Actinidia arguta extract attenuates inflammasome activation: Potential involvement in NLRP3 ubiquitination

J Ethnopharmacol. 2018 Mar 1:213:159-165. doi: 10.1016/j.jep.2017.11.023. Epub 2017 Nov 21.

Abstract

Ethnopharmacological relevance: Actinidia arguta (A. arguta) has been widely used in Asian countries as a traditional medicinal herb to treat inflammation-related diseases, such as gastritis, bronchitis, and arthritis.

Aim of the study: The inhibitory effect of A. arguta leaves' extract (AA) on inflammasome activation was investigated to verify its traditional use in treating inflammation-related diseases.

Materials and methods: Bone marrow-derived macrophages (BMDMs) primed by lipopolysaccharide (LPS) were activated by selective inflammasome stimulators, and the effect of AA on inflammasome activation was investigated. A monosodium urate crystal (MSU)-induced peritonitis mouse model was used to study the in vivo efficacy of AA on inflammasome activation.

Results: In the in vitro study, AA regulated NLRP3 ubiquitination and apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, leading to the inhibition of NLRP3 inflammasome-mediated interleukin (IL)-1β secretion. The inhibitory effect of AA on inflammasome activation in vitro was further confirmed in vivo using an MSU-induced peritonitis mouse model.

Conclusion: AA provided scientific evidence, substantiating the traditional claims for its use in the treatment of inflammation and inflammation-mediated metabolic disorders, including gout.

Keywords: ASC; Actinidia arguta; Inflammasome; NLRP3; Peritonitis; Ubiquitination.

MeSH terms

  • Actinidia*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Caspase 1 / metabolism
  • Cells, Cultured
  • Female
  • Inflammasomes / metabolism*
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Peritonitis / chemically induced
  • Peritonitis / drug therapy
  • Peritonitis / metabolism
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Plant Leaves
  • Ubiquitination
  • Uric Acid

Substances

  • Anti-Inflammatory Agents
  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Plant Extracts
  • Uric Acid
  • Caspase 1