Discovery of Enantiomeric Monoterpene-Coumarins with Neuroprotective Activities from the Rhizomes of Luvunga scandens.

Twenty-two new monoterpene-coumarins, comprising the initial disclosure of 11 enantiomeric pairings, were isolated from the rhizomes of Luvunga scandens with the aid of LC-MS/MS based on molecular networking. Luvunscandins A-G (1-7) are dihydrofurancoumarins with a furan ring connection, and luvunscandins H-K (8-11) are dihydrofurancoumarins connected through a pyran ring. Chemical structures and absolute configurations were determined by analysis of spectroscopic data and X-ray diffraction analysis. The neuroprotective effects of all the isolates on LPS-stimulated NO production in BV2 microglia were evaluated. Compounds 6a, 7a, 7b, 8b, 9a, 9b, 11a, and 11b demonstrated more potent inhibitory effects than the positive control PDTC. Structural-activity relationship analysis revealed that neuroprotective activity was primarily associated with pyran-type dihydrofurancoumarins or compounds bearing a C3'R,6'R configuration, whereas furan-type analogs or compounds with a C3'S,6'S configuration exhibited weak or no activity. (+)-Luvunscandin I (9a) showed the most significant inhibitory activity (IC50 = 4.9 ± 0.6 μg/mL) through suppression of the inflammatory transcription factors p65NF-κB and iNOS.