Cryptotanshinone induces apoptosis of activated hepatic stellate cells via modulating endoplasmic reticulum stress  

作　　者：Xiao-Xue Hou Yu-Wen Li Jia-Li Song Wen Zhang Rui Liu Hui Yuan Tian-Tong Feng Zheng-Yi Jiang Wen-Ting Li Chuan-Long Zhu 

机构地区：[1]Department of Infectious Disease,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210009,Jiangsu Province,China [2]Department of Pediatrics,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210009,Jiangsu Province,China [3]Department of Infectious and Tropical Diseases,The Second Affiliated Hospital of Hainan Medical University,Haikou 570000,Hainan Province,China

出　　处：《World Journal of Gastroenterology》2023年第17期2616-2627,共12页世界胃肠病学杂志（英文版）

基　　金：Science and Technology Plan of Hainan Province(Clinical Research Center),No.LCYX202103 and No.LCYX202204;Hainan Province Science and Technology Special Fund,No.ZDYF2022SHFZ067;Hainan Province Clinical Medical Center.

摘　　要：BACKGROUND Cryptotanshinone(CPT)has wide biological functions,including anti-oxidative,antifibrosis,and anti-inflammatory properties.However,the effect of CPT on hepatic fibrosis is unknown.AIM To investigate the effects of CPT treatment on hepatic fibrosis and its underlying mechanism of action.METHODS Hepatic stellate cells(HSCs)and normal hepatocytes were treated with different concentrations of CPT and salubrinal.The CCK-8 assay was used to determine cell viability.Flow cytometry was used to measure apoptosis and cell cycle arrest.Reverse transcription polymerase chain reaction(RT-PCR)and Western blot analyses were used to measure mRNA levels and protein expression of endoplasmic reticulum stress(ERS)signaling pathway related molecules,respectively.Carbon tetrachloride(CCL4)was used to induce in vivo hepatic fibrosis in mice.Mice were treated with CPT and salubrinal,and blood and liver samples were collected for histopathological examination.RESULTS We found that CPT treatment significantly reduced fibrogenesis by modulating the synthesis and degradation of the extracellular matrix in vitro.CPT inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in cultured HSCs.Furthermore,we found that CPT promoted apoptosis of activated HSCs by upregulating expression of ERS markers(CHOP and GRP78)and activating ERS pathway molecules(PERK,IRE1α,and ATF4),which were inhibited by salubrinal.Inhibition of ERS by salubrinal partially eliminated the therapeutic effect of CPT in our CCL4-induced hepatic fibrosis mouse model.CONCLUSION CPT can promote apoptosis of HSCs and alleviate hepatic fibrosis through modulating the ERS pathway,which represents a promising strategy for treating hepatic fibrosis.

关 键 词：Hepatic fibrosis Endoplasmic reticulum stress CRYPTOTANSHINONE Hepatic stellate cells APOPTOSIS 

分 类 号：R285[医药卫生—中药学]