Biochemical Investigation of Inhibitory Activities of Plant-Derived Bioactive Compounds Against Carbohydrate and Glucagon-Like Peptide-1 Metabolizing Enzymes
Muhammad Fiaz Khalid, Kanwal Rehman, Kanwal Irshad, Tahir Ali Chohan, Muhammad Sajid Hamid Akash
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 via in vitro analysis which was further validated by in silico 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 IC 50 values, 47.93 ± 5.21 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mi>μ</mml:mi> <mml:mi mathvariant="normal">M</mml:mi> </mml:mrow> </mml:math> and 45.86 ± 3.78 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mi>μ</mml:mi> <mml:mi mathvariant="normal">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" overflow="scroll"> <mml:mrow> <mml:mi>μ</mml:mi> <mml:mi mathvariant="normal">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" overflow="scroll"> <mml:mrow> <mml:mi>μ</mml:mi> <mml:mi mathvariant="normal">M</mml:mi> </mml:mrow> </mml:math> and 31.26 ± .556 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mi>μ</mml:mi> <mml:mi mathvariant="normal">M</mml:mi> </mml:mrow> </mml:math> , respectively). IC 50 value of resveratrol and taxifolin (5.638 ± .0016 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mi>μ</mml:mi> <mml:mi mathvariant="normal">M</mml:mi> </mml:mrow> </mml:math> and 6.691 ± .004 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mi>μ</mml:mi> <mml:mi mathvariant="normal">M</mml:mi> </mml:mrow> </mml:math> ) in comparison to diprotin A (IC 50 : 7.21 ± .021 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mi>μ</mml:mi> <mml:mi mathvariant="normal">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 via 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.