Resveratrol: Its Biologic Targets and Functional Activity

Abstract

2852 The polyphenolic phytoalexin resveratrol (RSV) and its analogues have received tremendous attention over the past couple of decades because of a number of reports highlighting their benefits in vitro and in vivo in a variety of human disease models, including cardio- and neuroprotection, immune regulation, and cancer chemoprevention. These studies have underscored the high degree of diversity in terms of the signaling networks and cellular effector mechanisms that are affected by RSV. The activity of RSV has been linked to cell-surface receptors, membrane signaling pathways, intracellular signal-transduction machinery, nuclear receptors, gene transcription, and metabolic pathways. The promise shown by RSV has prompted heightened interest in studies aimed at translating these observations to clinical settings. In this review, we present a comprehensive account of the basic chemistry of RSV, its bioavailability, and its multiple intracellular target proteins and signaling pathways. Antioxid. Redox Signal. 11, 2851–2897. Sources and Chemistry of RSV The metabolism and bioavailability of RSV Modulation of Cellular Functions by RSV The influence of RSV on signal transduction RSV and hormone signaling RSV and growth-factor signaling RSV and secondary messengers RSV and cAMP/cGMP-mediated signaling RSV and PI3K/AKT (PKB) signaling RSV and MAP kinase signaling RSV and Jak/STAT signaling RSV and ion channels RSV as a modulator of cellular redox status RSV and oxidative stress RSV and NO RSV and thiol-based redox systems RSV-mediated control of the cell cycle and gene expression RSV and p53 RSV and the retinoblastoma protein RSV and the early-response factors RSV and redox-regulated transcription factors RSV and lipoxygenase and cyclooxygenase Modulation of DNA Damage and Cell Death by RSV RSV and DNA damage Cell death RSV and membrane-mediated apoptosis signaling RSV and mitochondria-dependent intrinsic apoptosis RSV and autophagy The Beneficial Effects of RSV in Physiological Models The influence of RSV on lifespan and metabolism through sirtuins RSV and osteoporosis and diabetes RSV and neurologic disorders RSV and the cardiovascular system RSV and inflammation The antimicrobial activity of RSV The anticancer properties of RSV Concluding Remarks and Implications