Inhibitory effects of resveratrol analogs on unopsonized zymosan-induced oxygen radical production

Resveratrol, a natural hydroxystilbene, has been reported to have anti-inflammatory and anticarcinogenic activities. Inhibitory effects of resveratrol and its analogs on reactive oxygen species (ROS) production in unopsonized zymosan-stimulated murine macrophage Raw264.7 cells, human monocytes, and neutrophils were analyzed to investigate if the anti-inflammatory and anticarcinogenic activities of resveratrol are related to the inhibition of ROS production. Resveratrol was a potent inhibitor of ROS production in both unopsonized zymosan-stimulated Raw264.7 cells and human monocytes and neutrophils. Resveratrol exhibited 50% inhibition values ( ic 50) of 17 μM in activated Raw264.7 cells, 18 μM in human monocytes, and 23 μM in human neutrophils. 3,5-Dihydroxy-4′-methoxystilbene or 3,4′-dimethoxy-5-hydroxystilbene exhibited ic 50 values of 63 or 73 μM in Raw264.7 cells, 51 or >100 μM in human monocytes, and 10 or 37 μM in human neutrophils, respectively. Trimethylresveratrol, piceid, and 3,5-dihydroxy-4′-methoxystilbene-3- O-β- d-glucoside were weak inhibitors of ROS production. Thus, resveratrol was identified as a potent inhibitor of ROS production, which might be one biochemical mechanism related to its anti-inflammatory and anticarcinogenic activities. The number and position of hydroxy substituents in resveratrol analogs seem to play an important role in the inhibitory potency of ROS production.