Resveratrol binding to human complement fragment 5a (^hC5a) may modulate the C5aR signaling axes

Resveratrol (RSV), the active pharmaceutical ingredient (API) found in several fruits, nuts and marketed nutraceuticals is one of the promiscuous phytoalexin known to promote good health. The health benefits of RSV could be due to its antioxidant activity or its direct interaction with target proteins, resulting modulation of several cells signaling and inflammatory pathways. Among many of its disease preventing activities, RSV has been shown to ameliorate inflammation by directly binding the COX-1 and COX-2 enzymes, the established targets of common non-steroidal anti-inflammatory drugs (NSAIDs). As a follow up to our recent study, we have now identified that RSV can also directly target ^hC5a, a pro-inflammatory glycoprotein of the complement system, whose upregulation has been linked to exacerbate the chronic inflammation induced diseases, by recruitment of C5a receptor (C5aR) expressed in both immune and non-immune cells. The data derived from the molecular dynamics, automated docking and binding free energy calculation as well as from the circular dichroism, and steady state fluorescence studies indicate that glycosylation of ^hC5a may not alter its structure significantly and further confirms that RSV strongly bind to the ^hC5a, which may be responsible for the anti-inflammatory activity demonstrated by RSV in ^hC5a-C5aR induced inflammatory pathways.Communicated by Ramaswamy H. Sarma.