Eudesmane-guaiane sesquiterpenoid dimers from Aucklandia cos-tus trigger paraptosis-like cell death via ROS accumulation and MAPK hyperactivation  

作　　者：XIAO Longgao ZHAO Yueqin DING Xiao LIU Hui ZHU Guangyu LI Yanxi YAN Huan FANG Xin ZHAO Yuhan LIU Haiyang 

机构地区：[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 [3]Yunnan Characteristic Plant Extraction Laboratory,Kunming 650106,China

出　　处：《Chinese Journal of Natural Medicines》2024年第11期1011-1019,共9页中国天然药物（英文版）

基　　金：supported by Yunnan RevitalizationTalentSupport Program“Top Team”Project(No.202305AT350001);“Young Talent”Project(No.YNQR-QNRC-2019-091);the National Natural Science Foundation of China(Nos.32170408,32000280,and 32000548);the Ten Thousand Talents Plan of Yunnan Province for Industrial Technology Leading Talents(No.YNWR-CYJS-2019-011);the Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform(No.2022YKZY001);the CAS Pioneer Hundred Talents Program,the Training of Technological Innovation Talents of Yunnan Province(No.202305AD160009);the Special Research Assistant of Chinese Academy of Sciences(No.E3292211Q1);the Young Academic and Technical Leader Raising Foundation of Yunnan Province(No.202005AC160035).

摘　　要：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.

关 键 词：Aucklandia costus Sesquiterpenoid heterodimers Auckcostusolides A-CParaptosis MAPK signaling pathway 

分 类 号：R965[医药卫生—药理学] R917[医药卫生—药学]