Resveratrol, a natural nonflavonoid polyphenol found in grapes and red wine, is recognized as a bioactive agent with potential benefits for health. A large number of pharmacological properties, including cardioprotective, antioxidant, and anticancer effects, are thought to be associated with its beneficial effects (Figure 1). Few studies have been performed with resveratrol in humans, and the results of these studies appear fragmentary and sometimes contradictory due to variations in conditions of administration, protocols, and methods of assessment; for example, it appears that the presence of the matrix in which resveratrol is administered (e.g., in alcohol, or other polyphenolic compounds in wine) or feeding conditions (fed versus fasting) results in discrepancies between studies. Although differences in resveratrol administration, doses, and assay methods make data from different studies difficult to compare, these data nevertheless provide important information and raise some interesting questions. First, resveratrol seems to be well tolerated; however, no information is available on long-term administration. For use in chronic diseases such as diabetes, colorectal cancer, or Alzheimer's disease, or for the prevention of cardiovascular disease and antiaging antioxidative care, resveratrol administration would occur over several months/years at doses that have yet to be determined. Although resveratrol is considered a food supplement and a relatively safe natural medication, further investigations are required to determine its long-term effects. Second, resveratrol is rapidly absorbed and metabolized, mainly as sulfo- and gluco-conjugates that are excreted in urine. This high metabolic rate probably allows the transport, the distribution, and the excretion of resveratrol. In rodents, the gut epithelium has been shown to be highly implicated in the metabolic process, resulting in polar resveratrol compounds that require specific transporters to cross cell membranes. Several ATP-binding cassette transporters may be involved in the tissue distribution and subsequent elimination of resveratrol from the body. However, concentrations of free trans-resveratrol are very low in plasma, and hence several authors have raised doubts about its efficiency. Because many lacunae in our understanding of resveratrol action and biochemistry remain to be filled, humans clinical trials have understandably lagged behind other animal and in vitro studies.
Several studies on elucidating the effects of resveratrol demonstrate that it may have potential beneficial activities against cancer, cardiovascular disease, diabetes, and autoimmune diseases; and it may even interfere with the normal physiological processes of aging. But to fully realize the potential of resveratrol, clinical trials are needed. Its analogues, with improved pharmacokinetic and pharmacodynamics, will also help the field move forward. Safety during long-term administration, combined with its cost and future therapeutic potential, makes resveratrol an ideal agent for both prevention and therapy of chronic illnesses, either alone or in combination with other drugs. Reverse pharmacology, in the case of resveratrol, is likely to prove correct Hippocrates correct, who remarked 25 centuries ago, “Let food be thy medicine and medicine be thy food.” Natural products such as resveratrol have gained considerable attention as cancer chemopreventive or cardioprotective agents and as antitumor agents. Among its wide range of biological activities, resveratrol has been reported to interfere with many intracellular signaling pathways that regulate cell survival or apoptosis. Hence, resveratrol may hold promise in the near future as a chemotherapeutic drug in the treatment of cancer and other diseases.