中药药效物质进入体内后的血药浓度很低，能发挥药理作用吗；药效物质实际以什么形式（原形、代谢产物或两者兼有）发挥药效。针对问题，本文提出中药药效物质的“显效形式”新概念及“叠加作用”新假说：“中药药效物质显效形式的集合或叠加是药效的核心物质基础；各个显效形式的血药浓度的叠加作用是药效作用机制之一”。某中药药效物质各种显效形式的叠加作用是指其众多化学成分或/及代谢产物在同一个靶点上的叠加作用，是其各个化合物的浓度的叠加所产生的药理作用和药效，是“多成分单靶点的叠加作用”，不同于“多成分多靶点的协同作用”。中药体内研究表明，一种化学成分可产生众多代谢产物（多达50 种以上）；不同化学成分可产生相同代谢产物；代谢产物存在众多类似物、同系物甚至同分异构体（多达10 种）；有些化学成分之间可相互转化；部分代谢产物具有活性。这些结构极相近的化合物有可能具有相同药理作用靶点，为显效形式和叠加作用概念提供实验依据。建议开展显效形式和叠加作用研究，为中药药效物质本质和作用机制提供新解读，为“中药为何毒副作用小”提供新解释-“毒性分散效应”学说，为中药质量控制提出新策略。

The blood concentrations of the pharmacodynamic substances of traditional Chinese medicines (TCMs) are usually very low. How can they exert pharmacological actions, in which forms (original form, metabolite or the both) do they exert the actions. To answer these questions, we proposed a new concept of "Effective Forms" of pharmacodynamic substances of TCMs and a hypothesis of additive effect of multiple constituents of TCMs. The hypothesis includes that the aggregate or summation of Effective Forms of pharmacodynamic substances of TCMs is the core material base of the efficacy of TCMs, and the additive effect of the blood concentrations of different Effective Forms is one part of the action mechanism. The additive effect of the different Effective Forms of a TCMs means an additive effect of numerous constituents or/and metabolites on a same target, and therefore the efficacy brought by the addition of the concentrations of all these compounds, which different from the synergy effect of multi-constituents on multi-targets. Studies on the disposition of TCMs showed that a constituent can be biotransformed to many metabolites (up to more than 50 metabolites); different constituents can produce the same metabolites; many metabolites (up to 10 compounds for each metabolite) are isomers or homologues; some constituents can be converted to each other in vivo; and some metabolites are bioactive. These compounds having the similar structure are likely to have the same pharmacological effects on the same target, which could provide experimental evidences for the concept of "Effective Forms" and the hypothesis of "Additive Effect". We suggest that the Effective Forms and Additive Effects of the pharmacodynamic substances of TCMs should be extensively investigated in the future, and the results of such researches will help us further understand the pharmacodynamic substances and action mechanism of TCMs, and give a new explanation 'Toxicities Scattering Effect' for 'Why the toxicities of TCMs are low', and propose a new strategy for quality control of TCMs.

国家中医药管理局九五攀登计划项目：补阳还五汤治疗缺血性脑中风的作用机理研究，负责人：蔡少青；国家自然科学基金委重点项目（30830120）：多成分组方揭示补阳还五汤治疗缺血性脑中风的多靶点作用机制及配伍内涵的探索研究，负责人：蔡少青。