Abstract
Resveratrol increases the production of nitric oxide (NO) in endothelial cells by upregulating the expression of endothelial NO synthase (eNOS), stimulating eNOS enzymatic activity, and preventing eNOS uncoupling. At the same time, resveratrol inhibits the synthesis of endothelin-1 and reduces oxidative stress in both endothelial cells and smooth muscle cells. Pathological stimuli-induced smooth muscle cell proliferation, vascular remodeling, and arterial stiffness can be ameliorated by resveratrol as well. In addition, resveratrol also modulates immune cell function, inhibition of immune cell infiltration into the vascular wall, and improves the function of perivascular adipose tissue. All these mechanisms contribute to the protective effects of resveratrol on vascular function and blood pressure in vivo. Sirtuin 1, AMP-activated protein kinase, and estrogen receptors represent the major molecules mediating the vascular effects of resveratrol.
Highlights
The polyphenolic phytoalexin 3,5,4 -trihydroxy-trans-stilbene, better known under its trivial name resveratrol, can be found in numerous plants, such as white hellebore (Veratrum grandiflorum), mulberry (Morus rubra), peanut (Archis hypogaea), and grapes (Vitis vinifera) [1,2,3]
Resveratrol increases sirtuin 1 (SIRT1) activity either through elevation of intracellular NAD+ concentration, which is dependent on an inhibition of phosphodiesterase (PDE) [10,11], or through an enhancement of the binding of SIRT1 to lamin A, an endogenous SIRT1 activator [12]
Another suggested pathway for AMPK activation is based on LKB1 stimulation, e.g., by reduction of the intracellular ATP level [17,18] or its deacetylation by SIRT1 [19,20]
Summary
The polyphenolic phytoalexin 3,5,4 -trihydroxy-trans-stilbene, better known under its trivial name resveratrol, can be found in numerous plants, such as white hellebore (Veratrum grandiflorum), mulberry (Morus rubra), peanut (Archis hypogaea), and grapes (Vitis vinifera) [1,2,3]. Since resveratrol gained popularity in 1992 [4], many targets responsible for its pharmacological effects have been identified [5,6]. These targets can be divided into those which directly interact with resveratrol (over 20) and those whose effects are indirectly changed, e.g., by modulation of their expression level [6]. Resveratrol has been linked to PDE inhibition One result of this effect is the phosphorylation of AMPK [11]. The effects of resveratrol in vivo may involve its actions on potassium channels [27,28,29], gut microbiota [30,31], and circadian gene expression [32]
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