Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a non-flavonoid polyphenolic compound belonging to the stilbene group which is the main compound found in grapes. Resveratrol has shown a wide range of preventive and therapeutic alternatives against several diseases including distinct types of cancer, heart disease, stroke, diabetes, obesity, inflammation, antioxidant. It is a highly efficient treatment, which might be due to the three hydroxyl groups in its structure. Consumption of resveratrol has been shown to improve health status and has the positive effect of treatment of many diseases. Moreover, it has been demonstrated that resveratrol possesses the potential of lifespan extension in various organism and animal models. However, the long-term use of resveratrol may have some adverse effects and should be studied deeper. This chapter will outline some pharmacological effects of resveratrol.
TopBackground
Name: Resveratrol
Different name: 3,4',5-stilbenetriol; 3,5,4'-trihydroxystilbene; trans-resveratrol-3-O-sulfate; trans-resveratrol; cis-resveratrol; resveratrol-3-sulfate.
Resveratrol has been known since 1939, when the Japanese by chance extracted the rhizomes of the “Veratrum” (Arichi et al., 1982). Its chemical texture was published in the “Journal of Japanese Chemistry Association” and was named Resveratrol, meaning “resorcinol from Veratrum”. Resveratrol is a white powder, a molecular weight of 228.35, which is one of the simplest phenolic compounds from plants.Resveratrol is a substance found in at least 70 types of plants, most commonly found in foods, including grapes, peanuts, pineapple, strawberry, etc. (Figure 1). Resveratrol has a ring structure composed of many hydroxy acids (Figure 2). Hydroxy groups can be oxidized to promote antioxidant activity, provide for resveratrol stronger antioxidant activity than vitamin C, E, and glutathione (Sobolev & Cole, 1999).
Figure 1. Examples of fruits and food rich in resveratrol
Figure 2. The structure of the trans-cis of resveratrol
TopThe Potential Of Resveratrol In Cardiovascular Disease Treatment
Cardiovascular diseases (CVDs) are considered to be the most common cause of the death in the global population and account for much treatment expenditures. The cardiovascular protection of resveratrol are associated with multiple molecular targets and which can lead to the development of novel therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, and heart failure, so on…
Hypertension
Hypertension is a chronic medical condition that is showed by sustained arterial blood pressure elevation. Several investigators have demonstrated that resveratrol can lower BP in experimental animal models of hypertension with the molecular target of sirtuins and SIRT1 (Figure 3). With regard to its endothelium-dependent effects, resveratrol supplementation has been shown to improve flow-mediated vasodilation, a surrogate for endothelial function, in several animal models (Pearson et al., 2008; Rush, Quadrilatero, Levy, & Ford, 2007; Soylemez, Sepici, & Akar, 2009; Toklu et al., 2010). Resveratrol increases the bioavailability of nitric oxide (NO) by increasing endothelial nitric oxide synthase (eNOS) expression to show the vasodilatory effects (Leikert et al., 2002; Wallerath et al., 2002). Three isoforms of NO synthase (NOS), eNOS, neuronal NOS (nNOS), and inducible NOS (iNOS) could mediated level of NO (Calvert & Lefer, 2009). eNOS plays important role in cardiovascular physiology because it regulates vascular tone via the release of NO in the vascular endothelium (Calvert & Lefer, 2009).It has been showed that resveratrol involves the effects of resveratrol on silent information regulator 1 (SIRT1), AMP-activated protein kinase (AMPK), and reactive oxygen species (ROS) to increasing the NO bioavailability. SIRT1 is a class III histone deacetylase which stimulates the NO production by deacetylating eNOS at lysine residues(Arunachalam, Yao, Sundar, Caito, & Rahman, 2010). Resveratrol activates SIRT1 then mediates both activity and expression of eNOS (Csiszar et al., 2009). It has been shown that resveratrol activates AMPK to stimulate NO production (Dolinsky et al., 2013).AMPK, a major regulator of energy metabolism (Nagendran, Waller, & Dyck, 2013), also regulates NO bioavailability via eNOS. AMPK phosphorylatea and activatea eNOS on serine 1177, resulting in a subsequent increase in NO production (Z.-P. Chen et al., 1999). In addition to the involvement of SIRT1 and AMPK in mediating the endothelium-dependent vasodilatory effects, resveratrol has been shown to enhance NOS activity by increasing tetrahydrobiopterin (BH4) levels, a cofactor necessary for proper function of NOS (Carrizzo et al., 2013).
Figure 3. Proposed anti-hypertensive effect of resveratrol. Resveratrol showed its anti-ischemic effects through activation of AMP-activated protein kinase (AMPK), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF), and inhibition of reactive oxygen species (ROS) and atherosclerosis