Available Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one, which is derived from the ellagic acid (EA. Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO and lactoperoxidase (LPO when compared to the parent compound EA. In addition, chrome azurol S (CAS assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2, implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the

  10. Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation

    International Nuclear Information System (INIS)

    Cuadrado, Irene; Cidre, Florencia; Herranz, Sandra; Estevez-Braun, Ana; Heras, Beatriz de las; Hortelano, Sonsoles

    2012-01-01

    Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE 2 production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE 2 in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showed that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Highlights: ► LAME reduced the production of NO and PGE 2 in LPS-activated macrophages. ► IL-6, TNF-α and IP-10 were also inhibited by LAME. ► Inhibition of TAK-1 activation is the mechanism involved in this process. ► LAME improved survival in a mouse model of endotoxemia. ► LAME reduced the circulatory levels of cytokines (IL-6, TNF-α).

  11. Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation

    Energy Technology Data Exchange (ETDEWEB)

    Cuadrado, Irene [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Cidre, Florencia; Herranz, Sandra [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain); Estevez-Braun, Ana [Instituto Universitario de Bio-Orgánica “Antonio González”. Universidad de La Laguna. Avda. Astrofísico Fco. Sánchez 2. 38206. La Laguna, Tenerife (Spain); Instituto Canario de Investigaciones del Cáncer (ICIC) (Spain); Heras, Beatriz de las, E-mail: lasheras@farm.ucm.es [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Hortelano, Sonsoles, E-mail: shortelano@isciii.es [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain)

    2012-01-01

    Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE{sub 2} production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showed that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Highlights: ► LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. ► IL-6, TNF-α and IP-10 were also inhibited by LAME. ► Inhibition of TAK-1 activation is the mechanism involved in this process. ► LAME improved survival in a mouse model of endotoxemia. ► LAME reduced the circulatory levels of cytokines (IL-6, TNF-α).

  12. Ursolic acid inhibits adipogenesis in 3T3-L1 adipocytes through LKB1/AMPK pathway.

    Directory of Open Access Journals (Sweden)

    Yonghan He

    Full Text Available BACKGROUND: Ursolic acid (UA is a triterpenoid compound with multiple biological functions. This compound has recently been reported to possess an anti-obesity effect; however, the mechanisms are less understood. OBJECTIVE: As adipogenesis plays a critical role in obesity, the present study was conducted to investigate the effect of UA on adipogenesis and mechanisms of action in 3T3-L1 preadipocytes. METHODS AND RESULTS: The 3T3-L1 preadipocytes were induced to differentiate in the presence or absence of UA for 6 days. The cells were determined for proliferation, differentiation, fat accumulation as well as the protein expressions of molecular targets that regulate or are involved in fatty acid synthesis and oxidation. The results demonstrated that ursolic acid at concentrations ranging from 2.5 µM to 10 µM dose-dependently attenuated adipogenesis, accompanied by reduced protein expression of CCAAT element binding protein β (C/EBPβ, peroxisome proliferator-activated receptor γ (PPARγ, CCAAT element binding protein α (C/EBPα and sterol regulatory element binding protein 1c (SREBP-1c, respectively. Ursolic acid increased the phosphorylation of acetyl-CoA carboxylase (ACC and protein expression of carnitine palmitoyltransferase 1 (CPT1, but decreased protein expression of fatty acid synthase (FAS and fatty acid-binding protein 4 (FABP4. Ursolic acid increased the phosphorylation of AMP-activated protein kinase (AMPK and protein expression of (silent mating type information regulation 2, homolog 1 (Sirt1. Further studies demonstrated that the anti-adipogenic effect of UA was reversed by the AMPK siRNA, but not by the Sirt1 inhibitor nicotinamide. Liver kinase B1 (LKB1, the upstream kinase of AMPK, was upregulated by UA. When LKB1 was silenced with siRNA or the inhibitor radicicol, the effect of UA on AMPK activation was diminished. CONCLUSIONS: Ursolic acid inhibited 3T3-L1 preadipocyte differentiation and adipogenesis through the LKB1/AMPK

  13. Inhibition of breast cancer cell proliferation in repeated and non-repeated treatment with zoledronic acid

    Directory of Open Access Journals (Sweden)

    Ibrahim Toni

    2012-11-01

    Full Text Available Abstract Background Zoledronic acid is used to treat bone metastases and has been shown to reduce skeletal-related events and exert antitumor activity. The present in vitro study investigates the mechanism of action of Zoledronic Acid on breast cancer cell lines with different hormonal and HER2 patterns. Furthermore, we investigated the efficacy of repeated versus non-repeated treatments. Methods The study was performed on 4 breast cancer cell lines (BRC-230, SkBr3, MCF-7 and MDA-MB-231. Non-repeated treatment (single exposure of 168 hrs’ duration with zoledronic acid was compared with repeated treatment (separate exposures, each of 48 hrs’ duration, for a total of 168 hrs at different dosages. A dose–response profile was generated using sulforhodamine B assay. Apoptosis was evaluated by TUNEL assay and biomolecular characteristics were analyzed by western blot. Results Zoledronic acid produced a dose-dependent inhibition of proliferation in all cell lines. Anti-proliferative activity was enhanced with the repeated treatment, proving to be statistically significant in the triple-negative lines. In these lines repeated treatment showed a cytocidal effect, with apoptotic cell death caused by caspase 3, 8 and 9 activation and decreased RAS and pMAPK expression. Apoptosis was not observed in estrogen receptor-positive line: p21 overexpression suggested a slowing down of cell cycle. A decrease in RAS and pMAPK expression was seen in HER2-overexpressing line after treatment. Conclusions The study suggests that zoledronic acid has an antitumor activity in breast cancer cell lines. Its mechanism of action involves the decrease of RAS and RHO, as in osteoclasts. Repeated treatment enhances antitumor activity compared to non-repeated treatment. Repeated treatment has a killing effect on triple-negative lines due to apoptosis activation. Further research is warranted especially in the treatment of triple-negative breast cancer.

  14. TNF-alpha and IL-6 synergistically inhibit ketogenesis from fatty acids and alpha-ketoisocaproate in isolated rat hepatocytes.

