Integrated HPLC Profiling and Network Pharmacology Reveal PI3K–Akt–Mediated Antidiabetic Mechanisms of Ageratum conyzoides l

To identify the major phytoconstituents of Ageratum conyzoides l. and elucidate their molecular mechanisms against diabetes mellitus using a comprehensive in-silico systems-pharmacology approach. Phytochemical screening of AC leaves was performed using HPLC. The drug-likeness and ADME properties of identified compounds were evaluated using SwissADME and MolSoft. Compound-associated and DM-associated genes were retrieved from STP, SEA, DisGeNET, OMIM, and GeneCLiP3 databases, and intersected using Venny 2.1. Protein–protein interaction (PPI) networks were constructed via STRING and analyzed in Cytoscape using the MCC algorithm. GO and KEGG pathway enrichment were performed to identify key biological processes and signaling pathways modulated by AC phytochemicals. Molecular docking performs using discovery studio, Autodock 4.2.6 and SwissDock. HPLC analysis identified three major compounds: scutellarin, kaempferol, and umbelliferone. Drug-likeness screening narrowed these to scutellarin, kaempferol and umbelliferone as orally active candidates. A total of 149 overlapping genes were identified between AC compounds and DM-related targets. PPI network analysis revealed key hub genes including AKT1, IGF1R, PIK3R1, EGFR, ERBB2, MET, HSP90AA1, KDR, and CCND1. KEGG enrichment demonstrated significant involvement of PI3K–Akt signaling, xenobiotic metabolism, steroid hormone biosynthesis, and oxidative-stress regulation pathways. Both compounds showed strong convergence on insulin signaling and metabolic regulatory targets. Molecular docking was used to identify scutellarin as the most effective multi-target ligand, followed by kaempferol, andumbelliferone. Ageratum conyzoides l. Exhibits substantial antidiabetic potential through multi-target modulation of insulin signaling, glucose metabolism, oxidative stress reduction, and inflammatory pathways. The strong enrichment of PI3K–Akt signaling provides a robust mechanistic basis for its antihyperglycemic activity.