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Sedighi M, Ghorbanzadeh V, Abaszadeh S, Karimi A, Cheraghi M, Rafieian-Kopaei M, Moghimian M, Mohammadi A, Veiskarami S, Mokhayeri Y, Nazari A. Up-regulation of chemokine receptor type 4 expression in the ischemic reperfused heart by alcoholic extract of Cichorium intybus rescue the heart from ischemia injury in male rat. J Pharm Pharmacol 2021; 73:1351-1360. [PMID: 34076244 DOI: 10.1093/jpp/rgab076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 05/11/2021] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Cichorium intybus is used in traditional medicine for various diseases including heart disease. This study aimed at evaluating the chemokine receptor type 4 up-regulation and cardioprotective effects of hydroalcoholic extract of C. intybus in a rat model of ischemic reperfusion. METHODS Animals in four groups of eight rats each received vehicle or one of three doses of C. intybus (50, 100 or 200 mg/kg/d) for 14 days. Then they were subjected to 30 min of ischemia followed by 7 days of reperfusion. At the end of the experiment, blood specimens were prepared for serum assays. The level of myocardium chemokine receptor type 4 was also measured using RT-PCR. KEY FINDINGS Cichorium intybus (CI-50) improved infarct size, episodes of the ventricular ectopic beat, ventricular tachycardia, and duration of ventricular tachycardia, QTc shortening. It also stabilized the ST segment changes and increased heart rate during ischemia. The blood pressure decreased in CI-50 group in comparison to the control and CI-200 group. C. intybus increased serum superoxide dismutase and reduced lactate dehydrogenase activity, Cardiac Troponin I and malondialdehyde levels. C. intybus led to an increase in the expression of chemokine receptor type 4. CONCLUSIONS These findings suggest that C. intybus administration before ischemia is able to induce cardioprotective effect against ischemic reperfusion injury, probably through chemokine receptor type 4 over-expression and antioxidant activity.
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Affiliation(s)
- Mehrnoosh Sedighi
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khoramabad, Iran
| | - Vajihe Ghorbanzadeh
- Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Saber Abaszadeh
- Department of clinical biochemistry, Lorestan University of Medical Science, Khorramabad, Iran
| | - Arash Karimi
- Department of Anesthesiology, Anesthesiologist, Faculty of Medicine, Lorestan University of Medical Science, Khorramabad, Iran
| | - Mostafa Cheraghi
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khoramabad, Iran
| | - Mahmoud Rafieian-Kopaei
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Siences, Shahrekord, Iran
| | - Maryam Moghimian
- Department of Physiology, Gonabad University of Medical Science, Gonabad, Iran
| | - Asghar Mohammadi
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khoramabad, Iran
| | - Saeid Veiskarami
- Lorestan Agricultural and Natural Resources Research and Education Center, Department of animal science, Iran
| | - Yaser Mokhayeri
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khoramabad, Iran
| | - Afshin Nazari
- Department of Physiology, Lorestan University of Medical Science, Khorramabad, Iran
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Bostancıeri N, Elbe H, Eşrefoğlu M, Vardı N. Cardioprotective potential of melatonin, quercetin and resveratrol in an experimental model of diabetes. Biotech Histochem 2021; 97:152-157. [PMID: 33906539 DOI: 10.1080/10520295.2021.1918766] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
Oxygen radicals participate in the pathogenesis of heart damage. Diabetes accelerates the formation of reactive oxygen species (ROS). We investigated the effects of the antioxidants, melatonin, quercetin and resveratrol, on cardiomyopathy and apoptosis in rats with streptozotocin (STZ) induced diabetes mellitus (DM). Rats were divided into five groups of seven: control, DM, DM + melatonin, DM + quercetin and DM + resveratrol. All treatments were begun with a single dose of STZ to induce diabetes and experimental treatments were continued daily for 30 days. Morphologic and apoptotic changes were analyzed by histological assessment. The heart tissue of the control group exhibited normal histology, whereas the heart tissue of the DM group exhibited vacuolization, necrosis, congestion, infiltration and myofibril loss. The DM group exhibited significantly increased apoptosis compared to the control group. Differences in anti-apoptotic effects were statistically significant for all three antioxidant treatment groups; the anti-apoptotic effects of quercetin and resveratrol were similar. Melatonin, resveratrol and quercetin exhibited protective effects against diabetic heart damage.
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Affiliation(s)
- N Bostancıeri
- Department of Histology and Embryology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - H Elbe
- Department of Histology and Embryology, Faculty of Medicine, Sıtkı Koçman University, Muğla, Turkey
| | - M Eşrefoğlu
- Department of Histology and Embryology, Faculty of Medicine, Bezmiâlem University, İstanbul, Turkey
| | - N Vardı
- Department of Histology and Embryology, Faculty of Medicine, Inönü University, Malatya, Turkey
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Rysz J, Franczyk B, Kujawski K, Sacewicz-Hofman I, Ciałkowska-Rysz A, Gluba-Brzózka A. Are Nutraceuticals Beneficial in Chronic Kidney Disease? Pharmaceutics 2021; 13:231. [PMID: 33562154 PMCID: PMC7915977 DOI: 10.3390/pharmaceutics13020231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/29/2021] [Accepted: 02/03/2021] [Indexed: 12/18/2022] Open
Abstract
Chronic kidney disease (CKD) is a worldwide health problem in which prevalence is constantly rising. The pathophysiology of CKD is complicated and has not been fully resolved. However, elevated oxidative stress is considered to play a vital role in the development of this disease. CKD is also thought to be an inflammatory disorder in which uremic toxins participate in the development of the inflammatory milieu. A healthy, balanced diet supports the maintenance of a good health status as it helps to reduce the risk of the development of chronic diseases, including chronic kidney disease, diabetes mellitus, and hypertension. Numerous studies have demonstrated that functional molecules and nutrients, including fatty acids and fiber as well as nutraceuticals such as curcumin, steviol glycosides, and resveratrol not only exert beneficial effects on pro-inflammatory and anti-inflammatory pathways but also on gut mucosa. Nutraceuticals have attracted great interest recently due to their potential favorable physiological effects on the human body and their safety. This review presents some nutraceuticals in which consumption could exert a beneficial impact on the development and progression of renal disease as well cardiovascular disease.
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Affiliation(s)
- Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.); (K.K.)
| | - Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.); (K.K.)
| | - Krzysztof Kujawski
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.); (K.K.)
| | | | | | - Anna Gluba-Brzózka
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.); (K.K.)
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Sedighi M, Cheraghi M, Faghihi M, Rahimi-Madiseh M, Kiani AA, Dehghani M, Rasoulian B, Nazari A. Hypotensive effect of Cichorium intybus extract in rats. JOURNAL OF HERBMED PHARMACOLOGY 2021. [DOI: 10.34172/jhp.2021.29] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Introduction: Oxidative stress is involved in many diseases, including hypertension, kidney failure, and heart disease. This study aimed to evaluate the effect of hydroalcoholic Cichorium intybus extract on blood pressure in rats. Antioxidant activity, phenolic and flavonoid contents of the plant extract were also evaluated. Methods: In this study, 32 male Wistar rats weighing 250-300 g were divided into four groups of eight each. Animals in the control group were administered with normal saline and in the C. intybus groups with extract at 25, 50, and 100 mg/kg for two weeks. Then, the homodynamic parameters were examined by the Power lab. The phenolic and flavonoid contents were also evaluated by a spectrophotometer and the rate of free radical scavenging activity was measured by the diphenyl-1-picyryl-hydrazyl (DPPH) free radical method. Results: The free radical scavenging activity of C. intybus extract was obtained 47.85% of DPPH, and flavonoid and phenolic contents were 8.21 and 27.19 mg/g of dry extract, respectively. Meanwhile, median (MAP), systolic (SAP) and diastolic arterial pressure (DAP) significantly decreased in the 50 mg/kg extract-treated group compared to the control and 200 mg/kg extract-treated groups. Conclusion: Ethanol extract of C. intybus plays a protective role against hypertension, which, in part, might be due to antioxidant compounds of the plant against free radicals.
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Affiliation(s)
- Mehrnoosh Sedighi
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khoramabad, Iran
| | - Mostafa Cheraghi
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khoramabad, Iran
| | - Mahdieh Faghihi
- Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Rahimi-Madiseh
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Ali Asghar Kiani
- Razi Herbal Medicines Research Center and School of Allied Medical Sciences, Department of Hematology and Blood Transfusion, Lorestan University of Medical Science, Khorramabad, Iran
| | - Mostafa Dehghani
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khoramabad, Iran
| | - Bahram Rasoulian
- Razi Herbal Medicines Research Center, Department of Physiology, Lorestan University of Medical Science, Khorramabad, Iran
| | - Afshin Nazari
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khoramabad, Iran
- Razi Herbal Medicines Research Center, Department of Physiology, Lorestan University of Medical Science, Khorramabad, Iran
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Kazemirad H, Kazerani HR. Cardioprotective effects of resveratrol following myocardial ischemia and reperfusion. Mol Biol Rep 2020; 47:5843-5850. [PMID: 32712855 DOI: 10.1007/s11033-020-05653-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 07/08/2020] [Indexed: 01/24/2023]
Abstract
Resveratrol (RSV), a plant origin polyphenol, has shown beneficial cardiovascular effects. In this study, isolated hearts from male Wistar rats were studied using the Langendorff technique. Following 30 min stabilization, the hearts underwent 30 min global ischemia and 120 min reperfusion. The perfusion solution in the test group contained RSV (10 μM). Hemodynamics of the hearts, the markers of myocardial damage including creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and troponin I were studied during the study. Furthermore, the infarct size and the markers of oxidative stress including catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPX) were assayed in the homogenates of the hearts. The release of nitrite from the hearts and the occurrence of ventricular arrhythmias were also monitored throughout the experiment. Resveratrol caused a significant improvement in the restoration of the mechanical performance of the hearts following myocardial ischemia and reperfusion (MIR). Besides, the infarct size, CK-MB, LDH, and troponin I declined in the test group. Besides, the cardiac release of nitrite increased, and the redox status of the heart was improved as indicated by the levels of CAT, SOD, GPX, and MDA. Finally, the treatment caused significant decreases in the occurrences of single and salvo arrhythmias, ventricular tachycardia, and ventricular fibrillation. The current study suggests strong cardioprotective and antiarrhythmic effects for RSV following MIR.
