Methanol extract of Hopea odorata suppresses inflammatory responses via the direct inhibition of multiple kinases

J Ethnopharmacol. 2013 Jan 30;145(2):598-607. doi: 10.1016/j.jep.2012.11.041. Epub 2012 Dec 7.

Abstract

Ethnopharmacological relevance: Hopea odorata Roxb. (Dipterocarpaceae) is a representative Thai ethnopharmacological herbal plant used in the treatment of various inflammation-related diseases. In spite of its traditional use, systematic studies of its anti-inflammatory action have not been performed.

Materials and methods: The inhibitory activities of a Hopea odorata methanol extract (Ho-ME) on the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, and prostaglandin E(2) (PGE(2)) in RAW264.7 cells and peritoneal macrophages were investigated. The effects of Ho-ME on the gastritis symptoms induced by HCl/EtOH and on ear oedemas induced by arachidonic acid were also examined. Furthermore, to identify the immunopharmacological targets of this extract, nuclear fractionation, a reporter gene assay, immunoprecipitation, immunoblot analysis, and a kinase assay were employed.

Results: Ho-ME strongly inhibited the release of NO, PGE(2), and TNF-α in RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ho-ME also clearly suppressed the gene expression of pro-inflammatory cytokines and chemokines, such as interferon (IFN)-β, interleukin (IL)-12, and monocyte chemotactic protein-1 (MCP-1). By analysing the inhibited target molecules, Syk and Src were found to be suppressed in the inhibition of nuclear factor (NF)-κB pathway. In addition, the observed downregulation of activator protein (AP)-1 and cAMP response element-binding (CREB) was due to the direct inhibition of interleukin-1 receptor-associated kinase (IRAK)1 and IRAK4, which was also linked to the suppression of c-Jun N-terminal kinase (JNK) and p38. In agreement with the in vitro observations, this extract also ameliorated the inflammatory symptoms in EtOH/HCl-induced gastritis and arachidonic acid-induced ear oedemas in mice.

Conclusion: Ho-ME has potential as a functional herbal remedy targeting Syk- and Src-mediated anti-inflammatory mechanisms. Future pre-clinical studies will be needed to investigate this possibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cells, Cultured
  • Cytokines / genetics
  • Dinoprostone / metabolism
  • Dipterocarpaceae*
  • HEK293 Cells
  • Humans
  • Lipopolysaccharides
  • Macrophages, Peritoneal
  • Male
  • Methanol / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Plant Extracts / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / metabolism
  • RNA, Messenger / metabolism
  • Solvents / chemistry
  • Transcription Factor AP-1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Solvents
  • Transcription Factor AP-1
  • Nitric Oxide
  • Protein Kinases
  • Dinoprostone
  • Methanol