Molecular Insights and Therapeutic Potential of Lekhaniya Mahakashaya (LM): A Network Pharmacology Approach for Obesity

Background: Obesity and dyslipidaemia are global health concerns linked to insulin resistance, type 2 diabetes and cardiovascular diseases. Classical mono‑target drugs often fail to address the multifactorial nature of these disorders, prompting interest in multi‑target, plant-based interventions. Lekhaniya Mahakashaya (LM) is a classical Ayurvedic polyherbal formulation traditionally used to manage obesity and lipid imbalance. Objective: To use an Insilico network pharmacology approach to identify the bioactive phytoconstituents of LM, evaluate their drug‑likeness and ADME properties, predict their molecular targets, and elucidate the signalling pathways relevant to obesity. Methods: The methanolic extract of LM was subjected to LC-MS/MS analysis to identify its bioactive phytoconstituents. Drug-likeness and ADME (Absorption, Distribution, Metabolism, and Excretion) properties were evaluated using the SwissADME tool. Potential molecular targets were predicted through SwissTargetPrediction, and a Protein-Protein Interaction (PPI) network was generated using the STRING database. Cytoscape software was employed to construct and visualize the interaction network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by an evaluation of network synergy. Results: Among 44 identified phytochemicals, 28 met ADME and drug-likeness criteria. The compound 5,12,13‑triaza‑indeno[1,2‑b]anthracen‑13‑yl acetic acid ethyl ester showed 56 protein interactions. Eight proteins overlapped with obesity‑associated genes, yielding a significant interaction enrichment (p < 0.001). Enrichment analyses indicated involvement in adrenergic signalling, thermogenesis and monoamine transport, and pathways including cGMP–PKG signalling and neuroactive ligand–receptor interactions. Conclusion: LM exhibits a multi-target mode of action involving metabolic, neuroendocrine, and thermogenic pathways. These findings support its traditional use in managing obesity and lipid disorders and highlight its potential as a safe, synergistic polyherbal therapeutic.