Combination of Astragalus membranaceus and Euonymus alatus (THUNB.) SIEB. for treatment of diabetes: A network-based pharmacology research

Objective:To find the target genes in combination of astragalus root(Astragalus membranaceus)and spindle tree wings(Euonymus alatus(THUNB.)SIEB.)(Qijian Heji)with the function of regulating blood glucose levels in kk mice by real-time fluorescence quantitative PCR(RT-PCR).To achieve the primary exploration on the material basis for Qijian Heji to improve the blood glucose levels of type 2 diabetic kk mice.Methods:We applied RT-PCR to detecting the expression of gene targets in kidney tissues of type 2 diabetes model kk mice.The detected gene targets were predicted by the network pharmacology method in the early stage of the project.Through the observation of the hypoglycemic effect of different ratios of Qijian Heji,the optimal proportion was determined and then used to conduct research of material basis.Results:Continuous administration of Qijian Heji(astragalus root:spindle tree wings Z 3:1)for six weeks resulted in significantly lowering blood glucose levels in mice in the fourth week,dropping from 33.3 to 21.9 mmol/L;this lower level was maintained in the fifth to sixth weeks.Blood glucose values in the positive drug group decreased from 33.3 to 21.85 mmol/L in the fourth week and maintained steady decreasing in the fifth and sixth weeks.Conclusion:Qijian Heji,with proportion of 3:1,could significantly reduce the blood glucose values in kk mice,animal experiment results verified the accurate prediction of network pharmacology,and at the same time,it is verified there was a certain therapeutic effect about the combination of the two herbs on reducing the glucose value.Animal experiments and RT-PCR results showed that Qijian Heji conducted a hypoglycemic effect by modulating estrogen receptor(ESR1)and renin(REN)expression.

Potential molecular mechanism of Euonymus alatus in the treatment of type 2 diabetes based on network pharmacology

Objective:To investigate the potential molecular mechanism of Guijianyu(Euonymus Alatus)in the treatment of type 2 diabetes by network pharmacology approach.Methods:Relevant literature and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)were searched to screen the main active ingredients and targets of Guijianyu.The GeneCards database and OMIM database were searched to obtain target datasets for type 2 diabetes.And sorted out the intersection targets of drug and disease.The"drug-ingredient-target-disease"network model was constructed with the help of Cytoscape software,the protein-protein interaction(PPI)network was drawn using the STRING platform,and gene function and metabolic pathway enrichment analysis were also performed on the relevant targets of Guijianyu in the treatment of type 2 diabetes.Results:After the screening,8 main active ingredients and 154 drug-disease common targets were obtained,of which JUN,MAPK1,AKT1,RELA,and IL6 may be the key regulatory genes of Guijianyu in the treatment of type 2 diabetes.GO enrichment analysis yielded a total of 153 biological processes,mainly including nuclear receptor activity,transcription factor activity,direct ligand regulated sequence-specific DNA binding,steroid hormone receptor activity,cytokine receptor binding.KEGG analysis was enriched to a total of 156 significant pathways,mainly including AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,hepatitis B,prostate cancer,kaposi sarcoma-associated herpesvirus infection.Conclusion:Studies based on network pharmacology show that various active ingredients such as quercetin and kaempferol in Guijianyu could act on multiple targets such as JUN,MAPK1,AKT1,RELA,and IL6.It may play a role in the treatment of type 2 diabetes and related complications by synergistically regulating glucose and lipid metabolism,reducing insulin resistance,protecting pancreatic beta-cell function,anti-oxidative stress,anti-inflammatory repair and so on.