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 (IC 50 = 4.9 ± 0.6 μg/mL) through suppression of the inflammatory transcription factors p65NF-κB and iNOS.