Influence of the pK_a value on the antioxidant activity of licorice flavonoids under solvent‐mediated effects

Abstract

Licorice flavonoids (LCFs) have been widely used in food care and medical treatment due to their significant antioxidant activities. However, the molecular mechanism of their antioxidant activity remains unclear. Therefore, network pharmacology, ADMET, density functional theory (DFT), molecular docking, and molecular dynamics (MD) simulation were employed to explore the molecular mechanism of the antioxidant effects of LCF. The network pharmacology and ADMET studies showed that the active molecules of kumatakenin (pK a = 6.18), licoflavonol (pK a = 6.86), and topazolin (pK a = 6.21) in LCF are key antioxidant components and have good biosafety. Molecular docking and MD simulation studies demonstrated that active molecules interacted with amino acid residues in target proteins to form stable protein-ligand complexes and exert their antioxidant effects. DFT studies showed that the antioxidant activity of LCF could be significantly modulated under the solvent-mediated effect. In addition, based on the derivation of the Henderson-Hasselbalch and van't Hoff formulas, the functional relationships between the reaction-free energy (ΔG) of LCF and the pH and pK a values were established. The results showed that active molecules with larger pK a values will be more conducive to the improvement of their antioxidant activity under solventmediated effects. In conclusion, this study found that increasing the pK a value of LCF would be an effective strategy to improve their antioxidant activity under the effect of solvent mediation. The pK a value of an LCF will be a direct standard to evaluate its solvent-mediated antioxidant activity. This study will provide theoretical guidance for the development of natural antioxidants.

The King of Chinese Medicine——Glycyrrhiza glabra (Licorice): All-round Inquiry in its Chemical Composition, Pharmacodynamics, Traditional and Medicinal Value

“…GA is the aglycone of glycyrrhizic acid, and a study by Agarwal et al [39] demonstrated that glycyrrhizic acid was able to attenuate oxidative stress damage induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin. Licorice flavonoids also exhibit significant antioxidant activity [40,41] . Zeng et al [42] investigated the protective effect of licorice flavonoids against kainate (KA)-induced seizures in mice and found that treatment with licorice flavonoids after seizures reduced KA-induced SOD activity and malondialdehyde (MDA) content on the seventh as well as 28th day, indicating that licorice flavonoids have a protective effect against epilepsy-induced neuronal cell death and cognitive deficits, probably through their antioxidant effects.…”

Computational Chemistry Strategies to Investigate the Antioxidant Activity of Flavonoids—An Overview

“…Nevertheless, there are some studies showing the opposite. For example, Yi Hu et al found that for licorice flavonoids, a higher pK a value correlated with a higher solvent-mediated antioxidant activity [ 64 ]. Apparently, we have not yet found a clear-cut relationship between pK a and free radical scavenging ability, and this is the subject of ongoing research.…”

Investigation of the preparation, characterization, and whitening activity of co-amorphous glabridin and oxymatrine

“…RDF is a probability density distribution of finding another particle at a distance r in a system composed of atoms, molecules, or ions, which describes the density distribution of surrounding atoms or molecules at a distance r and can be used to describe the interaction between atoms, molecules, or ions in solids, liquids, or gases. [57][58][59] Generally, when the peak of g(r) is less than 3.5 Å, it indicates that hydrogen bonds are formed between molecules. 44 As shown in Fig.…”

“…1a), a natural flavonoid extracted from the root of licorice, has a variety of biological activities. 26,27 Firstly, it can be used as a sweetener and is widely used to sweeten foods and drugs. 28 Secondly, it has anti-inflammatory, 29 antioxidant, 30 and other effects, and has been used to treat AIDS 31 and other diseases.…”