Metabolic effects of resveratrol: addressing the controversies

Abstract

Resveratrol, a polyphenol found in a number of plant-based foods such as red wine, has received a great deal of attention for its diverse array of healthful effects. Beneficial effects of resveratrol are diverse; they include improvement of mitochondrial function, protection against obesity and obesity-related diseases such as type-2 diabetes, suppression of inflammation and cancer cell growth and protection against cardiovascular dysfunction, just to name a few. Investigations into the metabolic effects of resveratrol are furthest along and now include a number of clinical trials, which have yielded mixed results. There are a number of controversies surrounding resveratrol that have not been resolved. Here, we will review these controversies with particular emphasis on its mechanism of metabolic action and how lessons from resveratrol may help develop therapies that harness the effects of resveratrol but without the undesirable properties of resveratrol.

Antioxidants reveal an inverted U‐shaped dose‐response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans

“…RSV has been proposed to act as an inhibitor or agonist of a number of specific molecular targets rather than as a redox‐active molecule (Bhullar & Hubbard, 2015; Bitterman & Chung, 2015). This could in principle explain the observed additivity with pro‐oxidant and antioxidant ROS modulators.…”

“…This is despite the fact that there is no consensus as to its modes of action (Bhullar & Hubbard, 2015; Bitterman & Chung, 2015). In particular, RSV might act as an antioxidant, but other redox effects have also been documented (e.g., Miura et al ., 2000; Stivala et al ., 2001; Galati et al ., 2002; Ahmad et al ., 2003, 2005; Zheng et al ., 2006; de la Lastra & Villegas, 2007; Gadacha et al ., 2009; Queiroz et al ., 2009; Gueguen et al ., 2015).…”

“…In particular, RSV might act as an antioxidant, but other redox effects have also been documented (e.g., Miura et al ., 2000; Stivala et al ., 2001; Galati et al ., 2002; Ahmad et al ., 2003, 2005; Zheng et al ., 2006; de la Lastra & Villegas, 2007; Gadacha et al ., 2009; Queiroz et al ., 2009; Gueguen et al ., 2015). In addition, numerous distinct specific targets have been identified and characterized (reviewed in Bhullar & Hubbard, 2015; Bitterman & Chung, 2015). The effect of RSV on lifespan per se has also been widely tested and positive effects documented in both invertebrates and vertebrates (Bhullar & Hubbard, 2015).…”

p53 coordinates decidual sestrin 2/AMPK/mTORC1 signaling to govern parturition timing

“…In the same vein, resveratrol (Rsv), a natural derivative of grapes, was reported to have antioxidant and anti-aging properties with health benefits, including protection from heart disease and obesity, as well as improvement of mitochondrial function (16,17). However, Rsv's definitive mechanism of action remains under investigation (18). Therefore, we asked whether Met or Rsv would mitigate PTB in p53 d/d mice by altering AMPK and mTORC1 signaling without adverse effects on the mother and pups.…”

Biological Effects and Properties of Eukaryotic Sirtuins

“…Дослідженнями останніх років встановлено, що ген SIR2 здатний подовжувати тривалість життя дріжджів через пригнічення нестабіль-ності їхнього геному [1][2][3]. Sir2-подібні гени, відомі як сиртуїни, зустрічаються у більшості організмів, включаючи рослини, бактерії та тварин, вони відіграють ключову роль у процесі виживання організму [4,5].…”