Study on the mechanism of<italic style="font-style: italic"> Euphorbia hirta </italic>L.-derived exosome-like nanovesicles regulating Nrf2/HO-1/NQO1 pathway to improve acetaminophen-induced liver injury

WANG Yanyu; CHEN Lei; LIU Renjie; XIANG Shijian; ZHOU Benjie

doi:10.6039/j.issn.1001-0408.2026.09.05

您当前的位置：

首页 >

文章列表页 >

Study on the mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles regulating Nrf2/HO-1/NQO1 pathway to improve acetaminophen-induced liver injury

更新时间：2026-05-14

- Study on the mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles regulating Nrf2/HO-1/NQO1 pathway to improve acetaminophen-induced liver injury
- ZHONGGUO YAOFANG Vol. 37, Issue 9, Pages: 1134-1140(2026)
- 作者机构：
  
  1.中山大学药学院（深圳），广东深圳;518107
  2.中山大学附属第七医院药学部，广东深圳　518107
  3.深圳市中药活性物质筛选与转化重点实验室，广东深圳　518107
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2026.09.05
  CLC： R965;R285
- Received：04 March 2026，
  
  Revised：2026-04-28，
  
  Accepted：28 April 2026，
  
  Published：15 May 2026
- 稿件说明：
移动端阅览
王炎玉,陈磊,刘仁杰,等.大飞扬草外泌体纳米囊泡调控Nrf2/HO-1/NQO1通路改善对乙酰氨基酚诱导肝损伤的机制研究 [J].中国药房,2026,37(09):1134-1140.

WANG Yanyu,CHEN Lei,LIU Renjie,et al.Study on the mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles regulating Nrf2/HO-1/NQO1 pathway to improve acetaminophen-induced liver injury[J].ZHONGGUO YAOFANG,2026,37(09):1134-1140.
王炎玉,陈磊,刘仁杰,等.大飞扬草外泌体纳米囊泡调控Nrf2/HO-1/NQO1通路改善对乙酰氨基酚诱导肝损伤的机制研究 [J].中国药房,2026,37(09):1134-1140. DOI： 10.6039/j.issn.1001-0408.2026.09.05.

WANG Yanyu,CHEN Lei,LIU Renjie,et al.Study on the mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles regulating Nrf2/HO-1/NQO1 pathway to improve acetaminophen-induced liver injury[J].ZHONGGUO YAOFANG,2026,37(09):1134-1140. DOI： 10.6039/j.issn.1001-0408.2026.09.05.

摘要

目的

基于核因子E

相关因子（Nrf2）/血红素加氧酶1（HO-1）/醌氧化还原酶1（NQO1）通路，探讨大飞扬草外泌体纳米囊泡（Eh-ENVs）对对乙酰氨基酚（APAP）诱导肝损伤的改善作用及机制。

方法

通过考察Eh-ENVs对RAW264.7和AML12细胞活力的影响，以及对正常小鼠血清肝、肾功能指标和肝、肺等组织病理形态学的影响，评价其安全性。构建脂多糖（1 μg/mL）诱导的RAW264.7细胞炎症模型，考察10、20 μg/mL Eh-ENVs对模型细胞中炎症因子mRNA表达和活性氧（ROS）水平的影响，并考察RAW264.7细胞对Eh-ENVs的摄取效率。构建APAP诱导的肝损伤小鼠模型，考察4 mg/kg Eh-ENVs对模型小鼠血清肝功能指标，肝组织病理形态学，肝组织中炎症因子mRNA表达、丙二醛（MDA）水平、超氧化物歧化酶（SOD）水平以及Nrf2/HO-1/NQO1通路相关mRNA及其蛋白表达的影响。

结果

体外实验结果显示，Eh-ENVs对RAW264.7和AML12细胞均无增殖抑制作用；Eh-ENVs可被RAW264.7细胞高效摄取，并能显著降低细胞中白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）mRNA表达和ROS水平（

＜0.05）。体内实验结果显示，4 mg/kg Eh-ENVs对正常小鼠无明显毒副作用；可显著降低模型小鼠血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平（

＜0.05），上调/升高肝组织中IL-10 mRNA以及Nrf2、HO-1、NQO1 mRNA及其蛋白表达和SOD水平（

＜0.05），下调/降低肝组织中TNF-α、IL-1β mRNA表达和MDA水平（

＜0.05）。

结论

Eh-ENVs可能通过激活Nrf2/HO-1/NQO1通路，抑制炎症反应并减轻氧化应激，进而改善APAP诱导的肝损伤。

Abstract

OBJECTIVE

To investigate the ameliorative effect and mechanism of

Euphorbia hirta

L.-derived exosome-like nanovesicles（Eh-ENVs） on acetaminophen （APAP）-induced liver injury based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H：quinone oxidoreductase 1 （NQO1） pathway.

