International Journal of Scientific Research and Engineering Development

Insomnia is a widespread neurological disorder driven by disrupted inhibitory neurotransmission and multi-pathway dysregulation. Plant-derived compounds have historically offered sedative effects with fewer side effects compared to synthetic hypnotics, yet the precise molecular targets through which Citrus limon leaf phytoconstituents act remain unexplored. This study employed a network pharmacology workflow to pinpoint the genes shared between Citrus limon (CL) leaf bioactive compounds and insomnia-associated disease targets, then used molecular docking via AutoDock Tools to evaluate the binding strength of ten CL phytoconstituents i.e. myrcene, neryl formate, geranyl formate, beta-terpineol, d-borneol, linalool, citronellol, trans-sesquisabinene hydrate, eriocitrin, and hesperidin against six target proteins: BCL2 (PDB: 6O0K), CASP3 (PDB: 3KJF), EGFR (PDB: 4WKQ), STAT3 (PDB: 6NJS), BCL2L1 (PDB: 3ZK6), and GABA-A receptor (PDB: 6HUP), benchmarked against diazepam. Cross-referencing compound targets with insomnia genes via Venny returned 92 overlapping targets, forming a 92-node, 604-edge PPI network in STRING v12 (average node degree 13.1; clustering coefficient 0.515). The cytoHubba MCC algorithm identified BCL2, CASP3, EGFR, STAT3, and BCL2L1 as central hub genes. Docking revealed that eriocitrin (−9.4 kcal/mol) and hesperidin (−9.8 kcal/mol) outperformed diazepam (−7.3 kcal/mol) at the GABA-A receptor, while trans-sesquisabinene hydrate showed the broadest monoterpene affinity across all targets (BCL2L1: −7.6 kcal/mol). These findings establish a mechanistic multi-target framework for the anti-insomnia potential of CL leaf extract, grounded in GABAergic potentiation and neuroprotective hub-gene modulation.

Kamini K. Gosavi, Tabassum A. Patwegar, Pratiksha B. Jadhav, "Network Pharmacology and Molecular Docking Analysis of Citrus limon Leaf Phytoconstituents Against Insomnia-Associated Molecular Targets" International Journal of Scientific Research and Engineering Development, V9(4): Page(170-178) May-June 2026. ISSN: 2581-7175. www.ijsred.com. Published by Scientific and Academic Research Publishing.