Quercetin and Coumarin Inhibit Dipeptidyl Peptidase-IV and Exhibits Antioxidant Properties: In Silico, In Vitro, Ex Vivo

Abstract

Quercetin and coumarin, two naturally occurring phytochemicals of plant origin, are known to regulate hyperglycemia and oxidative stress. The present study was designed to evaluate the inhibitory activity of quercetin and coumarin on dipeptidyl peptidase-IV (DPP-IV) and their antioxidant potential. DPP-IV inhibition assays were performed, and evaluated IC₅₀ values of diprotin A, quercetin, coumarin, and sitagliptin were found to be 0.653, 4.02, 54.83, and 5.49 nmol/mL, respectively. Furthermore, in silico studies such as the drug-likeliness and docking efficiency of quercetin and coumarin to the DPP-IV protein were performed; the ex vivo antiperoxidative potential of quercetin and coumarin were also evaluated. The results of the present study showed that the DPP-IV inhibitory potential of quercetin was slightly higher than that of sitagliptin. Virtual docking revealed the tight binding of quercetin with DPP-IV protein. Quercetin and coumarin reduced oxidative stress in vitro and ex vivo systems. We report for the first time that both compounds inhibited the DPP-IV along with antioxidant activity and thus may be use as function food ingredients in the prevention of diabetes.

Keywords: antiperoxidative; coumarin; diabetes; dipeptidyl peptidase-IV; hyperglycemia; quercetin.

Figure 1

The hydrogen bonding (A), hydrophobic binding (B), electrostatic binding (C), and secondary protein interaction (D) of diprotin-A and dipeptidyl peptidase-IV protein.

Figure 2

The hydrogen bonds (A), hydrophobic binding (B), electrostatic binding (C), and secondary protein interaction (D) of quercetin and dipeptidyl peptidase-IV protein.

Figure 3

The hydrogen bonds (A), hydrophobic binding (B), electrostatic binding (C), and secondary protein interaction (D) of coumarin and dipeptidyl peptidase-IV protein.

Figure 4

The hydrogen bonds (A), hydrophobic binding (B), electrostatic binding (C), and secondary protein interaction (D) of sitagliptin and dipeptidyl peptidase-IV protein.

Figure 5

β carotene bleaching inhibition (%) in quercetin and coumarin as compared to the control; ascorbic acid. Each vertical bar represents the mean ± S.E.M. (n = 3), *** p < 0.001, ** p < 0.01 and * p < 0.05 as compared to the respective control values. A. acid, ascorbic acid; Que, quercetin; Cou, coumarin.

Figure 6

Hepatic lipid peroxidation inhibition activities of quercetin and coumarin as compared to the control; ascorbic acid. Each vertical bar represents the mean ± S.E.M. (n = 3). *** p < 0.001, ** p < 0.01 and * p < 0.05 as compared to the respective control values. A. acid, ascorbic acid; Que, quercetin; Cou, coumarin.

Figure 7

Erythrocyte haemolysis inhibition efficacies of quercetin and coumarin as compared to the control; ascorbic acid. Each vertical bar represents the mean ± S.E.M. (n = 3). *** p < 0.001, ** p < 0.01 and * p < 0.05 as compared to the respective control values. A. acid, ascorbic acid; Que, quercetin; Cou, coumarin.