    Science.gov (United States)

    Pailla, K; Lim, S K; De Bandt, J P; Aussel, C; Giboudeau, J; Troupel, S; Cynober, L; Blonde-Cynober, F

    1998-01-01

    During sepsis, lipid metabolism is shunted toward triacylglycerol synthesis and hepatic lipogenesis. A decrease in ketogenesis from free fatty acids also is observed, probably mediated by cytokines involved in host response to infection. Whether such an inhibition of ketogenesis occurs with other ketone body precursors such as ketoacids is not known. The aim of this study was to determine the effects of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) on hepatic ketone body production from octanoic acid, a medium-chain fatty acid, and from alpha-ketoisocaproate (KIC), the ketoanalogue of leucine. The experiments were conducted in cultured hepatocytes isolated from 24-hour-fasted Sprague-Dawley rats. Hepatocyte monolayers were incubated for 6 hours, with either KIC or octanoic acid (1 mmol/L), in the presence of glucagon and TNF-alpha (25 micro/L) IL-6 (15 microg/L) and/or IL-6. Acetoacetate, beta-hydroxybutyrate, and free fatty acids were determined in culture medium by enzymatic methods and KIC was measured by high-performance liquid chromatography. KIC and octanoic acid uptake by hepatocytes was 79% and 92%, respectively, over 6 hours, and cytokines had no influence. However, TNF-alpha and IL-6 caused inhibition of ketogenesis from alpha-ketoisocaproate (5.6% +/- 2.3% and 4.4% +/- 3.0%, respectively), and from octanoic acid (7.9% +/- 2.9%, 5.7% +/- 3.2%, respectively). In addition, when the two cytokines were present together in the culture medium, the inhibition was enhanced (inhibition of ketogenesis from KIC: 14.0% +/- 4.8%; from octanoic acid: 11.6% +/- 3.4%). In our experimental conditions, cytokines mediate an inhibition of ketogenesis; this process could be explained by a direct effect of cytokines on metabolic pathways of octanoic acid and KIC oran indirect effect by modification of the mitochondrial redox state.

  15. Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins

    DEFF Research Database (Denmark)

    Andreasen, Mette Findal; Landbo, A K; Christensen, L P

    2001-01-01

    Dietary antioxidants that protect low-density lipoprotein (LDL) from oxidation may help to prevent atherosclerosis and coronary heart disease. The antioxidant activities of purified monomeric and dimeric hydroxycinnamates and of phenolic extracts from rye (whole grain, bran, and flour) were...... investigated using an in vitro copper-catalyzed human LDL oxidation assay. The most abundant ferulic acid dehydrodimer (diFA) found in rye, 8-O-4-diFA, was a slightly better antioxidant than ferulic acid and p-coumaric acid. The antioxidant activity of the 8-5-diFA was comparable to that of ferulic acid......, but neither 5-5-diFA nor 8-5-benzofuran-diFA inhibited LDL oxidation when added at 10-40 microM. The antioxidant activity of the monomeric hydroxycinnamates decreased in the following order: caffeic acid > sinapic acid > ferulic acid > p-coumaric acid. The antioxidant activity of rye extracts...

  16. Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins

    DEFF Research Database (Denmark)

    Andreasen, M.F.; Landbo, Anne-Katrine Regel; Christensen, L.P.

    2001-01-01

    investigated using an in vitro copper-catalyzed human LDL oxidation assay. The most abundant ferulic acid dehydrodimer (diFA) found in rye, 8-O-4- diFA, was a slightly better antioxidant than ferulic acid and p-coumaric acid. The antioxidant activity of the 8-5-diFA was comparable to that of ferulic acid......, but neither 5-5-diFA nor 8- 5-benzofuran-diFA inhibited LDL oxidation when added at 10-40 muM. The antioxidant activity of the monomeric hydroxycinnamates decreased in the following order: caffeic acid > sinapic acid > ferulic acid > p-coumaric acid. The antioxidant activity of rye extracts was significantly...

  17. Boron Stress Activates the General Amino Acid Control Mechanism and Inhibits Protein Synthesis

    Science.gov (United States)

    Uluisik, Irem; Kaya, Alaattin; Fomenko, Dmitri E.; Karakaya, Huseyin C.; Carlson, Bradley A.; Gladyshev, Vadim N.; Koc, Ahmet

    2011-01-01

    Boron is an essential micronutrient for plants, and it is beneficial for animals. However, at high concentrations boron is toxic to cells although the mechanism of this toxicity is not known. Atr1 has recently been identified as a boron efflux pump whose expression is upregulated in response to boron treatment. Here, we found that the expression of ATR1 is associated with expression of genes involved in amino acid biosynthesis. These mechanisms are strictly controlled by the transcription factor Gcn4 in response to boron treatment. Further analyses have shown that boron impaired protein synthesis by promoting phosphorylation of eIF2α in a Gcn2 kinase dependent manner. The uncharged tRNA binding domain (HisRS) of Gcn2 is necessary for the phosphorylation of eIF2α in the presence of boron. We postulate that boron exerts its toxic effect through activation of the general amino acid control system and inhibition of protein synthesis. Since the general amino acid control pathway is conserved among eukaryotes, this mechanism of boron toxicity may be of general importance. PMID:22114689

  18. IR spectroscopic investigation of the inhibition of the glycation process by acetylsalicylic acid

    Science.gov (United States)

    Otero de Joshi, Virginia; Gil, Herminia; Contreras, Silvia; Velasquez, William; Joshi, Narahari V.

    2000-05-01

    An IR spectroscopic study was carried out at room temperature for Human Serum albumin (HSA) glycated with fructose and glucose and inhibited with acetylsalicylic acid. The glycation process was carried out in our laboratory by a conventional method to confirm earlier reported observation of the effect of glycation on the intensity variation of the IR spectra, particularly, in the range 1500 cm-1 to 1700 cm-1 and around 3300 cm-1. IR spectra reveal that the effects of glycation of HSA by fructose are more intense than with glucose, which is the expected. Bovine serum albumin was also glycated using Glucose-6-phosphate disodium salt, and gamma-globulin was glycate with glucose, As expected, the glycation process was more intense with glucose-t-phosphate disodium salt. Acetyl salicylic acid was also used and its inhibitor effects could be observed in both cases, with glucose and with glucose-6-phosphate disodium salt even though, to a smaller extent with the latter. This is consistent with the earlier data and is explained on the basis of the attachment of macromolecules to (epsilon) -NH2 groups of lysines. The experimental results confirm that acetylsalicylic acid, indeed, acts as an inhibitor by acetylation of the (epsilon) -NG2 group where the sugars are supposed to be attached.

