Derivatives of glycyrrhetinic acid with amino acid: Modifications, structural characterization, hypoglycemic activity and mechanism

Abstract

Glycyrrhetinic acid (GA) is found in the roots and rhizomes of the legume licorice genus. The sweetness of GA is 250 times of sucrose. GA has a variety of biological activities. To develop new functional additive with hypoglycemic properties, the GA was modified with amino acids. The carboxyl group in C-30 of GA was modified with glycine, aspartic acid and arginine, respectively, to successfully prepare three amino acid amide derivatives of GA. The total yields of N-glycyrrhetinylglycine, N-glycyrrhetinyl aspartic acid and N-glycyrrhetinylarginine were 43.60%, 39.33% and 35.10%, respectively. The modification of C-30 of GA was modified with amino acid can significantly reduce the logP value and promote the hydrophilicity of GA. The N-glycyrrhetinylarginine had effective inhibition on α-glucosidase and is superior to GA. The inhibition on α-glucosidase by GA and N-Glycyrrhetinyl amino acid were reversible and mixed type. The GA and N-glycyrrhetinylarginine can effectively increase glucose consumption and glycogen synthesis to regulate insulin resistance. The GA and N-glycyrrhetinylarginine can regulate the insulin resistance in HepG2-IR cells via PI3K/Akt signaling pathway.