Undescribed indole lactones from Alstonia scholaris protecting hepatic cell damage

Six previously undescribed rigidly monoterpenoid indole alkaloids, alstolactines F-K (1-6), were isolated from Alstonia scholaris. Among them, a pair of cage-like epimers, 1 and 2, featuring a rare 6/5/6/6/7 ring system, represent the first example of C5 -> C20-olide, while compound 3 possesses unique degraded C18 and C19. The structures of the isolates were established by multiple spectroscopic analyses, quantum computational chemistry methods, and X-ray diffraction. Furthermore, the expression levels of proteins including NLRP3, TLR4, P-p65, NF-kappa B, Notch-2, IL-18, P-p38, and p38 in LPS-induced human normal hepatocyte (LO2) cells could be signifi-cantly downregulated by compounds 1-6, which showed potent anti-inflammatory bioactivity.