Integrating Network Pharmacology and Molecular Docking Approaches to Decipher the Multi-Target Pharmacological Mechanism of Abrus precatorius L. Acting on Diabetes.
Fatima NoorAbdur RehmanUsman Ali AshfaqMuhammad Hamzah SaleemMohammad K OklaAbdulrahman Al-HashimiHamada AbdElgawadSidra AslamPublished in: Pharmaceuticals (Basel, Switzerland) (2022)
Type 2 diabetes mellitus (T2DM) is a notable health care load that imposes a serious impact on the quality of life of patients. The small amount of reported data and multiple spectra of pathophysiological mechanisms of T2DM make it a challenging task and serious economic burden in health care management. Abrus precatorius L. is a slender, perennial, deciduous, and woody twining plant used in various regions of Asia to treat a variety of ailments, including diabetes mellitus. Various in vitro studies revealed the therapeutic significance of A. precatorius against diabetes. However, the exact molecular mechanism remains unclarified. In the present study, a network pharmacology technique was employed to uncover the active ingredients, their potential targets, and signaling pathways in A. precatorius for the treatment of T2DM. In the framework of this study, we explored the active ingredient-target-pathway network and figured out that abrectorin, abrusin, abrisapogenol J, sophoradiol, cholanoic acid, precatorine, and cycloartenol decisively contributed to the development of T2DM by affecting AKT1, MAPK3, TNFalpha, and MAPK1 genes. Later, molecular docking was employed to validate the successful activity of the active compounds against potential targets. Lastly, we conclude that four highly active constituents, namely, abrusin, abrisapogenol J, precatorine, and cycloartenol, help in improving the body's sensitivity to insulin and regulate the expression of AKT1, MAPK3, TNFalpha, and MAPK1, which may act as potential therapeutic targets of T2DM. Integrated network pharmacology and docking analysis revealed that A. precatorius exerted a promising preventive effect on T2DM by acting on diabetes-associated signaling pathways. This provides a basis to understand the mechanism of the anti-diabetes activity of A. precatorius .
Keyphrases
- glycemic control
- signaling pathway
- molecular docking
- type diabetes
- pi k akt
- molecular dynamics simulations
- healthcare
- weight loss
- induced apoptosis
- epithelial mesenchymal transition
- cardiovascular disease
- oxidative stress
- insulin resistance
- end stage renal disease
- cell proliferation
- newly diagnosed
- ejection fraction
- skeletal muscle
- genome wide
- dna methylation
- small molecule
- human health
- patient reported
- metabolic syndrome
- big data
- electronic health record
- poor prognosis
- data analysis
- adipose tissue
- health insurance
- gene expression
- patient reported outcomes
- network analysis
- replacement therapy