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. 2025 May 25;54(3):307-317.
doi: 10.3724/zdxbyxb-2024-0381.

[Vitexin-4 ″- O-glucoside alleviates acetaminophen-induced acute liver injury]

[Article in Chinese]
Fan Dong  1 , Shanglei Lai  2 , Jiannan Qiu  3 , Xiaobing Dou  4
Affiliations

[Vitexin-4 ″- O-glucoside alleviates acetaminophen-induced acute liver injury]

[Article in Chinese]
Fan Dong et al. Zhejiang Da Xue Xue Bao Yi Xue Ban. .

Abstract
in English, Chinese

Objectives: 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.

目的: 研究牡荆素-4 ″-O-葡萄糖苷（VOG）对对乙酰氨基酚诱导的小鼠急性肝损伤的改善作用及潜在机制。方法: 将C57BL/6小鼠随机分为空白对照组、模型对照组、VOG小剂量组（VOG 30 mg/kg）和VOG大剂量组（VOG 60 mg/kg）。除空白对照组外，每组腹腔注射对乙酰氨基酚500 mg/kg建立急性肝损伤模型，VOG组在对乙酰氨基酚处理前两小时通过灌胃给予VOG。通过测定小鼠血浆中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）水平和苏木精-伊红染色评价肝损伤情况；测定小鼠肝组织中丙二醛含量、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性以评价肝氧化应激反应；定量逆转录聚合酶链反应（qRT-PCR）法检测小鼠肝组织肿瘤坏死因子-α（TNF-α）、Il-1β和Il-6的基因表达水平；蛋白质印迹法检测小鼠肝组织c-Jun氨基端激酶（JNK）、p38的蛋白磷酸化水平和肌醇需求酶1α（IRE-1α）、X盒结合蛋白1s（XBP1s）、葡萄糖调节蛋白78（GRP78）蛋白表达。在AML-12细胞上用衣霉素构建内质网应激模型，细胞计数试剂盒-8法检测细胞存活率，乳酸脱氢酶（LDH）法检测细胞损伤程度，并用qRT-PCR法检测细胞中Ire-1α、Xbp1s、Grp78的基因表达水平。结果: 动物实验结果显示，与模型对照组比较，VOG组显著改善小鼠血浆中ALT、AST含量和肝组织中丙二醛含量、SOD和CAT活性，降低肝组织中Tnf-α、Il-1β和Il-6基因表达，改善小鼠肝组织中JNK、p38的蛋白磷酸化水平和IRE-1α、XBP1s、GRP78蛋白表达。细胞实验结果显示，VOG预处理可提高细胞存活率、降低LDH释放量，降低细胞中Ire-1α、Xbp1s和Grp78的mRNA表达。结论: VOG可抑制炎症和氧化应激，通过抑制内质网应激和调控MAPK信号通路改善对乙酰氨基酚诱导的急性肝损伤。.

Keywords: Acetaminophen; Acute liver injury; Endoplasmic reticulum stress; Inflammation; Mice; Mitogen-activated protein kinase signaling pathway; Oxidative stress; Vitexin-4 ″- O-glucoside.

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Conflict of interest statement

所有作者均声明不存在利益冲突

The authors declare that there is no conflict of interests

Figures

图1
图1. 各组肝组织病理学结果（HE染色）
图2
图2. 各组肝组织中JNK和p38蛋白电泳图
图3
图3. 各组肝组织中内质网应激相关蛋白电泳图
See this image and copyright information in PMC

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