  19. Calcite growth-rate inhibition by fulvic acids isolated from Big Soda Lake, Nevada, USA, The Suwannee River, Georgia, USA and by polycarboxylic acids

    Science.gov (United States)

    Reddy, Michael M.; Leenheer, Jerry

    2011-01-01

    Calcite crystallization rates are characterized using a constant solution composition at 25°C, pH=8.5, and calcite supersaturation (Ω) of 4.5 in the absence and presence of fulvic acids isolated from Big Soda Lake, Nevada (BSLFA), and a fulvic acid from the Suwannee River, Georgia (SRFA). Rates are also measured in the presence and absence of low-molar mass, aliphatic-alicyclic polycarboxylic acids (PCA). BSLFA inhibits calcite crystal-growth rates with increasing BSLFA concentration, suggesting that BSLFA adsorbs at growth sites on the calcite crystal surface. Calcite growth morphology in the presence of BSLFA differed from growth in its absence, supporting an adsorption mechanism of calcite-growth inhibition by BSLFA. Calcite growth-rate inhibition by BSLFA is consistent with a model indicating that polycarboxylic acid molecules present in BSLFA adsorb at growth sites on the calcite crystal surface. In contrast to published results for an unfractionated SRFA, there is dramatic calcite growth inhibition (at a concentration of 1 mg/L) by a SRFA fraction eluted by pH 5 solution from XAD-8 resin, indicating that calcite growth-rate inhibition is related to specific SRFA component fractions. A cyclic PCA, 1, 2, 3, 4, 5, 6-cyclohexane hexacarboxylic acid (CHXHCA) is a strong calcite growth-rate inhibitor at concentrations less than 0.1 mg/L. Two other cyclic PCAs, 1, 1 cyclopentanedicarboxylic acid (CPDCA) and 1, 1 cyclobutanedicarboxylic acid (CBDCA) with the carboxylic acid groups attached to the same ring carbon atom, have no effect on calcite growth rates up to concentrations of 10 mg/L. Organic matter ad-sorbed from the air onto the seed crystals has no effect on the measured calcite crystal-growth rates.

  20. Chicoric Acid Found in Basil (Ocimum basilicum L.) Leaves

    Science.gov (United States)

    This is the first report to identify the presence of chicoric acid (cichoric acid; also known as dicaffeoyltartaric acid) in basil leaves. Rosmarinic acid, chicoric acid, and caftaric acid (in the order of most abundant to least; all derivatives of caffeic acid) were identified in fresh basil leaves...

  1. Effect of molecular structure of aniline-formaldehyde copolymers on corrosion inhibition of mild steel in hydrochloric acid solution.

    Science.gov (United States)

    Zhang, Yan; Nie, Mengyan; Wang, Xiutong; Zhu, Yukun; Shi, Fuhua; Yu, Jianqiang; Hou, Baorong

    2015-05-30

    Aniline-formaldehyde copolymers with different molecular structures have been prepared and investigated for the purpose of corrosion control of mild steel in hydrochloric acid. The copolymers were synthesized by a condensation polymerization process with different ratios of aniline to formaldehyde in acidic precursor solutions. The corrosion inhibition efficiency of as-synthesized copolymers for Q235 mild steel was investigated in 1.0 mol L(-1) hydrochloric acid solution by weight loss measurement, potentiodynamic polarization, and electrochemical impedance spectroscopy, respectively. All the results demonstrate that as-prepared aniline-formaldehyde copolymers are efficient mixed-type corrosion inhibitors for mild steels in hydrochloric acid. The corrosion inhibition mechanism is discussed in terms of the role of molecular structure on adsorption of the copolymers onto the steel surface in acid solution. Copyright © 2015. Published by Elsevier B.V.

  2. Study of Temperature Effect on the Corrosion Inhibition of C38 Carbon Steel Using Amino-tris(Methylenephosphonic Acid in Hydrochloric Acid Solution

    Directory of Open Access Journals (Sweden)

    Najoua Labjar

    2011-01-01

    Full Text Available Tafel polarization method was used to assess the corrosion inhibitive and adsorption behaviours of amino-tris(methylenephosphonic acid (ATMP for C38 carbon steel in 1 M HCl solution in the temperature range from 30 to 60∘C. It was shown that the corrosion inhibition efficiency was found to increase with increase in ATMP concentration but decreased with temperature, which is suggestive of physical adsorption mechanism. The adsorption of the ATMP onto the C38 steel surface was found to follow Langmuir adsorption isotherm model. The corrosion inhibition mechanism was further corroborated by the values of kinetic and thermodynamic parameters obtained from the experimental data.

  3. Inhibition of norsolorinic acid accumulation to Aspergillus parasiticus by marine actinomycetes

    Science.gov (United States)

    Yan, Peisheng; Shi, Cuijuan; Shen, Jihong; Wang, Kai; Gao, Xiujun; Li, Ping

    2014-11-01

    Thirty-six strains of marine actinomycetes were isolated from a sample of marine sediment collected from the Yellow Sea and evaluated in terms of their inhibitory activity on the growth of Aspergillus parasiticus and the production of norsolorinic acid using dual culture plate assay and agar diffusion methods. Among them, three strains showed strong antifungal activity and were subsequently identified as Streptomyces sp. by 16S rRNA gene sequencing analysis. The supernatant from the fermentation of the MA01 strain was extracted sequentially with chloroform and ethyl acetate, and the activities of the extracts were determined by tip culture assay. The assay results show that both extracts inhibited mycelium growth and toxin production, and the inhibitory activities of the extracts increased as their concentrations increased. The results of this study suggest that marine actinomycetes are biologically important for the control of mycotoxins, and that these bacteria could be used as novel biopesticides against mycotoxins.

