中药的间接调控作用与间接作用型中药的创新发展

On indirect actions of Chinese medicines and innovation of indirect-acting Chinese medicines

多年来,我国高水平创新中药的产出非常少;而抗体药物、小分子靶向药物、抗体偶联药物的创新产出很高。为了提高中药创新的效率和效果,需要方法论上有所突破。西方科学体系的思维是对抗医学(allopathic medicine),中药研究也受其影响而寻求直接抑制或对抗病灶靶点的药效机制。然而,很多中药活性成分在疾病靶器官的稳态浓度显著低于其所需要的起效浓度。该文从中医药学方法论的本源-系统论(systemism)和调和医学(harmonizing medicine)出发,通过分析既往的研究案例,提出中药的作用机制可以不局限于病灶靶点的直接对抗作用,还包括通过调控中间媒介物质(intermediate substances)发挥的跨器官(脏腑)、跨系统、远程的间接调控作用。从间接调控作用的角度,探究中药药效成分和作用机制,可能从根本上打破对抗医学思想对中医药研究的思维束缚,走出间接作用型创新中药的全新发展之路。

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.