Exploring antidiabetic potential of a polyherbal formulation Madhurakshak Activ: An in vitro and in silico study

Madhurakshak Activ (MA), a commercial polyherbal antidiabetic preparation is known to manage diabetes mellitus (DM) by reducing blood glucose levels. However, lacks systematic mechanistic evaluation for their molecular and cellular mode of actions. In the present study, hydro-alcoholic and aqueous extract of MA were evaluated for their effects on glucose adsorption, diffusion, amylolysis kinetics and transport across the yeast cells using in vitro techniques. Bioactive compounds identified from MA by LC-MS/MS were assessed for their binding potential against DPP-IV and PPARγ via an in silico approach. Our results revealed that the adsorption of glucose increased dose dependently (5 mM -100 mM). Both extracts exhibited linear glucose uptake into the yeast cells (5 mM - 25 mM), whereas glucose diffusion was directly proportional to time (30-180 min). Pharmacokinetic analysis revealed drug-like properties and low toxicity levels for all the selected compounds. Among the tested compounds, 6-hydroxyluteolin (-8.9 against DPP-IV and PPARγ) and glycyrrhetaldehyde (DPP-IV -9.7 and PPARγ -8.5) have exhibited higher binding affinity compared to the positive control. Therefore, the above compounds were further considered for molecular dynamics simulation which showed stability of the docked complexes. Hence, studied mode of actions might produce a concerted role of MA in increasing the rate of glucose absorption and uptake followed by the in silico studies which suggest that the compounds identified from MA may inhibit DPP-IV and PPARγ phosphorylation.