Resveratrol: French paradox revisited

Abstract

Resveratrol is a polyphenol that plays a potentially important role in many disorders and has been studied in different diseases. The research on this chemical started through the "French paradox," which describes improved cardiovascular outcomes despite a high-fat diet in French people. Since then, resveratrol has been broadly studied and shown to have antioxidant, anti-inflammatory, anti-proliferative, and anti-angiogenic effects, with those on oxidative stress possibly being most important and underlying some of the others, but many signaling pathways are among the molecular targets of resveratrol. In concert they may be beneficial in many disorders, particularly in diseases where oxidative stress plays an important role. The main focus of this review will be the pathways affected by resveratrol. Based on these mechanistic considerations, the involvement of resveratrol especially in cardiovascular diseases, cancer, neurodegenerative diseases, and possibly in longevity will be is addressed.

Keywords: cancer; cardiovascular diseases; resveratrol; signal transduction.

Figure 1

Physiological and pathological effects of resveratrol in the organisms. Resveratrol plays important roles in distinct processes and the parameters of these effects are summarized.

Figure 2

The effects of resveratrol on atherosclerosis process. Resveratrol (R) prevents the ROS formation directly or by the inhibition of NADPH oxidase, induces eNOS activity, inhibits monocyte chemoattractant protein-1 (MCP-1) expression, inhibits the tumor necrosis factor alpha (TNFα), and angiotensin II (AngII) induced endothelial cell apoptosis.

Figure 3

Resveratrol binds to integrin αvβ3 and activates ERK1/2 regulates cyclooxygenase-2 (COX-2) expression. COX-2 is associated with small ubiquitin-related modifier 1 (SUMO-1), and phosphoERK1/2 translocates to the nucleus where the complex binds to p53. In the nucleus, COX-2 is sumoylated (S), p53 is phosphorylated (P) and acetylated (A). The COX-2 and p53 complex binds to promoters of p53-responsive genes and initiates transcription. Activation of ERK1/2 and cell proliferation can be promoted by the binding of thyroid hormone and DHT each other to discrete sites on integrin αvβ3. Estrogen (E2) binds to estrogen receptor (ER) which is the cell surface receptor and integrin αvβ3 may assist in that process. Meanwhile, resveratrol and non-peptide hormone play a distinct role on the activation of ERK1/2 which differs from each other.