Planta Med 2003; 69(8): 710-714
DOI: 10.1055/s-2003-42787
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

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

Eun Yong Chung1 , Byung Hak Kim1 , Myung Koo Lee1 , Yeo-Pyo Yun1 , Seung Ho Lee2 , Kyung Rak Min1 , Youngsoo Kim1
  • 1College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea
  • 2College of Pharmacy, Yeungnam University, Kyeongsan, Korea
This work was financially supported by a grant (KRF-99-042-F00167) from Korea Research Foundation
Further Information

Publication History

Received: November 19, 2002

Accepted: April 13, 2003

Publication Date:
06 October 2003 (online)

Abstract

The anti-inflammatory activity of α-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. α-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. α-Viniferin showed an inhibitory effect with an IC50 value of 4.9 μM on COX-2 activity but a very weak inhibitory effect with 55.2 ± 2.1 % of the control (100 %) at 100 μM on COX-1 activity. α-Viniferin at doses of 3 μM to 10 μM inhibited the synthesis of COX-2 transcript in lipopolysaccharide (LPS)-activated murine macrophages Raw264.7. α-Viniferin showed an IC50 value of 2.7 μM on nitric oxide (NO) production in LPS-activated Raw264.7 cells when α-viniferin and LPS were treated simultaneously, but did not inhibit the NO production when α-viniferin was treated at 12 h after LPS stimulation. α-Viniferin inhibited synthesis of iNOS transcript with an IC50 value of 4.7 μM. Consequently, the inhibitory effect of α-viniferin on the release of prostanoids and NO could play an important role to show anti-inflammatory action.

References

  • 1 Kitanaka S, Ikezawa T, Yasukawa K, Yamanouchi S, Takido M, Sung H K. et al . Alpha-viniferin, an anti-inflammatory compound from Caragana chamlagu root.  Chem Pharm Bull. 1990;  38 432-5
  • 2 Kulanthaivel P, Janzen W P, Ballas L M, Jiang J B, Hue C Q, Darges J W. et al . Naturally occurring protein kinase C inhibitors; isolation of oligomeric stilbenes from Caragana sinica .  Planta Med. 1995;  61 41-4
  • 3 Keckeis K, Sarker S D, Dinan L. Resveratrol-type oligostilbenes from Iris clarkei antagonize 20-hydroxyecdysone action in the Drosophila melanogaster B (II) cell line.  Cell Mol Life Sci. 2000;  57 333-6
  • 4 Sung S H, Kang S Y, Lee K Y, Park M J, Kim J H, Park J H. et al . Alpha-viniferin, a stilbene trimer from Caragana chamlague, inhibits acetylcholinesterase.  Biol Pharm Bull. 2002;  25 125-7
  • 5 Lee S -H, Shin N -H, Kang S -H, Park J S, Chung S R, Min K R. et al . α-Viniferin: a prostaglandin H2 synthase inhibitor from root of C. humilis .  Planta Med. 1998;  64 204-7
  • 6 Min K R, Hwang B Y, Lim H -S, Kang B -S, Oh G -J, Lee J. et al . (-)-Epiafzelechin: cyclooxygenase-1 inhibitor and anti-inflammatory agent from aerial parts of Celastrus orbiculatus .  Planta Med. 1999;  65 460-2
  • 7 Eberhart C E, Dubois R N. Eicosanoids and the gastrointestinal tract.  Gastroenterology. 1995;  109 285-301
  • 8 Feng L, Xia Y, Garcia G E, Hwang D, Wilson C B. Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-alpha, and lipopolysaccharide.  J Clin Invest. 1995;  95 1669-75
  • 9 Brzozowski T, Konturek P C, Konturek S J, Sliwowski Z, Pajdo R, Drozdowicz D. et al . Classic NSAID and selective cyclooxygenase (COX)-1 and COX-2 inhibitors in healing of chronic gastric ulcers.  Microsc Res Tech. 2001;  53 343-53
  • 10 Maeda H, Akaike T. Nitric oxide and oxygen radicals in infection, inflammation, and cancer.  Biochemistry. 1998;  63 854-65
  • 11 Salvemini D, Wang Z Q, Wyatt P S, Bourdon D M, Marino M H, Manning P T. et al . Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation.  Br J Pharmacol. 1996;  118 829-38
  • 12 Huie R E, Padmaja S. The reaction of NO with superoxide.  Free Radic Res Commun. 1993;  18 195-9
  • 13 Xie Q W, Whisnant R, Nathan C. Promoter of the mouse gene encoding nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide.  J Exp Med. 1993;  177 1779-84
  • 14 Bhat K PL, Kosmeder J W, Pezzutto J M. Biological effects of resveratrol.  Antioxid Redox Signal.. 2001;  3 1041-64
  • 15 Gentilli M, Mazoit J X, Bouaziz H, Fletcher D, Casper R F, Benhamou D. et al . Resveratrol decreases hyperalgesia induced by carrageenan in the rat hind paw.  Life Sci. 2001;  68 1317-21
  • 16 Subbaramaiah K, Chung W J, Michaluart P, Telang N, Tanabe T, Inoue H. et al . Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells.  J Biol Chem. 1998;  273 21 875-82
  • 17 Tsai S H, Lin-Shiau S Y, Lin J K. Suppression of nitric oxide synthase and down-regulation of the activation of NFkappaB in macrophages by resveratrol.  Br J Pharmacol. 1999;  126 673-80

Prof. Youngsoo Kim, Ph. D.

College of Pharmacy

Chungbuk National University

Cheongju 361-763

Korea

Fax: +82-43-268-2732

Email: youngsoo@cbucc.chungbuk.ac.kr

    >