METHODS

The safety of Eh-ENVs was evaluated by examining their effects on the viability of RAW264.7 and AML12 cells， as well as serum liver and kidney function indicators and histopathology of liver， lung， and other tissues in normal mice. A lipopolysaccharide （1 μg/mL）-induced RAW264.7 cell inflammation model was constructed to investigate the effects of 10 and 20 μg/mL Eh-ENVs on the mRNA expression of inflammatory factors and reactive oxygen species （ROS） level in model cells， and the uptake efficiency of Eh-ENVs by RAW264.7 cells was also examined. An APAP-induced liver injury mouse model was established to investigate the effects of 4 mg/kg Eh-ENVs on serum liver function indicators， liver histopathology， mRNA expression of inflammatory factors， malondialdehyde （MDA） level， superoxide dismutase （SOD） level， and mRNA and protein expressions related to the Nrf2/HO-1/NQO1 pathway in liver tissue of model mice.

RESULTS

In vitro

results showed that Eh-ENVs had no inhibitory effect on the proliferation of RAW264.7 and AML12 cells；Eh-ENVs could be efficiently taken up by RAW264.7 cells and significantly reduced the mRNA expression of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and ROS level in cells （

＜0.05）.

In vivo

results showed that 4 mg/kg Eh-ENVs had no obvious toxic side effects on normal mice，could significantly decrease the serum alanine transaminase （ALT） and aspartate transaminase （AST） levels in model mice （

＜0.05），upregulated/increased the mRNA expressions of IL-10， as well as the mRNA and protein expressions of Nrf2， HO-1， and NQO1， and SOD level in liver tissue （

＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （

＜0.05）.

CONCLUSIONS

Eh-ENVs may activate the Nrf2/HO-1/NQO1 pathway to inhibit inflammatory response and alleviate oxidative stress， thereby improving APAP-induced liver injury.

关键词

Keywords

references

马世武，刘成海，刘晓琰，等 . 中国药物性肝损伤诊治指南：2023年版 [J ] . 胃肠病学， 2023 ， 28 （ 7 ）： 397 - 431 .

SHEN T ， LIU Y ， SHANG J ， et al . Incidence and etiology of drug-induced liver injury in mainland China [J ] . Gastroenterology ， 2019 ， 156 （ 8 ）： 2230 - 2241.e11 .

CHILVERY S ， YELNE A ， KHURANA A ， et al . Ace- taminophen induced hepatotoxicity：an overview of the promising protective effects of natural products and herbal formulations [J ] . Phytomedicine ， 2023 ， 108 ： 154510 .

RAMACHANDRAN A ， AKAKPO J Y ， CURRY S C ， et al . Clinically relevant therapeutic approaches against acetaminophen hepatotoxicity and acute liver failure [J ] . Biochem Pharmacol ， 2024 ， 228 ： 116056 .

ALRASHED M ， ALYOUSEF A ， BADRELDIN H A ， et al . Comparison of three-bag method acetylcysteine versus two-bag method acetylcysteine for the treatment of acetaminophen toxicity：an updated systematic review and meta-analysis [J ] . Diseases ， 2024 ， 12 （ 12 ）： 332 .

JAESCHKE H ， RAMACHANDRAN A . Acetaminophen hepatotoxicity：paradigm for understanding mechanisms of drug-induced liver injury [J ] . Annu Rev Pathol ， 2024 ， 19 ： 453 - 478 .

YOUNIS N S ， ABDELNABY R M ， MOHAMED M E . Hepatoprotective effects of linalool against liver ischemia-reperfusion：the role of Nrf2/HO-1/NQO1 and TLR4/RAGE/NF-κB pathways [J ] . Eur Rev Med Pharmacol ， 2023 ， 27 （ 20 ）： 10094 - 10111 .

罗美美，朱星宇，胡乐涛，等 . 基于Nrf2/HO-1信号通路的中药有效成分缓解肝损伤研究进展 [J ] . 药物评价研究， 2024 ， 47 （ 7 ）： 1638 - 1644 .

庞玉新，张新蕊，于福来，等 . 大飞扬总黄酮提取工艺优化及抗氧化活性测定 [J ] . 广西植物， 2015 ， 35 （ 1 ）： 115 - 119 .

DAD H A ， GU T W ， ZHU A Q ， et al . Plant exosome-like nanovesicles：emerging therapeutics and drug delivery nanoplatforms [J ] . Mol Ther ， 2021 ， 29 （ 1 ）： 13 - 31 .

