Eudesmane-guaiane sesquiterpenoid dimers from Aucklandia cos-tus trigger paraptosis-like cell death via ROS accumulation and MAPK hyperactivation
10.1016/S1875-5364(24)60592-3
- Author:
Longgao XIAO
1
;
Yueqin ZHAO
;
Xiao DING
;
Hui LIU
;
Guangyu ZHU
;
Yanxi LI
;
Huan YAN
;
Xin FANG
;
Yuhan ZHAO
;
Haiyang LIU
Author Information
1. State Key Laboratory of Phytochemistry and Plant Resources in West China,and Yunnan Key Laboratory of Natural Medicinal Chemistry,Kunming Institute of Botany,Chinese Academy of Sciences,Kunming 650201,China;University of Chinese Academy of Sciences,Beijing 100049,China
- Keywords:
Aucklandia costus;
Sesquiterpenoid heterodimers;
Auckcostusolides A-C;
Paraptosis;
MAPK signaling pathway
- From:
Chinese Journal of Natural Medicines (English Ed.)
2024;22(11):1011-1019
- CountryChina
- Language:Chinese
-
Abstract:
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.
