浙江大学学报（医学版）2025，Vol.54Issue(3)：307-317,11.DOI:10.3724/zdxbyxb-2024-0381
牡荆素-4"-O-葡萄糖苷对对乙酰氨基酚诱导急性肝损伤有改善作用
Vitexin-4"-O-glucoside alleviates acetaminophen-induced acute liver injury
摘要
Abstract
Objective:To explore the protective effect of vitexin-4"-O-glucoside(VOG)against acetaminophen-induced acute liver injury in mice and its underlying mechanism.Methods:C57BL/6 mice were randomly divided into 4 groups:normal control group,model control group,low-dose group of VOG(30 mg/kg),and high-dose group of VOG(60 mg/kg).Acute liver injury was induced by intraperitoneal injection of acetaminophen(500 mg/kg).VOG was administrated by gavage 2 h before acetaminophen treatment in VOG groups.The protective effect of VOG against acute liver injury was evaluated by detecting alanine transaminase(ALT),aspartate transaminase(AST)levels and hematoxylin and eosin staining.The malondialdehyde(MDA)content,superoxide dismutase(SOD)and catalase(CAT)activity in liver were detected to evaluate the hepatic oxidative stress.The expression levels of tumor necrosis factor(TNF)-α,Il-1β,and Il-6 in liver were detected by quantitative reverse transcription polymerase chain reaction(qRT-PCR).The expression levels of phosphorylated c-jun N-terminal kinase(JNK)/JNK,phosphorylated p38/p38,inositol-requiring enzyme 1 alpha(IRE-1α),X-box binding protein 1s(XBP1s),and glucose-regulated protein 78(GRP78)in liver were detected by Western blotting.An endoplasmic reticulum stress model was established in AML-12 cells using tunicamycin.Cell viability was assessed using the CCK-8 assay,and the degree of cell damage was detected by lactate dehydrogenase(LDH)assay.The gene expression levels of Ire-1α,Xbp1s,and Grp78 in the cells were detected using qRT-PCR.Results:In the animal experiments,compared with the model control group,VOG significantly improved plasma ALT and AST levels,liver MDA content,as well as SOD and CAT activities.VOG also reduced the expression levels of Tnf-α,Il-1β,and Il-6 in the liver,and improved protein phosphorylation levels of JNK and p38,as well as the protein expression levels of IRE-1α,XBP1s,and GRP78.In cell experiments,VOG pretreatment enhanced cell viability,reduced LDH release and decreased the mRNA expression of Ire-1α,Xbp1s,and Grp78.Conclusions:VOG can suppress inflammation and oxidative stress,and alleviate acetaminophen-induced acute liver injury in mice by suppressing endoplasmic reticulum stress and modulating the MAPK signaling pathway.关键词
牡荆素-4"-O-葡萄糖苷/对乙酰氨基酚/急性肝损伤/内质网应激/丝裂原活化蛋白激酶信号通路/氧化应激/炎症/小鼠Key words
Vitexin-4"-O-glucoside/Acetaminophen/Acute liver injury/Endoplasmic reticulum stress/Mitogen-activated protein kinase signaling pathway/Oxidative stress/Inflammation/Mice分类
医药卫生引用本文复制引用
董凡,赖尚磊,邱剑楠,窦晓兵..牡荆素-4"-O-葡萄糖苷对对乙酰氨基酚诱导急性肝损伤有改善作用[J].浙江大学学报（医学版）,2025,54(3):307-317,11.基金项目
国家自然科学基金(82374102) （82374102）
浙江省自然科学基金(MS25H270057) （MS25H270057）
浙江省博士后科研项目(ZJ2024067) The study was supported by the National Natural Science Foundation of China(82374102),Natural Science Foundation of Zhejiang Province(MS25H270057),and Zhejiang Provincial Postdoctoral Research Project(ZJ2024067) （ZJ2024067）
