Network pharmacology-based elucidation of Navaka Guggulu’s mechanistic role in obesity and associated metabolic disorders

BACKGROUND: Obesity has emerged as a leading global health concern, contributing significantly to the poor quality of life and burden of noncommunicable diseases. Despite rising prevalence, therapeutic options remain limited due to safety and efficacy challenges. Navaka Guggulu (NG) is indicated in the management of Medoroga (obesity). However, its molecular targets and pharmacological mechanisms remain unexplored. This study aimed to elucidate its molecular mechanisms in the management of obesity through an integrated network pharmacology and molecular docking approach. METHODS: Bioactive constituents of NG were curated from the Indian Medicinal Plants, Phytochemistry and Therapeutics 2.0 database and screened for drug-likeness. Disease relevance was assessed via SuperPred. A compound–protein–disease network was constructed in Cytoscape, followed by protein–protein interaction and functional enrichment analyses using Metascape, g:Profiler, and ShinyGO. Molecular docking was performed using Schrödinger’s Glide module to evaluate ligand–target affinities. RESULTS: Enrichment analysis revealed significant involvement of NG targets in adenosine monophosphate-activated protein kinase signaling, peroxisome proliferator-activated receptor signaling, lipolysis in adipocytes, glucagon signaling, and neuroactive ligand–receptor interactions. Strong associations of target genes were found with the liver, pancreas, and hypothalamus. Carvacrol, plumbagin, ellagic acid, and Z-guggulsterone exhibited the strongest binding affinity to the selected target genes associated with obesity. CONCLUSION: NG demonstrates multi-targeted therapeutic potential through modulation of key metabolic and signaling pathways such as lipid metabolism, energy balance, and insulin sensitivity. These findings provide a molecular rationale for NG’s traditional use and lay the groundwork for novel drug development.