Screening Inhibitors of α-Amylase in Polygala Radix Based on an Online Targeted Detection System and Molecular...

Targeted screening of inhibitors of key enzymes in the progression of diabetes from natural products is one of the effective methods for the treatment of diabetes. Polygala has been proved to reduce glucose levels; however, the bioactive compounds in Polygalae Radix (PR) that have anti-diabetic properties are unknown.

The purpose of this study was to explore the material basis of the anti-diabetic effect of PR by inhibiting α-amylase through an online detection system and molecular docking.

An online analysis platform was established and optimized for the screening of potent enzyme inhibitors from complex mixtures based on ultra-performance liquid chromatography-photodiode array-quadrupole-time-of-flight-mass spectrometry-α-amylase-fluorescence detector (UHPLC-PDA-Q-TOF-MSⁿ-α-amylase-FLD) detection system and molecular docking, which could efficiently separate extracts, quickly detect α-amylase inhibitors, and determine their structures. Molecular docking confirms the inhibition of these compounds. The molecular interaction between α-amylase and the active compound was evaluated.

Among the 101 compounds identified, 28 compounds had a strong inhibitory effect on α-amylase. Molecular docking screening confirmed the inhibition of these compounds and evaluated the molecular interactions between α-amylase and 30 active compounds, which strongly supported the experimental results. Among the evaluated compounds, onjisaponin R (83) and polygalaxanthone III (11) have the strongest inhibitory activity to α-amylase (the binding energies were -9.639 and -8.972 kcal/mol, respectively) and are potential lead compounds against diabetes.

This study proved the feasibility of using the existing platform to screen the active ingredients in PR extract, and provided a practical method for the rapid screening of potential anti-diabetic active ingredients in traditional Chinese medicine.