New quinolone alkaloids from Euodia Fruit, and their pancreatic lipase inhibitory and PPAR-γ ligand-binding activities.

Euodia Fruit is a crude drug used to treat migraine and headaches and is well-known to contain indole alkaloids, which may contribute to the observed pharmacological activities. A methanolic extract of Euodia Fruit exhibited pancreatic lipase inhibitory activity (IC 13.9 mg/mL). Bioassay-guided fractionation of the extract led to the isolation of 14 quinolone alkaloids (1-14), three indole alkaloids: rutaecarpine (15), evodiamine (16), and dehydroevodiamine (17), and a limonoid: rutaevine acetate (18), among which three quinolone alkaloids (12-14) have been previously undescribed. The structures of 12-14 were determined by extensive spectroscopic analyses, including two-dimensional (2D) NMR. Compounds 2, 3, 6-9, 13, and 14 exhibited pancreatic lipase inhibitory activity, with IC values ranging from 1.40 to 7.37 mM. The results revealed that the length of the aliphatic side chain and the presence of an olefinic bond at the C-2 side chain of the quinolone alkaloids could impact lipase inhibitory activity. In soybean oil-loaded mice, orally administered evocarpine (8) reduced serum triglyceride levels in a dose-dependent manner. Furthermore, 8-14 at 5.0 and 50 μM exhibited peroxisome proliferator-activated receptor (PPAR)-γ ligand-binding activity.