In Silico Evaluation of Phaseolus vulgaris Seeds as Appetite-Suppressing Agents via Melanocortin-4 and GLP-1 Receptor Activation

¹ Department of Pediatric, Faculty of Medicine, Universitas Islam Malang, Malang 65144, Indonesia
² Department of Pharmacy, Faculty of Medicine, Universitas Islam Malang, Malang 65144, Indonesia

¹ Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Childhood obesity is strongly influenced by dysregulated appetite signalling, particularly within pathways involving melanocortin-4 receptor (MC4R) and glucagon-like peptide-1 receptor (GLP-1R). Phaseolus vulgaris has been reported to reduce body weight, yet its specific molecular interactions with appetite-regulating receptors remain unclear. This study aimed to evaluate the potential of P. vulgaris bioactive compounds as appetite-suppressing agents through MC4R and GLP-1R activation using an in silico approach. A total of 46 compounds were screened for physicochemical and ADMET properties using pkCSM, followed by molecular docking against MC4R and GLP-1R using PyRx. Interaction profiles were visualized with Discovery Studio, and docking validation was conducted using re-docking RMSD criteria. Twenty-six compounds met Lipinski's criteria and demonstrated acceptable pharmacokinetic profiles. Sterol derivatives, including stigmasterol, 24-α-methyllophenol, and obtusifoliol, showed the strongest binding affinities (AG -8.9 to -12.4 kcal/mol) and occupied key hydrophobic pockets similar to native agonists. Flavonoids and anthocyanins exhibited lower binding energies but formed extensive hydrogen-bond and aromatic interactions that may stabilize receptor-ligand complexes. These findings suggest that P. vulgaris seeds contain compounds with promising anorexigenic potential through MC4R and GLP-1R modulation. Further in vitro and in vivo studies are required to confirm their therapeutic relevance for obesity management.