目的 基于方证代谢组学的研究策略，探讨泽泻汤对眩晕症的治疗作用及机制，阐释泽泻汤治疗眩晕症的药效物质基础。方法 基于眩晕症膜迷路积水豚鼠模型，寻找模型生物标记物及相关代谢通路，从代谢组学角度评价泽泻汤对眩晕症的治疗作用及其机制；在泽泻汤有效状态下，构建泽泻汤体内显效成分与内源性生物标记物的网络关系，揭示泽泻汤治疗眩晕症的药效物质基础。结果 发现33个眩晕症膜迷路积水豚鼠模型生物标记物，其中14个生物标记物轨迹经泽泻汤治疗后显著回调，在代谢组学层面证明泽泻汤对眩晕症的治疗作用；筛选出33个以原型入血的血中移行成分，挖掘6个泽泻汤体内显效成分与眩晕症膜迷路积水豚鼠模型生物标记物高度关联的化合物作为泽泻汤治疗眩晕症的主要药效物质基础。结论 确定泽泻萜醇F、alisolide、泽泻醇C、白术内酯Ⅲ、13,17-环氧泽泻醇A和泽泻醇P为泽泻汤治疗眩晕症的主要药效物质基础，初步阐明泽泻汤治疗眩晕症的作用机制，为泽泻汤复方制剂的新药开发奠定理论依据。

Objective This study was designed to explore the therapeutic effects and underlying mechanisms of Zexie Tang on vertigo through Chinmedomics, with the aim of elucidating its effective constituents. Methods Based on a guinea pig model of vertigo with endolymphatic hydrops, biomarkers and associated metabolic pathways were identified. This enables an evaluation of the therapeutic effects and mechanisms of Zexie Tang from a metabolomic perspective. Under the effective state of Zexie Tang, a network relationship between the constituents absorbed into blood and endogenous biomarkers was constructed to reveal the effective constituents for its treatment. Results Thirty-three biomarkers were found in endolymphatic hydrops model. Among them, 14 biomarkers were significantly reversed after treatment with Zexie Tang, thus substantiating its therapeutic efficacy from a metabolomic perspective. Furthermore, 33 prototype constituents of Zexie Tang in vivo were screened, and six compounds with a high correlation between endolymphatic hydrops biomarkers and constituents absorbed into blood after oral administration of Zexie Tang were identified as the main effective constituents for the treatment of vertigo. Conclusion This investigation identifies orientalol F, alisolide, alisol C, atractylenolide Ⅲ, 13,17-epoxy alisol A and alisol P as the main effective constituents for treating vertigo. The mechanism was initially clarified, laying a theoretical foundation for the development of new drugs from the Zexie Tang preparation.

R284

河北省自然科学基金资助项目（H2022106061）