Bethesda, MDNational Institutes of Health researchers have identified how resveratrol may confer its health benefits. Resveratrol is a naturally occurring chemical found in plants like grapes. The researchers found that resveratrol does not directly activate sirtuin 1, a protein associated with aging. Instead, it inhibits phosphodiesterases (PDEs), proteins that help regulate cell energy. The chemical has gained some interest from pharmaceutical companies for its potential to fight diabetes, inflammation and cancer.

“Resveratrol has potential as a therapy for diverse diseases such as type-2 diabetes, Alzheimer’s disease, and heart disease,” said the lead study author Jay H Chung, Ph.D, M.D, chief of the Laboratory of Obesity and Aging Research at the NIH’s National Heart, Lung, and Blood Institute. He also stresses the importance of researchers knowing what resveratrol targets in cells before formulating with it.

Previous studies indicated resveratrol’s primary target is sirtuin 1. Chung and researchers suspected otherwise when they discovered resveratrol activity required AMPK.  This would not occur if resveratrol interacted directly with sirtuin 1.

For this study, researchers followed the metabolic activity in cells treated with resveratrol and found PDE4 in the skeletal muscle was the main target for the phytonutrient's health benefits. By inhibiting PDE4, resveratrol sets off a cascade of cellular events, which indirectly activate sirtuin 1.

To prove their findings, Chung’s group gave mice rolipram, a drug that inhibits PDE4. Rolipram recreated all of the biochemical effects and health benefits of resveratrol, including the prevention of diet-induced obesity and increased physical endurance as well as glucose tolerance.

Chung noted that since resveratrol in its natural form interacts with many proteins in addition to PDEs, it may cause toxicities with long-term use. This has yet to be proven, however. He also stated that the amount of resveratrol found in foods and wine is not high enough to cause problems. 

Other contributors to this study include: Collaborators in the Cardiovascular Pulmonary Branch of the NHLBI; the University of California, Davis; the University of North Carolina, Chapel Hill: University of Texas Southwestern Medical Center, Dallas; Sun Yat-sen University, Guangzhou, China; University Medical Center, Utrecht, The Netherlands; and emerald BioStructures, Bainbridge Island, Washington.

Published in WholeFoods Magazine, April 2012, online 2/23/12