Targeting inflammatory and insulin-regulatory proteins in type 2 diabetes mellitus: Insights from Argemone ochroleuca (sweet) via multi-omics and network pharmacology with experimental verification.

Argemone ochroleuca is recognized for its traditional use in managing diabetes; however, no systematic study has explored its molecular mechanisms targeting biological macromolecules. Therefore, current study aimed to elucidate the underlying mechanisms of A. ochroleuca ethanolic extract (AOE) in T2DM management using multi-omics and network pharmacology-based methods, focusing on key regulatory proteins. The AOE yielded 7.04 %, and GC-MS, as well as other data mining approaches, were used to identify 45 phytoconstituents in AOE, from which seven key bioactive compounds-β-sitosterol, 4H-Pyran-4-one, butyrolactone, hexadecanoic acid, sanguinarine, allocryptopine, and berberine - were selected. Thereafter, these compounds were predicted to target several core proteins, including AKT1, INS, TP53, TNF, IL6, and FOXO1, which are involved in T2DM pathology. However, these proteins participate in critical signaling pathways, including the PI3K/Akt, MAPK, AGE/RAGE, and PPARγ pathways, among others. Moreover, Microarray data (GSE184050) validated the relevance of these targets, showing upregulation of INS, TNF, IL6, and downregulation of FOXO1 in T2DM patients. Additionally, AOE demonstrated dose-dependent inhibition of α-amylase (111.21 ± 4.7 μg/ml) and α-glucosidase (135.02 ± 12.08 μg/ml) enzymes, revealing therapeutic effects in STZ-induced diabetic rats by improving glucose metabolism, reducing inflammation, and protecting hepatic and renal tissues. Hence, AOE exerts antidiabetic effects through multi-target modulation of specific proteins, highlighting its clinical potential.