基于药效物质基础的中药药物发现策略及其迭代发展  

Version updates of strategies for drug discovery based on effective constituents of traditional Chinese medicine

作　　者：葛楠 闫广利[1] 孙晖[1] 杨乐 孔玲[1] 孙野 韩莹[1] 赵琦琦 康舒宇 王喜军[1,2,3] Nan Ge;Guangli Yan;Hui Sun;Le Yang;Ling Kong;Ye Sun;Ying Han;Qiqi Zhao;Shuyu Kang;Xijun Wang(State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese medicines,National Chinmedomics Research Center,National TCM Key Laboratory of Serum Pharmacochemistry,Heilongjiang University of Chinese Medicine,Harbin 150040,China;State Key Laboratory of Dampness Syndrome,The Second Affiliated Hospital Guangzhou University of Chinese Medicine,Guangzhou,510120,China;Haihe Laboratory of Modern Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]黑龙江中医药大学经方与现代中药融合创新全国重点实验室,国家中医药管理局中医方证代谢组学研究中心,中药血清药物化学重点研究室 [2]广州中医药大学第二附属医院省部共建中医湿证国家重点实验室 [3]天津中医药大学现代中医药海河实验室

出　　处：《Acupuncture and Herbal Medicine》2023年第3期158-179,共22页针灸和草药（英文）

基　　金：This work was supported by key projects of National Natural Science Foundation of China(No.81830110);Heilongjiang Province key research and development plan(No.2022ZX02C04).

摘　　要：中药药效物质基础发现是中药新药创制的重要途径,青蒿素、黄连素和麻黄碱等国际知名药物均是由此途径陆续被发现及开发出来。然而,由于中医药理论及实践的复杂性,中药药效物质基础发现技术仍然不能完全满足创新药物的需要,仍然是制约中药创新药物的关键科学问题。中医临床是以多味中药组成方剂作为药物针对证候而表达临床疗效,而方剂的复杂性和证候的模糊性使得与临床疗效相关的中药体内药效物质基础发现充满挑战性。几十年来,中医药研究人员不断地建立及发展多项交叉学科的技术和方法,努力去发现发挥疗效的中药药效物质基础。本文回顾总结了中药药效物质基础发现的策略及其迭代发展历史,主要包括植物化学方法,即经典的系统分离筛选法(提取、分离、纯化、结构鉴定和药理活性测试);生物活性导向分离;中药血清药物化学方法;以及将体内成分与证候生物标志物关联分析的中医方证代谢组学方法。而中医方证代谢组学是近年来出现的一种符合中医药理论与特点的药效物质基础发现策略,该方法基于证候标记物与方剂体内显效成分关联分析,揭示方剂发挥疗效的体内药效物质及作用靶点与通路,推动基于临床疗效的创新药物研发及先导化合物的发现,促进中医药的现代化及产业化发展。The discovery of effective constituents of traditional Chinese medicine(TCM)is an important approach in new drug development.Several well-known drugs,such as artemisinin,berberine,and ephedrine have been developed using this approach.However,the efficacy and safety of TCM,two key issues for drug development based on TCM clinical experience,remain unclear worldwide.The discovery strategy of relevant constituents is the most important step for determining efficacy and safety,which still a key scientific problem that restricts the development of new drugs.Furthermore,TCM formulas used as clinical drugs address a specific TCM syndrome(Zheng),and the complexity of the formula and vagueness of the syndrome make the identification of the effective constituents related to clinical effectiveness challenging.Over decades,researchers have developed transdisciplinary technologies and research methodologies to identify effective constituents in vivo.In this paper,the history of strategy development for identifying the effective constituents related to the clinical efficacy of TCM is reviewed and summarized.The main approaches include the phytochemical method,which involves the classical systematic separation and screening(extraction,separation,purification,structure identification,and activity test);bioactivity-guided separation;serum pharmacochemistry of TCM in vivo;and Chinmedomics,which connects in vivo constituents with the biomarkers of the relevant TCM syndrome.Chinmedomics is a promising strategy that conforms to the theory and characteristics of TCM.By clarifying the effective constituents,targets and pathways of medicines,it can promote the discovery of lead compounds and the research of innovative drugs,and continuously promote the modernization of TCM.

关 键 词：中医方证代谢组学 中药药效物质基础 新药开发策略 中药血清药物化学 中医药现代化 

分 类 号：R285[医药卫生—中药学]