Review Article | Published:

Therapeutic potential of resveratrol: the in vivo evidence

Nature Reviews Drug Discovery volume 5, pages 493506 (2006) | Download Citation

Subjects

Abstract

Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Despite scepticism concerning its bioavailability, a growing body of in vivo evidence indicates that resveratrol has protective effects in rodent models of stress and disease. Here, we provide a comprehensive and critical review of the in vivo data on resveratrol, and consider its potential as a therapeutic for humans.

Key points

  • Resveratrol, a small polyphenol, has been discovered and re-discovered as a potential therapeutic in recent years. Although putative cardioprotective effects were first noted in 1982, it was only after a 1992 report of high levels of resveratrol in red wine that these effects were investigated extensively. In 1997, resveratrol was isolated in a screen for cyclooxygenase inhibitors, and was shown to be an effective chemotherapeutic and chemopreventive agent. Moreover, in 2003, it was identified as the top hit in a screen for activators of sirtuin deacetylases and was shown to extend the lifespans of lower organisms.

  • The number of reported effects for resveratrol is constantly growing. Many direct targets have been identified in vitro, and protective effects have been demonstrated in various rodent models of disease.

  • Pharmacokinetic studies have consistently shown that levels of resveratrol in serum do not reach the concentrations required for most of the reported in vitro effects, or do so only transiently. In vivo evidence has therefore become increasingly important in efforts to understand how resveratrol elicits its effects in mammals.

  • One possibility that has been suggested based on data from lower organisms is that resveratrol acts as a caloric restriction mimetic. This hypothesis is intriguing because caloric restriction seems to slow the intrinsic rate of ageing, and improve general health, rather than block specific disease processes.

  • The many reported in vivo effects of resveratrol are reviewed here and, whenever possible, have been related to putative mechanisms and targets. Determining the mechanism(s) by which resveratrol and similar molecules act, and developing methods to improve bioavailability and/or specificity, has enormous potential to benefit human health.

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Affiliations

  1. Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.

    • Joseph A. Baur
    •  & David A. Sinclair

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  1. Search for Joseph A. Baur in:

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Competing interests

D.A.S. and J.A.B. are inventors on provisional patents for the use of resveratrol in treating age-associated diseases.

D.A.S. is a co-founder of and consultant to Sirtris, a company whose goal is to treat diseases of ageing by activating sirtuins.

Research in the laboratory of D.A.S. is not funded by industry.

Corresponding author

Correspondence to David A. Sinclair.

Supplementary information

Glossary

Phytoalexin

A toxic compound produced by higher plants in response to infection or other stresses, such as nutrient deprivation.

Caloric restriction

A reduction of calorie intake (typically by 30–40% in rodents) to a level that does not cause malnutritionand that has been shown to increase lifespan and stress-resistance in multiple species.

Sirtuin

A member of the family of NAD+-dependent deacetylases named after the Saccharomyces cerevisiae silent information regulator 2 (Sir2) protein (class III histone deacetylases).

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