Prenylated flavonoids from Morus nigra and their insulin sensitizing activity

Abstract

Six undescribed prenylated flavonoids, nigragenons H-M, and four known compounds, were isolated from Morus nigra L. Their structures were elucidated through extensive analysis of spectroscopic data, and their absolute configurations were established by time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculation. The insulin sensitizing activities of all compounds were investigated using insulin-resistant 3T3-L1 adipocytes. At a high concentration (30 μM), all compounds except nigragenon I enhanced insulin-stimulated glucose uptake in insulin-resistant 3T3-L1 adipocytes. Furthermore, nigragenons J-L and the promoted adiponectin secretion in the model cells. Among them, nigragenon L showed the most potent effect at a low concentration of 10 μM, which was comparable to that of rosiglitazone at a concentration of 1 μM. Furthermore, using the Lantha Screen™ TR-FRET assay, nigragenon L was confirmed to be the ligand of PPARγ, showing potent binding affinity toward PPARγ with an IC₅₀ value of 2.8 μM.

Keywords: Adiponectin; Glucose uptake; Insulin-sensitizing activity; Moraceae; Morus nigra L.; PPARγ; Prenylated flavonoids.