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Human and Experimental Toxicology, 29(12) 1016–1017

Commentary on ‘Resveratrol commonly displays hormesis: Occurrence and biomedical significance’

Dipak K Das
Cardiovascular Research Center, University of Connecticut, Farmington, CT, USA

Abstract

Resveratrol, a grape skin and red wine-derived polyphenolic phytoalexin, exhibits hormetic action delivering numerous health benefits at lower doses while being detrimental at higher doses. Epidemiologic and clinical trials need to be based on the clear understanding of hormetic health benefits of resveratrol.

Hormesis is defined as a dose-response relationship that is stimulatory at low doses but detrimental at higher doses, resulting in a J-shaped or an inverted U-shaped dose response curve. It has been known for quite some time that cardioprotective effects of alcohol or wine intake follow a J-shaped curve.1 Extensive literature search implicates that resveratrol present in red wine also demonstrates a similar health benefit, being highly effective at lower doses and detrimental at higher doses. Such hormesis has been known for  more than hundred years, and is frequently observed among the toxins. Resveratrol is a phytoalexin, whose growth is stimulated by environmental stress such as fungal infection, UV radiation and water deprivation.2 Cardioprotective effects of resveratrol is exerted through its ability to precondition a heart, which causes the  development of intracellular stress leading to the upregulation of intracellular defense system such as  antioxidants and heat shock protein.3 Preconditioning is another example of hormesis, which is potentiated  by subjecting an organ like heart to cyclic episodes of short durations of ischemia, each followed by another  short durations of reperfusion.4 Such small but therapeutic amount of stress renders the heart resistant to  subsequent lethal ischemic injury. Such an adaptive response is commonly observed with aging. Consistent  with this idea, resveratrol has been found to stimulate longevity genes, and at least in prokaryotic species  extend the life span.5,6 In this respect,resveratrol may fulfil the definition of a hormetins.7 There is no doubt  that alcohol, wine and wine-derived resveratrol all display hormesis.The present review by Calabrese and his co-authors from an extensive literature search describes how resveratrol displays hormesis. The review  should be very important for the basic scientists, clinicians as well as for the common people to understand  the importance of using resveratrol only at lower doses as completely opposite effects can occur at higher  doses, resulting in adverse effects on health. Epidemiologic and clinical trials need to be based on the clear  understanding of hormetic beneficial effects of resveratrol.

References

1. Constant J. Alcohol, ischemic heart disease, and the french paradox. Clin Cardiol 1997; 20:  420–424.
2. Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, et al. Resveratrol, a polyphenolic  phytoalexin present in red wine, enhances expression and activit yof endothelial nitric oxide  synthase. Circulation 2002; 106: 1652–1658.
3. Das DK, Maulik N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine.  Mol Interven 2006; 6: 36–47.
4. Das DK, Maulik N. Preconditioning potentiates redox signaling and converts death signal into  survival signal. Arch Biochem Biophys 2003; 420: 305–311.
5. Mukherjee S, Lekli I, Gurusamy N, Bartelli AAA, and Das DK. Expression of the longevity proteins  by both red and white wines and their cardioprotective components, resveratrol, tyrosol, and  hydroxytyrosol. Free Rad Biol Med 2009; 46: 573–578.
6. Wood JG, Rogina B, Lavu S, Howltz K, Holfand SL, Tatar M, et al. Sirtuin activators mimic calorie  estriction and delay ageing in metazoans. Nature 2004; 430: 686–689.
7. Rattan SIS. Hormesis in aging. Aging Res Rev 2008; 7: 63–78.