Lutein-naringin combination inhibits APAP liver injury by inhibiting endoplasmic reticulum stress mediated by SPHK1
10.16303/j.cnki.1005-4545.2025.10.23
- VernacularTitle:木犀草素-柚皮素组合通过抑制SPHK1介导的内质网应激抗APAP肝损伤
- Author:
Huimin LIU
1
;
Yangyang PAN
1
;
Sisi PU
1
;
Jianhui ZHANG
1
;
Qian ZHANG
1
;
Libin WANG
1
;
Liang LI
1
;
Zhiyong ZHANG
1
;
Meng WANG
1
Author Information
1. 甘肃农业大学动物医学院,甘肃兰州 730070
- Publication Type:Journal Article
- Keywords:
luteolin-naringin;
acetaminophen liver injury;
oxidative stress;
SPHK1;
endoplasmic re-ticulum stress;
mice
- From:
Chinese Journal of Veterinary Science
2025;45(10):2273-2281
- CountryChina
- Language:Chinese
-
Abstract:
This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.
