中药新药与临床药理2026，Vol.37Issue(4)：703-715,13.DOI:10.19378/j.issn.1003-9783.2026.04.013
藏药甲嘎松汤通过靶向肠道微生物群及色氨酸代谢途径改善酒精性肝病小鼠的作用机制
Mechanism of Tibetan Medicine Jiagasong Decoction in Improving Alcoholic Liver Disease in Mice by Targeting the Gut Microbiota and Tryptophan Metabolism Pathway
摘要
Abstract
Objective To investigate the effects and mechanism of Tibetan medicine Jiagasong Decoction on alcoholic liver disease(ALD)in mice based on gut microbiota,fecal metabolomics,and network pharmacology.Methods(1)An ALD mouse model was induced by intragastric administration of an ethanol liquid diet for 28 days.C57BL/6 mice were randomly divided into control,model,silymarin,and low-,medium-,and high-dose Jiagasong Decoction groups(n=6 per group).One week after model induction began,drug administration via gavage was initiated.The low-,medium-,and high-dose Jiagasong Decoction groups received 0.17,0.33,and 0.66 g·kg-1 of Jiagasong Decoction decoction,respectively,while the silymarin group received 50 mg·kg-1,once daily for 21 consecutive days.Biochemical methods were used to measure liver tissue levels of triglycerides(TG),malondialdehyde(MDA),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT).Lipid accumulation in liver tissue was observed using Oil Red O staining,and histopathological changes were examined via HE staining.16S rRNA gene sequencing of gut microbiota and metabolic profiling of fecal samples were performed.(2)Network pharmacology was used to predict potential therapeutic targets of Jiagasong Decoction for ALD,and core active components and core targets were screened.Metabolomic and network pharmacology analyses were combined to construct a"differential metabolite-reaction-enzyme-gene"network,and key targets in the tryptophan metabolism pathway were identified and intersected with the core targets from network pharmacology.Molecular docking was performed to validate the interactions between the core active component dehydrodiisoeugenol and the core targets CYP1A1,MAOA,and MAOB.(3)AML-12 cells were treated with low-,medium-,and high-doses of dehydrodiisoeugenol(6.25,12.5,25 µmol·L-1)for 24 hours,followed by induction with 400 mmol·L-1 ethanol for 2 hours.Biochemical methods were used to measure cellular TG,total cholesterol(TC),MDA,ALT,and AST levels.qRT-PCR was employed to assess mRNA expression levels of CYP1A1,MAOA,and MAOB.Results(1)Compared with the control group,the model group showed significantly elevated liver tissue levels of TG,MDA,LDL-C,AST,and ALT(P＜0.05,P＜0.01,P＜0.001)and significantly reduced HDL-C levels(P＜0.001).Liver tissue displayed disrupted hepatocyte structure,disorganized hepatic cords,prominent fatty vacuoles,and extensive lipid droplet accumulation.Compared with the model group,all treatment groups exhibited significantly reduced liver tissue levels of TG,MDA,LDL-C,AST,and ALT(P＜0.05,P＜0.01,P＜0.001)and significantly increased HDL-C levels(P＜0.05).Liver tissue showed more orderly hepatic cord structures,reduced hepatocyte space,and decreased numbers of fatty vacuoles and lipid droplets.(2)Compared with the control group,the model group exhibited differences in gut microbiota community structure:an increase in Firmicutes and a decrease in Actinobacteria.The abundance of Coriobacteriaceae_UCG-002(Actinobacteria)was significantly reduced,while the abundance of Muribaculaceae was significantly increased,with statistical significance(P＜0.05,P＜0.01).Compared with the model group,the high-dose Jiagasong Decoction group displayed a microbiota structure more similar to the control group.Jiagasong Decoction reversed ethanol-induced dysbiosis by reshaping the relative abundance of microbiota:the abundance of Firmicutes was significantly reduced,while that of Actinobacteria was significantly increased.The abundance of Coriobacteriaceae_UCG-002 was significantly elevated,and that of Muribaculaceae was significantly reduced,with statistical significance(P＜0.05,P＜0.01).(3)Intersection analysis of differential metabolites between the control vs.model groups and the model vs.high-dose Jiagasong Decoction groups identified 275 shared differential metabolites,which were significantly enriched in the tryptophan metabolism pathway.Correlation analysis revealed that Jiagasong Decoction could influence the levels of differential metabolites in the tryptophan pathway by modulating the gut microbiota.Network pharmacology analysis identified 28 core targets,with dehydrodiisoeugenol having the highest degree value among core components.Integrated metabolomic analysis identified the core targets CYP1A1,MAOA,and MAOB.Molecular docking indicated stable binding of dehydrodiisoeugenol to these three targets.(4)Compared with the control group,the model group showed significantly increased cellular levels of TG,TC,MDA,AST,and ALT(P＜0.05,P＜0.01)and significantly decreased MAOA mRNA expression(P＜0.05).Compared with the model group,the low-,medium-,and high-dose dehydrodiisoeugenol groups exhibited significantly reduced cellular levels of TG,TC,MDA,AST,and ALT(P＜0.05,P＜0.01)and significantly increased MAOA mRNA expression(P＜0.01).Conclusion Jiagasong Decoction can ameliorate lipid accumulation,oxidative stress,and histopathological damage in the liver,and improve liver function in mice with alcoholic liver disease.This effect may be associated with the regulation of gut microbiota and tryptophan metabolic disorders by active components such as dehydrodiisoeugenol.关键词
藏药/甲嘎松汤/酒精性肝病/肠道菌群/色氨酸代谢通路/去氢二异丁香酚/网络药理学/粪便代谢组学/小鼠Key words
Tibetan medicine/Jiagasong Decoction/alcoholic liver disease/gut microbiota/tryptophan metabolism pathway/dehydrodiisoeugenol/network pharmacology/fecal metabolomics/mice分类
医药卫生引用本文复制引用
肖如,熊天琴,祝苑,黄钦坡,袁瑞,陈颖,李钊铭,钟溢源,王懋慈,张韫..藏药甲嘎松汤通过靶向肠道微生物群及色氨酸代谢途径改善酒精性肝病小鼠的作用机制[J].中药新药与临床药理,2026,37(4):703-715,13.基金项目
国家自然科学基金项目(8237140578). （8237140578）
