Target Prediction And Mechanism Of UCG And Tangshen Formula Based On Network Pharmacology

pharmacological function is characterized by multi-level and multi-target.The combination of multiple pathogenic factors causes imbalance of the body and eventually leads to human diseases,which is in accordance with the systematic treatment principle of Chinese herbal compound.The core theory of network pharmacology,multi-component and multi-target,precisely combines Chinese herbal compound with disease together.In this study,the composition of Chinese herbal compound was analyzed by multi-mass spectrometry information based on liquid chromatography-mass spectrometry.The components were detected by time of flight mass spectrometry to obtain the precise mass and then were identified according to their multistage molecular fragments that were get from ion traps mass spectrometry.Due to the different response of Chinese herbal compound in different scanning modes,both positive and negative ion modes were collected to obtain complementary information of the compounds.The results showed that 83 small molecule compounds were identified,which belong to anthraquinones,alkaloids,flavonoids,triterpenoid saponins,organic acids.Chembiodraw Ultra 12 software was used to drew and transforme these small molecule compounds to three-dimensional form.230 targets was predicted by PharmMapper database based on reverse pharmacophore matching method.In these targets,AKR1B1,GSTA1,CDK2,VDR and ESR1 are related to the gene of chronic renal failure disease and VDR,CA2,ACE,and AMY2 A are the common targets associating with chronic renal failure treatment chemicals.Through the integration of the targets of UCG,disease and chemical drugs by using Mass 3.0 database,PPAR,Focal adhesion,Cytokine-cytokine receptor interaction,Jak-STAT signaling pathway and Renal cell carcinoma signaling pathway that are closely related to the disease treatment were obtain.It is suggested that UCG compound may improve renal function by inhibiting the proliferation of renal tubular epithelial cells,improving renal fibrosis,mediating and regulating immune and inflammatory responses and regulating the genes of JAK1,JAK2 and STAT3.Based on the technique of multi-mass spectrometry combination analysis,73 chemical constituents of Tangshen Formula were identified,including flavonoid glycosides,gallocylglucoside,organic acids,iridoid glycosides,tris Terpene saponins and dihydrogen flavonoids.Tangshen formula components were predicted to act on 207 targets,and three targets,CASP3,LGALS3 and VDR were related to the diabetic nephropathy,suggesting that Tangshen formula could achieve the purpose of delaying renal injury through the regulation of the above genes.Tangshen formula components and the chemical drugs for disease treatment have the same targets,INSR and ACE,suggesting that the compound may play the same efficacy with the chemical drugs through acting on the same targets.The result of GO analysis found that the regulation of Tangshen formula was involved in cell proliferation regulation,gluconeogenesis,positive regulation of glycogen biosynthesis,mitochondria,transport protein activity and other molecular processes.Tangshen formula acts on the key pathways such as Insulin signaling pathway,Fc epsilon RI signaling pathway,VEGF signaling pathway,Th17 cell differentiation pathways,presuming that it plays a pharmacological effect by stimulating insulin levels,regulating immune inflammation and promoting vascular permeability to enhance immunity.In this study,through the combination of liquid chromatography mass spectrometry and network pharmacology,the use of multi-mass spectrometry information strategy,the chemical basis of the compound was preliminarily elucidated.Compared with the traditional method,the way to predict compound action mechanism and combine with disease genes and chemical drugs targets is higher efficiency and more persuasive.This study provides a new way for exploring the mechanism of Chinese herbal compound in the treatment of diseases.