KUMAR J ， SHRIVASTAVA D M ， JORIYA A . Synergistic gastroprotective，hepatoprotective，and antioxidant activities of ethanolic leaf extracts of achyranthes aspera and euphorbia hirta：a comprehensive phytochemical and pharmacological study [J ] . Am J Psychiatr Rehabil ， 2025 ， 28 （ 2 ）： 120 - 130 .

吴嘉宇，张泓 . 虎杖来源外泌体的提取、纯化及鉴定技术 [J ] . 安徽医科大学学报， 2025 ， 60 （ 11 ）： 2076 - 2082 .

蔡秀萍 . 巴戟天纳米颗粒提取方法比较和对BV2细胞凋亡的影响 [D ] . 广州：广州中医药大学， 2021 .

JADEJA R N ， URRUNAGA N H ， DASH S ， et al . Withaferin：a reduces acetaminophen-induced liver injury in mice [J ] . Biochem Pharmacol ， 2015 ， 97 （ 1 ）： 122 - 132 .

QI H ， YANG L ， LI X ， et al . Exosomes separated based on the “STOP” criteria for tumor-targeted drug delivery [J ] . J Mater Chem B ， 2018 ， 6 （ 18 ）： 2758 - 2768 .

LI Q ， CHEN F ， WANG F . The immunological mechanisms and therapeutic potential in drug-induced liver injury：lessons learned from acetaminophen hepatotoxicity [J ] . Cell Biosci ， 2022 ， 12 ： 187 .

LI L ， LI X ， ZHANG F . The pivotal role of cytokines in liver disease pathogenesis and therapeutic potential [J ] . Frontiers Immunol ， 2025 ， 17 （ 16 ）： 1694582 .

CHAO S ， SHAN S ， LIU Z ， et al . Both TREM2-dependent macrophages and kupffer cells play a protective role in APAP-induced acute liver injury [J ] . Int Immunopharmacol ， 2024 ， 141 ： 112926 .

LIU W ， HUAN L ， ZHANG C ， et al . Amelioration of acetaminophen-induced hepatic oxidative stress and inflammation by RNAi targeting Cyp2e1 in vivo [J ] . Curr Issues in Mol Biol ， 2025 ， 47 （ 5 ）： 372 .

POLJŠAK B ， JAMNIK P ， MILISAV I . The importance of multifaceted approach for accurate and comprehensive evaluation of oxidative stress status in biological systems [J ] . Antioxidants （Basel）， 2025 ， 14 （ 9 ）： 1083 .

WEINBERG S E ， CHANDEL N S . Mitochondria reactive oxygen species signaling in immune responses [J ] . Immunity ， 2025 ， 58 （ 8 ）： 1904 - 1921 .

LADDHA A P ， WU H ， MANAUTOU J E . Deciphering acetaminophen-induced hepatotoxicity：the crucial role of transcription factors like nuclear factor erythroid 2-related factor 2 as genetic determinants of susceptibility to drug-induced liver injury [J ] . Drug Metab Dispos ， 2024 ， 52 （ 8 ）： 740 - 753 .

DONG Y ， JIA R ， JIANG Y ， et al . SMND-309 activates Nrf2 signaling to alleviate acetaminophen-induced hepatotoxicity and oxidative stress [J ] . PLoS One ， 2025 ， 20 （ 3 ）： e0310879 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effects of ω-3 polyunsaturated fatty acid combined with clomiphene on clinical efficacy， pregnancy and safety in patients with polycystic ovary syndrome

Research progress on the mechanism of traditional Chinese medicine regulating oxidative stress to promote diabetic wound healing

Effect of morin on alveolar bone resorption in periodontitis mice by regulating the SIRT1/PGC-1α/Nrf2 pathway

Protective effect and mechanism of chikusetsu saponin Ⅳa on the kidney in diabetic nephropathy rats

Research progress on the molecular mechanisms of traditional Chinese medicine monomers in ameliorating renal ischemia-reperfusion injury

Related Author

HU Hailing

ZHOU Qiongjiao

XIE Dan

CAI Yu

LU Chang

DANG Ying

WANG Lu

SHI Jianping

Related Institution

Dept. of Gynecology， Hunan Hospital of Integrated Traditional Chinese and Western Medicine

Dept. of Obstetrics and Gynecology， the Fourth Hospital of Changsha

Dept. of Obstetrics and Gynecology， Hunan Prevention and Treatment Institute for Occupational Diseases

Laboratory and Experimental Equipment Management Center， Inner Mongolia Medical University

Medical Simulation Center， Inner Mongolia Medical University

⁰

Study on the mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles regulating Nrf2/HO-1/NQO1 pathway to improve acetaminophen-induced liver injury

DOI：10.6039/j.issn.1001-0408.2026.09.05

摘要

Abstract

关键词

Keywords

references