Essential oil of Artemisia argyi suppresses inflammatory responses by inhibiting JAK/STATs activation

J Ethnopharmacol. 2017 May 23:204:107-117. doi: 10.1016/j.jep.2017.04.017. Epub 2017 Apr 21.

Abstract

Ethnopharmacological relevance: Artemisia argyi is a herbal medicine traditionally used in Asia for the treatment of bronchitis, dermatitis and arthritis. Recent studies revealed the anti-inflammatory effect of essential oil in this plant. However, the mechanisms underlying the therapeutic potential have not been well elucidated. The present study is aimed to verify its anti-inflammatory effect and investigate the probable mechanisms.

Materials and methods: The essential oil from Artemisia argyi (AAEO) was initially tested against LPS-induced production of inflammatory mediators and cytokines in RAW264.7 macrophages. Protein and mRNA expressions of iNOS and COX-2 were determined by Western blotting and RT-PCR analysis, respectively. The effects on the activation of MAPK/NF-κB/AP-1 and JAK/STATs pathway were also investigated by western blot. Meanwhile, in vivo anti-inflammatory effect was examined by histologic and immunohistochemical analysis in TPA-induced mouse ear edema model.

Results: The results of in vitro experiments showed that AAEO dose-dependently suppressed the release of pro-inflammatory mediators (NO, PGE2 and ROS) and cytokines (TNF-α, IL-6, IFN-β and MCP-1) in LPS-induced RAW264.7 macrophages. It down-regulated iNOS and COX-2 protein and mRNA expression but did not affect the activity of these two enzymes. AAEO significantly inhibited the phosphorylation of JAK2 and STAT1/3, but not the activation of MAPK and NF-κB cascades. In animal model, oral administration of AAEO significantly attenuated TPA-induced mouse ear edema and decreased the protein level of COX-2.

Conclusion: AAEO suppresses inflammatory responses via down-regulation of the JAK/STATs signaling and ROS scavenging, which could contribute, at least in part, to the anti-inflammatory effect of AAEO.

Keywords: 1400W (PubChem CID: 1433); Anti-inflammatory; Artemisia argyi; JAK/STATs; borneol (PubChem CID: 64685); camphor (PubChem CID: 2537); cineole (PubChem CID: 2758); indomethacin (PubChem CID: 3715); α-(−)-thujone (PubChem CID: 261491).

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Artemisia*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Dinoprostone / metabolism
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / pathology
  • Janus Kinase Inhibitors / pharmacology*
  • Janus Kinase Inhibitors / therapeutic use
  • Janus Kinases / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Oils, Volatile / pharmacology*
  • Oils, Volatile / therapeutic use
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • STAT Transcription Factors / antagonists & inhibitors
  • Tetradecanoylphorbol Acetate

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Janus Kinase Inhibitors
  • Lipopolysaccharides
  • Oils, Volatile
  • Reactive Oxygen Species
  • STAT Transcription Factors
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Janus Kinases
  • Dinoprostone
  • Tetradecanoylphorbol Acetate