Objective:This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli(FZ)against type 2 diabetes mellitus(T2DM)based on network pharmacology and experimen-tal validation.Methods:Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry,and gas chromatography-mass spectrometry were used to identify the constituents of FZ.Next,the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases(including Gene Expression Omnibus database and Swiss Target Prediction online database),and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG).Finally,the pathway was verified by in vitro exper-iments,and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM.Results:A total of 43 components were identified from FZ,and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM.The dug component-target network indicated that PPARA,PPARG,PIK3R3,JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM.Interestingly,the enrichment analysis of KEGG showed that effects of FZ against T2DM were clo-sely correlated with the adenosine monophosphate-activated protein kinase(AMPK)and phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling pathways.In vitro experiments fur-ther confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in HepG2 cells.Moreover,FZ treatment was able to promote the AMPK and PI3K/Akt expressions in HepG2 cells.Conclusion:Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.

Ting Zhang;Qing Zhang;Wei Zheng;Ting Tao;Ruo-lan Li;Li-yu Wang;Wei Peng;Chun-jie Wu

School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan Province,China

结合医学学报（英文版）

[1]Ting Zhang;Qing Zhang;Wei Zheng;Ting Tao;Ruo-lan Li;Li-yu Wang;Wei Peng;Chun-jie Wu-.Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway:Network pharmacology and experimental validation)[J].结合医学学报（英文版）,2022(06):543-560

Zanthoxyli,dug,GPR88

Fructus,extract,improves,glycolipid,metabolism,disorder,type,diabetes,mellitus,via,activation,AMPK,PI3K,Akt,Network,pharmacology,experimental,validation,Objective,This,study,investigated,potential,mechanisms,behind,beneficial,effects,FZ,against,T2DM,network,Methods,Ultra,high,performance,liquid,chromatography,coupled,hybrid,quadrupole,orbitrap,resolution,mass,spectrometry,gas,were,used,identify,constituents,Next,differentially,expressed,genes,linked,treatment,screened,using,online,databases,including,Expression,Omnibus,Swiss,Target,Prediction,overlapping,their,enrichment,analyzed,by,Kyoto,Encyclopedia,Genes,Genomes,Finally,was,verified,vitro,staining,oil,Nile,showed,that,had,therapeutic,Results,total,components,identified,from,possible,targets,indicated,PPARA,PPARG,PIK3R3,JAK2,might,core,targeted,Interestingly,analysis,sely,correlated,adenosine,monophosphate,activated,protein,kinase,phosphatidylinositol,signaling,pathways,experiments,fur,confirmed,significantly,inhibited,palmitic,acid,induced,formation,HepG2,cells,Moreover,able,promote,expressions,Conclusion,combined,revealed

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