靶向色氨酸代谢通路整合PK-PD关联分析的逍遥散治疗肝郁脾虚型抑郁症的体内药效物质研究

抑郁症预计到2030年将成为世界第一大负担疾病，但其现代医药治疗存在局限。疏肝健脾中药经典方逍遥散改善抑郁症的临床疗效确切且安全，但体内药效物质不清。为此，本研究在前期已成功建立肝郁脾虚型抑郁大鼠模型及成熟的生物学评价体系基础上，提出中医“病-证结合、方-证相关”指导下的外源物PK-内源物PD靶向动态关联分析策略；通过表征逍遥散在模型动物体内的外源性药效候选成分的动力学特征，并靶向描绘与抑郁症密切相关的色氨酸代谢通路中内源性成分的动态变化规律，建立PK-PD关联分析，发掘逍遥散体内潜在药效物质；结合网络药理学和细胞活性评价的药效辅助验证，尝试揭示逍遥散治疗肝郁脾虚型抑郁症的体内药效物质。上述研究有助于诠释逍遥散为何能发挥抗抑郁作用的科学内涵，有望为其质量标准的提升、临床合理应用，乃至相关创新药物研发提供科学依据，也可能作为研究示范为中药复方的体内药效物质研究提供有价值的思路借鉴。

Depression is estimated to become the world's largest burden disease by 2030, but its modern medical treatment has limitations. Xiaoyaosan (XYS), a classic Traditional Chinese Medicine (TCM) prescription for soothing liver and strengthening spleen, has a significant clinical effect on improving depression symptoms, but the corresponding in vivo pharmacodynamic ingredients are still unclear. In view of this, based on the successful establishment of a depressive rat model of liver stagnation and spleen deficiency syndrome and the mature biological evaluation system in the previous study, this study proposes a strategy of targeted dynamic correlation analysis of pharmacokinetics (PK) of exogenous components - pharmacodynamics (PD) of endogenous components under the guidance of “combination of disease-syndrome，correlation of formula-syndrome” of TCM. By describing the PK characteristics of the exogenous pharmacodynamic candidate components of XYS in model animals and targeting to characterize the dynamic changes of the endogenous components of tryptophan metabolic pathway closely related to depression, the PK-PD correlation analysis will be applied to explore the potential in vivo effective ingredients of XYS. Combined with the efficacy-assisted verification of network pharmacology and cell activity evaluation, this study is attempted to reveal the in vivo pharmacodynamic ingredients of XYS in the treatment of depression of the liver stagnation and spleen deficiency syndrome. Taken together, this study will be helpful to explain the scientific connotation of why XYS can play an antidepressant effect, and is expected to provide a reliable scientific basis for improving its quality standard, clinical reasonable application, and even the researches for development of related innovative drugs, and it may also provide an idea as a reference example for revealing the bioactive ingredients of other classical TCM prescriptions.