Integrative Approach to Elucidate the Antidiabetic Efficacy of <i>Cipadessa baccifera</i> (Roth) Miq.: A Study Based on Metabolomics, Network Pharmacology, and Animal Models

Cipadessa baccifera (Roth) Miq. (Family- Meliaceae) has been traditionally used to treat various ailments, including diabetes. The present study aimed to validate the antidiabetic efficacy of C. baccifera using both in vitro and in vivo diabetic models, followed by a mechanistic evaluation. UPLC-Q-ToF/MS analysis, enzyme inhibition assays, and in silico studies were performed. Cytotoxicity and glucose uptake studies were conducted on MIN6 cell line. qRT‒PCR was carried to assess GLUT4 expression in adipocytes. Immunostaining was performed to examine the differential expression of pancreatic cell subtypes. UPLC-Q-ToF/MS analysis identified 93 compounds, of which 18 were further selected for in silico protein‒protein interaction (PPI) network analysis. PPI network and pathway enrichment analyses predicted that the PPARG, AKT1, SIRT1, and FOXO1 genes are key regulators in diabetes. The in vitro enzyme inhibition assay revealed significant inhibition by the 70% hydroethanolic extract. The mechanistic study showed notable upregulation of GLUT4 mRNA expression, which also supports the network analysis algorithm. The in vivo study demonstrated a significant decrease in blood glucose, insulin, and HbA1c levels in the treated model. Immunostaining revealed significant restoration of insulin and myosin expression. These combined results highlight the potential of C. baccifera as a valuable supplement for diabetes management.