Exploring mechanism of Shenge Formula in treating metabolic associated fatty liver disease based on network pharmacology and animal experiments

FANG Miao; CHEN Zhaolan; ZHU Minying; ZHENG Yanxi; LI Man; GAO Yueqiu; ZHANG Xin; LYU Jia

doi:10.16305/j.1007-1334.2025.z20240925005

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Exploring mechanism of Shenge Formula in treating metabolic associated fatty liver disease based on network pharmacology and animal experiments

更新时间：2025-11-06

- Exploring mechanism of Shenge Formula in treating metabolic associated fatty liver disease based on network pharmacology and animal experiments
- Shanghai Journal of Traditional Chinese Medicine Vol. 59, Issue 11, Pages: 23-34(2025)
- 作者机构：
  
  1.上海中医药大学附属曙光医院（上海 201203）
  2.上海市中医临床重点实验室（上海 201203）
  3.上海市闵行区马桥社区卫生服务中心（上海 201100）
  4.同济大学附属杨浦医院（上海 200090）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2025.z20240925005
  CLC：
- Received：25 September 2024，
  
  Published：10 November 2025
- 稿件说明：
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方淼,陈兆兰,朱敏莹,等.基于网络药理学和动物实验探讨参葛方治疗代谢相关脂肪性肝病的作用机制[J].上海中医药杂志,2025,59(11):23-34.

FANG Miao,CHEN Zhaolan,ZHU Minying,et al.Exploring mechanism of Shenge Formula in treating metabolic associated fatty liver disease based on network pharmacology and animal experiments[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(11):23-34.
方淼,陈兆兰,朱敏莹,等.基于网络药理学和动物实验探讨参葛方治疗代谢相关脂肪性肝病的作用机制[J].上海中医药杂志,2025,59(11):23-34. DOI： 10.16305/j.1007-1334.2025.z20240925005.

FANG Miao,CHEN Zhaolan,ZHU Minying,et al.Exploring mechanism of Shenge Formula in treating metabolic associated fatty liver disease based on network pharmacology and animal experiments[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(11):23-34. DOI： 10.16305/j.1007-1334.2025.z20240925005.

摘要

目的

探讨参葛方治疗代谢相关脂肪性肝病（MAFLD）的作用机制。

方法

①利用TCMSP、Uniprot、GeneCards、OMIM、DrugBank、PharmGKB数据库搜索参葛方活性成分和MAFLD相关靶点，采用String平台构建蛋白-蛋白相互作用网络，并进行京都基因和基因组数据库（KEGG）富集分析，利用Autodock Vina软件进行分子对接。②C57Bl/6J小鼠随机分为对照组、模型组、多烯磷脂酰胆碱组（0.205 2 g/kg）及低、中、高剂量药物组（3.9 g/kg、7.8 g/kg、15.6 g/kg参葛方）。采用ALMN饲料喂养20周造模后，对照组和模型组灌胃饮用水（每天0.3 mL/只），其余各组灌胃给予相应干预，共干预16周。干预结束后检测小鼠血清肝功能、血脂、炎症因子等生化指标。肝组织进行苏木精-伊红染色、油红O染色和天狼猩红染色并观察病理情况。实时荧光定量逆转录聚合酶链式反应（RT-qPCR）法和Western blot法检测过氧化物酶体增殖物激活受体α（PPARA）信号通路表达。

结果

①通过网络药理学筛选出参葛方治疗MAFLD的核心药物靶点6个及主要有效成分6个；通过分子对接后发现PPARA-槲皮素、过氧化物酶体增殖物激活受体γ（PPARG）-木犀草素、PPARG-槲皮素、PPARG-山柰酚和白细胞介素-6（IL-6）-槲皮素均显示有较强结合活性，表明参葛方可能通过PPARA、PPARG和IL-6等靶点发挥抗MAFLD的作用。②与模型组相比，参葛方高剂量组小鼠肝体比、总胆固醇（TC）、三酰甘油（TG）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、低密度脂蛋白胆固醇（LDL-C）水平显著降低（

0.05）；肝组织病理炎症、脂肪沉积及纤维化方面均有明显改善；肝组织PPARG和固醇调节元件结合蛋白1c（SREBP-1c）表达水平降低（

0.05），肉碱棕榈酰转移酶1A（CPT1A）和酰基辅酶A氧化酶1（ACOX1）表达水平升高（

0.05），肿瘤坏死因子-α（TNF-α）和IL-6表达水平显著降低（

0.05）。

结论

参葛方可通过抑制PPARA-CPT1A-ACOX1轴及下调PPARG表达，遏制MAFLD疾病进展。

Abstract

Objective

To explore the mechanism of Shenge Formula in treating metabolic associated fatty liver disease （MAFLD）.

Methods

①TCMSP， Uniprot， GeneCards， OMIM， DrugBank and PharmGKB databases were used to search for active ingredients of Shenge Formula and gene targets of MAFLD. The protein-protein interaction network was constructed using the String platform， and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis was performed. Molecular docking was carried out using the Autodock Vina software. ②The C57Bl/6J mice were randomly divided into control group， model group， phosphatidylcholine group （0.205 2 g/kg）， and low， medium and high-dose drug groups （3.9 g/kg， 7.8 g/kg， 15.6 g/kg of Shenge Formula）. After 20 weeks of model establishment using the ALMN diet， the control group and the model group were given drinking water by gavage （0.3 mL per rat per day）， while the other groups were given corresponding interventions by gavage for a total of 16 weeks. After the intervention， the biochemical indicators such as liver function， blood lipids， and inflammatory factors in the mouse serum were detected. The liver tissue was stained with hematoxylin-eosin， oil red O and picrosirius red， and the pathological conditions were observed. Real-time fluorescence quantitative reverse transcription polymerase chain reaction （RT-qPCR） and Western blot were used to detect the expression of the peroxisome proliferator-activated receptor α （PPARA） signaling pathway.

Results

①Through network pharmacology， 6 core drug targets and 6 main active ingredients for the treatment of MAFLD by Shenge Formula were identified； after molecular docking， it was found that PPARA-quercetin， peroxisome proliferator-activated receptor γ （PPARG）-luteolin， PPARG-quercetin， PPARG-kaempferol， and interleukin-6 （IL-6） -quercetin all showed strong binding activity， indicating that the Shenge Formula may exert anti-MAFLD effects through these targets such as PPARA， PPARG and IL-6. ②Compared with the model group， mice in the high-dose Shenge Formula group showed significantly reduced liver-to-body weight ratio

， total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and low-density lipoprotein cholesterol （LDL-C） levels （

0.05）. Histopathological examination revealed marked improvements in hepatic inflammation， lipid deposition， and fibrosis. Furthermore， hepatic expression levels of PPARG and sterol regulatory element-binding protein-1c （SREBP-1c） were significantly decreased （

0.05）， while the expression levels of carnitine palmitoyltransferase 1A （CPT1A） and acyl-CoA oxidase 1 （ACOX1） were significantly increased （

0.05）. In addition， the expression levels of tumor necrosis factor-α （TNF-α） and IL-6 were significantly reduced （

0.05）.

Conclusions

Shenge Formula inhibits the progression of MAFLD by suppressing the PPARA-CPT1A-ACOX1 axis and downregulating the expression of PPARG.

关键词

Keywords

references

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