Elucidating the therapeutic efficacy of polyherbal formulation for the management of diabetes through endogenous pancreatic β-cell regeneration

Abstract

Diabetes mellitus is characterized by the progressive loss of pancreatic β-cells. Owing to the adverse side effects of conventional antidiabetic, ethnopharmacological agents have emerged as adjunct therapies for their management. The present study aims to validate the antidiabetic activity of an aqueous polyherbal extract (APE) via in silico, in vitro, and in vivo models.

UHPLC–Q-TOF-MS and HPLC analysis of APE were performed to identify bioactive secondary plant metabolites. In silico approaches implemented to predict the binding efficacy of the active phytoconstituents. Biochemical estimation, antioxidant activity, and in vitro and in vivo antidiabetic activities of APE were performed. Histomorphological and immunohistological studies of the pancreatic islets were carried out in diabetic animals for microarchitectural study.

UHPLC-Q-TOF-MS identified a total of 60 compounds in APE, of which 39 were reported to have antidiabetic activity, and 16 marker compounds were identified via high-performance liquid chromatography (HPLC). An in silico study revealed a strong interaction of verbacoside B with the target proteins. APE is characterized by high flavonoid and phenolic contents with strong antioxidant properties. In an in vitro enzymatic assay, APE significantly inhibited α-amylase and α-glucosidase enzymes, with calculated IC₅₀ values of 54.26 ± 0.14 and 26.47 ± 0.12 μg/ml, respectively. An in vitro glucose uptake assay revealed increased uptake with APE treatment in a dose-dependent manner. APE significantly decreased blood glucose and HbA1c levels and had no side effects on liver or kidney function, as measured from blood parameters. Immunohistological observation revealed 47% regeneration of pancreatic β-cells with APE treatment in diabetic animals.