[Research initiative of new thought on "main effect" of TCM formulae--new thinking on mechanism of compound action and compatibility mechanism of Chinese herbal compound formulae].Zhongguo Zhong Yao Za Zhi 2018; 43(18):3782-3786ZZ
This article proposes a new thought on the study of "main effect" of traditional Chinese medicine (TCM) formulae. The blood concentrations of the pharmacodynamic substances of Chinese material medica（CMM）are usually very low, with lower toxic and side effects than western medicine. Therefore, according to a recent hypothesis of additive effect of multiple components for a single target, local targets in multi-component multi-target synergistic effect network of TCM may have the additive effect of similar components. Studies on the disposition of CMM showed that a constituent could bebio-transformed to many metabolites; these compounds with a similar structure are likely to have the same pharmacological effects on the same target, which could provide experimental evidences for the hypothesis of "additive effect". The authors of this article further believe that additive effect of TCM multi-components only comes up under a limited conditions/concentration. Because of the complexity of TCM-organism system, the complex effect of multicomponent addition and competition/antagonism is more likely to appear in single targets of drug effect. This complex effect may be the key to impact the synergistic effect of TCM multi-targets. In theory, choose and create a single target additive effect could realize the scientific compatibility of TCM and improve the curative effect and attenuate toxicity. According to the clinical demand and under the guidance of the above thought, we proposed the "main effect" of TCM formulae. Because traditional Chinese medicine (compounds) have diverse and complex effects, how to better study TCM formulae compatibility mechanism and improve the curative effect? Efforts shall be made to select one or several effects relating to clinical specific syndromes from the complex and diverse effects of TCM as the "main effect". The "main effect" of TCM formulae is the macroscopic manifestation of the synergistic effect of multi-component/multi-target. The study of the Formulae "main effect" can contain at least two aspects: one is the study of pharmacokinetic application of TCM formulae, and another is the study for pharmacodynamics effect. In the study of main effect, there are two main elements. First, which drug targets are directly related to the main effect? This requires identifying the target network. Second, which drug components positively or negatively control the single target of the target network? And what change in single target effect as well as the multi-target synergistic effect will be caused by the regulatory component concentration or the change in number? These two elements is the key to elucidate the mechanism of compound action and compatibility mechanism of Chinese herbal compound formulae. Through the study of the main effect, the clinical curative effect and the mechanism of the TCM formulae shall be improved.