  4. The SCFA butyrate stimulates the epithelial production of retinoic acid via inhibition of epithelial HDAC.

    Science.gov (United States)

    Schilderink, Ronald; Verseijden, Caroline; Seppen, Jurgen; Muncan, Vanesa; van den Brink, Gijs R; Lambers, Tim T; van Tol, Eric A; de Jonge, Wouter J

    2016-06-01

    In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory disease, and allergy. We hypothesized that SCFAs contribute to mucosal homeostasis by enhancing RA production in intestinal epithelia. With the use of human and mouse epithelial cell lines and primary enteroids, we studied the effect of SCFAs on the production of RA. Functional RA conversion was analyzed by Adlefluor activity assays. Butyrate (0-20 mM), in contrast to other SCFAs, dose dependently induced aldh1a1 or aldh1a3 transcript expression and increased RA conversion in human and mouse epithelial cells. Epithelial cell line data were replicated in intestinal organoids. In these organoids, butyrate (2-5 mM) upregulated aldh1a3 expression (36-fold over control), whereas aldh1a1 was not significantly affected. Butyrate enhanced maturation markers (Mucin-2 and villin) but did not consistently affect stemness markers or other Wnt target genes (lgr5, olfm4, ascl2, cdkn1). In enteroids, the stimulation of RA production by SCFA was mimicked by inhibitors of histone deacetylase 3 (HDAC3) but not by HDAC1/2 inhibitors nor by agonists of butyrate receptors G-protein-coupled receptor (GPR)43 or GPR109A, indicating that butyrate stimulates RA production via HDAC3 inhibition. We conclude that the SCFA butyrate inhibits HDAC3 and thereby supports epithelial RA production. Copyright © 2016 the American Physiological Society.

  5. All-trans-retinoic Acid Modulates the Plasticity and Inhibits the Motility of Breast Cancer Cells

    Science.gov (United States)

    Zanetti, Adriana; Affatato, Roberta; Centritto, Floriana; Fratelli, Maddalena; Kurosaki, Mami; Barzago, Maria Monica; Bolis, Marco; Terao, Mineko; Garattini, Enrico; Paroni, Gabriela

    2015-01-01

    All-trans-retinoic acid (ATRA) is a natural compound proposed for the treatment/chemoprevention of breast cancer. Increasing evidence indicates that aberrant regulation of epithelial-to-mesenchymal transition (EMT) is a determinant of the cancer cell invasive and metastatic behavior. The effects of ATRA on EMT are largely unknown. In HER2-positive SKBR3 and UACC812 cells, showing co-amplification of the ERBB2 and RARA genes, ATRA activates a RARα-dependent epithelial differentiation program. In SKBR3 cells, this causes the formation/reorganization of adherens and tight junctions. Epithelial differentiation and augmented cell-cell contacts underlie the anti-migratory action exerted by the retinoid in cells exposed to the EMT-inducing factors EGF and heregulin-β1. Down-regulation of NOTCH1, an emerging EMT modulator, is involved in the inhibition of motility by ATRA. Indeed, the retinoid blocks NOTCH1 up-regulation by EGF and/or heregulin-β1. Pharmacological inhibition of γ-secretase and NOTCH1 processing also abrogates SKBR3 cell migration. Stimulation of TGFβ contributes to the anti-migratory effect of ATRA. The retinoid switches TGFβ from an EMT-inducing and pro-migratory determinant to an anti-migratory mediator. Inhibition of the NOTCH1 pathway not only plays a role in the anti-migratory action of ATRA; it is relevant also for the anti-proliferative activity of the retinoid in HCC1599 breast cancer cells, which are addicted to NOTCH1 for growth/viability. This effect is enhanced by the combination of ATRA and the γ-secretase inhibitor N-(N-(3,5-difluorophenacetyl)-l-alanyl)-S-phenylglycine t-butyl ester, supporting the concept that the two compounds act at the transcriptional and post-translational levels along the NOTCH1 pathway. PMID:26018078

  6. Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation and enhance cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Ionta, M. [Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas MG (Brazil); Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Rosa, M.C.; Almeida, R.B.; Freitas, V.M.; Rezende-Teixeira, P.; Machado-Santelli, G.M. [Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil)

    2012-05-25

    Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM) and cAMP (1 mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3β) and liver differentiation [E-cadherin, connexin 26 (Cx26), and connexin 32 (Cx32)]. RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3β (inactive form) expression while the expression of Cx43, Tyr216-GSK-3β (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.

  7. Inhibition of Listeria monocytogenes by propionic acid-based ingredients in cured deli-style Turkey.

    Science.gov (United States)

    Glass, Kathleen A; McDonnell, Lindsey M; Von Tayson, Roxanne; Wanless, Brandon; Badvela, Mani

    2013-12-01

    Listeria monocytogenes growth can be controlled on ready-to-eat meats through the incorporation of antimicrobial ingredients into the formulation or by postlethality kill steps. However, alternate approaches are needed to provide options that reduce sodium content but maintain protection against pathogen growth in meats after slicing. The objective of this study was to determine the inhibition of L. monocytogenes by propionic acid-based ingredients in high-moisture, cured turkey stored at 4 or 7°C. Six formulations of sliced, cured (120 ppm of NaNO2 ), deli-style turkey were tested, including control without antimicrobials, 3.2% lactate-diacetate blend (LD), 0.4% of a liquid propionate-benzoate-containing ingredient, or 0.3, 0.4, and 0.5% of a liquid propionate-containing ingredient. Products were inoculated with 5 log CFU L. monocytogenes per 100-g package (3 log CFU/ml rinsate), vacuum-sealed, and stored at 4 or 7°C for up to 12 weeks; and populations were enumerated by plating on modified Oxford agar. As expected, the control without antimicrobials supported rapid growth, with >2 log average per ml rinsate increase within 4 weeks of storage at 4°C, whereas growth was observed at 6 weeks for the LD treatment. For both replicate trials, all treatments that contained liquid propionate or propionate-benzoate limited L. monocytogenes growth to an increase of 1-log increase) was observed in individual samples for all propionate-containing treatments at weeks 10, 11, and 12. As expected, L. monocytogenes grew more rapidly when products were stored at 7°C, but trends in relative inhibition were similar to those observed at 4°C. These results verify that propionate-based ingredients inhibit growth of L. monocytogenes on sliced, high-moisture, cured turkey and can be considered as an alternative to reduce sodium-based salts while maintaining food safety.

