Inhibitory Mechanisms of Water Extract of Oplopanax elatus on Lipopolysaccharide-Induced Inflammator

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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 μ 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)=135.2 μ g/mL]and inducible nitric oxide synthase (iNOS)-induced NO production (IC50=242.9 μ g/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 (50-300 μ g/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.
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