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Affiliation(s)
- Hamideh Kazemirad
- Department of Physiology, The School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, PO Box: 91775 1793, Iran
| | - Hamid Reza Kazerani
- Department of Physiology, The School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, PO Box: 91775 1793, Iran.
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Kruse NT. Nutraceuticals as a potential adjunct therapy toward improving vascular health in CKD. Am J Physiol Regul Integr Comp Physiol 2019; 317:R719-R732. [PMID: 31577157 DOI: 10.1152/ajpregu.00152.2019] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Chronic kidney disease (CKD) is a major public health epidemic and increases risk for developing cardiovascular disease (CVD). Vascular dysfunction is a major independent risk factor toward increased risk for CVD in CKD. Several mechanisms have been postulated to result in vascular dysfunction in CKD, including oxidative stress-mediated inflammation by redox imbalance and reduced nitric oxide (NO) bioavailability and synthesis. Therefore, strategies that decrease oxidative stress and/or increase NO bioactivity may have major clinical implications toward improving vascular health and reducing the burden of CVD in CKD. Nutraceutical therapy in the form of polyphenols, dietary nitrates, or selective mitochondria-targeting therapies has recently been shown to improve vascular function by reducing oxidative stress and/or increasing NO bioavailability and synthesis. This review, therefore, highlights these three emerging nutraceuticals recently implicated in pathophysiological improvement of vascular function in CKD. This review also describes those pathophysiological mechanisms thought to be responsible for the beneficial effects on the vasculature and possible experimental considerations that may exist within human CKD populations. It is clear throughout this review that human-based mechanistic preclinical and health-related clinical studies are lacking regarding whether nutraceuticals do indeed improve vascular function in patients with CKD. As such, a comprehensive, detailed, and fully integrated understanding of nutraceuticals and vasculature function is necessary in patients with CKD. Many opportunities exist for original mechanistic and therapeutic discoveries and investigations on select nutraceuticals and their impact on vascular outcomes in patients with CKD, and these will remain exciting avenues of research in the future.
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Affiliation(s)
- Nicholas T Kruse
- Department of Internal Medicine, Division of Nephrology, Carver College of Medicine, University of Iowa, Iowa City, Iowa
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Pandey RP, Parajuli P, Shin JY, Lee J, Lee S, Hong YS, Park YI, Kim JS, Sohng JK. Enzymatic Biosynthesis of Novel Resveratrol Glucoside and Glycoside Derivatives. Appl Environ Microbiol 2014; 80:7235-43. [PMID: 25239890 PMCID: PMC4249177 DOI: 10.1128/aem.02076-14] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2014] [Accepted: 08/27/2014] [Indexed: 11/20/2022] Open
Abstract
A UDP glucosyltransferase from Bacillus licheniformis was overexpressed, purified, and incubated with nucleotide diphosphate (NDP) d- and l-sugars to produce glucose, galactose, 2-deoxyglucose, viosamine, rhamnose, and fucose sugar-conjugated resveratrol glycosides. Significantly higher (90%) bioconversion of resveratrol was achieved with α-d-glucose as the sugar donor to produce four different glucosides of resveratrol: resveratrol 3-O-β-d-glucoside, resveratrol 4'-O-β-d-glucoside, resveratrol 3,5-O-β-d-diglucoside, and resveratrol 3,5,4'-O-β-d-triglucoside. The conversion rates and numbers of products formed were found to vary with the other NDP sugar donors. Resveratrol 3-O-β-d-2-deoxyglucoside and resveratrol 3,5-O-β-d-di-2-deoxyglucoside were found to be produced using TDP-2-deoxyglucose as a donor; however, the monoglycosides resveratrol 4'-O-β-d-galactoside, resveratrol 4'-O-β-d-viosaminoside, resveratrol 3-O-β-l-rhamnoside, and resveratrol 3-O-β-l-fucoside were produced from the respective sugar donors. Altogether, 10 diverse glycoside derivatives of the medically important resveratrol were generated, demonstrating the capacity of YjiC to produce structurally diverse resveratrol glycosides.
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Affiliation(s)
- Ramesh Prasad Pandey
- Institute of Biomolecule Reconstruction, Department of Pharmaceutical Engineering, Sun Moon University, Tangjeonmyun, Asan-si, Chungnam, South Korea
| | - Prakash Parajuli
- Institute of Biomolecule Reconstruction, Department of Pharmaceutical Engineering, Sun Moon University, Tangjeonmyun, Asan-si, Chungnam, South Korea
| | - Ju Yong Shin
- Institute of Biomolecule Reconstruction, Department of Pharmaceutical Engineering, Sun Moon University, Tangjeonmyun, Asan-si, Chungnam, South Korea
| | - Jisun Lee
- Department of Biotechnology, Catholic University of Korea, Bucheon, Gyeonggi-do, South Korea
| | - Seul Lee
- Department of Biotechnology, Catholic University of Korea, Bucheon, Gyeonggi-do, South Korea
| | - Young-Soo Hong
- Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang-eup, Chungbuk, South Korea
| | - Yong Il Park
- Department of Biotechnology, Catholic University of Korea, Bucheon, Gyeonggi-do, South Korea
| | - Joong Su Kim
- Bioindustry Process Center, Jeonbuk Branch Institute, Korea Research Institute of Bioscience and Biotechnology, Jeonbuk, Jeong-Ub, South Korea
| | - Jae Kyung Sohng
- Institute of Biomolecule Reconstruction, Department of Pharmaceutical Engineering, Sun Moon University, Tangjeonmyun, Asan-si, Chungnam, South Korea
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Saha L, Chakrabarti A. Understanding the anti-kindling role and its mechanism of Resveratrol in Pentylenetetrazole induced-kindling in a rat model. Pharmacol Biochem Behav 2014; 120:57-64. [DOI: 10.1016/j.pbb.2014.01.010] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 01/18/2014] [Accepted: 01/22/2014] [Indexed: 12/18/2022]
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Zhu Y, Peng QZ, Du C, Li KG, Xie DY. Characterization of Flavan-3-ols and Expression of MYB and Late Pathway Genes Involved in Proanthocyanidin Biosynthesis in Foliage of Vitis bellula. Metabolites 2013; 3:185-203. [PMID: 24957897 PMCID: PMC3901255 DOI: 10.3390/metabo3010185] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2012] [Revised: 02/04/2013] [Accepted: 03/07/2013] [Indexed: 01/26/2023] Open
Abstract
Proanthocyanidins (PAs) are fundamental nutritional metabolites in different types of grape products consumed by human beings. Although the biosynthesis of PAs in berry of Vitis vinifera has gained intensive investigations, the understanding of PAs in other Vitis species is limited. In this study, we report PA formation and characterization of gene expression involved in PA biosynthesis in leaves of V. bellula, a wild edible grape species native to south and south-west China. Leaves are collected at five developmental stages defined by sizes ranging from 0.5 to 5 cm in length. Analyses of thin layer chromatography (TLC) and high performance liquid chromatography-photodiode array detector (HPLC-PAD) show the formation of (+)-catechin, (-)-epicatechin, (+)-gallocatechin and (-)-epigallocatechin during the entire development of leaves. Analyses of butanol-HCl boiling cleavage coupled with spectrometry measurement at 550 nm show a temporal trend of extractable PA levels, which is characterized by an increase from 0.5 cm to 1.5 cm long leaves followed by a decrease in late stages. TLC and HPLC-PAD analyses identify cyanidin, delphinidin and pelargonidin produced from the cleavage of PAs in the butanol-HCl boiling, showing that the foliage PAs of V. bellula include three different types of extension units. Four cDNAs, which encode VbANR, VbDFR, VbLAR1 and VbLAR2, respectively, are cloned from young leaves. The expression patterns of VbANR and VbLAR2 but not VbLAR1 and VbDFR follow a similar trend as the accumulation patterns of PAs. Two cDNAs encoding VbMYBPA1 and VbMYB5a, the homologs of which have been demonstrated to regulate the expression of both ANR and LAR in V. vinifera, are also cloned and their expression profiles are similar to those of VbANR and VbLAR2. In contrast, the expression profiles of MYBA1 and 2 homologs involved in anthocyanin biosynthesis are different from those of VbANR and VbLAR2. Our data show that both ANR and LAR branches are involved in PA biosynthesis in leaves of V. bellula.
