Inhibitory Mechanisms of Water Extract of Oplopanax elatus on Lipopolysaccharide-Induced Inflammatory Responses in RAW 2

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hinese Journal of Integrative Medicine

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Available online at link.springer.com/journal/11655 Journal homepage: www.cjim.cn/zxyjhen/zxyjhen/ch/index.aspx E-mail: [email protected]

Original Article

Inhibitory Mechanisms of Water Extract of Oplopanax elatus on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Murine Macrophage Cells Ki Sun Kwon1, Hyun Lim1, Yong Soo Kwon1, Myong Jo Kim2, Ji Hye Yoo3, Nam Ho Yoo2, and Hyun Pyo Kim1 Objective: To study the anti-inflammatory action and cellular mechanism of Oplopanax elatus . ABSTRACT Objective: Methods:: A hot water extract of OE (WOE) was prepared and a major constituent, syringin, was successfully Methods isolated. Its content in WOE was found to be 214.0 μg/g dried plant (w/w). Their anti-inflammatory activities Results:: 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 μg/mL] and inducible nitric oxide synthase (iNOS)-induced NO production (IC50=242.9 μg/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 μg/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 Conclusion:: Water extract of OE exhibited multiple anti-inflammatory action mechanisms edematic inflammation. Conclusion and may have potential for treating inflammatory disorders. KEYWORDS Oplopanax elatus , Chinese medicine, stem, syringin, anti-inflammation, RAW 264.7

Although most acute inflammatory symptoms are properly controlled by currently-used drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), consistent inflammatory stimulation without proper resolution may lead to chronic inflammatory condition. In chronic inflammatory disorders such as rheumatoid arthritis, the long-term use of NSAIDs and steroidal anti-inflammatory drugs (SAID) often produces serious adverse effects. (1,2) Recently developed biologics including monoclonal antibody against interleukin-6 (IL-6) also have some limitations as far as safe, longterm usage.(3) Furthermore, some patients in the initial phase of a disease and/or those exhibiting borderline symptoms of diseases are sometimes advised not to take drugs. In cases such as these, it would be useful to have plant-derived products with fewe