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
,
2
;
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
2. 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.
