The diterpenoid esters from Euphorbia lathyris L. induce intestinal inflammation via LXRα/ABCA1-regulated lipid rafts and TLR4-mediated pathway  

作　　者：Hui-Nan Wang Xiao-Yu Wang Pei-Hua Wang Ming-Rui Jiang Si-Yuan Ma Hai-Ting Zhu Jun-Li Zhang Xin-Ning Zhang Wen-Jing Chen Yi-Fan Mao Hua Xu Ying-Zi Wang 

机构地区：[1]School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China.

出　　处：《Natural Therapy Advances》2024年第4期30-37,共8页

基　　金：supported by the National Natural Science Foundation of China(Grant no.82074021,82374040);the Beijing Nova Program(Grant no.20240484548).

摘　　要：Background:Diterpenoid esters are considered to be the main toxic components and bioactive constituents of Euphorbia lathyris L.(EL).Euphorbia factors L1(EF1),L2(EF2),and L3(EF3),the main diterpenoid esters of EL,have been found to cause intestinal diarrhea and induce intestinal inflammation in mice.This research aimed to explore the effects of major diterpenoid esters from EL on intestinal inflammation,as well as to clarify their possible targets and molecular mechanisms in vivo and vitro.Methods:Caco-2 cells and BALB/c mice were intervened with EFL1,EFL2,and EFL3,respectively.The expressions of TLR4,NLRP3,NF-κB p65,LXRα,ABCA1,TNF-αand IL-1βwere measured by Real-time PCR and ELISA.Cholesterol efflux levels were examined using cholesterol efflux kit.Flow cytometry was applied to detect lipid rafts abundance.Confocal microscopy was applied to investigate co-localization of lipid rafts and TLR4.Results:Our results revealed that EFL1,EFL2,and EFL3 inhibited LXRα,ABCA1 expression,and cholesterol efflux,promoted colocalization of TLR4 and lipid rafts,and up-regulated TLR4,NLRP3,NF-κB p65,TNF-αand IL-1βexpressions.Conclusion:These findings reveal that the mechanisms by which EFL1,EFL2,and EFL3 induce intestinal inflammation may be associated with LXRα/ABCA1-regulated lipid rafts and TLR4-mediated pathways.

关 键 词：diterpenoid esters Euphorbia lathyris L. LXRα/ABCA1 lipid rafts TLR4 

分 类 号：R284[医药卫生—中药学]