Review Article

Tu-San-Qi (Gynura japonica): the culprit behind pyrrolizidine alkaloid-induced liver injury in China

Lin Zhu1,2, Chun-yuan Zhang1,2, Dong-ping Li3, Hu-biao Chen4, Jiang Ma1,2, Hong Gao3, Yang Ye2,5, Ji-yao Wang3, Peter P. Fu6, Ge Lin1,2
1 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
2 Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines between The Chinese University of Hong Kong and Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Beijing 201203, China
3 Division of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 201203, China
4 School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
5 State Key Laboratory of Drug Research and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
6 National Center for Toxicological Research, USA Food and Drug Administration, Jefferson, AR 72079, USA
Correspondence to: Ge Lin:,
DOI: 10.1038/s41401-020-00553-9
Received: 10 July 2020
Accepted: 5 October 2020
Advance online: 5 November 2020


Herbs and dietary supplement-induced liver injury (HILI) is the leading cause of drug-induced liver injury in China. Among different hepatotoxic herbs, the pyrrolizidine alkaloid (PA)-producing herb Gynura japonica contributes significantly to HILI by inducing hepatic sinusoidal obstruction syndrome (HSOS), a liver disorder characterized by hepatomegaly, hyperbilirubinemia, and ascites. In China, G. japonica has been used as one of the plant species for Tu-San-Qi and is often misused with non-PA-producing Tu-San-Qi (Sedum aizoon) or even San-Qi (Panax notoginseng) for self-medication. It has been reported that over 50% of HSOS cases are caused by the intake of PA-producing G. japonica. In this review, we provide comprehensive information to distinguish these Tu- San-Qi-related herbal plant species in terms of plant/medicinal part morphologies, medicinal indications, and chemical profiles. Approximately 2156 Tu-San-Qi-associated HSOS cases reported in China from 1980 to 2019 are systematically reviewed in terms of their clinical manifestation, diagnostic workups, therapeutic interventions, and outcomes. In addition, based on the application of our developed mechanism-based biomarker of PA exposure, our clinical findings on the definitive diagnosis of 58 PA-producing Tu- San-Qi-induced HSOS patients are also elaborated. Therefore, this review article provides the first comprehensive report on 2214 PA-producing Tu-San-Qi (G. japonica)-induced HSOS cases in China, and the information presented will improve public awareness of the significant incidence of PA-producing Tu-San-Qi (G. japonica)-induced HSOS and facilitate future prevention and better clinical management of this severe HILI.
Keywords: herb-induced liver injury; hepatic sinusoidal obstruction syndrome; pyrrolizidine alkaloids; Tu-San-Qi; Gynura japonica

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