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论中药的间接作用与间接作用中药的创新

[On indirect actions of Chinese medicines and innovation of indirect-acting Chinese medicines].

作者信息

Wang Jia-Bo, Xiao Xiao-He

机构信息

School of Traditional Chinese Medicine, Capital Medical University Beijing 100069, China.

China Military Institute of Chinese Medicine, PLA General Hospital Beijing 100039, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2021 Nov;46(21):5443-5449. doi: 10.19540/j.cnki.cjcmm.20210978.601.

Abstract

The output of high level innovative Chinese medicines(CM) is very rare for a few years, which is in sharp contrast to the reality that antibody drugs, small molecular targeted therapy, antibody-drug conjugate and other innovative drugs have heavy investment and high yield. Acceleration for the research and development of innovative CM drugs obviously relies on breakthrough of the modes of thinking and methodology. Deeply influenced by the thinking of allopathic medicine in Western science system, the mainstream of current basic researches on CM is to find the components and their molecular mechanisms that can directly inhibit or antagonize the target in disease focal. However, it is difficult to explain the mechanism of the reported " active" components in many CMs, since their steady-state concentrations in disease focal are usually significantly lower than the effective concentrations of those components. Therefore, based on the original methodology of CM-systemism and harmonizing medicine, this paper proposed that the mechanism of action of CMs may not be limited to the direct antagonistic effect on the target in disease focal. Instead, it may involve indirect action through the intermediate substances across different organs or systems with a long-distance action pattern.A fundamentally break may be achieved when exploring the mechanism of action of CM active components from the perspective of indirect action. It may also change the thinking of allopathic medicine in the researches of CM and start a new innovative road for the development of indirect-acting CMs.

摘要

多年来,高水平创新中药的产出极为稀少,这与抗体药物、小分子靶向治疗、抗体药物偶联物等创新药物投资巨大且产出颇丰的现实形成了鲜明对比。创新中药研发的加速显然依赖于思维模式和方法学的突破。受西方科学体系中对抗疗法医学思维的深刻影响,当前中药基础研究的主流是寻找能够直接抑制或拮抗疾病病灶靶点的成分及其分子机制。然而,许多中药中已报道的“活性”成分的作用机制难以解释,因为它们在疾病病灶中的稳态浓度通常显著低于这些成分的有效浓度。因此,基于中药的原创方法——系统论和调和医学,本文提出中药的作用机制可能不限于对疾病病灶靶点的直接拮抗作用。相反,它可能涉及通过跨不同器官或系统的中间物质以长距离作用模式产生的间接作用。从间接作用的角度探索中药活性成分的作用机制可能实现根本性的突破。这也可能改变对抗疗法医学在中药研究中的思维方式,并为间接作用中药的开发开辟一条新的创新之路。

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