Dual Incretin Modulation by <I>Ipomoea batatas</I> L. Flavonoids Capsule: In Vivo and In Silico Evidence of GLP-1 Activation and DPP-IV Inhibition in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) remains a major global health challenge, with the incretin pathway involving glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-IV (DPP-IV) serving as a key therapeutic target. Although flavonoids from Ipomoea batatas L. (IBL). have shown potential modulatory effects, their molecular mechanisms and pharmacokinetic properties remain poorly understood. This study aimed to evaluate the efficacy and underlying mechanisms of IBL capsule using integrated in vivo and in silico approaches. A 21-day in vivo experiment was performed using Wistar rats with T2DM to evaluate GLP-1, C-peptide, and HbA1c levels as indicators of incretin activity. Bioactive flavonoids were characterized using HPTLC-MS, and their molecular interactions with GLP-1 receptor and DPP-IV enzyme were examined through molecular docking, followed by ADME-based pharmacokinetic prediction to evaluate systemic activity. The IBL capsule, with a total flavonoid content of 0.891 mgEQ/g, significantly increased GLP-1 and C-peptide levels while reducing HbA1c levels in the T2DM model. HPTLC-MS analysis identified small, stable flavonoid compounds in the formulation. Molecular docking indicated strong potential interactions between these flavonoids and the GLP-1 receptor, as well as potential inhibition of the DPP-IV enzyme. Pharmacokinetic predictions indicated that flavonoids with molecular weights below 500 Da have favorable systemic absorption and may contribute to the observed antidiabetic effects. The IBL capsule exhibits promising antidiabetic potential through dual mechanisms, GLP-1 receptor activation and DPP-IV enzyme inhibition. These effects are supported by in vivo hypoglycemic activity, the presence of stable bioactive flavonoids, and favorable pharmacokinetic characteristics indicating good systemic bioavailability.