中药毒性认知创新与安全精准用药

Cognition innovation of toxicity of Chinese medicine and safe and precise medication

中医药在中华民族防病治病及繁衍生息进程中做出了卓越贡献,目前,中医药传承创新发展已经上升为国家战略。然而,近年来中药不良反应/事件频发,尤其针对新发现“有毒”中药的安全性问题,往往难以做出科学的回答并制定有效解决方案,面对国际舆论和社会公众质疑时,常陷入“被动应对”的窘迫局面。破解中药安全性难题亟需在中药毒性认知及安全风险防控方面实现突破。该文基于笔者团队既往在新发现“有毒”中药安全性评价及风险防控方面取得的原创性成果,提出并创新了中药毒性认知理论和方法,开辟了中药特异质毒性和间接毒性研究新领域,创建了病证结合的中药安全性评价模式和方法——病证毒理学,基于病证毒理学研究揭示了何首乌等中药致肝损伤的客观性及特异质属性,系统阐释了其诱发免疫特异质肝损伤的成因机制,提出并证实了中药免疫特异质肝损伤“三因致毒”机制假说;发现了多种中药诱发特异质或间接毒性的物质往往为非直接毒性物质,由此提出了“中药毒性相关物质”的概念;结合中药毒性现代科学认知提出基于成分效应靶标互作的中药配伍减毒策略和方法,为全面揭示“有毒”中药毒副反应科学内涵并建立科学有效的风险防控对策提供了基础。基于中药毒性认知的创新发展,将为科学评价与精准防控“有毒”中药安全风险提供重要的理论指导和方法学支撑。

Traditional Chinese medicine(TCM)has made outstanding contributions to disease prevention and treatment,survival,and reproduction of the Chinese nation.Currently,the inheritance and innovative development of TCM have become a national strategy.However,in recent years,adverse reactions/events of Chinese medicine frequently occurred.In particular,in terms of the safety problem of newly discovered"toxic"Chinese medicine,it is often difficult to answer the question scientifically and develop effective solutions.When facing international public opinions and public questioning,they are often"passively criticized".To solve the difficult problem about the safety of Chinese medicine,we urgently need to make breakthroughs in the cognition of toxicity of Chinese medicine and prevention and control of risks.This research team has been committed to the research on the safety of Chinese medicine for the long term.In particular,in terms of safety evaluation and risk prevention and control of newly discovered"toxic"Chinese medicine,they have made a series of original discoveries.On the basis of the discoveries,they innovated the cognition theory and methods of the toxicity of Chinese medicine,opened up a new field of research on the idiosyncratic toxicity and indirect toxicity of Chinese medicine,and proposed and established the disease-syndrome-based toxicology(DSBT),the model and method of safety evaluation of Chinese medicine related to diseases and syndromes.In light of the theory and methods of DSBT which have been applied to the objective eva-luation and analysis of the mechanism of the hepatotoxicity of Chinese medicine such as Polygoni Multiflori Radix,the mechanism hypothesis of"toxicity due to three causes"of idiosyncratic hepatotoxicity of Chinese medicine was proposed and confirmed.The findings revealed that the substances that induced idiosyncratic or indirect toxicity in Chinese medicine often did not possess definite direct toxi-city.Therefore,this research team proposed the concept of toxicity-related substances(TRS)in Chinese medicine.Based on the mo-dern scientific cognition of toxicity of Chinese medicine,the team proposed the strategy and method of Chinese medicine compatibility to reduce the toxicity based on the component-effect-target interaction to underpin the demonstration of the scientific connotation of toxicity and side effects of"toxic"Chinese medicine and establishment of scientific and effective risk prevention and control strategies.In light of the innovative development of toxicity cognition of Chinese medicine,this study is expected to provide important theoretical guidance and methodological support for scientific evaluation and precise prevention and control of the safety risk of"toxic"Chinese medicine.