Alkaloids and Coumarins with Adiponectin-Secretion-Promoting Activities from the Leaves of Orixa japonica

Fractionation of a methanol extract of Orixa japonica leaves led to the identification of five new quinoline alkaloids (1, 2, 4, 8, and 9), three new coumarins (15, 17, and 19), and 20 known compounds. The structures were determined by analysis of 1D and 2D NMR spectroscopic data. The absolute configuration of 19 was proposed by electronic circular dichroism calculation. Among the compounds tested in the phenotypic screening to measure adiponectin secretion in human bone marrow mesenchymal stem cells, metabolites 4 and 12 stimulated adiponectin secretions with EC50 values of 13.8 and 25.8 μM, respectively. Further PPARγ binding assay and molecular modeling suggested that compounds 4 and 12 are selective PPARγ agonists.