Prenylated flavonoids from Morus nigra and their insulin sensitizing activity

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. Six undescribed prenylated flavonoids, including nigragenons H–J with unusual prenylations at C-3, were isolated from the stems of Morus nigra L. Nigragenon L improved insulin resistant and showed potent binding affinity for PPARγ. [Display omitted] •Six undescribed prenylated flavonoids were isolated from Morus nigra.•Nigragenons H-J possessed unprecedent prenylations at C-3.•Nigragenon L improved insulin resistance and showed binding affinity for PPARγ.