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Affiliation(s)
- Yue Zhu
- Hunan Provincial Key Laboratory of Plant Resources Conservation and Utilization, College of Biology and Environmental Sciences, Jishou University, No.120 Ren Min Nan Lu, Jishou City, Hunan Province, 416000, China.
| | - Qing-Zhong Peng
- Hunan Provincial Key Laboratory of Plant Resources Conservation and Utilization, College of Biology and Environmental Sciences, Jishou University, No.120 Ren Min Nan Lu, Jishou City, Hunan Province, 416000, China.
| | - Ci Du
- Hunan Provincial Key Laboratory of Plant Resources Conservation and Utilization, College of Biology and Environmental Sciences, Jishou University, No.120 Ren Min Nan Lu, Jishou City, Hunan Province, 416000, China.
| | - Ke-Gang Li
- Hunan Provincial Key Laboratory of Plant Resources Conservation and Utilization, College of Biology and Environmental Sciences, Jishou University, No.120 Ren Min Nan Lu, Jishou City, Hunan Province, 416000, China.
| | - De-Yu Xie
- Hunan Provincial Key Laboratory of Plant Resources Conservation and Utilization, College of Biology and Environmental Sciences, Jishou University, No.120 Ren Min Nan Lu, Jishou City, Hunan Province, 416000, China.
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Anestopoulos I, Kavo A, Tentes I, Kortsaris A, Panayiotidis M, Lazou A, Pappa A. Silibinin protects H9c2 cardiac cells from oxidative stress and inhibits phenylephrine-induced hypertrophy: potential mechanisms. J Nutr Biochem 2013; 24:586-94. [PMID: 22818713 DOI: 10.1016/j.jnutbio.2012.02.009] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Revised: 01/26/2012] [Accepted: 02/17/2012] [Indexed: 02/07/2023]
Abstract
Cardiac hypertrophy is the main response of the heart to various extrinsic and intrinsic stimuli, and it is characterized by specific molecular and phenotypic changes. Recent in vitro and in vivo studies indicate the involvement of reactive oxygen species in the hypertrophic response. In this study, silibinin, a plant flavonolignan extracted from milk thistle with potent antioxidant activity, was evaluated for its effects in (a) preventing hydrogen peroxide (H2O2)-induced cellular damage and (b) blocking the phenylephrine-induced hypertrophic response. Using the in vitro model of embryonic rat heart-derived H9c2 cells, we showed that silibinin has a rather safe profile as concentrations up to 200μM did not affect cell viability. Pretreatment of H9c2 cells with silibinin resulted in better protection of H9c2 cells under conditions of H2O2-induced cellular stress compared to untreated cells as indicated by cell viability and DNA fragmentation assays. Furthermore, silibinin attenuated the phenylephrine-induced hypertrophic response as evidenced by the measurement of cell surface, up-regulation of atrial natriuretic peptide and increase of cellular protein levels. Moreover, silibinin repressed the phenylephrine-induced phosphorylation of ERK1/2 kinases, while it appeared to inhibit the weakly activated by phenylephrine phosphorylation of Akt. Based on our results, silibinin may attenuate the phenylephrine-induced hypertrophic response of H9c2 cells via antioxidant mechanisms involving mainly the inhibition of the intracellular signaling pathways mediated by ERK1/2 MAPKs and Akt.
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Affiliation(s)
- Ioannis Anestopoulos
- Department of Molecular Biology and Genetics, Democritus University of Thrace, University Campus, Dragana, Alexandroupolis 68100, Greece
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Lee YH, Kumar NC, Glickman RD. Modulation of photochemical damage in normal and malignant cells by naturally occurring compounds. Photochem Photobiol 2012; 88:1385-95. [PMID: 22486439 DOI: 10.1111/j.1751-1097.2012.01156.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Certain phytochemicals, such as the stilbene, resveratrol (RES, found in red grapes and berries), and the triterpenoid, ursolic acid (UA, found in waxy berries and herbs such as rosemary and oregano), have antioxidant, anti-inflammatory and antiproliferative effects. Two human-derived cell lines, hTERT-RPE with a nonmalignant phenotype derived from retinal pigment epithelium, and ATCC CRL-11147 derived from a malignant skin melanoma, were used as in vitro models of photooxidative stress produced by exposure to the broadband output of a 150 W Hg vapor arc lamp at an irradiance of 19-26 mW cm(-2). In untreated cells, UV-VIS broadband light exposure produced a loss of proliferative ability, an activation of NF-κB and an increase in protein carbonyl adducts at 24 h postexposure. Pretreatment of the cells with RES or UA at 1-2 μmsignificantly reduced the amount of phosphorylated NF-κB at 24 h postexposure. RES pretreatment reduced the burden of light-induced protein carbonyl adducts by up to 25% in exposed cells. UA treatment markedly increased the sensitivity of melanoma cells to UV radiation, while conferring some photoprotection to RPE cells. These observations indicate that phytochemicals modulate the cellular response to photochemical stress by interacting with specific cell-signaling pathways.
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Affiliation(s)
- Yuan-Hao Lee
- Department of Radiological Sciences, University of Texas Health Science Center, San Antonio, TX, USA
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12
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Resveratrol role in cardiovascular and metabolic health and potential mechanisms of action. Nutr Res 2012; 32:648-58. [DOI: 10.1016/j.nutres.2012.07.002] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Revised: 07/03/2012] [Accepted: 07/05/2012] [Indexed: 12/18/2022]
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Liu X, Qiu J, Zhao S, You B, Ji X, Wang Y, Cui X, Wang Q, Gao H. Grape seed proanthocyanidin extract alleviates ouabain-induced vascular remodeling through regulation of endothelial function. Mol Med Rep 2012; 6:949-54. [PMID: 22895622 PMCID: PMC3493090 DOI: 10.3892/mmr.2012.1026] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2012] [Accepted: 08/01/2012] [Indexed: 11/29/2022] Open
Abstract
Recent studies indicate that chronic ouabain treatment leads to hypertension and hypertensive vascular remodeling. Grape seed proanthocyanidin extract (GSPE) has been reported to be effective in treating arteriosclerosis, while little is known about its effect on systolic blood pressure and vascular remodeling. In this study, the effects of GSPE on systolic blood pressure and vascular remodeling were analyzed by treating ouabain-induced hypertensive rats with GSPE (250 mg/kg·d). The expression of nitric oxide (NO) and endothelin-1 (ET-1) in thoracic aorta was examined by ELISA; the mRNA and protein levels of TGF-β1 were detected using real-time PCR and western blotting, respectively. The results showed that the systolic blood pressure was significantly decreased following treatment with GSPE, with blocked vascular remodeling. The ET-1 content was reduced while NO production was increased in the GSPE group, which showed improved vascular endothelial function. Moreover, GSPE also reduced TGF-β1 expression in the thoracic aorta, which is a determinant in vascular remodeling. In conclusion, GSPE antagonized ouabain-induced hypertension and vascular remodeling and is recommended as a potential anti-hypertensive agent for patients with hypertensive vascular diseases.
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Affiliation(s)
- Xiangju Liu
- Department of Geriatrics, Shandong University Qilu Hospital, Jinan, Shandong 250012, PR China
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Guler A, Sahin MA, Yucel O, Yokusoglu M, Gamsizkan M, Ozal E, Demirkilic U, Arslan M. Proanthocyanidin prevents myocardial ischemic injury in adult rats. Med Sci Monit 2012; 17:BR326-331. [PMID: 22037735 PMCID: PMC3539496 DOI: 10.12659/msm.882042] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background Proanthocyanidin is a bioflavonoid known to have protective effect against oxidative injury. We investigated the cardioprotective effect of proanthocyanidin. Material/Methods Thirty-two Rattus Norvegicus rats were categorized equally as the control group (CG), proanthocyanidin group (PCG), ischemia group (IG) and proanthocyanidin-treated group (PCT). Rats in CG and IG were fed standard rat food and PCG and PCT were fed standard rat food plus proanthocyanidin (100 mg/kg/day twice a day by oral gavage) for 3 weeks. In CG and PCG the myocardial samples were prepared immediately, and in IG and PCT hearts were placed in transport solution and kept at 4°C for 5 hours, then prepared for evaluation. Malondialdehyde (MDA) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were measured. Results MDA levels were significantly higher in IG and PCT than in CG and PCG. The activity of SOD was significantly lower in IG and higher in PCG than in the other groups. The activity of GPx was significantly lower in IG than in the other groups. The activities of CAT were significantly lower in IG and PCT than in the other groups and were significantly lower in IG than PCT. Histopathologic evaluation revealed normal findings in CG and PCG. While ischemic injury was observed in IG, the content of muscle fibers was better preserved in PCT. Conclusions Proanthocyanidin may have a protective effect on myocardial ischemic injury.
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Affiliation(s)
- Adem Guler
- Department of Cardiovascular Surgery, Gulhane Military Medical School, Ankara, Turkey
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15
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Aiello EA, Cingolani HE. A possible subcellular mechanism underlying the "French paradox": the opening of mitochondrial K(ATP) channels. Appl Physiol Nutr Metab 2012; 36:768-72. [PMID: 21999300 DOI: 10.1139/h11-089] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
A reduction in the risk of coronary heart disease has been associated to moderate red wine consumption. We tested whether a nonalcoholic red wine extract would open mitochondrial K(ATP) channels in guinea pig myocytes. The opening of mitochondrial K(ATP) channels was assessed by endogenous flavoprotein fluorescence. Red wine extract (100 μg·mL(-1)) increased flavoprotein oxidation (10.9% ± 1.2%, n = 20). This effect was prevented by the mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate (500 µmol·L(-1); 0.3% ± 1.1%, n = 13), confirming the hypothesis that red wine extract opens mitochondrial K(ATP) channels.
