The dietary polyphenols trans-resveratrol (commonly found in red wine) and curcumin (commonly found in curry powders) have potent antioxidant and anti-inflammatory properties, among other properties. Numerous studies have suggested that these polyphenols have therapeutic value in the treatment of a wide range of conditions, although their mechanisms of action remain poorly defined. Interestingly, the activities of the polyphenols mirror some of the activities of the cannabinoids. In this issue, Seely et al., evaluates trans-resveratrol, curcumin, and ASC-J9 [1,7-bis(3,4-dimethoxyphenyl)-5-hydroxy-1E,4E,6E-heptatriene-3-one], a curcumin analog as ligands for the cannabinoid receptors CB1 and CB2. The study demonstrates that all three polyphenols bind to both human (h)CB1 and mouse CB1 receptors with high affinity but with low affinity for hCB2 receptors. Trans-resveratrol also seems to bind to other receptors, which have not been identified. The polyphenols antagonize G-protein activation triggered by a CB1 agonist. They also inhibit G-protein activity, and this block is reversed with a CB1 antagonist. Thus, these compounds exhibit characteristics of inverse agonists and act as competitive antagonists against inhibition of adenylyl cyclase activity by CB1 agonists. They also reduce body weight when chronically administered to mice, similar to other CB1 antagonists/inverse agonists. Based on these results, the authors suggest that these compounds might be useful for treatment of obesity, diabetes, drug dependence, and other conditions where CB1 antagonists are already indicated.
See article at J Pharmacol Exp Ther 2009, 330:31–39.
- The American Society for Pharmacology and Experimental Therapeutics