Inhibitory Mechanisms of Water Extract of Oplopanax elatus on Lipopolysaccharide-lnduced Inflammatory Responses in RAW 264.7 Murine Macrophage Cells

Objective:To study the anti-inflammatory action and cellular mechanism of Oplopanax elatus.Methods:A hot water extract of OE(WOE)was prepared and a major constituent,syringin,was successfully isolated.Its content in WOE was found to be 214.0 p.g/g dried plant(w/w).Their anti-inflammatory activities were examined using RAW 264.7 macrophages and a mouse model of croton oil-induced ear edema.Results:In lipopolysaccharide(LPS)-treated RAW 264.7 cells,a mouse macrophage cell line,WOE was found to significantly and strongly inhibit cyclooxygenase-2(COX-2)-induced prostaglandin E2(PGE2)production[half maximal inhibitory concentration(IC50)=135.2μg/mL]and inducible nitric oxide synthase(iNOS)-induced NO production(IC50=242.9μg/mL).In the same condition,WOE was revealed to inhibit NO production by downregulating iNOS expression,mainly by interrupting mitogen activated protein kinases(MAPKs)/activator protein-1(AP-1)pathway.The activation of all three major MAPKs,p38 MAPK,extracellular signal-regulated kinase(ERK),and c-Jun N-terminal kinase,was inhibited by WOE(50-300μg/mL).On the other hand,WOE reduced PGE2 production by inhibiting COX-2 enzyme activity,but did not affect COX-2 expression levels.In addition,WOE inhibited the production of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α.In croton oil-induced ear edema in mice,oral administration of WOE(50-300 mg/kg)dose-dependently inhibited edematic inflammation.Conclusion:Water extract of OE exhibited multiple anti-inflammatory action mechanisms and may have potential for treating inflammatory disorders.