Anti-inflammatory effect of the oligomeric stilbene α-viniferin and its mode of the action through inhibition of cyclooxygenase-2 and inducible nitric oxide synthase

The anti-inflammatory activity of alpha-viniferin, a trimer of resveratrol, has been demonstrated in an animal model of carrageenin-induced paw edema, and inhibitory effects of the compound on cyclooxygenase (COX) and inducible nitric oxide synthase (iNOS) have been investigated in order to understand the mode of the observed action. alpha-Viniferin at doses > 30 mg/kg (p. o.) or > 3 mg/kg (i. v.) showed significant anti-inflammatory activity on carrageenin-induced paw edema in mice. alpha-Viniferin showed an inhibitory effect with an IC50 value of 4.9 muM on COX-2 activity but a very weak inhibitory effect with 55.2 +/- 2.1 % of the control (100%) at 100 muM on COX-1 activity. alpha-Viniferin at doses of 3 muM to 10 muM inhibited the synthesis of COX-2 transcript in lipopolysaccharide (LPS)-activated murine macrophages Raw264.7. alpha-Viniferin showed an IC50 value of 2.7 muM on nitric oxide (NO) production in LPS-activated Raw264.7 cells when alpha-viniferin and LPS were treated simultaneously, but did not inhibit the NO production when alpha-viniferin was treated at 12 h after LPS stimulation. alpha-Viniferin inhibited synthesis of iNOS transcript with an IC50 value of 4.7 muM. Consequently, the inhibitory effect of alpha-viniferin on the release of prostanoids and NO could play an important role to show anti-inflammatory action.