A Systematic Antidiabetic Screening Approach Integrating In Vitro Assays and In Silico Analysis: Evaluation of Glucose-Regulatory Activity and Prediction of Bioactive Components in Plant Derived Materials

Background: Type 2 diabetes mellitus involves multifactorial metabolic dysfunction necessitating therapeutic strategies capable of modulating multiple biological pathways.Methods: This study implemented a 4-stage integrated screening platform to identify natural products with multitarget antidiabetic potential.Results: Five plant samples samples were evaluated through α-glucosidase inhibition, protein tyrosine phosphatase 1B inhibition, glucoseuptake enhancement assays in C2C12 myotubes, and network pharmacology. Amongst them, <i>Lagerstroemia speciosa</i> (banaba leaf) was the only material that demonstrated coherent activity across all assays. Banaba extract significantly inhibited α-glucosidase, enhanced glucose uptake in a dose-dependent manner, and exhibited measurable protein tyrosine phosphatase suppression. Network pharmacology further supported these findings and 13 overlapping targets and 19 hub genes enriched in insulin signaling pathways (PI3K-Akt, AMPK, MAPK, and FOXO) were identified. This reflected strong mechanistic relevance of banaba leaf to Type 2 diabetes mellitus.Conclusion: Collectively, these results demonstrate the utility of a systematic, multilevel screening framework which highlights banaba leaf as a promising candidate for further antidiabetic research. Nevertheless, reliance on in vitro and in silico analyses underscores the need for in vivo validation to determine physiological efficacy, bioavailability, and systemic metabolic effects.