In Silico exploration of Karanjin for anti-obesity potential through ADMET profiling, network pharmacology, molecular docking, and molecular dynamics simulations

Obesity is a growing public health concern, particularly in Malaysia, where prevalence rates continue to rise. Despite the availability of pharmacological interventions, existing anti-obesity drugs are often limited by modest efficacy and undesirable side effects. Natural compounds have emerged as promising alternatives, offering multi-target therapeutic potential with improved safety profiles. Karanjin, a furanoflavonoid isolated from Pongamia pinnata, has demonstrated anti-inflammatory and antioxidant activities, but its role in obesity management remains largely unexplored. In this study, an integrated in silico method was employed to explore the anti-obesity potential of Karanjin. Pharmacokinetic profiling indicated favourable absorption, distribution, and toxicity profiles. Network pharmacology analysis identified 145 overlapping targets between Karanjin and obesity-related genes, with enriched significant pathways such as AGE-RAGE signalling, which is implicated in oxidative stress and metabolic dysregulation. Molecular docking against eight hub proteins revealed strong binding affinities, with Karanjin exhibiting superior binding energies compared to reference anti-obesity drugs. Notably, the PIK3CA-Karanjin complex demonstrated the most favourable interaction profile. Confirmed molecular dynamics simulations results in a stable structure of the PIK3CA-Karanjin complex in a span of 100 ns, supported by root mean square deviation (RMSD), radius of gyration (Rg), root mean square fluctuation (RMSF), and solvent accessible surface area (SASA) analyses. Binding free energy calculations using the molecular mechanics Poisson-Boltzmann surface area (MMPBSA) method further validated the thermodynamic favourability of the interaction. Collectively, the findings provide a strong computational foundation supporting the potential of Karanjin as a multi-target candidate for obesity management, warranting further experimental validation.