Systematic review and meta-analysis of efficacy of Gexia Zhuyu Decoction in the treatment of nonalcoholic fatty liver disease

Objective:To evaluate the efficacy of Gexia Zhuyu Decoction in the treatment of nonalcoholic fatty liver disease(NAFLD).Methods:Four Chinese databases(CNKI,CMB,Wanfang,VIP)and four English databases(PubMed,Embase,Cochrane Library,Medline)were searched to screen randomized controlled trials(RCTs)of Gexia Zhuyu Decoction in the treatment of NAFLD.The enrollment of RCTs is from the starting date of database establishment till November 2,2022.and clinical registration tests and grey literatures were also searched.RCTs screening and relevant data exreacting were based on preset criteria.RevMan5.4.1 software was used for risk of bias assessment and Meta analysis of the included studies.Results:Eleven RCTs were included finally having 963 patients with NAFLD,including 499 in experimental group and 494 in control group.Meta-analysis results showed that GexiaZhuyu Decoction alone or combining with other medications for the treatment of NFALD was superior to that in control group in terms of total effective rate[RR=1.23,95%CI[1.16,1.31],Z=6.58(P<0.05)].Improve liver function index significantly:ALT[subgroup①WMD=-14.93,95%CI[-18.66,-9.42],Z=7.84(P<0.01);subgroup②WMD=-3.97,95%CI[-8.01,0.07],AST[subgroup①WMD=-13.25,95%CI[-18.10,-8.41],Z=5.36(P<0.05);subgroup②WMD=-2.70,95%CI[-6.94,1.54],Z=1.25(P>0.05)];GGT[WMD=-9.30,95%CI[-15.78,-2.81],Z=2.81(P<0.05)].Moreover,patients with therapy obviously decreased hepatic fibrosis index:桇-C[SMD=-1.15,95CI%[-1.48,-0.81],Z=6.77(P<0.05)],LN[SMD=-1.49,95CI%[-2.23,-0.75],Z=3.97(P<0.05)].Effectively reduce the level of LDL-C[WMD=-0.30,95CI%[-0.54,-0.06],Z=2.48(P<0.05)]and improve the rate of ultrasound renormalization[RR=1.94,95%CI[1.45,2.60],Z=4.48(P<0.05)].However,existing data cannot prove that the effect of reducing TC,TG and BMI in the treatment group is better than that in the control group:TC[WMD=-0.88,95CI%[-1.88,0.11],Z=1.74(P>0.05)],TG[WMD=-0.50,95CI%[-1.05,0.06],Z=1.76(P>0.05)],BMI[WMD=-1.61,95CI%[-4.77,1.54],Z=1.00(P>0.05)].Descriptive analysis results showed that the levels of LDL,HA and PCIII were significantly reduced in the treatment group,and the differences were statistically significant(P<0.05).In addition,no adverse drug reactions related to Gexia Zhuyu Decoction have been reported.Conclusion:Gexia Zhuyu Decoction can significantly improve the liver function,liver fibrosis,and hepatic steatosis in NAFLD patients,thereby improving the clinical efficacy.

Research on the Mechanism of the treatment of non‑alcoholic fatty liver by Jianwei Gexia Zhuyu Decoction based on network pharmacology and molecular docking

Objective:To analyse the key compounds,targets and pathways of the treatment of non‑alcoholic fatty liver disease(NAFLD)by Jianwei Gexia Zhuyu Decoction based on network pharmacology,in order to explore the molecular mechanism of its therapeutic effects.Methods:The differential genes between sick and normal conditions were screened by GEO‑Datasets,and the heat map and volcano map were drawn.The active compounds in Jianwei Gexia Zhuyu Decoction were searched by TCMSP platform and Drugbank database.OB≥30%and DL≥0.18 were set as thresholds to screen potential active compounds and action targets.The molecular target maps of Jianwei Gexia Zhuyu Decoction and NAFLD differential genes were constructed,and the PPI network and network topology parameters were obtained by STRING database.The PPI network and network topology parameters were visually analyzed by Cytoscape,and the core regulatory genes were screened.At the same time,the SwissDock platform was used to dock the main active components with the target.The main pathways were determined by GO biological function enrichment analysis and KEGG metabolic pathway enrichment analysis by DAVID.Results:After screening,377 differential genes(127 up‑regulated genes and 250 down‑regulated genes),225 active compounds of Jianwei Gexia Zhuyu Decoction,308 corresponding targets were obtained;14 key targets were screened,corresponding to 168 compounds,and the key targets involved MYC,FOSL2,FOS,etc.The results of GO functional enrichment analysis showed that Jianwei Gexia Zhuyu Decoction mainly regulated the activity expression of DNA binding transcriptional activator and the specific transcription of RNA polymeraseⅡ;The results of molecular docking showed that the main active components quercetin and baicalein had good binding activity with VCAM1,HSPB1,MYC,JUN and so on;The results of KEGG enrichment analysis showed that it was mainly involved in IL‑17 signal pathway,Wnt receptor signal pathway,NF‑κB signal pathway,TNF signal pathway and AGE‑RAGE signal pathway in diabetic complications.Conclusion:Through the interaction of multi‑components and multi‑targets,Jianwei Gexia Zhuyu Decoction has achieved the goal of overall treatment of NAFLD from many ways.The application of network pharmacology provides a new research approach and scientific basis for further study on the mechanism of Jianwei Gexia Zhuyu Decoction in the treatment of NAFLD.