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Affiliation(s)
- Ernesto A Aiello
- Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, UNLP, La Plata, Argentina.
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16
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Abstract
The oxidative stress theory has been associated with atherosclerosis and has prompted a multitude of studies to evaluate the effects of antioxidants on cardiovascular disease prevention. Resveratrol, a relatively new antioxidant has gained considerable curiosity. This polyphenol stilbene identified in grape skin, is believed to be the main component contributing to the anti-atherosclerotic benefits linked to red wine consumption. It has demonstrated the ability to protect endothelial cells from lipid damage, promote vasodilation via modulation of nitric oxide synthesis, and inhibit platelet aggregation and smooth muscle proliferation. Although the complete mechanism of Resveratrol has yet to be fully elucidated, the Sirtuin system, consisting of 7 highly conserved families of regulator genes, are thought to be instrumental in establishing the various health benefits. In this article we assess the current applications, mechanism, pharmacokinetics, bioavailability, and safety profile of the novel antioxidant Resveratrol and provide an in-depth review of the influence of the Sirtuin system on the Resveratrol mechanism of action. We resolve that while early data on Resveratrol are promising, the anti-oxidative and ultimately, anti-atherosclerotic potential depends on further clarification of the intricate and complex relationship between Resveratrol and the Sirtruin system.
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Affiliation(s)
- Dilbahar S Mohar
- Division of Cardiology, University of California, Irvine, California, USA
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17
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Yi CO, Jeon BT, Shin HJ, Jeong EA, Chang KC, Lee JE, Lee DH, Kim HJ, Kang SS, Cho GJ, Choi WS, Roh GS. Resveratrol activates AMPK and suppresses LPS-induced NF-κB-dependent COX-2 activation in RAW 264.7 macrophage cells. Anat Cell Biol 2011; 44:194-203. [PMID: 22025971 PMCID: PMC3195823 DOI: 10.5115/acb.2011.44.3.194] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2011] [Revised: 08/10/2011] [Accepted: 08/23/2011] [Indexed: 02/02/2023] Open
Abstract
AMP-activated protein kinase (AMPK), an enzyme involved in energy homeostasis, regulates inflammatory responses, but its precise mechanisms are not fully understood. Recent evidence has shown that resveratrol (RES), an AMPK activator, reduces prostaglandin E2 production in lipopolysaccharide (LPS)-treated microglia. Here, we examined the effect of RES on nuclear factor kappa B (NF-κB) dependent cyclooxygenase (COX)-2 activation in LPS-treated RWA 264.7 macrophages. We found that treatment with RES increased AMPK activation. AMPK and acetyl CoA carboxylase phosphorylation were attenuated in cells treated with LPS+RES, compared to cells treated with LPS alone. RES inhibited tumor necrosis factor (TNF)-α and TNF receptor 1 in LPS-treated cells. Finally, RES inhibited LPS-induced NF-κB translocation into the nucleus and COX-2 expression. Moreover, the effects of 5-aminoimidazole-4-carboxamide ribose and compound C were consistent with the effects of RES in LPS-treated cells. Taken together, these results suggest that the anti-inflammatory action of RES in RAW 264.7 macrophages is dependent on AMPK activation and is associated with inhibition of the LPS-stimulated NF-κB-dependent COX-2 signaling pathway.
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Affiliation(s)
- Chin-Ok Yi
- Department of Anatomy and Neurobiology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
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18
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Shetty AK. Promise of resveratrol for easing status epilepticus and epilepsy. Pharmacol Ther 2011; 131:269-86. [PMID: 21554899 PMCID: PMC3133838 DOI: 10.1016/j.pharmthera.2011.04.008] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2011] [Accepted: 03/29/2011] [Indexed: 12/26/2022]
Abstract
Resveratrol (RESV; 3,5,4'-tri-hydroxy stilbene), a naturally occurring phytoalexin, is found at a high concentration in the skin of red grapes and red wine. RESV mediates a wide-range of biological activities, which comprise an increased life span, anti-ischemic, anti-cancer, antiviral, anti-aging and anti-inflammatory properties. Studies in several animal prototypes of brain injury suggest that RESV is an effective neuroprotective compound. Ability to enter the brain after a peripheral administration and no adverse effects on the brain or body are other features that are appealing for using this compound as a therapy for brain injury or neurodegenerative diseases. The goal of this review is to discuss the promise of RESV for treating acute seizures, preventing the acute seizure or status epilepticus induced development of chronic epilepsy, and easing the chronic epilepsy typified by spontaneous recurrent seizures and cognitive dysfunction. First, the various beneficial effects of RESV on the normal brain are discussed to provide a rationale for considering RESV treatment in the management of acute seizures and epilepsy. Next, the detrimental effects of acute seizures or status epilepticus on the hippocampus and the implications of post-status epilepticus changes in the hippocampus towards the occurrence of chronic epilepsy and cognitive dysfunction are summarized. The final segment evaluates studies that have used RESV as a neuroprotective compound against seizures, and proposes studies that are critically needed prior to the clinical application of RESV as a prophylaxis against the development of chronic epilepsy and cognitive dysfunction after an episode of status epilepticus or head injury.
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Affiliation(s)
- Ashok K Shetty
- Medical Research and Surgery Services, Veterans Affairs Medical Center, Durham, NC 27705, USA.
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19
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Kovacic P, Somanathan R. Multifaceted approach to resveratrol bioactivity: Focus on antioxidant action, cell signaling and safety. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2010; 3:86-100. [PMID: 20716933 DOI: 10.4161/oxim.3.2.11147] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Resveratrol (RVT) is a naturally occurring trihydroxy stilbene that displays a wide spectrum of physiological activity. Its ability to behave therapeutically as a component of red wine has attracted wide attention. The phenol acts as a protective agent involving various body constituents. Most attention has been given to beneficial effects in insults involving cancer, aging, cardiovascular system, inflammation and the central nervous system. One of the principal modes of action appears to be as antioxidant. Other mechanistic pathways entail cell signaling, apoptosis and gene expression. There is an intriguing dichotomy in relation to pro-oxidant property. Also discussed are metabolism, receptor binding, rationale for safety and suggestions for future work. This is the first comprehensive review of RVT based on a broad, unifying mechanism.
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Affiliation(s)
- Peter Kovacic
- Department of Chemistry, San Diego State University, San Diego, CA, USA.
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Crataegus oxycantha Extract Attenuates Apoptotic Incidence in Myocardial Ischemia-Reperfusion Injury by Regulating Akt and Hif-1 Signaling Pathways. J Cardiovasc Pharmacol 2010; 56:526-31. [DOI: 10.1097/fjc.0b013e3181f64c51] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Assessment of 3-nitropropionic acid-evoked peripheral neuropathy in rats: Neuroprotective effects of acetyl-l-carnitine and resveratrol. Neurosci Lett 2010; 480:117-21. [DOI: 10.1016/j.neulet.2010.06.020] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2010] [Revised: 05/11/2010] [Accepted: 06/05/2010] [Indexed: 11/24/2022]
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Abstract
Epidemiological and experimental studies have revealed that a mild to moderate drinking of wine, particularly red wine, attenuates the cardiovascular, cerebrovascular, and peripheral vascular risk. However, the experimental basis for such health benefits is not fully understood. The cardioprotective effect of wine has been attributed to both components of wine: the alcoholic portion and, more importantly, the alcohol-free portion containing antioxidants. Wines are manufactured from grapes, which also contain a large variety of antioxidants, including resveratrol, catechin, epicatechin, and proanthocyanidins. Resveratrol is mainly found in the grape skin, whereas proanthocyanidins are found only in the seeds. Recent studies have demonstrated that resveratrol and proanthocyanidin are the major compounds present in grapes and wines responsible for cardioprotection. The purpose of this review is to provide evidence that grapes, wines, and resveratrol are equally important in reducing the risk of morbidity and mortality due to cardiovascular complications. Both wines and grapes can attenuate cardiac diseases such as atherosclerosis and ischemic heart disease. Recently, wine was also found to increase life span by inducing longevity genes. It appears that resveratrol and proanthocyanidins, especially resveratrol, present in grapes and wines play a crucial role in cardioprotective abilities of grapes and wines.
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23
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Resveratrol protects against experimental stroke: putative neuroprotective role of heme oxygenase 1. Exp Neurol 2010; 224:325-9. [PMID: 20381489 DOI: 10.1016/j.expneurol.2010.03.032] [Citation(s) in RCA: 126] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2009] [Revised: 03/12/2010] [Accepted: 03/30/2010] [Indexed: 11/23/2022]
Abstract
Epidemiological and experimental reports have linked mild-to-moderate wine and/or grape consumption to a lowered incidence of cardiovascular, cerebrovascular, and peripheral vascular risk. This study revealed that resveratrol, an enriched bioactive polyphenol in red wine, selectively induces heme oxygenase 1 (HO1) in a dose- and time-dependent manner in cultured mouse cortical neuronal cells and provides neuroprotection from free-radical or excitotoxicity damage. This protection was lost when cells were treated with a protein synthesis or heme oxygenase inhibitor, suggesting that HO1 induction is at least partially required for resveratrol's prophylactic properties. Furthermore, resveratrol pretreatment dose-dependently protected mice subjected to an optimized ischemic-reperfusion stroke model. Mice in which HO1 was selectively deleted lost most, if not all, of the beneficial effects. Together, the data suggest a potential intracellular pathway by which resveratrol can provide cell/organ resistance against neuropathological conditions.
