State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China; Department of Pharmacy, College of Medicine and Health Sciences, Wollo University, P. O. Box 1145, Dessie, Ethiopia.
State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China.
J Ethnopharmacol. 2021 May 10;271:113864. doi: 10.1016/j.jep.2021.113864. Epub 2021 Jan 21.
Polygonum multiflorum Thunb.(PM), (known as Heshouwu () in China) is one of the most important and well mentioned Chinese medicinal herbs in the literature for its use in blackening hair, nourishing liver and kidney, anti-aging, anti-hyperlipidemia, antioxidant, anti-inflammatory, anticancer, hepatoprotection, cardio-protection and improving age-related cognitive dysfunction. The purpose of this review is to give a comprehensive and recent update on PM: new compounds or isolated for the first time, potential hepatotoxic compounds and their mechanisms. Moreover, future perspectives and challenges in the future study of this plant are conversed which will make a new base for further study on PM.
A comprehensive review of relevant published literature on PM using the scientific databases SCOPUS, PubMed, and Science Direct was done.
PM is broadly produced in many provinces of China and well known in other Eastern Asian Countries for its ethno-medical uses. Previous phytochemical investigation of PM had led to the isolation of more than 175 compounds including recently isolated 70 new compounds. Most of the new compounds isolated after 2015 are majorly dianthrone glycosides and stilbene glycosides. Processing has also a significant effect on chemical composition, pharmacological activities, and toxicity of PM. PM-induced liver injury is increasing after the first report in Hong Kong in 1996. Hepatotoxicity of PM was constantly reported in Japan, Korea, China, Australia, Britain, Italy, and other countries although its toxicity is related to idiosyncratic hepatotoxicity. More interestingly, although there is indispensable interest to predict idiosyncratic hepatotoxicity of PM and understand its mechanisms, the responsible hepatotoxic compounds and mechanisms of liver damage induced by PM are still not clear. There is a big controversy on the identification of the most responsible constituent. Anthraquinone and stilbene compounds in PM, mainly emodine and TSG are mentioned in the literature to be the main responsible hepatotoxic compounds. However, comparing the two compounds, which one is the more critical toxic agent for PM-induced hepatotoxicity is not well answered. Affecting different physiological and metabolic pathways such as oxidative phosphorylation and TCA cycle pathway, metabolic pathways, bile acid excretion pathway and genetic polymorphisms are among the mechanisms of hepatotoxicity of PM.
Deeper and effective high throughput experimental studies are still research hotspots to know the most responsible constituent and the mechanism of PM-induced hepatotoxicity.
何首乌（PM）（在中国俗称何首乌）是文献中记载的最重要、最常用的中药之一，用于黑发、滋养肝肾、抗衰老、抗高血脂、抗氧化、抗炎、抗癌、保肝、心脏保护和改善与年龄相关的认知功能障碍。本综述的目的是对 PM 进行全面和最新的更新：首次分离的新化合物或化合物，潜在的肝毒性化合物及其机制。此外，还讨论了该植物未来研究的未来展望和挑战，为进一步研究 PM 奠定了新的基础。
使用 SCOPUS、PubMed 和 Science Direct 等科学数据库对 PM 的相关已发表文献进行了全面综述。
PM 在我国许多省份广泛生产，在其他东亚国家因其民族医学用途而广为人知。对 PM 的先前植物化学研究导致分离出 175 多种化合物，包括最近分离出的 70 种新化合物。2015 年后分离出的大部分新化合物主要为二蒽酮糖苷和二苯乙烯糖苷。炮制对 PM 的化学成分、药理活性和毒性也有显著影响。1996 年香港首次报道 PM 引起肝损伤后，PM 引起的肝损伤呈上升趋势。尽管 PM 的肝毒性与体质性肝毒性有关，但日本、韩国、中国、澳大利亚、英国、意大利和其他国家不断有 PM 引起肝损伤的报道。更有趣的是，尽管人们对预测 PM 的体质性肝毒性及其机制有浓厚的兴趣，但 PM 引起肝损伤的毒性化合物和机制仍不清楚。对于鉴定最负责任的成分存在很大争议。PM 中的蒽醌和二苯乙烯化合物，主要是大黄素和 TSG，被文献提到是主要的肝毒性化合物。然而，比较这两种化合物，哪一种对 PM 诱导的肝毒性更具毒性还没有得到很好的回答。影响氧化磷酸化和 TCA 循环途径、代谢途径、胆汁酸排泄途径和遗传多态性等不同生理和代谢途径是 PM 肝毒性的机制之一。
更深入和有效的高通量实验研究仍然是研究热点，以了解最负责任的成分和 PM 诱导的肝毒性机制。
