基于超高效液相色谱-四极杆-轨道阱质谱联用技术结合代谢组学和网络药理学探究三黄泻心汤治疗高胆固醇血症的生物活性成分及作用机制

Exploring the Bioactive Constituents and Therapeutic Mechanisms of Sanhuang Xiexin Decoction in Hypercholesterolemia Treatment Using UHPLC-Q-Orbitrap-MS/MS Integrated With Metabolomics and Network Pharmacology.

作者信息

Zhu Yatong, Yang Xinlei, Wang Furong, Zhao Mengting, Hong Junli, Zhang Jun, Wang Lin

机构信息

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China.

School of Pharmacy, Nanjing Medical University, Nanjing, China.

出版信息

Rapid Commun Mass Spectrom. 2025 Aug 15;39(15):e10035. doi: 10.1002/rcm.10035.

DOI:10.1002/rcm.10035

PMID:40320474

Abstract

RATIONAL

Sanhuang Xiexin Decoction (SHD), a traditional Chinese medicine, has been used widely in East Asian Countries for hundreds of years and recent studies have implied its lipid-lowering and cardiovascular protective effects. However, the active components and potential mechanism of SHD in treating hypercholesterolemia (HC) remain unclear.

METHODS

UHPLC-Q-Orbitrap-MS/MS was used to annotate the components in SHD, and then, the efficacy of SHD in alleviating HC was demonstrated in vitro and in vivo. Subsequently, metabolomics by UHPLC-Q-Orbitrap-MS/MS was employed to identify discriminative metabolites and metabolic pathways involved in SHD against HC. Network pharmacology was applied to explore the potential bioactive components. Then, the integrated approach was proposed to elucidate the possible targets and mechanisms. Finally, molecular docking was operated to validate the potential targets and bioactive components.

RESULTS

A total of 180 chemical components were identified in SHD, and 18 prototype components were confirmed in vivo. Metabolomics study revealed 12 metabolites, and five metabolic pathways were associated with the efficacy of SHD. Network pharmacology analysis further identified 18 active compounds and 107 targets. Finally, the integrated approach suggested that SHD exerts its protective effects against HC by modulating purine and glycerophospholipid metabolism through the regulation of key targets, including phosphodiesterase 5 (PDE5), acetylcholinesterase (ACHE), phospholipase A2 group VII (PLA2G7), and xanthine dehydrogenase (XDH).

CONCLUSION

SHD exerts its therapeutic effects on HC through multiple targets and multiple mechanisms. This study lays the groundwork for the clinical application of SHD in the treatment of HC and paves the way for further exploration of its underlying mechanisms.

摘要

理论依据

中药三黄泻心汤（SHD）在东亚国家已被广泛使用数百年，近期研究表明其具有降血脂和心血管保护作用。然而，SHD治疗高胆固醇血症（HC）的活性成分和潜在机制仍不清楚。

方法

采用超高效液相色谱-四极杆-轨道阱串联质谱（UHPLC-Q-Orbitrap-MS/MS）对SHD中的成分进行注释，然后在体外和体内验证SHD缓解HC的疗效。随后，采用UHPLC-Q-Orbitrap-MS/MS代谢组学方法鉴定SHD抗HC的差异代谢物和代谢途径。应用网络药理学探索潜在的生物活性成分。然后，提出综合方法以阐明可能的靶点和机制。最后，进行分子对接以验证潜在靶点和生物活性成分。

结果

在SHD中总共鉴定出180种化学成分，在体内确认了18种原型成分。代谢组学研究揭示了12种代谢物，5条代谢途径与SHD的疗效相关。网络药理学分析进一步鉴定出18种活性化合物和107个靶点。最后，综合方法表明SHD通过调节关键靶点，包括磷酸二酯酶5（PDE5）、乙酰胆碱酯酶（ACHE）、磷脂酶A2第VII组（PLA2G7）和黄嘌呤脱氢酶（XDH），调节嘌呤和甘油磷脂代谢，从而对HC发挥保护作用。