The ethyl acetate fraction from Physalis alkekengi inhibits LPS-induced pro-inflammatory mediators in BV2 cells and inflammatory pain in mice

J Ethnopharmacol. 2016 Apr 2:181:26-36. doi: 10.1016/j.jep.2016.01.023. Epub 2016 Jan 19.

Abstract

Ethnopharmacological relevance: Physalis alkekengi is an edible herb whose fruit and calyx are traditionally used to treat a wide range of diseases including inflammation, toothache, and rheumatism. However, the effects of Physalis alkekengi fruit along with its calyx (PAF) on neuroinflammation and inflammatory pain behavior have not been reported yet.

Aim of the study: This study evaluated the anti-inflammatory effect of PAF on lipopolysaccharide (LPS)-induced neuroinflammation and several in vivo model of inflammatory pain in mice.

Materials and methods: Here, first we studied the effects of PAF fractions on the production of pro-inflammatory mediators in LPS-treated BV2 microglial cells using enzyme-linked immunosorbent assay. The translocation of nuclear factor-kappa B (NF-κB) and the involvements of Akt and mitogen-activated protein (MAP) kinases in ethyl acetate fraction of PAF (PAF-EA)-mediated anti-inflammatory effect were measured using Western blotting. In in vivo experiments, the efficacy of PAF-EA was evaluated at the doses of 100 and 200mg/kg using several chemical-induced models of inflammatory pain such as acetic acid-induced writhing, formalin-induced paw licking and edema.

Results: We found that compared to other fractions, the PAF-EA more potently inhibited the LPS-induced generation of nitric oxide, tumor necrosis factor-α, interleukin-6 and reactive oxygen species. It also inhibited LPS-induced nuclear translocation of NF-κB. These actions of EA fraction were found to be associated with a disruption of Akt and MAP kinases signaling pathways. The EA fraction also significantly inhibited acetic acid-induced writhing, formalin-induced licking time and edema in mice.

Conclusions: Our findings support the ethnopharmacological use of P. alkekengi fruit along with its calyx as an anti-inflammatory agent and suggest that the EA fraction of PAF may serve as a potential candidate to treat different neurological disorders and pain associated with inflammation.

Keywords: Anti-inflammatory effect; BV2 cells; Inflammatory pain; Physalis alkekengi fruit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry*
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism*
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microglia / drug effects
  • Microglia / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Pain / drug therapy
  • Pain / metabolism
  • Physalis / chemistry*
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Acetates
  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • ethyl acetate
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases