Abstract
Background The incidence of type 2 diabetes mellitus (T2DM) has increased year by year, which not only seriously affects people's quality of life, but also imposes a heavy economic burden on the family, society, and country. Currently, the pathogenesis, diagnosis, and treatment of T2DM are still unclear. Therefore, exploration of a precise multitarget treatment strategy is urgent. Here, we attempt to screen out the active components, effective targets, and functional pathways of therapeutic drugs through network pharmacology with taking advantages of traditional Chinese medicine (TCM) formulas for multitarget holistic treatment of diseases to clarify the potential therapeutic mechanism of TCM formulas and provide a systematic and clear thought for T2DM treatment. Methods First, we screened the active components of Da-Chai-Hu Decoction (DCHD) by absorption, distribution, metabolism, excretion, and toxicity (ADME/T) calculation. Second, we predicted and screened the active components of DCHD and its therapeutic targets for T2DM relying on the Traditional Chinese Medicine Systems Pharmacology Analysis Platform (TCMSP database) and Text Mining Tool (GoPubMed database), while using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to obtain T2DM targets. Third, we constructed a network of the active component-target, target-pathway of DCHD using Cytoscape software (http://cytoscape.org/,ver.3.5.1) and then analyzed gene function, related biological processes, and signal pathways through the DAVID database. Results We screened 77 active components from 1278 DCHD components and 116 effective targets from 253 ones. After matching the targets of T2DM, we obtained 38 important targets and 7 core targets were selected through further analysis. Through enrichment analysis, we found that these important targets were mainly involved in many biological processes such as oxidative stress, inflammatory reaction, and apoptosis. After analyzing the relevant pathways, the synthetic pathway for the treatment of T2DM was obtained, which provided a diagnosis-treatment idea for DCHD in the treatment of T2DM. Conclusions This article reveals the mechanism of DCHD in the treatment of T2DM related to inflammatory response and apoptosis through network pharmacology, which lays a foundation for further elucidation of drugs effective targets.
Highlights
Type 2 diabetes mellitus (T2DM), as the most common type of diabetes, refers to metabolic imbalance of glucose, protein, lipid, water, and electrolyte, caused by genetic, environmental, and psychological factors
Some targets can be modulated by only one compound, such as tumor necrosis factor (TNF) and CYP1A2 targets, while PTGS2 target can be controlled by all 77 compounds, which may be the pivotal targets in Da-Chai-Hu Decoction (DCHD). us, from the network, we can have a general observation on the relationships between active compounds and targets from the compound-compound target network. e targets of all herbal composition in DCHD correspond to a variety of diseases besides T2DM, which can exert pharmacological effects on multiple diseases. erefore, this network fully reflects the characteristics of multicomponent-multitarget-multidisease of traditional Chinese medicine (TCM) formula
In order to illuminate the significance of degree in compound targets, we created a proteinprotein interaction (PPI) network about the relationship of the common targets between compounds and T2DM. is network was composed of 38 nodes and 349 edges. e more the edges between two nodes are, the greater the degree of Prostaglandin G/H synthase 1 Coagulation factor Xa
Summary
Type 2 diabetes mellitus (T2DM), as the most common type of diabetes, refers to metabolic imbalance of glucose, protein, lipid, water, and electrolyte, caused by genetic, environmental, and psychological factors. It is pathophysiologically characterized by a declined ability of insulin to regulate glucose metabolism accompanied by a decrease or relative decrease in insulin secretion due to defects of islet B-cell function. As the largest number of people with diabetes worldwide [8], the overall prevalence of diabetes is 9.1% in China, with the highest prevalence of 65–74 years old accounting for 14.1% [9]. China’s medical expenses for diabetes in 2014 reached 80.33 billion yuan, and the per capita treatment cost was 2,188.73 yuan [10], which showed that a large amount of medical and health resources were consumed due to diabetes in China
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