Researchers at the NIH have proposed a new mechanism to explain the beneficial metabolic effects of resveratrol, a polyphenol compound from red wine thought by many to act primarily on sirtuin 1. The NIH team suggests resveratrol works by inhibiting phosphodiesterase-4, an enzyme that sits far upstream of sirtuin 1 and affects a signaling pathway that leads to increased energy utilization.1
The findings could provide repurposing opportunities for the plethora of phosphodiesterase-4 (PDE-4) inhibitors on the market or in the clinic, primarily for pulmonary indications.
Prior work by researchers at Harvard University and the Massachusetts Institute of Technology suggested resveratrol promotes the consumption of energy and other antidiabetic effects by activating sirtuin 1 (SIRT1), a protein deacetylase implicated in a variety of metabolic and neurodegenerative processes.2 Indeed, that research led to the formation of Sirtris Pharmaceuticals Inc., which was acquired in 2008 by GlaxoSmithKline plc for $651 million.
In 2010, GSK discontinued development of Sirtris' lead compound, SRT501, after data from an open-label Phase