The structure modification with glucosamine of glycyrrhetinic acid extracted from Glycyrrhiza uralensis Fisch offal and mechanism of action based on network pharmacology and molecular docking against type II diabetes.

In order to improve the solubility and hypoglycemic activity of glycyrrhetinic acid (GA), the active mechanism of action of new compounds was explored. A novel 2-(N-3-acetylglycyrrhetinoyl)-N-glucopyranosyl-2-acetamide (compound 9) was synthesized by adding glucosamine (GlcN) to the C-30 carboxyl group of GA, and the hypoglycemic activity mechanism of compound 9 was explored by network pharmacology and molecular docking. The results showed that the solubility of compound 9 was better than GA, and the α-glucosidase inhibitory effect of compound 9 (IC50 = 0.160 mmol/L) was better than GA (IC50 = 0.381 mmol/L). The HepG2 insulin resistance (HepG2-IR) model found that glucose consumption in insulin-resistant cells can increase with the help of GA and compound 9. Network pharmacology screened 268 targets of compound 9 and disease. The core genes in the protein interaction network are epidermal growth factor receptor (EGFR), phosphokinase (SRC), MAPK1, MMP2, mmp9, etc., which are involved in prostate cancer, blood lipid and atherosclerosis, peroxisome proliferation activation receptor (PPAR) signaling pathway, Th17 cell differentiation and other pathways.