FBMN/HPLC-PDA guided isolation of sesquiterpene coumarins from Ferula bungeana

Sesquiterpene coumarins (SCs) represent a group of bioactive natural compounds known for their potential anti-neuroinflammatory, antioxidative, and anticancer activities. To efficiently identify new compounds in this class, we utilized an integrated approach that combines feature-based molecular networking (FBMN) and photodiode array detection (PDA), guided by screening Ferula species known to be rich in SCs. The study isolated 21 SCs and 13 additional compounds from Ferula bungean a Kitagawa. These included three new SCs, namely ferubungeanol I, ferubungeanol J, and ferubungeanol K ( 1-3 ), two undescribed phenylpropionic acid derivatives, bungeanol A ( 25 ) and bungeanol B ( 26 ), and one undescribed eudesmane-type sesquiterpene bungeanol C ( 27 ). Structural identification was accomplished using a combination of high-resolution-electrospray ionization mass spectrometry (HR-ESI MS), nuclear magnetic resonance (1D/2D NMR), and Electronic Circular Dichroism (ECD) spectral comparison. Compounds 1-3 , 8 , 9 , 12 , 13 , 17 , 25 , 28 , and 34 demonstrated significant anti-neuroinflammatory effects by effectively reducing NO production in lipopolysaccharide (LPS)-induced BV2 cells, with IC 50 values ranging from 0.65 to 25.18 μM. These findings underscore the efficacy of the FBMN and PDA-guided isolation approach for discovering bioactive sesquiterpene coumarins from F. bungeana .