传统的天然产物药物开发价值评判模式，多以直接构建疾病或病理模型为先导，通过观测药效强弱，继而深入开展成药性评估。这种传统路径呈现出较为显著的随机性与盲目性，不可避免地导致开发难度的大幅提升以及研发成本的急剧增加。相较而言，基于“生理-机制-病理”的反向开发模式，创新性地以正常动物模型为切入点，首先全面细致观察天然产物所引发的生理效应及毒性作用，进而深入挖掘其内在的作用机制，以此反向推断可能蕴含的药理活性，最终针对性地设计并构建相应的疾病或病理模型进行验证。此策略凭借对天然产物与机体相互作用规律的精准解析，以及对药理效应所提供线索的有效整合，实现了精准化模型构建与有效性科学评估，在一定程度上显著提升了研发的成功率与效率。以银杏叶萜类内酯为研究对象完成了该模式的全流程实践，成功发现其降胆红素-抗黄疸的新药理活性，验证了模式的可行性与实用性。通过系统解析该模式的产生背景、理论基础及技术路径，并展望其在天然药物研发中的多元应用场景，为推动天然药物研发的策略创新与实践应用提供理论依据与方向指引。

Evaluation models for the development value of traditional natural product-based drugs often take the direct construction of disease or pathological models as a precursor. By observing the strength of drug efficacy, further evaluation of in-depth drugability is carried out. However, this traditional approach shows significant randomness and blindness, inevitably leading to a substantial increase in development difficulty and a sharp rise in research and development (R&D) costs. In contrast, the reverse development model based on “physiology-mechanism-pathology” innovatively starts with normal animal models. First, it comprehensively and meticulously observes the physiological effects and toxic effects caused by natural products, and then delves into their underlying mechanisms of action. Based on this, it infers the potential pharmacological activities in a reverse manner. Finally, it specifically designs and constructs corresponding disease or pathological models for rigorous verification. This strategy, through the accurate analysis of the interaction rules between natural products and the body and the effective integration of clues provided by pharmacological effects, achieves precise model construction and scientific evaluation of effectiveness, significantly improving the success rate and efficiency of R&D to a certain extent. In this study, the whole process of the model was practiced with ginkgo terpenoid lactones as the research object, and its new pharmacological activity of reducing bilirubin and anti-jaundice was successfully discovered, which verified the feasibility and practicability of the model. This paper systematically reviews and deeply analyzes the background, basic principles, and technical processes of this innovative approach. At the same time, it predicts and prospects its diverse application prospects in the field of natural medicine R&D. The aim is to provide a solid theoretical basis and forward-looking direction for promoting the strategic innovation and practical application of natural medicine R&D.

R28

山东省中医药科技重点项目（Z20242118）；烟台市自然科学基金重点项目（ZR2025Z052）；烟台市科技创新发展计划（政策引导类）项目（2025YD018）