Review Article

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

Tai Rao1,2,3,4, Ya-ting Liu1,2,3,4, Xiang-chang Zeng1,2,3,4, Chao-peng Li5, Dong-sheng Ou-Yang1,2,3,4,5
1 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China
2 Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410008, China
3 Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha 410008, China
4 National Clinical Research Center for Geriatric Disorders, Changsha 410008, China
5 Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha 410205, China
Correspondence to: Tai Rao:, Dong-sheng Ou-Yang:,
DOI: 10.1038/s41401-020-0360-3
Received: 20 October 2019
Accepted: 2 January 2020
Advance online: 2 March 2020


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

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