  8. Ellagic acid promotes Aβ42 fibrillization and inhibits Aβ42-induced neurotoxicity

    International Nuclear Information System (INIS)

    Feng, Ying; Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min; Sun, Gui-yuan; Liu, Rui-tian

    2009-01-01

    Smaller, soluble oligomers of β-amyloid (Aβ) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of Aβ oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against Aβ neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on Aβ42 aggregation and neurotoxicity in vitro. EA promoted Aβ fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited Aβ aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in Aβ42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic Aβ aggregates to render them harmless, our MTT results showed that EA could significantly reduce Aβ42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  9. Inhibition of the corrosion of mild steel in hydrochloric acid by isatin and isatin glycine

    Directory of Open Access Journals (Sweden)

    B.I. Ita

    2006-12-01

    Full Text Available The inhibition of corrosion of mild steel in hydrochloric acid by isatin glycine (ING and isatin (IN at 30-60 oC and concentrations of 0.0001 M to 0.0005 M was studied via weight loss method. At the highest inhibitor concentration studied ING exhibited inhibition efficiency of 87% while IN exhibited 84% at 60 oC. A chemical adsorption mechanism was proposed on the basis of the temperature effect and obtained average activation energy values of 143.9 kJ/mol for ING and 118.5 kJ/mol for IN. The two inhibitors were confirmed to obey the Langmuir adsorption isotherm equation at the concentrations studied. Also a first-order type of mechanism was proposed from the kinetic treatment of the result. The difference in the inhibitory properties of the inhibitors was explained in terms of the difference in their molecular structures and solubility rather than difference in molecular weights alone.

  10. A study of the inhibition of iron corrosion in HCl solutions by some amino acids

    International Nuclear Information System (INIS)

    Amin, Mohammed A.; Khaled, K.F.; Mohsen, Q.; Arida, H.A.

    2010-01-01

    The performance of three selected amino acids, namely alanine (Ala), cysteine (Cys) and S-methyl cysteine (S-MCys) as safe corrosion inhibitors for iron in aerated stagnant 1.0 M HCl solutions was evaluated by Tafel polarization and impedance measurements. Results indicate that Ala acts mainly as a cathodic inhibitor, while Cys and S-MCys function as mixed-type inhibitors. Cys, which contains a mercapto group in its molecular structure, was the most effective among the inhibitors tested, while Ala was less effective than S-MCys. The low inhibition efficiency recorded for S-MCys compared with that of Cys was attributed to steric effects caused by the substituent methyl on the mercapto group. Electrochemical frequency modulation (EFM) technique and inductively coupled plasma atomic emission spectrometry (ICP-AES), were also applied to make accurate determination of corrosion rates. Validation of the Tafel extrapolation method for measuring corrosion rates was tested. Rates of corrosion rates (in μm y -1 ) obtained from Tafel extrapolation method are in good agreement with those measured using EFM and ICP methods. Some theoretical studies, including molecular dynamics (MD) and density functional theory (DFT), were also employed to establish the correlation between the structure (molecular and electronic) of the three tested inhibitors and the inhibition efficiency. Adsorption via hydrogen bonding was discussed here based on some theoretical studies. Experimental and theoretical results were in good agreement.

  11. Suberoylanilide hydroxamic acid sensitizes neuroblastoma to paclitaxel by inhibiting thioredoxin-related protein 14-mediated autophagy.

    Science.gov (United States)

    Zhen, Zijun; Yang, Kaibin; Ye, Litong; You, Zhiyao; Chen, Rirong; Liu, Ying; He, Youjian

    2017-07-01

    Paclitaxel is not as effective for neuroblastoma as most of the front-line chemotherapeutics due to drug resistance. This study explored the regulatory mechanism of paclitaxel-associated autophagy and potential solutions to paclitaxel resistance in neuroblastoma. The formation of autophagic vesicles was detected by scanning transmission electron microscopy and flow cytometry. The autophagy-associated proteins were assessed by western blot. Autophagy was induced and the autophagy-associated proteins LC3-I, LC3-II, Beclin 1, and thioredoxin-related protein 14 (TRP14), were found to be upregulated in neuroblastoma cells that were exposed to paclitaxel. The inhibition of Beclin 1 or TRP14 by siRNA increased the sensitivity of the tumor cells to paclitaxel. In addition, Beclin 1-mediated autophagy was regulated by TRP14. Furthermore, the TRP14 inhibitor suberoylanilide hydroxamic acid (SAHA) downregulated paclitaxel-induced autophagy and enhanced the anticancer effects of paclitaxel in normal control cancer cells but not in cells with upregulated Beclin 1 and TRP14 expression. Our findings showed that paclitaxel-induced autophagy in neuroblastoma cells was regulated by TRP14 and that SAHA could sensitize neuroblastoma cells to paclitaxel by specifically inhibiting TRP14. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  12. Electrochemical evaluation of inhibition efficiency of ciprofloxacin on the corrosion of copper in acid media

    Energy Technology Data Exchange (ETDEWEB)

    Thanapackiam, P. [Department of Chemistry, Coimbatore Institute of Technology, Coimbatore, Tamilnadu, 641 014 (India); Rameshkumar, Subramaniam [Department of Chemistry, Sri Vasavi College, Erode, Tamilnadu, 638 316 (India); Subramanian, S.S. [Department of Chemistry, PSG College of Technology, Coimbatore, Tamilnadu, 641 004 (India); Mallaiya, Kumaravel, E-mail: mkvteam.research@gmail.com [Department of Chemistry, PSG College of Technology, Coimbatore, Tamilnadu, 641 004 (India)

    2016-05-01

    The inhibition efficiency of ciprofloxacin on the corrosion of copper was studied in 1.0MHNO{sub 3} and 0.5MH{sub 2}SO{sub 4} solutions by electrochemical impedance spectroscopy and potentiodynamic polarization techniques. The corrosion inhibition action of ciprofloxacin was observed to be of mixed type in both the acid media, but with more of a cathodic nature. The experimental data were found to fit well with the Langmuir adsorption isotherm. The thermodynamic parameters such as adsorption equilibrium constant(K{sub ads}), free energy of adsorption(ΔG{sub ads}), activation energy(E{sub a}) and potential of zero charge(PZC) showed that the adsorption of ciprofloxacin onto copper surface involves both physisorption and chemisorption. - Highlights: • The inhibitor efficiency increases with increase in ciprofloxacin concentration. • Polarization measurements show that ciprofloxacin acts as a mixed type inhibitor. • The adsorption of the inhibitor on copper surface follows Langmuir adsorption isotherm. • The negative values of ΔG{sub ads} indicates that the adsorption is spontaneous and exothermic.

