Ginsenoside metabolite 20(S)-protopanaxatriol from Panax ginseng attenuates inflammation-mediated NLRP3 inflammasome activation

J Ethnopharmacol. 2020 Apr 6:251:112564. doi: 10.1016/j.jep.2020.112564. Epub 2020 Jan 10.

Abstract

Ethnopharmacological relevance: Panax ginseng C.A. Meyer (Araliaceae), has been used in traditional medicine for preventive and therapeutic purposes in Asian countries. One of the active ginsenoside metabolites, 20(S)-Protopanaxatriol (PPT), has been associated with diverse pharmacological effects, including anti-inflammatory properties.

Aim of the study: Although the capacity of PPT as an anti-inflammatory agent has been studied, this study aimed to explore the intrinsic mechanism of PPT in regulating inflammasome activation-mediated inflammatory responses in experimental models.

Materials and methods: Lipopolysaccharide (LPS)-primed peritoneal macrophages in vitro was used to study the role of PPT on inflammasome activation. LPS-induced septic shock and monosodium urate (MSU)-induced murine peritonitis models were employed for in vivo evaluations.

Results: PPT attenuated NLRP3 inflammasome activation and also reduced ASC oligomerization, leading to attenuation of interleukin (IL)-1β secretion. Further, PPT inhibited IL-1β secretion in both LPS-induced septic shock and MSU-induced mouse peritonitis models.

Conclusions: This study revealed that ginsenoside metabolite PPT, inhibits inflammation-mediated inflammasome activation and supported the traditional use of ginseng in treating various inflammatory disorders.

Keywords: 20(S)-protopanaxatriol; IL-1β; Inflammasome; NLRP3; Peritonitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Ginsenosides / metabolism
  • Inflammasomes / immunology*
  • Interleukin-1beta / immunology
  • Lipopolysaccharides / pharmacology
  • Macrophages, Peritoneal / drug effects
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology*
  • Panax*
  • Peritonitis / chemically induced
  • Peritonitis / drug therapy*
  • Peritonitis / immunology
  • Sapogenins / pharmacology
  • Sapogenins / therapeutic use*
  • Shock, Septic / drug therapy*
  • Shock, Septic / immunology
  • Uric Acid

Substances

  • Anti-Inflammatory Agents
  • Ginsenosides
  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Sapogenins
  • Uric Acid
  • protopanaxatriol