In Vitro Anti-Inflammatory Activity of Panduratin A Isolated from Kaempferia pandurata in RAW264.7 Cells

Abstract

An active compound identified as panduratin A was isolated from a methanol extract of Kaempferia pandurata (Zingiberaceae). We examined the effect of panduratin A on nitric oxide (NO) and prostaglandin E₂ (PGE₂) production induced by lipopolysaccharide (LPS) in RAW264.7 cells. Modulations of iNOS and COX-2 enzyme expression were evaluated by Western blotting. Panduratin A strongly inhibited both NO (IC₅₀ : 0.175 μM) and PGE₂ (IC₅₀ : 0.0195 μM) production and suppressed both iNOS and COX-2 enzyme expression without any appreciable cytotoxic effect on RAW264.7 cells in a dose-dependent manner. Panduratin A also suppressed the phosphorylation of inhibitor κBα (IκBα) and degradation of IκBα associated with nuclear factor κB (NF-κB) activation. Furthermore, panduratin A inhibited LPS-induced NF-κB transcriptional activity in a dose-dependent manner. These results suggest that panduratin A could exert its inhibitory effects on the production of NO and PGE₂ through the suppression of NF-κB activation, indicating its potential for use as an anti-inflammatory agent.

Kaempferia pandurata - Zingiberaceae - panduratin A - inducible nitric oxide synthase - cyclooxygenase-2 - NF-κB - RAW264.7 cells

References

• 1 Marnett L J. Aspirin and the potential role of prostaglandins in colon cancer.  Cancer Res. 1992;  52 5575-89
• 2 Moncada S, Palmer R M, Higgs E A. Nitric oxide: physiology, pathophysiology, and pharmacology.  Pharmacol Rev. 1991;  43 109-42
• 3 Anggard E. Nitric oxide: mediator, murderer, and medicine.  Lancet. 1994;  343 1199-206
• 4 Surh Y J, Chun K S, Cha H H, Han S S, Keum Y S, Park K K. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-κB activation.  Mutat Res. 2001;  480 - 481 243-68
• 5 Hibbs J B, Taintor R R, Vavrin Z. Macrophage cytotoxicity: role of l-arginine deiminase and imino nitrogen oxidation to nitrite.  Science. 1987;  235 473-6
• 6 Baeuerle P A, Baichwal V R. NF-κB as a frequent target for immunosuppressive and anti-inflammatory molecules.  Adv Immunol. 1997;  65 111-37
• 7 Trakoontivakorn G ., Nakahara K, Shinmoto H, Takenaka M, Onishi-kameyama M, Ono H, Yoshida M, Nagata T, Tsushida T. Structural analysis of a novel antimutagenic compound, 4-hydroxypanduratin A, and antimutagenic activity of flavonoids in a Thai spice, fingerroot (Boesenbergia pandurata Schult.) against mutagenic heterocyclic amines.  J Agric Food Chem. 2001;  49 3046-50
• 8 Tuchinda P, Reutrakul V, Claeson P, Ponprayoon U, Sematong T, Santosuk T, Taylor W C. Anti-inflammatory cyclohexenyl chalcone derivatives in Boesenberia pandurata .  Phytochemistry. 2002;  59 169-73
• 9 Tubaro A, Florio C, Luxich E, Vertua R, Loggia R D, Yasumoto T. Suitability of the MTT-based cytotoxicity assay to detect okadaic acid contamination of mussels.  Toxicon.. 1996;  34 965-74
• 10 Schmidt H HHW, Kelm M. Determination of nitrite and nitrate by the Griess reaction. In: Methods in Nitric Oxide Research. London; John Wiley & Sons Ltd 1996: 491-7
• 11 Hsieh H K, Tsao L T, Wang J P, Lin C N. Synthesis and anti-inflammatory effect of chalcones.  J Pharm Pharmacol. 2000;  52 163-71
• 12 Madan B, Batra S, Ghosh B. 2′-hydroxychalcone inhibits nuclear factor-κB and blocks tumor necrosis factor-α and lipopolysaccharide-induced adhesion of neutrophils to human umbilical vein endothelial cells.  Mol Pharmacol. 2000;  58 536-34
• 13 Cheng Z J, Lin C, Hwang T, Teng C. Broussochalcone A, a potent antioxidant and effective suppressor of inducible nitric oxide synthase in lipopolysaccharide-activated macrophages.  Biochem Pharmacol. 2001;  61 939-46
• 14 Yin M J, Yamamoto Y, Graynor R B. The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB-β.  Nature. 1998;  396 77-80
• 15 Chan M M, Fong D. Modulation of the nitric oxide pathway by natural products. In: Laskin J, Laskin D, editors Cellular and Molecular Biology of Nitric Oxide. New York; Marcel Dekker 1999: pp. 333-51