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 (IC₅₀ 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 IC₅₀ 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.