Deciphering the mechanism of Chaihu Shugan San in the treatment of nonalcoholic steatohepatitis using network pharmacology and molecular docking

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmacy and Pharmacology Pub Date : 2024-09-09 DOI:10.1093/jpp/rgae103

Yi Ren, Kaihui Xiao, Yujia Lu, Wei Chen, Li Li, Jingjie Zhao

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Abstract

Objectives In China, there is a long history and rich clinical experience in treating nonalcoholic steatohepatitis (NASH) with traditional Chinese herbal medicines, including Chai Hu Shu Gan San. This study aims to investigate the potential regulatory effects of Chaihu Shugan San (CSS) on liver lipid metabolism and inflammatory damage in mice with experimental nonalcoholic steatohepatitis (NASH) induced by a choline-deficient high-fat diet (CDHFD). Utilizing network pharmacology, we systematically explore the mechanisms of action and therapeutic potential of CSS against NASH. Methods Potential targets in CSS and targets for NASH were identified using online databases. Functional enrichment and protein–protein interaction analyses were conducted to identify hub-targeted genes and elucidate the underlying molecular mechanisms. The affinities of active compounds in CSS with hub-targeted genes were evaluated using molecular docking. Finally, hub-targeted genes were validated through real-time polymerase chain reaction, western blotting, and immunofluorescence in choline-deficient high-fat diet mice, both with and without CSS treatment. Key findings CSS reduces serum ALT and AST levels in NASH mice(P < 0.05) and ameliorates ballooning degeneration in the livers of NASH mice, thereby lowering the NAS score(P < 0.05). Including naringenin, high-performance liquid chromatography/mass spectrometrys identified 12 chromatographic peaks. Based on network pharmacology analysis, CSS contains a total of 103 active compounds and 877 target genes. Transferase activity represents a potential mechanism for therapeutic intervention of CSS in NASH. The transcriptional levels and protein expression of the SIRT1 gene in NASH mice are significantly increased by CSS (P < 0.05). Conclusions Naringenin is probable active compound in CSS and SIRT1 is the hub gene by which CSS is involved in NASH treatment.

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利用网络药理学和分子对接破译柴胡疏肝散治疗非酒精性脂肪性肝炎的机制

目的在中国，以柴胡舒肝散为代表的传统中药治疗非酒精性脂肪性肝炎（NASH）有着悠久的历史和丰富的临床经验。本研究旨在探讨柴胡舒肝散（CSS）对胆碱缺乏性高脂饮食（CDHFD）诱导的实验性非酒精性脂肪性肝炎（NASH）小鼠肝脂代谢和炎症损伤的潜在调节作用。利用网络药理学，我们系统地探讨了 CSS 对 NASH 的作用机制和治疗潜力。方法利用在线数据库确定 CSS 的潜在靶点和 NASH 的靶点。我们进行了功能富集和蛋白-蛋白相互作用分析，以确定中心靶向基因并阐明其潜在的分子机制。利用分子对接技术评估了 CSS 中活性化合物与枢纽靶向基因的亲和力。最后，通过实时聚合酶链式反应、Western 印迹法和免疫荧光法对胆碱缺陷高脂饮食小鼠中的枢纽靶向基因进行了验证。主要发现 CSS 可降低 NASH 小鼠的血清谷丙转氨酶和谷草转氨酶水平（P &;lt;0.05），改善 NASH 小鼠肝脏的气球变性，从而降低 NAS 评分（P &;lt;0.05）。包括柚皮苷在内，高效液相色谱/质谱鉴定出 12 个色谱峰。根据网络药理学分析，CSS 共包含 103 种活性化合物和 877 个靶基因。转氨酶活性是CSS干预NASH治疗的潜在机制。CSS 能显著提高 NASH 小鼠 SIRT1 基因的转录水平和蛋白表达量（P < 0.05）。结论柚皮甙可能是 CSS 的活性化合物，SIRT1 是 CSS 参与治疗 NASH 的枢纽基因。

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来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.

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