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研究 SLXG 治疗胆固醇性胆结石的潜在机制和治疗效果。

Investigating the potential mechanism and therapeutic effects of SLXG for cholesterol gallstone treatment.

机构信息

Department of Intervention Medicine and Microinvasive Oncology, The Second Hospital of Shandong University, Jinan, PR China; Institute of Interventional Oncology, Shandong University, Jinan, PR China.

Department of Intervention Medicine and Microinvasive Oncology, The Second Hospital of Shandong University, Jinan, PR China; Institute of Interventional Oncology, Shandong University, Jinan, PR China.

出版信息

Phytomedicine. 2024 Sep;132:155886. doi: 10.1016/j.phymed.2024.155886. Epub 2024 Jul 17.

DOI:10.1016/j.phymed.2024.155886
PMID:39059092
Abstract

BACKGROUND

Shugan Lidan Xiaoshi Granules (SLXG) is a traditional Chinese medicine (TCM) formulation frequently employed to prevent and treat cholesterol gallstones. SLXG is formulated based on the Chaihu Shugan Formula found in an ancient Chinese medical book, a traditional remedy in China for centuries, and has demonstrated successful treatment of numerous patients with gallbladder stones.

PURPOSE

This research sought to clarify the therapeutic impact and molecular mechanisms of SLXG and its active components in the treatment of cholesterol gallbladder stones.

METHODS

The study employed network pharmacology, UPLC-HRMS transcriptome sequencing, animal model experiments, molecular docking, and Surface Plasmon Resonance (SPR) to explore the molecular mechanisms of SLXG and its relationship with Traditional Chinese Medicines (TCMs) and potential targets. Furthermore, PPI network analysis, along with GO and KEGG enrichment analyses, were performed to explore the potential mechanisms through which SLXG and its active ingredient, naringenin, prevent and treat cholesterol gallstones. The mechanism of action was further elucidated using an animal model for gallbladder stone formation.

RESULTS

The study employed a network pharmacology and UPLC-HRMS to investigate the active compounds of SLXG for the treatment of cholesterol gallbladder stones, and subsequently constructed a network of therapeutic targets of SLXG. The results from gene enrichment analyses indicated that SLXG targets the metabolic pathway of bile secretion and the cholesterol metabolism pathway in addressing cholesterol gallbladder stones. The molecular docking results confirmed the interaction between the genes enriched in the pathways and the active ingredients in SLXG. Transcriptome sequencing results demonstrated that SLXG exerts its therapeutic effect on gallstones by regulating cholesterol and bile acid synthesis and metabolism. Furthermore, animal model experiments and SPR provided evidence that SLXG and its active ingredient, naringenin, exert therapeutic effects on cholesterol gallbladder stones by targeting the genes HMGCR, SOAT2, and UGT1A1, and influencing substances associated with cholesterol synthesis and metabolism.

CONCLUSIONS

Using systematic network pharmacology methods combined with in vivo validation experiments, we uncovered the fundamental pharmacological effects and potential mechanisms of SLXG and its active ingredient, naringenin, in the treatment of cholesterol gallstones. This research underscores the valuable role that traditional remedies can play in addressing medical challenges and suggests a promising direction for further exploration of natural treatments for the disease.

摘要

背景

舒肝利胆消石颗粒(SLXG)是一种常用于预防和治疗胆固醇胆结石的中药配方。SLXG 是基于古代中医书籍中的柴胡疏肝配方研制而成的,在中国已有数百年的传统疗法,已成功治疗了许多胆囊结石患者。

目的

本研究旨在阐明 SLXG 及其活性成分治疗胆固醇胆结石的治疗作用及分子机制。

方法

本研究采用网络药理学、UPLC-HRMS 转录组测序、动物模型实验、分子对接和表面等离子体共振(SPR)技术,探讨 SLXG 及其与中药(TCM)的关系及潜在靶点的分子机制。此外,还进行了 PPI 网络分析、GO 和 KEGG 富集分析,探讨 SLXG 及其活性成分柚皮苷预防和治疗胆固醇胆结石的潜在机制。并利用胆囊结石形成动物模型进一步阐明其作用机制。

结果

本研究采用网络药理学和 UPLC-HRMS 技术研究 SLXG 治疗胆固醇胆结石的活性化合物,构建了 SLXG 的治疗靶点网络。基因富集分析结果表明,SLXG 通过调控胆汁分泌代谢途径和胆固醇代谢途径治疗胆固醇胆结石。分子对接结果证实了所富集通路的基因与 SLXG 中活性成分的相互作用。转录组测序结果表明,SLXG 通过调节胆固醇和胆汁酸的合成和代谢对胆结石发挥治疗作用。此外,动物模型实验和 SPR 结果表明,SLXG 和其活性成分柚皮苷通过靶向基因 HMGCR、SOAT2 和 UGT1A1 以及影响胆固醇合成和代谢相关物质对胆固醇胆结石发挥治疗作用。

结论

本研究采用系统的网络药理学方法结合体内验证实验,揭示了 SLXG 及其活性成分柚皮苷治疗胆固醇胆结石的基本药理作用和潜在机制。这一研究突显了传统疗法在应对医学挑战方面的重要作用,并为进一步探索天然疗法治疗该疾病提供了有前景的方向。

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