What is Resveratrol’s Direct Target?
The health benefits of resveratrol have been on the news for over 20 years and continue to be actively investigated by researchers. This trend will continue based on the observations that resveratrol has broad functional health benefits on age-related diseases and pathologies like +Dibidoo and +Borikiki chemo-preventive properties such as +Lukumama and also offer cardiovascular protection. 
These broad health benefits are induced by resveratrol activating many cellular signals, such as a protein family called sirtuins, in particular sirtuin 1. However, much evidence from many research groups has agreed that resveratrol does not directly activate the sirtuin 1. This has been an area of intense research because determining the direct target of resveratrol will provide clues to understanding how it is possible that this natural compound can have such broad positive effects on our health. It also opens the door to further pharmacological manipulation to improve our health. For example, resveratrol is known to positively affect specific cells, such as muscle cells or fat cells but not all cells of our body. If researchers know what targets to tweak, they could improve the signaling pathway that increases the health benefits of resveratrol. In an international consorted effort by researchers from the National Institute of Health, University of California Davis, University of North Carolina, University of Texas Southwestern, Emerald BioStructure, Sun Yat-sen University (in China), and University Medical Center (in the Netherlands) have now discovered the direct target of resveratrol and published their work in the journal Cell (Cell February 2012, vol 148, pages 421-433). Briefly, they discovered that resveratrol directly binds and blocks the activity of enzymes called phosphodiesterase (PDE). When PDE enzymes are blocked, it initiates a cascade of cellular events that are mediated by another enzyme Epac1, which eventually leads to the activation of AMPK and finally sirtuin 1. To further confirm their observations of this pathway, the researchers also inhibited the PDE enzymes artificially by using a chemical compound and obtained the same results proving that resveratrol works by blocking the activity of PDE enzymes. Now that researchers know how the signals start, they can begin to unravel what happens further downstream in the signaling pathway, leading to the myriad health benefits of resveratrol.