The hepatotoxicity of Polygonum multiflorum: The emerging role of the immune-mediated liver injury

Acta Pharmacol Sin. 2021 Jan;42(1):27-35. doi: 10.1038/s41401-020-0360-3. Epub 2020 Mar 2.

Abstract

Herbal and dietary supplements (HDS)-induced liver injury has been a great concern all over the world. Polygonum multiflorum Thunb., a well-known Chinese herbal medicine, is recently drawn increasing attention because of its hepatotoxicity. According to the clinical and experimental studies, P. multiflorum-induced liver injury (PM-DILI) is considered to be immune-mediated idiosyncratic liver injury, but the role of immune response and the underlying mechanisms are not completely elucidated. Previous studies focused on the direct toxicity of PM-DILI by using animal models with intrinsic drug-induced liver injury (DILI). However, most epidemiological and clinical evidence demonstrate that PM-DILI is immune-mediated idiosyncratic liver injury. The aim of this review is to assess current epidemiological, clinical and experimental evidence about the possible role of innate and adaptive immunity in the idiosyncratic hepatotoxicity of P. multiflorum. The potential effects of factors associated with immune tolerance, including immune checkpoint molecules and regulatory immune cells on the individual's susceptibility to PM-DILI are also discussed. We conclude by giving our hypothesis of possible immune mechanisms of PM-DILI and providing suggestions for future studies on valuable biomarkers identification and proper immune models establishment.

Keywords: Chinese herbal medicine; Polygonum multiflorum; adaptive immunity; idiosyncratic drug-induced liver injury; immune tolerance; inflammatory stress.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / drug effects*
  • Adaptive Immunity / genetics
  • Animals
  • Asian People
  • Chemical and Drug Induced Liver Injury / physiopathology*
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / adverse effects*
  • Drugs, Chinese Herbal / toxicity
  • Fallopia multiflora / adverse effects*
  • Fallopia multiflora / toxicity
  • HLA-B35 Antigen / genetics
  • Humans
  • Immune Tolerance / physiology
  • Immunity, Innate / drug effects*
  • Lipopolysaccharides / toxicity
  • Liver / drug effects*

Substances

  • Drugs, Chinese Herbal
  • HLA-B*35:01 antigen
  • HLA-B35 Antigen
  • Lipopolysaccharides