Inhibitory Effects of Myricetrin and Dihydromyricetin toward α-Glucosidase and Pancreatic Lipase with Molecular Docking Analyses and Their Interaction

Siyuan Mi,Jia Liu,Xiaojing Liu,Shengbao Cai,Junjie Yi,Yishan Fu,Antoni Szumny

doi:10.1155/2021/9943537

Abstract

The aim of the current study was to evaluate the interaction effects of myricetrin and dihydromyricetin in inhibiting α-glucosidase and pancreatic lipase at different combination ratios and concentrations and to illuminate the underlying mechanisms of their inhibitions by molecular docking analyses. Results showed that both phenolic compounds possessed good inhibitory effects toward two enzymes in a dose-dependent manner. Myricetrin demonstrated a stronger inhibition against α-glucosidase (IC50, 41.14 ± 2.52 and more than 200 μg/mL, respectively), while dihydromyricetin had a better pancreatic lipase inhibition (IC50, 244.96 ± 4.24 and 373.26 ± 21.36 μg/mL, respectively). Different interaction types were observed when myricetrin and dihydromyricetin inhibited α-glucosidase and pancreatic lipase in combination, which were closely related to the combination ratio and concentration. For α-glucosidase inhibition, synergistic effects were observed at relative low concentrations when the combination ratio of myricetrin to dihydromyricetin was set as 1 : 2, while strong synergistic effects existed at relative high concentrations for pancreatic lipase inhibition. In other combination ratios (1 : 1 or 2 : 1), additive and/or antagonistic effects occurred. Molecular docking analyses showed that myricetrin formed nine hydrogen bonds with α-glucosidase, while only three hydrogen bonds were formed between dihydromyricetin and α-glucosidase. However, these two phenolic compounds had similar hydrogen bonds and hydrophobic interactions with pancreatic lipase. The present study suggested that myricetrin and dihydromyricetin or food materials rich in these two phenolic compounds could be exploited as α-glucosidase and/or pancreatic lipase inhibitors to deal with health problems caused by excessive energy intake, and the combination ratio and concentration of these two phenolic compounds should be considered when producing new functional foods.

Highlights

Along with the improvement of living standards and the enrichment of material conditions, the diet pattern with high sugar and high fat has become more common, coupled with the sedentary lifestyle with little exercise, resulting in a serious excess of energy intake and thereby leading to the prevalence of many chronic diseases, such as obesity, diabetes, fatty liver, and cardiovascular disease [1, 2]. ese chronic diseases have caused heavy burden to the medical system all over the world. erefore, how to effectively deal with these chronic diseases has become an urgent problem to be solved, which is a hot and difficult research topic in many disciplines
Molecular Docking Results of α-Glucosidase and Pancreatic Lipase. e enzyme inhibitory mechanisms of myricetrin and dihydromyricetin on α-glucosidase and pancreatic lipase were illuminated by the molecular docking method with the computational modeling software SYBYLX 2.1.1, and the hydrophobic interactions were analyzed by Ligplot+ software. e related parameters of the docking scores, hydrogen bond parameters, and hydrophobic effects of these standards with α-glucosidase or pancreatic lipase are summarized in Tables 3 and 4, respectively. e parameters in Tables 3 and 4 displayed the detailed information of the receptor-ligand interactions, including reliability, charge, van der Waals force, hydrogen bond, lipophilic, and so on
Myricetrin and dihydromyricetin may be due to the slightly different amino acid residues they interacted with in hydrogen bonds and hydrophobic interactions. Results showed that both myricetrin and dihydromyricetin exhibited good inhibitory effects toward α-glucosidase and pancreatic lipase in a dose-dependent manner

Summary

Introduction

Along with the improvement of living standards and the enrichment of material conditions, the diet pattern with high sugar and high fat has become more common, coupled with the sedentary lifestyle with little exercise, resulting in a serious excess of energy intake and thereby leading to the prevalence of many chronic diseases, such as obesity, diabetes, fatty liver, and cardiovascular disease [1, 2]. ese chronic diseases have caused heavy burden to the medical system all over the world. erefore, how to effectively deal with these chronic diseases has become an urgent problem to be solved, which is a hot and difficult research topic in many disciplines. Carbohydrates and fats in food are the main contributors to the body’s energy intake, and reducing. Journal of Food Quality carbohydrate and/or fat intake is considered an effective way to suppress energy intake [5,6,7]. As for carbohydrates, α-glucosidase is one of the main enzymes for their digestion, and inhibiting α-glucosidase can reduce energy intake derived from carbohydrate and effectively control postprandial blood glucose of diabetic patients [8, 9]. For fats in food, pancreatic lipase is the main digestive enzyme, and inhibiting pancreatic lipase is considered an effective method to reduce fat absorption [10, 11]. Acarbose and orlistat are inhibitors of α-glucosidase and pancreatic lipase, respectively. A large number of previous studies have found that many secondary metabolites of edible plants, especially phenolic compounds, have good inhibitory effects toward α-glucosidase and/or pancreatic lipase [6, 7, 10, 12, 13]

Methods

Results

Conclusion