Cytoprotection by Natural and Synthetic Polyphenols in the Heart: Novel Mechanisms and Perspectives

Abstract

While many naturally occurring polyphenols have been shown to have therapeutic benefits against myocardial injury following ischemia-reperfusion in various experimental models, our studies have demonstrated that synthetic flavonoids may also have potent cardiac cytoprotective actions. Together with the results reported in the literature, we suggest that synthetic polyphenols may be an ideal replacement for natural compounds in the development of myocardial protective drugs. Polyphenols exert myocardial protective effects via antioxidant activities, preservation of nitric oxide, antiinflammatory activities and modulation of matrix metalloproteinases. Recent studies have identified some novel mechanisms that may also contribute to polyphenol-induced myocardial protection, including prevention of mitochondrial dysfunction, pharmacological preconditioning, and modulation of the function of enzymes involved in epigenetic modifications such as histone acetyltransferases. In addition to the protective effects against acute myocardial injury, there has been experimental evidence showing that polyphenols may also modulate the development of cardiac hypertrophy, ventricular remodeling and fibrosis after myocardial infarction.

Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

“…Genistein, an isoflavone and phytoestrogen present in soybeans and some medicinal plants, is cardioprotective when administered at a low dose in a coronary artery occlusion-reperfusion model (Tissier et al, 2007), whereas a high dose can exacerbate ischemic damage (Imagawa et al, 1997). In addition to protecting against ischemic injury, polyphenol phytochemicals have been reported to modify the development of cardiac hypertrophy, ventricular remodeling, and fibrosis after myocardial infarction (Jiang et al, 2010).…”

Aspalathin, a dihydrochalcone C‐glucoside, protects H9c2 cardiomyocytes against high glucose induced shifts in substrate preference and apoptosis

“…Flavonoids as antioxidants have the ability to scavenge and reduce free radical formation . In the human body, flavonoids function as antioxidants and exert their protective effect through their ability to increase levels of endogenous antioxidant defenses such as superoxide dismutase (SOD), catalase, glutathione peroxidase, and glutathione (GSH), which allow for the elimination of excessive ROS in the body . Therefore, preventing redox disequilibrium caused by increased oxidative stress.…”

Targeting Cell Signaling and Apoptotic Pathways by Luteolin: Cardioprotective Role in Rat Cardiomyocytes Following Ischemia/Reperfusion

“…To date, a large number of studies have shown that cardiomyocytes of rat is assessed in I/R by luteolin pretreatment and only cardiomyocytes in other systems such as murine, H9c2, etc. [16,17]. Thus, only cardiomyocytes of rat is emphasized in this paper.…”