摘要
近年来,中草药相关的不良反应/事件频繁被报道,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。中药由于自身的复杂性及缺乏系统性研究,使得我们对中草药相关肝损伤的成因机制了解有限。因此,破解中草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。笔者团队以何首乌肝损伤作为典型范例,基于首创中药药源性肝损伤因果关系评价“整合证据链法”,证实了何首乌致肝损伤的客观真实性。进一步基于团队创新性建立的病证毒理学方法,科学揭示了何首乌肝损伤的物质基础及成因机制,也提出并证实了中药免疫特异质肝损伤“三因致毒”机制假说。在此基础上,阐明了何首乌特异质肝损伤易感人群的病证特征,并筛选发现了多种生物标志物,包括基因标志物HLA-B*35:01、免疫学及代谢组标志物。最后,探索创建了基于易感人群识别、易感物质控制以及个性化用药的“人-药-用”三维风险防控的安全用药策略和方法,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。
In recent years,adverse reactions and events associated with traditional Chinese medicines(TCM)and herbal medicines(HM)have frequently occurred.In particular,with regard to the safety of newly discovered TCM that have been deemed“toxic,”providing a scientifically based answer and developing effective solutions is challenging.Owing to the complexity of TCM/HM products and lack of systematic research,our understanding of the potential causes of TCM/HM-induced liver injury is limited.Therefore,significant advancements in understanding the toxicity of TCM and preventing and managing safety risks are urgently needed to address the safety concerns associated with TCM/HM.Using Polygoni Multiflori Radix(PMR)hepatotoxicity as a typical example,we evaluated the“integrated evidence chain”based on the causality evaluation of TCM-induced liver injury,and confirmed the objective authenticity of PMR hepatotoxicity.Furthermore,we first proposed and established a disease-syndrome-combined toxicology model that was applied to the material basis and analysis of the mechanism of PMR-induced hepatotoxicity.The mechanism hypothesis of“three-factor-induced toxicity”of idiosyncratic hepatotoxicity of TCM was proposed and confirmed.Based on this,the disease characteristics of the population susceptible to PMR idiosyncratic hepatotoxicity were elucidated,and various biomarkers were screened and identified,including the genetic marker HLA-B*35:01 and immunological and metabolomic markers.Finally,the study explored and established a safe medication strategy and method for“host-drug-use”three-dimensional risk prevention and control based on identifying susceptible individuals,controlling susceptible substances,and clinical precision medication.This study provides a foundation for comprehensively understanding the scientific implications of TCM/HM toxic side reactions and establishing scientific and effective risk prevention and control strategies.
作者
涂灿
高源
柏兆方
肖小河
王伽伯
Can Tu;Yuan Gao;Zhaofang Bai;Xiaohe Xiao;Jiabo Wang(Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing,China;School of Traditional Chinese Medicine,Capital Medical University,Beijing,China;China Military Institute of Chinese Medicine,Fifth Medical Center of Chinese PLA General Hospital,Beijing,China)
基金
funded by the National Natural Science Foundation of China,grant number 82104522
the Beijing Talent Youth Science Foundation (JQ21026)。
关键词
何首乌
肝损伤
因果关系评价
机制
风险防控
Causality evaluation
Liver injury
Mechanism
Polygoni Multiflori Radix
Risk prevention and control
作者简介
Corresponding author:Jiabo Wang,E-mail:pharm_sci@126.com;Corresponding author:Xiaohe Xiao,E-mail:pharmacy302xxh@126.com.
