Anti-inflammatory effect of the oligomeric stilbene alpha-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 IC (50) value of 4.9 microM on COX-2 activity but a very weak inhibitory effect with 55.2 +/- 2.1 % of the control (100 %) at 100 microM on COX-1 activity. alpha-Viniferin at doses of 3 microM to 10 microM inhibited the synthesis of COX-2 transcript in lipopolysaccharide (LPS)-activated murine macrophages Raw264.7. alpha-Viniferin showed an IC50 value of 2.7 microM 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 microM. Consequently, the inhibitory effect of alpha-viniferin on the release of prostanoids and NO could play an important role to show anti-inflammatory action.
Chung
Eun Yong
EY
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea.
Kim
Byung Hak
BH
Lee
Myung Koo
MK
Yun
Yeo-Pyo
YP
Lee
Seung Ho
SH
Min
Kyung Rak
KR
Kim
Youngsoo
Y
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D032602:Caragana; D002351:Carrageenan; D002460:Cell Line; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D008517:Phytotherapy; D011451:Prostaglandin-Endoperoxide Synthases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001572:Benzofurans; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D007527:Isoenzymes; D013267:Stilbenes; C064176:alpha-viniferin; D002351:Carrageenan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases