Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload

Li, Wei; Wang, Yuepeng; Gao, Ling; Zhang, Peng‐Pai; Zhou, Qing; Qiao, Xu; Zhou, Zhiwen; Guo, Kai; Chen, Renhua; Yang, Huang‐Tian; Li, Yi‐Gang

doi:10.1038/aps.2013.82

Cited by 20 publications

(11 citation statements)

References 34 publications

(66 reference statements)

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“…ACCEPTED MANUSCRIPT 27 inhibits oxidative stress-induced arrhythmogenic activity in rabbit ventricular myocytes through inhibition of late Na + current and L-type Ca 2+ current [288]. Of interest, resveratrol inhibited delayed after depolarization induced by ouabain in guinea pig papillary muscle independently from its NO or estrogen-modulating effects [289], suggesting that the anti-arrhythmic properties of resveratrol may be distinct from its other cardioprotective effects.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

Zordoky

Robertson

Dyck

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

277

217

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Cardiovascular disease is the leading cause of death worldwide. Despite advancements in diagnosis and treatment of cardiovascular disease, the incidence of cardiovascular disease is still rising. Therefore, new lines of medications are needed to treat the growing population of patients with cardiovascular disease. Although the majority of the existing pharmacotherapies for cardiovascular disease are synthesized molecules, natural compounds, such as resveratrol, are also being tested. Resveratrol is a non-flavonoid polyphenolic compound, which has several biological effects. Preclinical studies have provided convincing evidence that resveratrol has beneficial effects in animal models of hypertension, atherosclerosis, stroke, ischemic heart disease, arrhythmia, chemotherapy-induced cardiotoxicity, diabetic cardiomyopathy, and heart failure. Although not fully delineated, some of the beneficial cardiovascular effects of resveratrol are mediated through activation of silent information regulator 1 (SIRT1), AMP-activated protein kinase (AMPK), and endogenous anti-oxidant enzymes. In addition to these pathways, the anti-inflammatory, anti-platelet, insulin-sensitizing, and lipid-lowering properties of resveratrol contribute to its beneficial cardiovascular effects. Despite the promise of resveratrol as a treatment for numerous cardiovascular diseases, the clinical studies for resveratrol are still limited. In addition, several conflicting results from trials have been reported, which demonstrates the challenges that face the translation of the exciting preclinical findings to humans. Herein, we will review much of the preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular disease and provide information about the physiological and molecular signaling mechanisms involved. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

Zordoky

Robertson

Dyck

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

277

217

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“…Drugs that activate these pathways, such as resveratrol and metformin, can extend the healthspan of most organisms. Resveratrol, a polyphenol present in grapes, decreases ischemia-reperfusion injury of the heart, prevents atherosclerosis and interferes with Ca 2+ handling by cardiomyocytes [4, 5], restoring heart contractility in cardiomyopathies and acting as an anti-arrhythmic drug [6–9]. Some of its cardioprotective effects have been attributed to its antioxidant properties, exerted by activation of the antioxidant-defense gene Nrf2, increased expression of mitochondrial SOD2, inhibition of NOX2 and NOX4 expression, and direct ROS scavenging [4, 10].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Reverses Functional Chagas Heart Disease in Mice

et al. 2016

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Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol’s actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC.

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“…Resveratrol (RSV) is a naturally occurring polyphenolic phytoalexin that is produced by polygonum cuspidatum, mulberry (Morus species), grapes, and red wine. It has diverse biological activities including anti-oxidation [21] , anti-cancer [22] , anti-inflammation [23] , cardioprotection [24] , and neuroprotection [25] . Several reports indicate that RSV is capable of preventing and treating diabetes and its related complications [26,27] .…”

Section: Introductionmentioning

confidence: 99%

Resveratrol ameliorates experimental periodontitis in diabetic mice through negative regulation of TLR4 signaling

et al. 2014

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Aim: To investigate the therapeutic effects of resveratrol (RSV) on periodontitis in diabetic mice and to explore the underlying mechanisms in vitro. Methods: Experimental periodontitis was induced in db/db mice by ligature application of porphyromonas gingivalis. The mice were treated with RSV (20 mg/kg, po) daily for 4 weeks. Alveolar bone loss, proinflammatory cytokines and TLR4 expression in the gingival tissue were measured. Cultured gingival epithelial cells (GECs) were used for in vitro studies. The transcriptional activity of TLR4 downstream signaling was analyzed using Western blotting. Results: RSV administration significantly decreased the blood glucose levels, and ameliorated alveolar bone loss in db/db mice with experimental periodontitis. RSV administration also suppressed the high levels of IL-1β, IL-6, IL-8, TNF-α, and TLR4 in gingival tissue of the mice. In the GECs incubated in high glucose medium, TLR4 expression was substantially upregulated, which was partly blocked in the presence of RSV. Lipopolysaccharides markedly increased the expression and secretion of IL-1β, IL-6, IL-8, and TNF-α in the GECs cultured in high glucose medium, which was also partly blocked in the presence of RSV. Furthermore, RSV significantly suppressed the phosphorylation of TLR4 downstream factors NF-κB p65, p38MAPK, and STAT3. Conclusion: RSV exerts protective effects against experimental periodontitis in db/db mice via negative regulation of TLR4 signaling.

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Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload

Cited by 20 publications

References 34 publications

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

Resveratrol Reverses Functional Chagas Heart Disease in Mice

Resveratrol ameliorates experimental periodontitis in diabetic mice through negative regulation of TLR4 signaling

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