  13. Studies on the Inhibitive Effect of Datura Stramonium Extract on the Acid Corrosion of Mild Steel

    Science.gov (United States)

    Raja, Pandian Bothi; Sethuraman, Mathur Gopalakrishnan

    The extract of Datura stramonium has been studied as a possible source of green inhibitor for corrosion of mild steel (MS) in HCl and H2SO4 media at different temperatures. The anticorrosion effect was evaluated by conventional weight loss studies, electrochemical studies viz., Tafel polarization, ac impedance, and SEM studies. The studies reveal that the plant extract acts as a good inhibitor in both the acid media and better in H2SO4 medium. Tafel polarization method indicate that the plant extract behaves as a mixed mode inhibitor. Double layer capacitance and charge transfer resistance values derived from Nyquist plots obtained from ac impedance studies give supporting evidence for the anticorrosive effect. The inhibitive effect may be attributed to the adsorption of the inhibitor on the surface of MS, following Temkin adsorption isotherm. Increase of inhibition efficiency with increase of temperature along with Ea values serve as a proof for chemisorption. SEM studies provide the confirmatory evidence for the protection of MS by the green inhibitor. The study reveals the potential of D. stramonium for combating corrosion which may be due to the adsorption of alkaloids and other phytoconstituents.

  14. Anti-fibrotic effect of rosmarinic acid on inhibition of pterygium epithelial cells

    Science.gov (United States)

    Chen, Ya-Yu; Tsai, Chia-Fang; Tsai, Ming-Chu; Chen, Wen-Kang; Hsu, Yu-Wen; Lu, Fung-Jou

    2018-01-01

    AIM To investigate the anti-fibrosis effect of rosmarinic acid (RA) in pterygium epithelial cells (PECs) to determine if RA is a potent agent for treating pterygium. METHODS The PECs (1×104 cells/mL) were treated with 100 µmol/L of RA for 1, 3 and 6h. After RA treatment, the cell viability was determined by staining with acridine orange/DAPI and analysis via a NucleoCounter NC-3000. The protein expression levels of type I collagen, transforming growth factor beta-1 (TGF-β1), TGF-β type II receptor (TGF-βRII), p-Smad1/5, p-Smad2, p-Smad3, and Smad4 of the cell lysates were measured by Western blot analysis. RESULTS The cell viability of PECs was significantly decreased after RA treatment (P<0.01). As the result, RA reduced the protein expression of type I collagen and TGF-β1 of PECs. Additionally, RA also inhibited TGF-β1/Smad signaling by decreasing the protein expressions of TGF-βRII, p-Smad1/5, p-Smad2, p-Smad3, and Smad4. CONCLUSION This study demonstrate that RA could inhibit fibrosis of PECs by down-regulating type I collagen expression and TGF-β1/Smad signaling. Therefore, RA is a potent therapeutic agent for the treatment of pterygium. PMID:29487805

  15. Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro

    Directory of Open Access Journals (Sweden)

    Lin Tao

    2011-06-01

    Full Text Available Abstract Background To study the effects of zoledronic acid (ZA on the vasculogenic mimicry of osteosarcoma cells in vitro. Methods A Three-dimensional culture of LM8 osteosarcoma cells on a type I collagen matrix was used to investigate whether osteosarcoma cells can develop vasculogenic mimicry, and to determine the effects of ZA on this process. In addition, the cellular ultrastructural changes were observed using scanning electron microscopy and laser confocal microscopy. The effects of ZA on the translocation of RhoA protein from the cytosol to the membrane in LM8 cells were measured via immunoblotting. Results ZA inhibited the development of vasculogenic mimicry by the LM8 osteosarcoma cells, decreased microvilli formation on the cell surface, and disrupted the F-actin cytoskeleton. ZA prevented translocation of RhoA protein from the cytosol to the membrane in LM8 cells. Conclusions ZA can impair RhoA membrane localization in LM8 cells, causing obvious changes in the ultrastructure of osteosarcoma cells and induce cell apoptosis, which may be one of the underlying mechanisms by which the agent inhibits the development of vasculogenic mimicry by the LM8 cells.

  16. UREMIC TOXIN GUANIDINE ACETIC ACID INHIBITS THE OXIDATIVE METABOLISM OF NEUTROPHILS IN DOGS

    Directory of Open Access Journals (Sweden)

    Priscila Preve Pereira

    2015-10-01

    Full Text Available Abstract Among the uremic toxins proven to affect the neutrophil function in humans with chronic kidney disease (CKD, guanidine compounds stand out. To achieve a clearer understanding of the mechanisms that affect the immunity of uremic patients, the hypothesis that guanidine acetic acid (GAA contributes to the inhibition of oxidative metabolism and an increase in neutrophil apoptosis in healthy dogs was investigated in vitro. To this end, neutrophils isolated from ten healthy dogs were incubated in pure RPMI 1640 (control and enriched with 5 mg/L of GAA. Capillary flow cytometry was used to quantify superoxide production in neutrophils with the probe (hydroethidine, in the presence and absence of phorbol-12-myristate-13-acetate (PMA, in order to assess oxidative metabolism. Apoptotic indices were quantified using the Annexin V-PE system, with and without the inductive effect of camptothecin. Neutrophils isolated and incubated in a GAA-enriched medium produced smaller amounts of superoxide (p<0.001 when activated with PMA, however, this inhibition of oxidative metabolism occurred without significantly altering their viability or rate of apoptosis. Thus, the results show guanidine compounds contribute to immunosuppression in dogs with CKD.

  17. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: sungy2004@sohu.com [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: rtliu@tsinghua.edu.cn [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)

    2009-12-25

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  18. Multifunctional Cinnamic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Aikaterini Peperidou

    2017-07-01

    Full Text Available Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX inhibition (IC50 = 6 μΜ and antiproteolytic activity (IC50 = 0.425 μΜ. The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315 μΜ and good LOX inhibitory activity (IC50 = 66 μΜ. Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.

  19. Andrographolide inhibits growth of acute promyelocytic leukaemia cells by inducing retinoic acid receptor-independent cell differentiation and apoptosis.

