Study on the mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles regulating Nrf2/HO-1/NQO1 pathway to improve acetaminophen-induced liver injury
- VernacularTitle: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
- Author:
Yanyu WANG
1
;
Lei CHEN
2
;
Renjie LIU
1
;
Shijian XIANG
2
;
Benjie ZHOU
3
Author Information
1. School of Pharmaceutical Sciences （Shenzhen），Sun Yat-sen University，Guangdong Shenzhen 518107，China
2. Dept. of Pharmacy，the Seventh Affiliated Hospital of Sun Yat-sen University，Guangdong Shenzhen 518107，China;Shenzhen Key Laboratory for Screening and Transformation of Active Substances from Traditional Chinese Medicine，Guangdong Shenzhen 518107，China
3. School of Pharmaceutical Sciences （Shenzhen），Sun Yat-sen University，Guangdong Shenzhen 518107，China;Dept. of Pharmacy，the Seventh Affiliated Hospital of Sun Yat-sen University，Guangdong Shenzhen 518107，China
- Publication Type:Journal Article
- Keywords:
Euphorbia hirta L.;
exosome-like nanovesicles;
drug-induced liver injury;
oxidative stress;
Nrf2/HO-1/NQO1
- From:
China Pharmacy
2026;37(9):1134-1140
- CountryChina
- Language:Chinese
-
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 （ P ＜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 （ P ＜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 （ P ＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （ P ＜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.