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Leone S, Cornetta T, Basso E, Cozzi R. Resveratrol induces DNA double-strand breaks through human topoisomerase II interaction. Cancer Lett 2010; 295:167-72. [PMID: 20304553 DOI: 10.1016/j.canlet.2010.02.022] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2009] [Revised: 02/22/2010] [Accepted: 02/25/2010] [Indexed: 01/22/2023]
Abstract
Resveratrol, a stilbene found in grapes and wine, is one of the most interesting natural compound due to its role exerted in cancer prevention and therapy. In particular, resveratrol is able to delay cell cycle progression and to induce apoptotic death in several cell lines. Here we report that resveratrol treatment of human glioblastoma cells induces a delay in cell cycle progression during S phase associated with an increase in histone H2AX phosphorylation. Furthermore, with an in vitro assay of topoisomerase IIalpha catalytic activity we show that resveratrol is able to inhibit the ability of recombinant human TOPO IIalpha to decatenate kDNA, so that it could be considered a TOPO II poison.
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Affiliation(s)
- Stefano Leone
- Dipartimento di Biologia, Università degli Studi Roma Tre, Roma, Italy
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25
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Perez-Vizcaino F, Duarte J, Andriantsitohaina R. Endothelial function and cardiovascular disease: Effects of quercetin and wine polyphenols. Free Radic Res 2009; 40:1054-65. [PMID: 17015250 DOI: 10.1080/10715760600823128] [Citation(s) in RCA: 119] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Endothelial dysfunction is an early pathophysiological feature and independent predictor of poor prognosis in most forms of cardiovascular diseases. Epidemiological studies report an inverse association between dietary flavonoid consumption and mortality from cardiovascular diseases. In the present paper, we review the effects of flavonoids, especially quercetin and wine polyphenols, on endothelial function and dysfunction and its potential protective role in hypertension, ischemic heart disease and stroke. In vitro studies show that flavonoids may exert multiple actions on the NO-guanylyl cyclase pathway, endothelium-derived hyperpolarizing factor(s) and endothelin-1 and protect endothelial cells against apoptosis. In vivo, flavonoids prevent endothelial dysfunction and reduce blood pressure, oxidative stress and end-organ damage in hypertensive animals. Moreover, some clinical studies have shown that flavonoid-rich foods can improve endothelial function in patients with hypertension and ischemic heart disease. Altogether, the available evidence indicates that quercetin and wine polyphenols might be of therapeutic benefit in cardiovascular diseases even though prospective controlled clinical studies are still lacking.
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Affiliation(s)
- Francisco Perez-Vizcaino
- Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
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26
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Qian Y, Agne A, Chira K, Teissèdre PL, Décordé K, Ventura E, Cristol JP, Rouanet JM. A moderate consumption of Côtes du Rhône red wines affects the progression of aortic lesions, and reduces oxidative stress and p22phoxNADPH oxidase activation in an experimental model of diet-induced atherosclerosis, according to the vinification process. Eur Food Res Technol 2009. [DOI: 10.1007/s00217-009-1065-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Singh RB, Elimban V, Dhalla NS. Differences in ischemia-reperfusion-induced endothelial changes in hearts perfused at constant flow and constant pressure. J Appl Physiol (1985) 2008; 105:1779-87. [DOI: 10.1152/japplphysiol.00076.2008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Isolated hearts subjected to ischemia-reperfusion (I/R) exhibit depressed cardiac performance and alterations in subcellular function. Since hearts perfused at constant flow (CF) and constant pressure (CP) show differences in their contractile response to I/R, this study was undertaken to examine mechanisms responsible for these I/R-induced alterations in CF-perfused and CP-perfused hearts. Rat hearts, perfused at CF (10 ml/min) or CP (80 mmHg), were subjected to I/R (30 min global ischemia followed by 60 min reperfusion), and changes in cardiac function as well as sarcolemmal (SL) Na+-K+-ATPase activity, sarcoplasmic reticulum (SR) Ca2+uptake, and endothelial function were monitored. The I/R-induced depressions in cardiac function, SL Na+-K+-ATPase, and SR Ca2+-uptake activities were greater in hearts perfused at CF than in hearts perfused at CP. In hearts perfused at CF, I/R-induced increase in calpain activity and decrease in nitric oxide (NO) synthase (endothelial NO synthase) protein content in the heart as well as decrease in NO concentration of the perfusate were greater than in hearts perfused at CP. These changes in contractile activity and biochemical parameters due to I/R in hearts perfused at CF were attenuated by treatment with l-arginine, a substrate for NO synthase, while those in hearts perfused at CP were augmented by treatment with NG-nitro-l-arginine methyl ester, an inhibitor of NO synthase. The results indicate that the I/R-induced differences in contractile responses and alterations in subcellular organelles between hearts perfused at CF and CP may partly be attributed to greater endothelial dysfunction in CF-perfused hearts than that in CP-perfused hearts.
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Abstract
The use of complimentary and alternative medicine is on the rise. This article reviews some of the commonly used herbal supplements and others focusing mainly on disease prevention. A summary table of medical conditions is provided, and when possible, a summary of efficacy and safety is provided to facilitate decision making.
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Affiliation(s)
- Wadie Najm
- Department of Family Medicine, University of California, Irvine School of Medicine, 101 The City Drive South, Building 200, Suite 512, Irvine, CA 92868, USA.
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29
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Ma HJ, Cao YK, Liu YX, Wang R, Wu YM. Microinjection of resveratrol into rostral ventrolateral medulla decreases sympathetic vasomotor tone through nitric oxide and intracellular Ca2+ in anesthetized male rats. Acta Pharmacol Sin 2008; 29:906-12. [PMID: 18664323 DOI: 10.1111/j.1745-7254.2008.00827.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
AIM To define the effect of resveratrol (RES) on the central regulation of blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA). METHODS RES was microinjected into the rostral ventrolateral medulla (RVLM), and BP, HR, and RSNA were recorded simultaneously in anesthetized rats. RESULTS A microinjection of RES (20, 40, and 80 micromol/L, 0.2 microL) into the RVLM dose dependently decreased BP, HR, and RSNA. Pretreatment with an anti-estrogen tamoxifen (100 micromol/L, 0.2 microL) did not affect the effects of RES. Pretreatment with NG-nitro- L-arginine methyl ester (100 micromol/L, 0.2 microL), an inhibitor of nitric oxide (NO) synthase, could completely abolish the effect of RES. A prior microinjection of Bay K8644 (500 nmol/L, 0.2 microL), an agonist of calcium channels, could also abrogate the effect of RES. Prior administration of a potent inhibitor of tyrosine phosphatase, sodium orthovanadate (1 mmol/L, 0.2 microL), could partially attenuate the inhibitory effect of RES. CONCLUSION The results suggest that a microinjection of RES into the RVLM inhibits BP, HR, and RSNA. The effects may be mediated by NO synthesis and a decrease in Ca2+ influx, in which protein tyrosine kinase is involved.
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Affiliation(s)
- Hui-juan Ma
- Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China
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Agrawal P, Halaweish F, Dwivedi C. Antioxidant Effects and Drug Interactions of Resveratrol Present in Wine. ACTA ACUST UNITED AC 2007. [DOI: 10.1080/09571260701660839] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Abstract
Numerous studies have used a J-shaped or U-shaped curve to describe the relationship between alcohol use and total mortality. The nadir of the curves based on recent meta-analysis suggested optimal benefit at approximately half a drink per day. Fewer than 4 drinks per day in men and fewer than 2 per day in women appeared to confer benefit. Reductions in cardiovascular death and nonfatal myocardial infarction were also associated with light to moderate alcohol intake. Although some studies suggested that wine had an advantage over other types of alcoholic beverages, other studies suggested that the type of drink was not important. Heavy drinking was associated with an increase in mortality, hypertension, alcoholic cardiomyopathy, cancer, and cerebrovascular events, including cerebrovascular hemorrhage. Paradoxically, light-to-moderate alcohol use actually reduced the development of heart failure and did not appear to exacerbate it in most patients who had underlying heart failure. Numerous mechanisms have been proposed to explain the benefit that light-to-moderate alcohol intake has on the heart, including an increase of high-density lipoprotein cholesterol, reduction in plasma viscosity and fibrinogen concentration, increase in fibrinolysis, decrease in platelet aggregation, improvement in endothelial function, reduction of inflammation, and promotion of antioxidant effects. Controversy exists on whether alcohol has a direct cardioprotective effect on ischemic myocardium. Studies from our laboratory do not support the concept that alcohol has a direct cardioprotective effect on ischemic/reperfused myocardium. Perhaps the time has come for a prospectively randomized trial to determine whether 1 drink per day (or perhaps 1 drink every other day) reduces mortality and major cardiovascular events.
