1.Eudesmane-guaiane sesquiterpenoid dimers from Aucklandia cos-tus trigger paraptosis-like cell death via ROS accumulation and MAPK hyperactivation
Longgao XIAO ; Yueqin ZHAO ; Xiao DING ; Hui LIU ; Guangyu ZHU ; Yanxi LI ; Huan YAN ; Xin FANG ; Yuhan ZHAO ; Haiyang LIU
Chinese Journal of Natural Medicines (English Ed.) 2024;22(11):1011-1019
Three novel sesquiterpenoid heterodimers,designated as auckcostusolides A-C(1-3),were isolated from Aucklandia costus leaves.The structures of compounds 1-3 were elucidated through comprehensive spectroscopic analysis,with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism(ECD)calculations.Notably,compounds 1 and 2,despite sharing identical planar structures derived from two identical sesquiterpenoids,exhibited oppos-ite configurations at C-11 and C-8'.This configurational difference can be attributed to distinct Diels-Alder cycloaddition processes between the sesquiterpenoid monomers.Additionally,the cytotoxic effects of compounds 1-3 were evaluated against colorectal can-cer HCT116 cells,fibrosarcoma HT1080 cells,and hepatocellular carcinoma HepG2 cells.Compounds 1-3 induced cell death was characterized by endoplasmic reticulum(ER)swelling and cytoplasmic vacuolization,typical morphological changes associated with paraptosis.Mechanistic studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of react-ive oxygen species(ROS),activation of ER stress,and stimulation of the MAPK signaling pathway.
Result Analysis
Print
Save
E-mail