Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono-Iodoacetate-Induced Arthritis

Int J Mol Sci. 2016 Feb 18;17(2):249. doi: 10.3390/ijms17020249.

Abstract

The fresh rhizome of Zingiber zerumbet Smith (Zingiberaceae) is used as a food flavoring and also serves as a folk medicine as an antipyretic and for analgesics in Taiwan. Zerumbone, a monocyclic sesquiterpene was isolated from the rhizome of Z. zerumbet and is the major active compound. In this study, the anti-inflammatory and antinociceptive effects of zerumbone on arthritis were explored using in vitro and in vivo models. Results showed that zerumbone inhibited inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase (COX)-2 expressions, and NO and prostaglandin E₂ (PGE₂) production, but induced heme oxygenase (HO)-1 expression in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. When zerumbone was co-treated with an HO-1 inhibitor (tin protoporphyrin (SnPP)), the NO inhibitory effects of zerumbone were recovered. The above results suggest that zerumbone inhibited iNOS and COX-2 through induction of the HO-1 pathway. Moreover, matrix metalloproteinase (MMP)-13 and COX-2 expressions of interleukin (IL)-1β-stimulated primary rat chondrocytes were inhibited by zerumbone. In an in vivo assay, an acetic acid-induced writhing response in mice was significantly reduced by treatment with zerumbone. Furthermore, zerumbone reduced paw edema and the pain response in a mono-iodoacetate (MIA)-induced rat osteoarthritis model. Therefore, we suggest that zerumbone possesses anti-inflammatory and antinociceptive effects which indicate zerumbone could be a potential candidate for osteoarthritis treatment.

Keywords: Zingiber zerumbet Smith; anti-inflammatory; arthritis; heme oxygenase-1; metalloproteinase; zerumbone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Arthritis / chemically induced
  • Arthritis / drug therapy
  • Arthritis / metabolism*
  • Arthritis / pathology*
  • Arthritis, Experimental
  • Cell Line
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Gene Expression
  • Heme Oxygenase-1 / metabolism
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / immunology
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Mice
  • Rats
  • Sesquiterpenes / pharmacology*

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • Lipopolysaccharides
  • Sesquiterpenes
  • zerumbone
  • Heme Oxygenase-1
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 13