Pharmacological Mechanism Of Total Eleutheroside In Treatment Of Diabetes Mellitus Type 2 Based On Network Pharmacology

Diabetes mellitus type 2 accounts for 90%-95% of all types of diabetes.It is a complex metabolic disease.Target tissue insulin resistance and insufficient insulin secretion caused by pancreatic islet β-cell dysfunction are the main pathology of diabetes mellitus type 2 characteristics.It can result in excessive blood glucose levels and lead to a series of related complications.The pathogenesis of diabetes mellitus type 2 is very complex,and the known pathogenesis may be related to factors such as insulin resistance,inflammation,oxidative stress,mitochondrial dysfunction and lipotoxicity.Diabetes mellitus type 2 cannot be completely cured at present.The clinical treatment is mainly based on western medicine with a single target,supplemented by diet and exercise.However,its significant side effects and inability of effectively controlling of complications limit its further development.Because of the limitations and shortcomings of western medicine,researchers are eager to find valuable treatments from traditional Chinese medicine and prescriptions.In the treatment of diabetes,traditional Chinese medicine has accumulated rich experience based on traditional Chinese medicine theory and individualized dialectical thinking.By adjusting the metabolic balance in the body,it can treat diabetes and its complications from multiple ways,and has achieved good result in clinical.Acanthopanax senticosus is the dry roots and rhizomes of the Acanthopanax senticosus family.Some studies have shown that Acanthopanax senticosus has a significant hypoglycemic effect,and the main active ingredient is eleutheroside.Acanthopanax senticosus can significantly increase blood glucose levels in diabetic rats,and regulate triglycerides and cholesterol,and increase SOD activity,while reduce LPO levels,and improve disorders of oxygen free radical metabolism.However,the multi-component,multi-target,and multi-path characteristics of traditional Chinese medicine indicate that the mechanism of anti-diabetes mellitus type 2 by Acanthopanax senticosus is difficult to be clarified.Because the target of the mixture is not clear,which limit drug screening and development.Network pharmacology is a new biological network analysis method which study the interaction among drugs,diseases and targets.Network pharmacology integrates modern computer technology with multiple disciplines such as bioinformatics,molecular pharmacology,and chemoinformatics,and builds a component-disease targets biological regulation network to reveal the complex regulatory relationship of traditional Chinese medicine with multiple components in the body.It has laid a theoretical foundation for future biological experimental research and drug screening.In this article,seven main components of eleutheroside of Acanthopanax senticosus were used as research objects,and the main components of eleutheroside of Acanthopanax senticosus were analyzed by network pharmacological methods,and their possible mechanism of action was discussed.First,the Swiss Target Prediction platform was used to predict the potential targets of these 7 components.The Gene Cards database was used to collect the diabetes mellitus type 2targets.After the PPI network analysis was performed on the String platform,the predicted targets were intersected to obtain the eleutheroside and diabetes mellitus type 2,and 35 targets remained.Then Cytoscape3.6.1 was used to build a "component-target" biological network relationship,and the built-in Networkanalyzer tool was used for topology analysis.In order to further clarify its mechanism,we performed GO enrichment analysis and KEGG pathway enrichment analysis on the DAVID6.8 bioinformatics platform,in-depth analysis of the biological process that Acanthopanax senticosus may participate in the body,“component-target-pathway” network map was constructed based on the KEGG enrichment results,and found out the 4 components that may be mainly used for treating of diabetes mellitus type 2 as core components.Then the core components were docked with key disease target proteins to verify the potential mechanism of the total eleutheroside,and combined with literature to analyze the mechanism of total eleutheroside.After screening,there were 8 important pathways associated with diabetes mellitus type 2 were identified,and 28 GO entries were identified,including 10 biological process entries,8 cell component entries,and 10 molecular function entries.This study shows that Eleutheroside A,Eleutheroside D,Eleutheroside E and Sesamin have good topological parameters in the "component-target" network,which may be mainly through the role of STAT,PTPN1,PTPN2,JNK,p38 proteins and other targets play a key role in insulin resistance,apoptosis and inflammation-related pathways.Finally,In order to further explore the medicinal value of Acanthopanax senticosus,we performed DO enrichment analysis on its predicted targets,and discussed the possibility of total eleutheroside in treating other diseases.In summary,the total eleutheroside of Acanthopanax senticosus through multiple components,multiple targets,and multiple pathways work together to achieve a integrated treatment effect on type 2diabetes and lay the foundation for the development of anti-diabetes mellitus type 2 drugs in the future.