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

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Abstract

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 µg/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 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 down-regulating 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 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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Acknowledgements

Bioassay facility of New Drug Development Institution (KNU) was used and greatly acknowledged.

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Authors and Affiliations

  1. College of Pharmacy, Kangwon National University, Chuncheon, 24341, Republic of Korea

    Ki Sun Kwon, Hyun Lim, Yong Soo Kwon & Hyun Pyo Kim

  2. Department of Bio-Resource Sciences, Kangwon National University, Chuncheon, 24341, Republic of Korea

    Myong Jo Kim & Nam Ho Yoo

  3. Bioherb Research Institute, Kangwon National University, Chuncheon, 24341, Republic of Korea

    Ji Hye Yoo

Authors
  1. Ki Sun Kwon
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  2. Hyun Lim
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  3. Yong Soo Kwon
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Contributions

Kwon KS: conceptualization, methodology, original draft writing. Lim H: methodology. Kwon YS: methodology. Kim MJ: conceptualization, resources, project administration, funding acquisition. Yoo JH: methodology. Yoo NH: methodology. Kim HP: conceptualization, manuscript review and editing, supervision, project administration, funding acquisition.

Corresponding author

Correspondence to Hyun Pyo Kim.

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Conflict of Interest

There are no conflicts of interest.

Supported by R&D Program for Forest Science Technology (No. 2017038B10-1819-BA01) provided by Korea Forest Service (Korea Forestry Promotion Institute) and BK21-Plus Project from the Ministry of Education, Republic of Korea

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

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Kwon, K.S., Lim, H., Kwon, Y.S. et al. Inhibitory Mechanisms of Water Extract of Oplopanax elatus on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Murine Macrophage Cells. Chin. J. Integr. Med. 26, 670–676 (2020). https://doi.org/10.1007/s11655-020-3188-2

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