Analysis Of Medication Rules And Mechanism Of Traditional Chinese Medicine In Treating Type 2 Diabetes Mellitus Based On Data Mining And Network Pharmacology

Type 2 diabetes mellitus（T2DM）is a chronic metabolic disease with damage to human organs,which causes a variety of complications and seriously harm human health.At present,the numbers of T2DM in China and all the world are increasing.The treatment of T2DM is mainly oral hypoglycemic drugs,most of which are Western drugs such as metformin and sitagliptin with great side effects.Therefore,the research on the prescription of Traditional Chinese medicine（TCM）in the treatment of T2DM is more and more popular.In this study,data mining was used to explore the medication rule of TCM in the treatment of T2DM,so as to provide reference and guidance for clinical practice.At the same time,the main components,key targets and pathways of representative prescription of TCM for the treatment of T2DM was screened and explored,and the mechanism of action of the prescription of TCM for the treatment of T2DM from the molecular level was studyed.The clinical literatures on TCM treatment of T2DM from January 2001 to December2021 were searched from Web of Science and China Knowledge Resources Database.The literatures were screened according to the standards and the data which were extracted to analyze the frequency,medicinal properties,medicinal taste,meridian distribution and efficacy of TCM.In this study,Eighty-one literatures were screened and 65 prescriptions were obtained,involving 128 Chinese medicines,and all the frequency of Chinese medicines was 520.The top 8 frequency Chinese medicines were Astragalus membranaceus,Rehmannia glutinosa,Yhaudiovideoe Always Be Moreen,Radix puerariae,Rhizoma Coptidis,Salvia miltiorrhiza,Radix ophiopogonis and Rhizoma Anemarrhenae.The meridian distribution frequency of TCM attributed to lung meridian was the highest,followed by spleen meridian.In terms of medicinal properties,cold medicine was the most frequently used.In terms of medicinal taste,flavor medicine,sweet medicine and bitter medicine were used most frequently.In this study,it was found that the TCM treatment of T2DM mainly follows the principle of deficiency supplementing Qi and activating blood circulation to quench thirst.Baihu Decoction and Zengye Decoction was regarded as a good prescription of TCM for the treatment of T2DM due to its significant effects of clearing heat and cooling blood,dissipating wind heat,clearing heat and dampness,Yin deficiency and quenching thirst.UPLC/Q-TOF-MS was used to analyze the components of Baihu Decoction and Zengye Decoction,and 107 compounds were obtained.On the premise of having pharmacological activity related to the treatment of T2DM,There were 42 components of Baihu Decoction and zengyu decoction were determined,such as neopsoralen isoflavone,dihydrosanguinarine,daidzein,berberrubine,apigetrin,berberine,daidzein,diosgenin,stigmasterol,Prunin,emodin,apigenin,formononetin.The components of Baihu Decoction and Zengye Decoction were investigated by network pharmacology.There were 256 potential targets of the compound active ingredients predicted by TCMSP and Swisstar Prediction database,among which 149 targets were involved in the treatment of T2DM.The components-intersection target interaction network was constructed.The top 11 targets of discovery value were PTGS2,PTGS1,ESR1,AR,NOS2,PRSS1,SCN5A,PPARG,ADRB2,DPP4 and CASP3,which were identified as the key targets of Baihu Decoction and Zengye Decoction.KEGG enrichment analysis demonstrated that targets were mainly related to T2DM,such as AGE-RAGE signaling pathway in diabetic complications,insulin resistance,PPAR signaling pathway and so on.The components have anti-T2DM activity through interacting in key targets and regulate pathways.Through molecular docking,the results revealed that the key targets had good binding activity with chemical components.All the docking scores were lower than-4.8 Kcal/mol^-1.There were hydrogen bond,hydrophobic interaction,P-πstacking,π-cation interaction,salt bridge and so on,so it could be indicated that the compounds have good space binding conformation with key targets.The test of inhibitory activities of DPP4 enzyme with dihydrosanguinarine,daidzein,berberrubine,apigetrin,diosgenin,stigmasterol,berberine,showed that diosgenin,stigmasterol,berberine and daidzein had inhibitory effects on DPP4 enzyme,and the inhibitory rates were 6.42%,8.07%,41.34%and 18.35%.This paper reveals the medication rule of TCM in treating T2DM,provides a reference for clinical practice.It also provides the important ideas theoretical guiding significance to find TCM components of anti-T2DM.