    Science.gov (United States)

    Manikam, Shiamala D; Manikam, Shiamala T; Stanslas, Johnson

    2009-01-01

    The growth inhibiting potential of andrographolide was evaluated in three acute promyelocytic leukaemia cell line models (HL-60, NB4 and all-trans retinoic acid (ATRA)-resistant NB4-R2). In elucidating the mechanisms of growth inhibition, a special emphasis was placed on assessing the induction of differentiation and apoptosis by andrographolide in the primary acute promyelocytic leukaemia NB4 cells. The compound was 2- and 3-fold more active in inhibiting the growth of HL-60 and NB4-R2 cells compared with NB4 cells, respectively. At IC50 (concentration at which growth of 50% of the cells (compared with medium only treated control cells) is inhibited; 4.5 microM) the compound exhibited strong cell-differentiating activity in NB4 cells, similar to ATRA (IC50 1.5 microM). In the presence of a pure retinoic acid receptor antagonist AGN193109, the growth inhibition of NB4 cells by ATRA was reversed, whereas the activity of andrographolide was not affected. This clearly suggested that andrographolide's cell differentiating activity to induce growth inhibition of NB4 cells most likely occurred via a retinoic acid receptor-independent pathway. At higher concentration (2xIC50), andrographolide was an efficient inducer of apoptosis in NB4 cells. Taken together, these results suggest andrographolide and its derivatives, apparently with a novel cell differentiating mechanism and with ability to induce apoptosis, might be beneficial in the treatment of primary and ATRA-resistant acute promyelocytic leukaemia.

  20. In-situ inhibition of Staphylococcus aureus by lactic acid bacteria consortia from two traditional Slovenian raw milk cheeses

    Directory of Open Access Journals (Sweden)

    Aljoša Trmčić

    2010-09-01

    Full Text Available Bacteriocin(s producing lactic acid bacteria naturally present in traditional cheeses represent an inexhaustive pool of microbes with safeguarding potential. Some bacteriocins produced by cheese lactic acid bacteria were already described as successful anti-staphylococcal agents. The presence of genes for bacteriocins with potential anti-staphylococcal activity was also demonstrated in two Slovenian traditional raw milk cheeses, “Tolminc” and “Kraški ovčji sir”. Same bacteriocin genes were also detected in viable lactic acid bacteria consortia’s isolated from “bacteriocin positive cheeses” on Rogosa, M17 and CATC agar media. The aim of the research was to elucidate whether or not this particular cheese consortia, in which bacteriocin genes were detected, actually exhibit anti-staphylococcal activity in milk and/or cheese. For this purpose different cheese consortia were selected in relation to versatility of detected bacteriocin genes and used to perform challenge tests against Staphylococcus aureus in milk and cheese. In milk following the time/temperature regime of traditional cheese production all cheese consortia effectively inhibited growth of Staphylococcus aureus in the range of app. 2 to 3 log. In cheese the inhibition of staphylococci was less pronounced but still evident since inhibition of app. 1.5 log was detected. Sole inhibition by lactic acid production was ruled out whilelinking inhibition directly to bacteriocin production would take some additional work.

  1. Some Anilides of 2-Alkylthio- and 2-Chloro-6-Alkylthio-4-Pyridinecarboxylic Acids: Synthesis and Photosynthesis-Inhibiting Activity

    Directory of Open Access Journals (Sweden)

    Miloš Macháček

    2001-06-01

    Full Text Available Many compounds containing a -CONH- group display photosynthesis inhibiting activity. Based on this structural feature, a group of anilides of 2-alkylthio-(1b-4f or 2-chloro-6-alkylthio-4-pyridinecarboxylic acids (5a-6c was synthesised. The prepared compounds were tested for their inhibition of the oxygen evolution rate (OER in spinach chloroplasts. A quasi-parabolic dependence between photosynthesis-inhibiting activity and the lipophilicity of the compounds was determined for 1b-4f as well as for 5a-6c. The inhibitory activity of compounds 1b-4f was higher than that of 5a-6c for comparable lipophilicity values.

  2. Physiologic actions of zinc related to inhibition of acid and alkali production by oral streptococci in suspensions and biofilms.

    Science.gov (United States)

    Phan, T-N; Buckner, T; Sheng, J; Baldeck, J D; Marquis, R E

    2004-02-01

    Zinc is a known inhibitor of acid production by mutans streptococci. Our primary objective was to extend current knowledge of the physiologic bases for this inhibition and also for zinc inhibition of alkali production by Streptococcus rattus FA-1 and Streptococcus salivarius ATCC 13419. Zinc at concentrations as low as 0.01-0.1 mm not only inhibited acid production by cells of Streptococcus mutans GS-5 in suspensions or in biofilms but also sensitized glycolysis by intact cells to acidification. Zinc reversibly inhibited the F-ATPase of permeabilized cells of S. mutans with a 50% inhibitory concentration of about 1 mm for cells in suspensions. Zinc reversibly inhibited the phosphoenolpyruvate: sugar phosphotransferase system with 50% inhibition at about 0.3 mm ZnSO4, or about half that concentration when the zinc-citrate chelate was used. The reversibility of these inhibitory actions of zinc correlates with findings that it is mainly bacteriostatic rather than bactericidal. Zinc inhibited alkali production from arginine or urea and was a potent enzyme inhibitor for arginine deiminase of S. rattus FA-1 and for urease of S. salivarius. In addition, zinc citrate at high levels of 10-20 mm was weakly bactericidal.

  3. Ascorbic acid inhibits TPA-induced HL-60 cell differentiation by decreasing cellular H₂O₂ and ERK phosphorylation.

    Science.gov (United States)

    Yiang, Giou-Teng; Chen, Jen-Ni; Wu, Tsai-Kun; Wang, Hsueh-Fang; Hung, Yu-Ting; Chang, Wei-Jung; Chen, Chinshuh; Wei, Chyou-Wei; Yu, Yung-Luen

    2015-10-01

    Retinoic acid (RA), vitamin D and 12-O‑tetradecanoyl phorbol-13-acetate (TPA) can induce HL-60 cells to differentiate into granulocytes, monocytes and macrophages, respectively. Similar to RA and vitamin D, ascorbic acid also belongs to the vitamin family. High‑dose ascorbic acid (>100 µM) induces HL‑60 cell apoptosis and induces a small fraction of HL‑60 cells to express the granulocyte marker, CD66b. In addition, ascorbic acid exerts an anti‑oxidative stress function. Oxidative stress is required for HL‑60 cell differentiation following treatment with TPA, however, the effect of ascorbic acid on HL‑60 cell differentiation in combination with TPA treatment remains to be fully elucidated. The aim of the present study was to investigate the cellular effects of ascorbic acid treatment on TPA-differentiated HL-60 cells. TPA-differentiated HL-60 cells were used for this investigation, this study and the levels of cellular hydrogen peroxide (H2O2), caspase activity and ERK phosphorylation were determined following combined treatment with TPA and ascorbic acid. The results demonstrated that low‑dose ascorbic acid (5 µM) reduced the cellular levels of H2O2 and inhibited the differentiation of HL‑60 cells into macrophages following treatment with TPA. In addition, the results of the present study further demonstrated that low‑dose ascorbic acid inactivates the ERK phosphorylation pathway, which inhibited HL‑60 cell differentiation following treatment with TPA.

