Resveratrol and Related Compounds as Antioxidants With an Allosteric Mechanism of Action in Epigenetic Drug Targets

Abstract

The present review is intended to focus on naturally occurring cytoprotective agents such as resveratrol (trans-3,4’,5-trihydroxystilbene) and other related compounds, probably with similar molecular mechanisms of action and high capacity to find applications in medical fields. Several physiological aspects have been ascribed to resveratrol and similar compounds. Resveratrol, among others, has been recently described as a silent information regulator T1 (SIRT1) activator that increases AMP-activated protein kinase (AMPK) phosphorylation and reduces the oxidative damage biomarkers during aging in laboratory settings. The reports on resveratrol and other SIRT1 activators from various sources are encouraging. The pharmacological strategies for modulation of sirtuins by small molecules through allosteric mechanisms should gain a greater momentum including human research. Resveratrol and resveratrol-like molecules seem to fulfill the requirement of a new horizon in drug research since these molecules cover a growing research means as antioxidants with allosteric mechanism in epigenetic drug targets. However, one should keep in mind the challenges of extrapolation of basic research into clinical results. Overall, the issue of sirtuins in biology and disease provides an insight on therapeutic potentials of sirtuin-based therapeutics and demonstrates the high complexity of drug-targeting these modalities for human applications.

Resveratrol Alleviates Ethanol-Induced Hormonal and Metabolic Disturbances in the Rat

“…Recently, resveratrol is of great interest because of its pleiotropic, health-promoting properties that have been documented not only in animals but also in humans. Rodent and human studies show that resveratrol exerts, among others, cardio-protective (Zordoky et al 2015), anti-cancer (Singh et al 2015), anti-diabetic (Szkudelski and Szkudelska 2015), anti-inflammatory (Poulsen et al 2015), anti-obesity Szkudelski 2010, de Ligt et al 2015), neuro-protective (Bastianetto et al 2015) and anti-oxidative (Farghali et al 2013) action.…”

“…It is known that resveratrol may also ameliorate some consequences of ethanol ingestion. In humans, alcohol abuse is associated with numerous abnormalities in the whole organism, such as metabolic disorders, increased risks of cancer, liver injury, cardiovascular diseases, neuropathies, myopathies and also with increased mortality (Sun et al 2014, Luo 2014, Fernandez-Solà et al 2007, Ceni et al 2014. Ethanol consumption is also accompanied by oxidative stress and inflammation in different tissues (Sun et al 2001, Setshedi et al 2010, Radek et al 2009, Kawaratani et al 2013.…”

The Roles of Natural Compounds in Epigenetics

“…For many years, this substance has been largely used as a healing medicine in much of the Traditional Chinese Medicine (TCM). Recently, curcumin has attracted attention of researchers because of its speculated anti-cancerous, anti-oxidant and anti-inflammatory properties [28]. Curcumin can induce the upregulation of DNA methyltransferase 2 (DNMT2) and promote RNA stabilization in vascular smooth muscle cells [29].…”

Chemoprevention by resveratrol and pterostilbene: Targeting on epigenetic regulation

“…Histone deacetylation is often associated with transcriptional repression and gene silencing, since it promotes the chromatin of higher order structures and the recruitment of silencers. Among this superfamily is an HDACs class III which includes NAD + ‐dependent deacetylases known as sirtuins (silent information regulator 2‐related proteins) . Resveratrol activates the SIRT1 catalytic core independent of its terminal domains, indicating the existence of a resveratrol binding site within the catalytic core of the enzyme.…”