Biochemical Investigation of Inhibitory Activities of Plant-Derived Bioactive Compounds Against Carbohydrate and Glucagon-Like Peptide-1 Metabolizing Enzymes

Abstract

The aim of current study was to investigate the inhibitory activities of resveratrol and taxifolin against α-amylase, α-glucosidase, and DPP-IV enzymes <i>via</i> <i>in vitro</i> analysis which was further validated by <i>in silico</i> studies. The analysis of molecular docking was also done to determine the binding capabilities of resveratrol and taxifolin with α-amylase, α-glucosidase, and DPP-IV enzymes. Resveratrol and taxifolin having IC₅₀ values, 47.93 ± 5.21 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>μ</mml:mi> <mml:mi>M</mml:mi></mml:mrow> </mml:math> and 45.86 ± 3.78 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>μ</mml:mi> <mml:mi>M</mml:mi></mml:mrow> </mml:math> , respectively, showed weaker effect than acarbose (4.6 ± 1.26 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>μ</mml:mi> <mml:mi>M</mml:mi></mml:mrow> </mml:math> ) on α-amylase but showed significant effect to inhibit α-glucosidase (32.23 ± .556 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>μ</mml:mi> <mml:mi>M</mml:mi></mml:mrow> </mml:math> and 31.26 ± .556 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>μ</mml:mi> <mml:mi>M</mml:mi></mml:mrow> </mml:math> , respectively). IC₅₀ value of resveratrol and taxifolin (5.638 ± .0016 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>μ</mml:mi> <mml:mi>M</mml:mi></mml:mrow> </mml:math> and 6.691 ± .004 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>μ</mml:mi> <mml:mi>M</mml:mi></mml:mrow> </mml:math> ) in comparison to diprotin A (IC₅₀: 7.21 ± .021 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>μ</mml:mi> <mml:mi>M</mml:mi></mml:mrow> </mml:math> ) showed that they have significant inhibitory effect on DPP-IV enzyme. Our results illustrated that resveratrol and taxifolin have potential to prevent the metabolism of carbohydrates <i>via</i> inhibition of α-amylase and α-glucosidase, and prolongs metabolic function of incretin by inhibiting the enzymatic activity of DPP-IV. The results of molecular docking have also revealed that resveratrol and taxifolin have significant affinity to bind with α-amylase, α-glucosidase, and DPP-IV in comparison with standard drugs such as acarbose, miglitol, and diprotin.