Mechanism Of Panax Notoginseng Powder In The Treatment Of Diabetic Foot Based On Network Pharmacology And Molecular Docking

Objective: Panax notoginseng powder is a traditional Chinese medicine with anti-tumor,antiinflammatory,immunomodulatory,neuroprotective and hypoglycemic effects,and it has the potential to become an effective drug for treating diabetic foot.In this study,the target of Panax notoginseng powder in treating diabetic foot was predicted by network pharmacology,and the docking mode and binding energy of the effective components of Panax notoginseng powder with the therapeutic target were predicted by molecular docking technology.Western blot was used to verify the predicted results,and the mechanism of Panax notoginseng powder in treating diabetic foot was deeply explored,which provided a reliable theoretical basis for subsequent experimental research and clinical application.Method: Experiment 1:(1)The effective components and targets of Panax notoginseng powder were screened out by using TCMSP and TCMID Chinese medicine system pharmacology platform;(2)The targets of diabetic foot were screened out by Dis Ge NET and OMIM databases;(3)Using Cytoscape 3.8.0 to draw the network diagram of Panax notoginseng powder-active ingredienttarget;(4)Drawing protein interaction network diagram with STRING database;(5)The function enrichment analysis of gene ontology(GO)and the signal pathway enrichment analysis of Kyoto Gene and Genome Encyclopedia(KEGG)were carried out by using DAVIED platform.Experiment 2:(1)The 3D structures of the effective components and action targets of Panax notoginseng powder were obtained from Pubchem database and PDB database,respectively.(2)The 3D structures of the active components and crucial targets of Panax notoginseng powder were subjected to water removal and hydrogenation pretreatment using Discovery Studio 2019.(3)setting the active pocket Grid-Box of the receptor;(4)the Lib Dock module is used for molecular docking experiments.Experiment 3: An experimental study of Panax notoginseng powder on diabetic foot ulcer: 40 patients with severe DFU were randomly divided into a control group,a15mg/kg group,a 45mg/kg group,and a 75mg/kg group according to visiting order,10 patients in each group;Each patient underwent VSD vacuum drainage twice and was orally administered for2 weeks per day after surgery according to group.The soft tissue samples collected in the first and second weeks after surgery were subjected to western blot to detect the expression levels of AKT1,p-CHUK(p-IKKα),and c-MYC,so as to verify the prediction of network pharmacology and molecular docking.Result: Experiment 1: 7 main crucial components and 164 active component related targets were obtained.789 disease targets;Among them,there are 20 co-targets.There are 189 items in GO analysis,among which Panax notoginseng powder may treat diabetic foot mainly by participating in biological processes such as cell proliferation regulation,inflammatory response and oxidative stress response;KEGG pathway analysis has obtained 170 signaling pathways,among which PI3K-AKT signaling pathway,MAPK signaling pathway and IL-17 signaling pathway have biological effects,and the therapeutic targets such as AKT1,CHUK(IKKα)and MYC have been identified.Experiment 2: The molecular docking results of receptors AKT1,CHUK(IKKα)and MYC with Panax notoginseng powder active substances all show high docking activity,and there are stable chemical bond/space interaction relationships such as hydrogen bond,carbon-hydrogen bond and alkyl.CHUK(IKKα)has higher docking activity than AKT1 and MYC.Among Panax notoginseng powder active substances,sterols and Panax notoginseng saponins have the highest docking activity with key targets,and their chemical bonds are stable.Experiment 3: The experimental results showed that the expression levels of AKT1,p-CHUK(p-IKKα)and c-MYC in each group were higher than those in the control group(P < 0.001;P < 0.001;P < 0.001).The expressions of AKT1,p-CHUK(p-IKKα)and c-MYC in 45mg/kg group were significantly higher than those in other groups(P < 0.01;P<0.001;P<0.001)。 The expressions of AKT1,pCHUK(p-IKKα)and c-MYC in 75mg/kg group were significantly lower than those in 45mg/kg group(P < 0.01;P>0.05;P<0.001)。 There was no significant difference among the groups(P >0.05;P > 0.05;P > 0.05).Conclusion:(1)Panax notoginseng powder plays a role in treating diabetic foot ulcer through related PI3K-AKT signaling pathways such as AKT1,CHUK(IKKα)and MYC.(2)The molecular docking results of receptors AKT1,CHUK(IKKα)and MYC with PNP active substances show that there are high docking activities,and there are stable chemical bond/space interaction relationships such as hydrogen bond,carbon-hydrogen bond and alkyl group.CHUK(IKKα)has higher docking activity than AKT1 and MYC.(3)Compared with the control group,the expressions of AKT1,p-CHUK(p-IKKα)and c-MYC in other groups were significantly upregulated.(4)The expressions of AKT1,p-CHUK(p-IKKα)and c-MYC in 45 mg/kg group were significantly different from those in other groups,and the results were in line with the results of network pharmacology and molecular docking experiments.(5)The expression levels of AKT1,p-IKKα and c-MYC in 75 mg/kg group were significantly lower than those in 45mg/kg group,indicating drug inhibition.(6)There was no difference between 1 week and 2 weeks after oral administration of Panax notoginseng powder.