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

Chin J Integr Med. 2020 Sep;26(9):670-676. doi: 10.1007/s11655-020-3188-2. Epub 2020 Jan 23.

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.

Keywords: Chinese medicine; Oplopanax elatus; RAW 264.7; anti-inflammation; stem; syringin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides
  • Macrophages / drug effects*
  • Macrophages / physiology
  • Mice
  • Oplopanax / chemistry*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • RAW 264.7 Cells
  • Water / chemistry

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Lipopolysaccharides
  • Plant Extracts
  • Water