The ameliorative effect of ursolic acid on liver injury induced by rare earth neodymium oxide through the Nrf2/GPX4 signaling pathway

LIU Jiaxin; SHI Mengqi; GUO Tengfei; ZHAO Xue; YIN Duo; ZHANG Wenlong; GE Na; YUAN Yajing; GE Shuyu

doi:10.3969/j.issn.1006-5725.2026.03.005

Abstract：Objective To investigate the effect of ursolic acid on liver injury induced by neodymium oxide in rats based on the Nrf2/GPX4 signaling pathway and explore its underlying mechanism.Methods Sixty 6-week-old specific pathogen-free(SPF)grade Sprague-Dawley(SD)rats were randomly allocated into six groups(n=10 per group):a blank control group,a neodymium oxide model group,low-dose,medium-dose,and high-dose urso-lic acid groups,and a diammonium glycyrrhizinate group.After a 9-week intervention period,the rats were fasted for 12 hours with free access to water prior to sacrifice.Hepatic histopathology was examined using hematoxylin and eosin(HE)staining.Serum biochemical markers of liver function were assayed.The levels of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),tumor necrosis factor-α(TNF-α),inter-leukin-1β(IL-1β),and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay(ELISA).The Fe²⁺ content in the liver was determined through colorimetry.The protein expression levels of nuclear factor erythroid 2-related factor 2(Nrf2)and glutathione peroxidase 4(GPX4)in liver tissue were measured by Western blotting.Results In comparison with the normal control group,the model group exhibited fatty vacuoles of varying sizes and extensive infiltration of inflammatory cells in the liver tissue.The activities of serum alanine aminotrans-ferase(ALT)and aspartate aminotransferase(AST),the levels of malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and the content of Fe²⁺ were significantly elevated(P<0.05),whereas the levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and interleukin-10(IL-10)were significantly decreased(P<0.05).After the intervention of ursolic acid,hepatic steatosis was remarkably improved,and the infiltration of inflammatory cells was reduced.The activities of serum ALT and AST,the levels of MDA,TNF-α,IL-1β,and the content of Fe²⁺ were significantly decreased(P<0.05),while the levels of SOD,GSH-Px,and IL-10 were significantly increased(P<0.05).Western blot results indicated that,when compared with the normal control group,the protein expression of nuclear factor erythroid 2-related factor 2(Nrf2)and glutathione peroxidase 4(GPX4)in the liver of the model group was significantly reduced(P<0.05).Never-theless,after the intervention of ursolic acid,the expression of Nrf2 and GPX4 proteins was significantly increased(P<0.05).Conclusion Ursolic acid exerts a protective effect against neodymium oxide-induced liver injury in rats.Its mechanism may be associated with the regulation of the Nrf2/GPX4 signaling pathway,which can reduce the inflammatory response,alleviate oxidative stress,and consequently inhibit ferroptosis.