  4. Hydrocortisone selectively inhibits IgE-dependent arachidonic acid release from rat peritoneal mast cells

    International Nuclear Information System (INIS)

    Heiman, A.S.; Crews, F.T.

    1984-01-01

    Purified rat mst cells were used to study the effects of antiinflammatory steroids on the release of [1-14C]-arachidonic acid ([1-14C]AA) and metabolites. Mast cell were incubated overnight with glucocorticoids, [1-14C]AA incorporated into cellular phospholipids and the release of [1-14C]AA, and metabolites determined using a variety of secretagogues. Release of [1-14C]AA and metabolites by concanavalin A, the antigen ovalbumin and anti-immunoglobulin E antibody was markedly reduced by glucocorticoid treatment. Neither the total incorporation of [1-14C]AA nor the distribution into phospholipids was altered by hydrocortisone pretreatment. Glucocorticoid pretreatment did not alter [1-14C]AA release stimulated by somatostatin, compound 48/80, or the calcium ionophore, A23187. These data indicate that antiinflammatory steroids selectively inhibit immunoglobulin dependent release of arachidonic acid from rat mast cells. These findings question the role of lipomodulin and macrocortin as general phospholipase inhibitors and suggest that they may be restricted to immunoglobulin stimuli

  5. Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-κB Activation in Mice.

    Science.gov (United States)

    Colombo, Bárbara B; Fattori, Victor; Guazelli, Carla F S; Zaninelli, Tiago H; Carvalho, Thacyana T; Ferraz, Camila R; Bussmann, Allan J C; Ruiz-Miyazawa, Kenji W; Baracat, Marcela M; Casagrande, Rúbia; Verri, Waldiceu A

    2018-04-10

    The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1β, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.

  6. Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes.

    Science.gov (United States)

    Lee, Bonggi; Kwon, Misung; Choi, Jae Sue; Jeong, Hyoung Oh; Chung, Hae Young; Kim, Hyeung-Rak

    2015-12-01

    Stamens of Nelumbo nucifera Gaertn have been used as a Chinese medicine due to its antioxidant, hypoglycemic, and antiatherogenic activity. However, the effects of kaempferol, a main component of N. nucifera, on obesity are not fully understood. We examined the effect of kaempferol on adipogenesis and fatty acid oxidation signaling pathways in 3T3-L1 adipocytes. Kaempferol reduced cytoplasmic triglyceride (TG) accumulation in dose and time-dependent manners during adipocyte differentiation. Accumulation of TG was rapidly reversed by retrieving kaempferol treatment. Kaempferol broadly decreased mRNA or protein levels of adipogenic transcription factors and their target genes related to lipid accumulation. Kaempferol also suppressed glucose uptake and glucose transporter GLUT4 mRNA expression in adipocytes. Furthermore, protein docking simulation suggests that Kaempferol can directly bind to and activate peroxisome proliferator-activated receptor (PPAR)-α by forming hydrophobic interactions with VAL324, THR279, and LEU321 residues of PPARα. The binding affinity was higher than a well-known PPARα agonist fenofibrate. Consistently, mRNA expression levels of PPARα target genes were increased. Our study indicates while kaempferol inhibits lipogenic transcription factors and lipid accumulation, it may bind to PPARα and stimulate fatty acid oxidation signaling in adipocytes.

  7. Cell motility is inhibited by the antiepileptic compound, valproic acid and its teratogenic analogues

    DEFF Research Database (Denmark)

    Walmod, P S; Foley, A; Berezin, A

    1998-01-01

    Valproic acid (VPA) is an established human teratogen that causes neural tube defects in 1-2% of human foetuses exposed to the drug during early pregnancy. In this study, individual cell motility was evaluated using short- and long-term time-lapse video-recording and computer assisted image analy......-actin and of a series of focal adhesion proteins, indicating that the effect of VPA on cell motility may be causally related to increased cell-substratum interactions or to alterations in the organisation or dynamics of the actin cytoskeleton.......Valproic acid (VPA) is an established human teratogen that causes neural tube defects in 1-2% of human foetuses exposed to the drug during early pregnancy. In this study, individual cell motility was evaluated using short- and long-term time-lapse video-recording and computer assisted image...... analysis, and it was found that VPA and selected VPA-analogues inhibited individual cell motility of L-cells in a dose-dependent manner. The compounds caused a decrease in the root-mean-square speed, S, and in the rate of diffusion, R, but an increase in the time of persistence in direction, P. Using short...

  8. Inhibition of monomethylarsonous acid (MMA(III))-induced cell malignant transformation through restoring dysregulated histone acetylation.

    Science.gov (United States)

    Ge, Yichen; Gong, Zhihong; Olson, James R; Xu, Peilin; Buck, Michael J; Ren, Xuefeng

    2013-10-04

    Inorganic arsenic (iAs) and its high toxic metabolite, monomethylarsonous acid (MMA(III)), are able to induce malignant transformation of human cells. Chronic exposure to these chemicals is associated with an increased risk of developing multiple cancers in human. However, the mechanisms contributing to iAs/MMA(III)-induced cell malignant transformation and carcinogenesis are not fully elucidated. We recently showed that iAs/MMA(III) exposure to human cells led to a decreased level of histone acetylation globally, which was associated with an increased sensitivity to arsenic cytotoxicity. In the current study, it demonstrated that prolonged exposure to low-level MMA(III) in human urothelial cells significantly increased the expression and activity of histone deacetylases (HDACs) with an associated reduction of histone acetylation levels both globally and lysine specifically. Administration of the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), at 4 weeks after the initial MMA(III) treatment inhibited the MMA(III)-mediated up-regulation of the expression and activities of HDACs, leading to increase histone acetylation and prevention of MMA(III)-induced malignant transformation. These new f