Type 2 diabetes (T2D), also known as non-insulin-dependent diabetes mellitus, represents the prevailing manifestation of diabetes, encompassing a substantial majority of cases, ~90-95%. Plant-derived antidiabetic leads are being intensively explored due to their safety and effectiveness. The main objective of the present study is to evaluate the anti-diabetic potential of the traditional formulation Karisalai Karpam through in-vitro and in-silico investigations. The in-vitro and in-silico investigation of traditional polyherbal preparation Karisalai Karpam (KK) chooranam were performed to ascertain its inhibitory potential against α-amylase and α-glucosidase enzymes along with antioxidant (DPPH and ABTS) and phytochemical analysis. The results of enzyme inhibitory activity of KK witnessed highest activity against α-glucosidase enzyme with a percentage inhibition of 84.66 ± 2.50% (IC50,187.9 ± 5.79 μg/ml) followed by moderate level of α-amylase inhibition exhibited with 72.94 ± 3.66% (IC50, 241.6 ± 9.76 μg/ml). Additionally, the strongest antioxidant activity was observed in quenching DPPH• (IC50,154.8 ± 14.53 μg/ml) and ABTS+• radicals (IC50,148.6 ± 29.74 μg/ml). The outcome of the molecular docking studies indicated that among the 17 compounds analysed, the lead such as acalyphin, apigenin, humulene, and indirubin exhibited a prominent binding affinity over the residual binding site of α-glucosidase. It's important to note that the catalytic site of the enzyme α-amylase is primarily occupied by amyrin, apigenin, arjunolic acid, β-sitosterol, geraniol, and tricetin. In conclusion, the formulation KK demonstrates robust alpha-glucosidase and alpha-amylase inhibitory activity. It's also worth noting that the formulation exhibits noteworthy antioxidant properties, which could provide additional health benefits. The binding mode and energies of the identified phytochemicals against the target enzymes further support the formulation's antidiabetic potential.
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