Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol‐ and melatonin‐induced cardioprotection

Abstract

Epidemiological studies suggest that regular moderate consumption of red wine confers cardioprotection but the mechanisms involved in this effect remain unclear. Recent studies demonstrate the presence of melatonin in wine. We propose that melatonin, at a concentration found in red wine, confers cardioprotection against ischemia-reperfusion injury. Furthermore, we investigated whether both melatonin and resveratrol protect via the activation of the newly discovered survivor activating factor enhancement (SAFE) prosurvival signaling pathway that involves the activation of tumor necrosis factor alpha (TNFα) and the signal transducer and activator of transcription 3 (STAT3). Isolated perfused male mouse (wild type, TNFα receptor 2 knockout mice, and cardiomyocyte-specific STAT3-deficient mice) or rat hearts (Wistars) were subjected to ischemia-reperfusion. Resveratrol (2.3 mg/L) or melatonin (75 ng/L) was perfused for 15 min with a 10-min washout period prior to an ischemia-reperfusion insult. Infarct size was measured at the end of the protocol, and Western blot analysis was performed to evaluate STAT3 activation prior to the ischemic insult. Both resveratrol and melatonin, at concentrations found in red wine, significantly reduced infarct size compared with control hearts in wild-type mouse hearts (25 ± 3% and 25 ± 3% respectively versus control 69 ± 3%, P < 0.001) but failed to protect in TNF receptor 2 knockout or STAT3-deficient mice. Furthermore, perfusion with either melatonin or resveratrol increased STAT3 phosphorylation prior to ischemia by 79% and 50%, respectively (P < 0.001 versus control). Our data demonstrate that both melatonin and resveratrol, as found in red wine, protect the heart in an experimental model of myocardial infarction via the SAFE pathway.

Melatonin modulates the expression of BCL-xl and improve the development of vitrified embryos obtained by IVF in mice

“…Wang and his colleagues [46] demonstrated that melatonin, as a powerful antioxidant, removes toxic hydroxyl radicals and plays an important role in the survival of neurons. Transcription signals promoted via melatonin receptors stimulate anti-apoptotic effects of this indole [47]. This activates stat3 and leads to Bcl-2 and Bclxl expression, thus inhibiting the mitochondrial-dependent apoptotic pathway [48].…”

Wine and heart health: learning from the French paradox

“…Slices through mouse hearts after control and or pre-treatment by melatonin or resveratrol followed ischaemia and reperfusion. Adapted from Lamont, et al (36) with permission. …”

“…(34,35) Our studies have shown that a low concentration of melatonin (corresponding to the concentration found in red wine), protects the heart against a lethal ischaemia-reperfusion injury in a rat model ( Figure 3). (36) Both melatonin and resveratrol confer cardioprotection via the activation of the recently discovered Survivor Activating Factor Enhancement (SAFE) pathway. (36) This is a THE FRENCH PARADOX prosurvival pathway involving the intrinsic activation of the innate immune system and the transcription factor, signal transducer and activator of transcription (STAT3).…”

“…(36) Both melatonin and resveratrol confer cardioprotection via the activation of the recently discovered Survivor Activating Factor Enhancement (SAFE) pathway. (36) This is a THE FRENCH PARADOX prosurvival pathway involving the intrinsic activation of the innate immune system and the transcription factor, signal transducer and activator of transcription (STAT3). (37,38) Thus, we postulate that there are cardioprotective properties of complex compounds found in red wine including melatonin and resveratrol.…”

Cardioprotection from metabolism to molecules to certainties

“…The impact on myocardial infarct size after coronary occlusion and reperfusion following administration of red wine, resveratrol, and melatonin to rats has been examined in our laboratory. 15 Both resveratrol and melatonin gave substantial protection. The group of Sandrine Lecour has in the past suggested that the resveratrol content of red wine may, with only modest intake, reach blood levels high enough to be cardioprotective although that conclusion is only inferential and hypothetical.…”