Therapeutic Potential of Aloe barbadensis Against Obesity-Associated Intestinal Inflammation: An Integrated Network Pharmacology, Molecular Modeling, and In Vivo Study

Acute intestinal inflammation, associated with obesity, is a new health problem affecting the whole world, which is characterised by chronic inflammation in the intestine and metabolic dysfunction. The therapeutic benefits of Aloe barbadensis on obesity-associated intestinal inflammation were explored by an integrated approach of phytochemical profiling, network pharmacology, molecular docking, and molecular dynamics simulation and in vivo validation. Seven tentatively annotated phytoconstituents were identified from the hydroalcoholic extract of Aloe barbadensis by HR-LC-MS. Based on the ADME, toxicity, and drug-likeness screening, tropinone, norlaudanosoline, hippeastrine, 7-O-acetyldaphnoretin, and galantamine were shortlisted as possible bioactive compounds. The key therapeutic target related to obesity and IBD-related pathways was determined by network pharmacology analysis, and AKT1 was identified. Molecular docking showed that galantamine has excellent binding to AKT1 with a docking score of −8.2 kcal/mol. The stability of the AKT1–galantamine complex was validated in subsequent MD simulations of 200 ns each by RMSD, RMSF, radius of gyration, solvent-accessible surface area, hydrogen bond, principal component, and free-energy landscape analyses. The favorable binding free energy obtained from MM-PBSA calculations confirmed the binding interactions between the protein and ligand. In vivo experiments with Wistar rats subjected to monosodium glutamate (MSG) and microplastics confirmed the significant improvement in body weight changes, normalization of lipid profiles, reduction of hepatic enzyme abnormalities, and reduction in lipid accumulation in faeces by the administration of Aloe barbadensis extract. Marked protection from tissue damage in the liver and intestine was confirmed from the histopathological analysis of both tissues. In summary, the presented results demonstrate the potential therapeutic role of Aloe barbadensis in obesity-associated intestinal inflammation and indicate that galantamine could represent a good starting point for developing drugs aimed at the AKT1-mediated pathway.