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Affiliation(s)
- Robert A Kloner
- Heart Institute, Good Samaritan Hospital, 1225 Wilshire Blvd, Los Angeles, CA 90017, USA.
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Buluc M, Ayaz M, Turan B, Demirel-Yilmaz E. Resveratrol-induced depression of the mechanical and electrical activities of the rat heart is reversed by glyburide: evidence for possible K(ATP) channels activation. Arch Pharm Res 2007; 30:603-7. [PMID: 17615680 DOI: 10.1007/bf02977655] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Resveratrol, a natural phytoalexin found in wine, has been suggested to have benefits in preventing cardiovascular diseases. However, the direct effects of resveratrol on the activity of cardiac tissues and its mechanism of action have not been determined. This study examined the effects of resveratrol on the right and left atrium and left papillary muscle isolated from the rat heart. The contractile responses of the right atrium and papillary muscle and the action potential from the left atrium were recorded and the effects of resveratrol on these responses were observed. The resting force of the isolated right atrium and the peak developed force of the left papillary muscle were depressed by resveratrol (0.1 nM - 0.1 mM). Exposure to the K(ATP) channel blocker glyburide (3 microM) prevented significantly the resveratrol-induced decrease. Resveratrol (0.1 mM) shortened the repolarization phase of action potential recorded from the left atrium and this effect of resveratrol was reversed by glyburide (3 microM). These results indicated that resveratrol depressed cardiac muscle contraction and shortened action potential duration probably due to the activation of K(ATP) channels in the rat heart.
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Affiliation(s)
- Mesut Buluc
- Department of Pharmacology and Clinical Pharmacology, Ankara University, Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey
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Szabolcs A, Varga IS, Varga C, Berkó A, Kaszaki J, Letoha T, Tiszlavicz L, Sári R, Lonovics J, Takács T. Beneficial effect of resveratrol on cholecystokinin-induced experimental pancreatitis. Eur J Pharmacol 2006; 532:187-93. [PMID: 16499907 DOI: 10.1016/j.ejphar.2006.01.055] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2005] [Revised: 01/23/2006] [Accepted: 01/25/2006] [Indexed: 12/28/2022]
Abstract
Resveratrol is a phytoalexin with strong antioxidant and anti-inflammatory effects reaching high concentrations in red wine. The aim of our study was to test the effects of resveratrol pretreatment on cholecystokinin-octapeptide (CCK-8)-induced acute pancreatitis in rats. Animals were divided into a control group, a group treated with CCK-8 and a group receiving 10 mg/kg resveratrol prior to CCK-8 administration. Resveratrol ameliorated the CCK-8-induced changes in the laboratory parameters, and reduced the histological damage in the pancreas. The drug failed to improve the pancreatic antioxidant state, but increased the amount of hepatic reduced glutathione and prevented the reduction of hepatic catalase activity. Resveratrol-induced inhibition of nuclear factor kappa B (NF-kappaB) activation or reduction of the pancreatic tumor necrosis factor-alpha (TNF-alpha) concentration could not be demonstrated. In conclusion, the beneficial effects of resveratrol on acute pancreatitis seem to be mediated by the antioxidant effect of resveratrol or by an NF-kappaB-independent anti-inflammatory mechanism.
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Affiliation(s)
- Annamária Szabolcs
- First Department of Medicine, University of Szeged, Faculty of Medicine, H-6720 Szeged, Korányi fasor 8, Hungary.
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Abstract
Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Despite scepticism concerning its bioavailability, a growing body of in vivo evidence indicates that resveratrol has protective effects in rodent models of stress and disease. Here, we provide a comprehensive and critical review of the in vivo data on resveratrol, and consider its potential as a therapeutic for humans.
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Affiliation(s)
- Joseph A Baur
- Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
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Gago-Dominguez M, Castelao JE, Pike MC, Sevanian A, Haile RW. Role of Lipid Peroxidation in the Epidemiology and Prevention of Breast Cancer. Cancer Epidemiol Biomarkers Prev 2005; 14:2829-39. [PMID: 16364997 DOI: 10.1158/1055-9965.epi-05-0015] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We have recently proposed a common mechanistic pathway by which obesity and hypertension lead to increased renal cell cancer risk. Our hypothesis posits lipid peroxidation, which is a principal mechanism in rodent renal carcinogenesis, as an intermediate step that leads to a final common pathway shared by numerous observed risks (including obesity, hypertension, smoking, oophorectomy/hysterectomy, parity, preeclampsia, diabetes, and analgesics) or protective factors (including oral contraceptive use and alcohol) for renal cell cancer [Cancer Causes Control 2002;13:287-93]. During this exercise, we have noticed how certain risk factors for renal cell carcinoma are protective for breast cancer and how certain protective factors for renal cell carcinoma increase risk for breast cancer. Parity and oophorectomy, for example, are positively associated with renal cell carcinoma but are negatively associated with breast cancer. Similarly, obesity and hypertension are positively associated with renal cell carcinoma, but obesity is negatively associated with breast cancer in premenopausal women and hypertension during pregnancy is negatively associated with breast cancer. Furthermore, alcohol intake, negatively associated with renal cell carcinoma, is also positively associated with breast cancer. We propose here the possibility that lipid peroxidation may represent a protective mechanism in breast cancer. Although this runs counter to the conventional view that lipid peroxidation is a process that is harmful and carcinogenic, we present here the chemical and biological rationale, based on epidemiologic and biochemical data, which may deserve further consideration and investigation.
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Affiliation(s)
- Manuela Gago-Dominguez
- USC/Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089-9181, USA.
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Celik O, Erdem G, Hascalik S, Karakas HM, Tamser M. Magnetic resonance spectroscopic comparison of the effects of resveratrol (3,4',5-trihydroxy stilbene) to conjugated equine estrogen, tibolone and raloxifene on ovariectomized rat brains. Eur J Obstet Gynecol Reprod Biol 2005; 120:73-9. [PMID: 15866090 DOI: 10.1016/j.ejogrb.2004.10.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2004] [Revised: 10/08/2004] [Accepted: 10/20/2004] [Indexed: 11/18/2022]
Abstract
OBJECTIVE To investigate the effects of resveratrol on basic cerebral metabolites of in the brains of ovariectomized rats. MATERIALS AND METHODS Twenty-four bilaterally ovariectomized rats were randomly assigned into six groups with four rats in each group. The groups consisted of sham-operated (control), ovariectomized, resveratrol, conjugated equine estrogen (CEE), tibolone and raloxifene treated rats. Drug administration started at the 5th day following ovariectomy and continued for 35 days. At the end of the entire course, in vivo single voxel magnetic resonance spectroscopy was performed on whole brains to determine choline, creatine and N-acetyl aspartate (NAA) concentrations. RESULTS Compared to sham-operated group, ovariectomized group had significantly lower NAA (P<0.008) but significantly higher choline levels (P<0.031). Administration of CEE and resveratrol resulted in NAA levels that were similar to those in the sham-operated group, showing that the NAA decrease due to ovariectomy was prevented. Treatment with tibolone and raloxifene resulted in a smaller increase in NAA and the effect failed to reach significance. Administration of resveratrol, CEE, tibolone and raloxifene resulted in choline levels similar to those in sham-operated group, showing that the increase in the ovariectomy group was prevented. CONCLUSION Resveratrol causes levels of cerebral metabolites that is similar to conventional hormone replacement agents. This finding may suggest that neuronal function in the postmenopausal state was preserved. More detailed investigation of this issue should be the task of future research.
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Affiliation(s)
- Onder Celik
- Inonu University, Medical Faculty, Department of Obstetric and Gynecology, Malatya, Turkey
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Doré S. Unique Properties of Polyphenol Stilbenes in the Brain: More than Direct Antioxidant Actions; Gene/Protein Regulatory Activity. Neurosignals 2005; 14:61-70. [PMID: 15956815 DOI: 10.1159/000085386] [Citation(s) in RCA: 84] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2004] [Accepted: 03/01/2005] [Indexed: 11/19/2022] Open
Abstract
The 'French Paradox' has been typically associated with moderate consumption of wine, especially red wine. A polyphenol 3,4',5-trihydroxy-trans-stilbene (a member of the non-flavonoids family), better known as resveratrol, has been purported to have many health benefits. A number of these valuable properties have been attributed to its intrinsic antioxidant capabilities, although the potential level of resveratrol in the circulation is likely not enough to neutralize free radical scavenging. The brain and the heart are uniquely vulnerable to hypoxic conditions and oxidative stress injuries. Recently, evidence suggests that resveratrol could act as a signaling molecule within tissues and cells to modulate the expression of genes and proteins. Stimulation of such proteins and enzymes could explain some the intracellular antioxidative properties. The modulation of genes could suffice as an explanation of some of resveratrol's cytoprotective actions, as well as its influence on blood flow, cell death, and inflammatory cascades. Resveratrol stimulation of the expression of heme oxygenase is one example. Increased heme oxygenase activity has led to significant protection against models of in vitro and in vivo oxidative stress injury. Resveratrol could provide cellular resistance against insults; although more work is necessary before it is prescribed as a potential prophylactic in models of either acute or chronic conditions, such as stroke, amyotrophic lateral sclerosis, Parkinson, Alzheimer, and a variety of age-related vascular disorders.
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Affiliation(s)
- Sylvain Doré
- Johns Hopkins University, School of Medicine, ACCM Department, Baltimore, MD 21205, USA.
