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

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry Pub Date : 2025-05-04 DOI:10.1002/rcm.10035

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

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引用次数: 0

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.

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利用UHPLC-Q-Orbitrap-MS/MS结合代谢组学和网络药理学研究三黄泻心汤治疗高胆固醇血症的活性成分及作用机制

三黄泻心汤作为一种传统中药，已在东亚地区广泛应用数百年，近年来研究表明其具有降脂和心血管保护作用。然而，SHD治疗高胆固醇血症（HC）的有效成分和潜在机制尚不清楚。方法采用超高效液相色谱- q - orbitrap -MS/MS技术，对其成分进行定量分析，并在体外和体内验证其对HC的缓解作用。随后，利用UHPLC-Q-Orbitrap-MS/MS进行代谢组学鉴定，确定SHD对抗HC的特异性代谢物和代谢途径。应用网络药理学方法，探索其潜在的生物活性成分。然后，提出了综合方法来阐明可能的靶点和机制。最后进行分子对接，验证潜在靶点和生物活性成分。结果在SHD中鉴定出180种化学成分，在体内鉴定出18种原型成分。代谢组学研究发现，12种代谢物和5种代谢途径与SHD的疗效相关。网络药理分析进一步鉴定出18个活性化合物和107个靶点。综上所示，SHD对HC的保护作用可能是通过调控关键靶点，包括磷酸二酯酶5 （PDE5）、乙酰胆碱酯酶（ACHE）、磷脂酶A2组VII （PLA2G7）和黄嘌呤脱氢酶（XDH），从而调节嘌呤和甘油磷脂代谢。结论SHD对HC的治疗作用是多靶点、多机制的。本研究为SHD治疗HC的临床应用奠定了基础，并为进一步探索其潜在机制铺平了道路。

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来源期刊

Rapid Communications in Mass Spectrometry 化学-分析化学

CiteScore

4.10

自引率

5.00%

发文量

219

审稿时长

2.6 months

期刊介绍： Rapid Communications in Mass Spectrometry is a journal whose aim is the rapid publication of original research results and ideas on all aspects of the science of gas-phase ions; it covers all the associated scientific disciplines. There is no formal limit on paper length ("rapid" is not synonymous with "brief"), but papers should be of a length that is commensurate with the importance and complexity of the results being reported. Contributions may be theoretical or practical in nature; they may deal with methods, techniques and applications, or with the interpretation of results; they may cover any area in science that depends directly on measurements made upon gaseous ions or that is associated with such measurements.