Deciphering the molecular mechanism of aloe-emodin in managing type II diabetes mellitus using network pharmacology, molecular docking , and molecular dynamics simulation approaches

Aloe-emodin (AE) has drawn interest due to its potential activity against type II diabetes mellitus (T2DM). However, the mechanisms underlying its antidiabetic activity are not well explored. Using network pharmacology, molecular docking and molecular dynamics simulation studies, we investigated its molecular mechanisms in the management of T2DM. Potential target genes of AE were predicted using the Swiss Target Prediction (http://www.swisstargetprediction.ch/) database. The GeneCards, OMIM and DisGeNET databases were used to compile a comprehensive list of genes associated with T2DM. A compound-disease-target network was constructed, and protein-protein interaction networks were analysed to identify hub genes. Finally, molecular docking and interaction analysis between AE and the identified proteins were performed using AutoDock tools. Investigation of AE targets and genes associated with T2DM identified 32 overlapping genes. Gene ontology studies revealed that AE may exert its anti-diabetic effects by modulating glucose metabolism and enhancing cellular response to glucose. Furthermore, KEGG pathway analysis suggested that AE influences these processes by targeting pathways related to apoptosis, insulin resistance, and T2DM signaling. The core target proteins identified were TNF, ALB, TP53, PPARG, BCL2, CASP3, and EGFR. AE interaction with each of these proteins exhibited a binding energy of > - 5 kcal/mol, with TNF showing the lowest binding energy (- 7.75 kcal/mol). Molecular dynamics simulation further validated the molecular docking results with TNF and EGFR exhibiting a strong affinity for AE and forming stable interactions. AE exerts its antidiabetic activity through multiple mechanisms, with the most significant being the amelioration of pancreatic β-cell apoptosis by binding to and inhibiting the actions of TNFα. Further cellular and molecular studies are needed to validate these findings.