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Takeda S, Mochizuki S, Saini HK, Elimban V, Dhalla NS. Modification of alterations in cardiac function and sarcoplasmic reticulum by vanadate in ischemic-reperfused rat hearts. J Appl Physiol (1985) 2005; 99:999-1005. [PMID: 15879166 DOI: 10.1152/japplphysiol.00234.2005] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
To study the cardioprotective effects of vanadate on ischemia-reperfusion (I/R) injury, isolated rat hearts perfused at constant flow were subjected to global ischemia for 30 min followed by reperfusion for 30 min. In this experimental model, I/R markedly decreased ventricular developed pressure and increased end-diastolic pressure. Pretreatment of hearts with 4 microM vanadate attenuated I/R-induced cardiac dysfunction. The reduction in sarcoplasmic reticulum (SR) Ca2+ uptake and Ca2+ release, as well as SR protein contents for Ca2+-pump ATPase and Ca2+-release channel, was also prevented by vanadate. Pretreatment of hearts with an antioxidant mixture containing superoxide dismutase + catalase exerted effects similar to those of vanadate in I/R hearts. Postischemic treatment of hearts with vanadate or superoxide dismutase + catalase also had beneficial effects on I/R-induced changes in cardiac performance and SR function. Alterations in cardiac function and SR Ca2+ transport due to an oxyradical-generating system (xanthine + xanthine oxidase) or an oxidant (H2O2) were attenuated by treatment with vanadate. These results suggest that vanadate may exert beneficial effects on cardiac performance and SR function in I/R hearts because of its antioxidant action.
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Affiliation(s)
- Satoshi Takeda
- Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Ave., Winnipeg, MB, Canada R2H 2A6
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McMichael M. Ischemia-reperfusion injury: assessment and treatment, part II. J Vet Emerg Crit Care (San Antonio) 2004. [DOI: 10.1111/j.1476-4431.2004.04005.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Wu SL, Sun ZJ, Yu L, Meng KW, Qin XL, Pan CE. Effect of resveratrol and in combination with 5-FU on murine liver cancer. World J Gastroenterol 2004; 10:3048-52. [PMID: 15378791 PMCID: PMC4576270 DOI: 10.3748/wjg.v10.i20.3048] [Citation(s) in RCA: 84] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To study the anti-tumor effect of resveratrol and in combination with 5-FU on murine liver cancer.
METHODS: Transplantable murine hepatoma22 model was used to evaluate the anti-tumor activity of resveratrol (RES) alone or in combination with 5-FU in vivo. H22 cell cycles were analyzed with flow cytometry.
RESULTS: Resveratrol could inhibit the growth of murine hepatoma22, after the mice bearing H22 tumor were treated with 10 mg/kg or 15 mg/kg resveratrol for ten days, and the inhibition rates were 36.3% (n = 10) and 49.3% (n = 9), respectively, which increased obviously compared with that in control group (85 ± 22 vs 68 ± 17, P < 0.01). RES could induce the S phase arrest of H22 cells, and increase the persentage of cells in S phase from 59.1% (n = 9) to 73.5% (n = 9) in a dose-dependent manner (P < 0.05). The enhanced inhibition of tumor growth by 5-FU was also observed in hepatoma22 bearing mice when 5-FU was administered in combination with 10 mg/kg resveratrol. The inhibition rates for 20 mg/kg or 10 mg/kg 5-FU in combination with 10 mg/kg resveratrol were 77.4% and 72.4%, respectively, compared with the group of 20 mg/kg or 10 mg/kg 5-FU alone, in which the inhibition rates were 53.4% and 43.8%, respectively (n = 8). There was a statistical significance between the combination group and 5-FU group.
CONCLUSION: RES could induce the S phase arrest of H22 cells and enhance the anti-tumor effect of 5-FU on murine hepatoma22 and antagonize its toxicity markedly. These results suggest that resveratrol, as a biochemical modulator to enhance the therapeutic effects of 5-FU, may be potentially useful in cancer chemotherapy.
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Affiliation(s)
- Sheng-Li Wu
- Department of Hepatobiliary Surgery, First Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
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Bertelli AAE, Morelli R, Lo Scalzo R, Ferrara F. Long-lasting antioxidant activity in a 600-year-old fermented fruit juice. Antioxid Redox Signal 2004; 6:934-40. [PMID: 15345153 DOI: 10.1089/ars.2004.6.934] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Abstract
The phytoantitoxin resveratrol is a plant-derived polyphenol with phytoestrogenic properties. Resveratrol protects the cardiovascular system by mechanisms that include defense against ischemic-reperfusion injury, promotion of vasorelaxation, protection and maintenance of intact endothelium, anti-atherosclerotic properties, inhibition of low-density lipoprotein oxidation, suppression of platelet aggregation, and estrogen-like actions. The purpose of this article is to review the mechanisms of these effects.
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Affiliation(s)
- Han Dong Hao
- Postgraduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Ranaivo HR, Diebolt M, Andriantsitohaina R. Wine polyphenols induce hypotension, and decrease cardiac reactivity and infarct size in rats: involvement of nitric oxide. Br J Pharmacol 2004; 142:671-8. [PMID: 15159281 PMCID: PMC1575045 DOI: 10.1038/sj.bjp.0705833] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
1. The effects of short-term oral administration of red wine polyphenolic compounds (RWPC, 20 mg x kg(-1) day(-1) for 7 days) on haemodynamics, ex vivo cardiac responsiveness and ischaemia-reperfusion injury were investigated in rats. The involvement of nitric oxide (NO) was evaluated using the NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME, 2 mg x kg(-1) day(-1) for 7 days), at a dose which did not affect blood pressure. 2. Ex vivo reactivity of hearts from RWPC-treated rats showed lower basal developed pressure, greater heart rate and decreased inotropic responses to either beta-adrenoceptor or muscarinic receptor stimulation with isoprenaline or carbachol, respectively.3. RWPC treatment did not modify cardiac expression of endothelial NO synthase or Cu/Zn superoxide dismutase. However, it increased nitrite in the coronary effluent. 4. In ischaemia-reperfusion, RWPC treatment reduced infarct size and oxidative stress, as shown by the myocardial content of the end products of lipid peroxidation, malondialdehyde and 4-hydroxynonenal, without affecting post-ischaemic contractile dysfunction. All the observed effects of RWPC were prevented by l-NAME treatment. 5. Altogether, these data show that short-term treatment with RWPC decreases blood pressure and cardiac responsiveness, and protects against post-ischaemic infarction via decreased oxidative stress. All the above effects of RWPC are sensitive to NO synthase inhibition that implies an involvement of NO-dependent pathway. This study suggests a basis for the beneficial effects of plant-derived polyphenols against cardiovascular disease.
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Affiliation(s)
- Hantamalala Ralay Ranaivo
- Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, Université Louis Pasteur de Strasbourg, UMR CNRS 7034, Faculté de Pharmacie, 67401 Illkirch, France
| | - Myriam Diebolt
- Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, Université Louis Pasteur de Strasbourg, UMR CNRS 7034, Faculté de Pharmacie, 67401 Illkirch, France
| | - Ramaroson Andriantsitohaina
- Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, Université Louis Pasteur de Strasbourg, UMR CNRS 7034, Faculté de Pharmacie, 67401 Illkirch, France
- Author for correspondence:
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Pagel PS, Kersten JR, Warltier DC. Mechanisms of myocardial protection produced by chronic ethanol consumption. PATHOPHYSIOLOGY 2004; 10:121-9. [PMID: 15006418 DOI: 10.1016/j.pathophys.2003.10.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2003] [Accepted: 10/03/2003] [Indexed: 10/26/2022] Open
Abstract
Recent evidence suggests that chronic ingestion of small quantities of ethanol may protect myocardium from ischemic injury by activating many of the endogenous signal transduction elements that have been implicated during other forms of preconditioning. Studies conducted in a variety of animal models in vitro and in vivo have indicated that chronic ethanol consumption improves functional recovery after global ischemia, reduces biochemical markers of ischemic injury, and decreases myocardial infarct size. Many of these beneficial actions appear to occur independent of alterations in systemic and coronary hemodynamics and transmural myocardial perfusion. To date, adenosine type 1 (A(1)) receptors, alpha(1)-adrenoceptors, the epsilon isoform of protein kinase C (PKC), and adenosine triphosphate-dependent potassium (K(ATP)) channels have been shown to mediate cardioprotection associated with chronic ethanol ingestion. These data suggest another mechanism by which chronic, intermittent consumption of ethanol may reduce overall cardiovascular mortality, decrease the incidence of coronary artery disease, and improve survival after myocardial infarction in humans. In this brief review, we discuss current evidence supporting a role for endogenous signaling in chronic ethanol-induced myocardial protection against ischemic injury.
