School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
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.
Acta Pharmacol Sin. 2021 Aug;42(8):1212-1222. doi: 10.1038/s41401-020-00553-9. Epub 2020 Nov 5.
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.
草药和膳食补充剂相关肝损伤（HILI）是中国药物性肝损伤的主要原因。在不同的肝毒性草药中，吡咯里西啶生物碱（PA）产生的草药Gynura japonica 通过诱导肝窦阻塞综合征（HSOS）导致 HILI，HSOS 是一种以肝肿大、高胆红素血症和腹水为特征的肝脏疾病。在中国，G. japonica 被用作土三七之一，常与非 PA 产生的土三七（Sedum aizoon）甚至三七（Panax notoginseng）一起被误用来自行治疗。据报道，超过 50%的 HSOS 病例是由摄入 PA 产生的 G. japonica 引起的。在这篇综述中，我们提供了全面的信息，以区分这些与土三七相关的草药植物物种，包括植物/药用部位形态、药用适应症和化学特征。从 1980 年到 2019 年，中国共报道了约 2156 例与土三七相关的 HSOS 病例，本文对其临床表现、诊断方法、治疗干预和结局进行了系统回顾。此外，基于我们开发的 PA 暴露的基于机制的生物标志物的应用，我们还详细阐述了对 58 例 PA 产生的土三七诱导的 HSOS 患者进行明确诊断的临床发现。因此，本文对中国首次全面报道了 2214 例由 PA 产生的土三七（G. japonica）诱导的 HSOS 病例，提供的信息将提高公众对 PA 产生的土三七（G. japonica）诱导的 HSOS 发病率的认识，并有助于未来对这种严重 HILI 的预防和更好的临床管理。
