Four New Compounds From Lactuca indica That Inhibit Nitric Oxide Production.

Abstract

Nitric oxide (NO) is produced by both endothelial and neuronal cells and is involved in various biological processes, including vasodilation, neuromodulation, the immune response, and platelet aggregation. Excessive NO production can trigger the progression of pathological conditions, including inflammation and oxidative stress. Lactuca indica L. is a well-known oriental medicinal plant used to treat several inflammatory diseases. To clarify the active ingredients thereof, four new compounds, (7R,8S,11S)-ferulin 15-O-β-D-glucopyranoside (1), (2R,3R)-2,3-dihydro-2-ethyl-3-methylmaleimide N-β-D-glucopyranoside (2), 7S,7S,8R,8R-(-)-neo-olivil-4-O-β-D-glucopyranoside (3), and (1R,4S,7R,5E)-1,4-dihydroxy-germacra-5,10(14)-diene (4), and six known compounds (5-10) were isolated from the plant and their NO inhibitory activities evaluated. The chemical structures of the new compounds, including the absolute configurations, were fully determined via high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance, and both experimental and time-dependent density functional theory-calculated electronic circular dichroism spectra. The new compounds and the known sesquiterpenoids were chemically diverse, major components of L. indica extracts. Compounds 2 and 10 potentially inhibit NO production (half-maximal inhibitory concentration of 25.3 and 21.4 µM), suggesting that maleimide derivatives could serve as both therapeutic inhibitors and lead compounds for the discovery of anti-inflammatory agents.