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Affiliation(s)
- Paul S Pagel
- Department of Anesthesiology, Division of Cardiovascular Diseases, The Medical College of Wisconsin and The Clement J. Zablocki Veterans Affairs Medical Center, MEB-M4280, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
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Rakotovao A, Berthonneche C, Guiraud A, de Lorgeril M, Salen P, de Leiris J, Boucher F. Ethanol, wine, and experimental cardioprotection in ischemia/reperfusion: role of the prooxidant/antioxidant balance. Antioxid Redox Signal 2004; 6:431-8. [PMID: 15025945 DOI: 10.1089/152308604322899503] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
It is now well established that oxidative stress resulting from reactive oxygen species (ROS) that are generated in cardiac myocytes subjected to ischemia/reperfusion plays a causative role in the development of heart failure and may contribute to promote cell death. During the last decade, several groups have reported that, in animal models of myocardial ischemia/reperfusion, certain nutrients, including ethanol and nonethanolic components of wine, may have a specific protective effect on the myocardium, independent of the classical risk factors implicated in vascular atherosclerosis and thrombosis. Mechanisms through which the consumption of alcoholic beverages protects against ischemia-induced cardiac injury are still unknown. One major open question is whether ethanol and nonethanolic components of wine are cardioprotective, at least in part, by interfering with the myocardial prooxidant/antioxidant balance. Important concepts, such as cardiac preconditioning, are now entering the field of nutrition, and recent experimental evidence suggests that ethanol and/or nonethanolic components of wine might exert preconditioning effects in animal models of myocardial ischemia/reperfusion. There is no doubt that such an observation, if confirmed in human subjects, might open new perspectives in the prevention and treatment of ischemic coronary heart disease.
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Hascalik S, Celik O, Turkoz Y, Hascalik M, Cigremis Y, Mizrak B, Yologlu S. Resveratrol, a red wine constituent polyphenol, protects from ischemia-reperfusion damage of the ovaries. Gynecol Obstet Invest 2004; 57:218-23. [PMID: 14970669 DOI: 10.1159/000076760] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2003] [Accepted: 12/08/2003] [Indexed: 11/19/2022]
Abstract
OBJECTIVE The aim of this study is to investigate the effects of resveratrol on histopathological changes, antioxidant status and lipid peroxidation, in torsion-detorsion injury in rat ovaries. METHOD To determine whether ischemia followed by reperfusion can induce ovarian oxidative damage, we created a model of adnexal ischemia-reperfusion by using rats. Ischemia was induced by unilateral occlusion of the tubo-ovarian vessels for 3 h. Reperfusion was achieved by releasing the occlusion and restoring the circulation for 3 h. Thirty-two adult female albino rats were divided equally into 4 groups: sham operation, torsion, saline/detorsion and resveratrol/detorsion. Rats in the torsion group were killed after 360 degrees clockwise adnexal torsion for 3 h. Resveratrol was injected intraperitoneally 30 min before detorsion in the resveratrol/detorsion group, and saline was administered in the saline/detorsion group. After 3 h of adnexal detorsion in both of these groups, the rats were killed and adnexa were removed. The tissue levels of malondialdehyde, reduced glutathione and xanthine oxidase activity were measured. RESULTS Malondialdehyde and xanthine oxidase levels in the saline/detorsion group were increased significantly when compared to the torsion and sham operation groups (p < 0.001). Malondialdehyde levels in the resveratrol group were lower than in the saline/detorsion group, and differences between the two groups were statistically significant (p < 0.001). Xanthine oxidase levels in the resveratrol group were lower than in the saline/detorsion and torsion groups, and differences between these groups were statistically significant (p < 0.001). Reduced glutathione levels in the saline/detorsion group were decreased significantly when compared to the torsion and sham operation groups. Reduced glutathione levels in the resveratrol group were significantly higher than in the saline/detorsion group (p < 0.006). Histological examination showed a significant improvement in ovarian morphology in the resveratrol-treated rats compared with the ischemia and ischemia-reperfusion groups. CONCLUSION Our results demonstrated that intraperitoneal resveratrol administration reduced the lipid peroxidation products of ischemic rats and ovarian damage was reduced as indicated by histological examination.
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Affiliation(s)
- Seyma Hascalik
- Department of Obstetrics and Gynecology, School of Medicine, Malatya, Turkey.
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Yu L, Sun ZJ, Wu SL, Pan CE. Effect of resveratrol on cell cycle proteins in murine transplantable liver cancer. World J Gastroenterol 2003; 9:2341-3. [PMID: 14562407 PMCID: PMC4656492 DOI: 10.3748/wjg.v9.i10.2341] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the antitumour activity of resveratrol and its effect on the expression of cell cycle proteins including cyclin D1, cyclin B1 and p34cdc2 in transplanted liver cancer of murine.
METHODS: Murine transplanted hepatoma H22 model was used to evaluate the in vivo antitumor activity of resveratrol. Following abdominal administration of resveratrol, the change in tumour size was recorded and the protein expression of cyclin D1, cyclin B1 and p34cdc2 in the tumor and adjacent noncancerous liver tissues were measured by immunohistochemistry.
RESULTS: Following treatment of H22 tumour bearing mice with resveratrol at 10 or 15 mg/kg bodyweight for 10 d, the growth of murine transplantable liver cancer was inhibited by 36.3% or 49.3%, respectively. The inhibitory effect was significant compared to that in control group (P < 0.05). The level of expression of cyclin B1 and p34cdc2 protein was decreased in the transplantable murine hepatoma 22 treated with resveratrol whereas the expression of cyclin D1 protein did not change.
CONCLUSION: Resveratrol exhibits anti-tumour activities on murine hepatoma H22. The underlying anti-tumour mechanism of resveratrol might involve the inhibition of the cell cycle progression by decreasing the expression of cyclinB1 and p34cdc2 protein.
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Affiliation(s)
- Liang Yu
- Department of Hepatobiliary Surgery, First Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
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Frishman WH, Del Vecchio A, Sanal S, Ismail A. Cardiovascular manifestations of substance abuse: part 2: alcohol, amphetamines, heroin, cannabis, and caffeine. HEART DISEASE (HAGERSTOWN, MD.) 2003; 5:253-71. [PMID: 12877759 DOI: 10.1097/01.hdx.0000080713.09303.a6] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The abuse of alcohol is associated with chronic cardiomyopathy, hypertension, and arrhythmia. Abstinence or using alcohol in moderation can reverse these cardiovascular problems. Alcohol is also distinguished among the substances of abuse by having possible protective effects against coronary artery disease and stroke when used in moderate amounts. Amphetamines (eg, speed, ice, ecstasy) have many of the cardiovascular toxicities seen with cocaine, including acute and chronic cardiovascular diseases. Heroin and other opiates can cause arrhythmias and noncardiac pulmonary edema, and may reduce cardiac output. Cardiovascular problems are less common with cannabis (marijuana) than with opiates, but major cognitive disorders may be seen with its chronic use. It is still controversial whether caffeine can cause hypertension and coronary artery disease, and questions have been raised about its safety in patients with heart failure and arrhythmia.
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Affiliation(s)
- William H Frishman
- Department of Medicine, The New York Medical College/Westchester Medical Center, Valhalla, NY 10595, USA
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Cantor EJF, Mancini EV, Seth R, Yao XH, Netticadan T. Oxidative stress and heart disease: cardiac dysfunction, nutrition, and gene therapy. Curr Hypertens Rep 2003; 5:215-20. [PMID: 12724053 DOI: 10.1007/s11906-003-0023-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Oxidative stress is defined as the imbalance between the generation of reactive oxygen species and antioxidant defense mechanisms. The cardiovascular system is a major target for reactive oxygen species. Cardiomyocytes and the vasculature of the heart can be severely damaged as a result of oxidative stress. In this paper, we discuss recent findings with respect to the role of oxidative stress in heart disease. The efficacies of treatments with vitamins and wine-derived compounds, as well as innovative gene therapeutic experiments that may potentially alleviate oxidative stress-induced disease, are also discussed.
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Affiliation(s)
- Elliott J F Cantor
- Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, Manitoba R2H 2A6, Canada
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Zhuang H, Kim YS, Koehler RC, Doré S. Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann N Y Acad Sci 2003; 993:276-86; discussion 287-8. [PMID: 12853318 DOI: 10.1111/j.1749-6632.2003.tb07534.x] [Citation(s) in RCA: 117] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Polyphenolic compounds, such as resveratrol, are naturally present at high concentration in grape skin, seeds, and red wine. Resveratrol is present in cis and trans isoforms and the major trans isomer is the biologically active one. Epidemiologic studies have revealed a reduced incidence of cardiovascular risk associated with consumers of red wine; this has been popularized as the French paradox. Resveratrol has been shown to have significant antioxidant properties in a variety of in vitro and in vivo models. It can reduce ischemic damage in heart ischemia reperfusion injury and also in brain ischemia/reperfusion in rodent models. Due to the high rate of oxygen consumption in the brain, and especially low levels of antioxidant defense enzymes, this organ is particularly susceptible of free radical damage. Most of the protective biological actions associated with resveratrol have been associated with its intrinsic radical scavenger properties. We have investigated the possibility of other indirect pathways by which resveratrol can exert its neuroprotective abilities. We have specifically tested whether heme oxygenase neuroprotective enzyme could be stimulated after resveratrol treatment. Using primary neuronal cultures, resveratrol was able to significantly induce heme oxygenase 1, whereas vehicle control showed no effect. No detectable toxicity was quantified. It is well established that after stroke significant levels of intracellular heme levels increase. The source of free heme comes mainly from several heme-containing enzymes. Heme (iron-protoporphyrin IX) is a pro-oxidant and its rapid degradation by heme oxygenase is believed to be protective. Moreover, the generation of heme metabolites can also have their own intrinsic cellular properties. All together, increased heme oxygenase activity by resveratrol is a unique pathway by which this compound can exert its neuroprotective actions.
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Affiliation(s)
- Hean Zhuang
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA
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