Mechanism of β-sitosterol regulating the PON1/Caspase-3 pathway to alleviate sodium iodate-induced retinal injury
10.3980/j.issn.1672-5123.2025.11.03
- VernacularTitle:β-谷甾醇调控PON1/Caspase-3通路减轻碘酸钠诱导视网膜损伤的机制研究
- Author:
Xiaoli LI
1
;
Wei WANG
1
;
Juan LI
1
;
Zhaoxia ZHAO
1
Author Information
1. Aier Eye Hospital Affiliated to Henan University;Zhengzhou Aier Eye Hospital, Zhengzhou 450000, Henan Province, China
- Publication Type:Journal Article
- Keywords:
age-related macular degeneration;
β-sitosterol;
PON1;
apoptosis
- From:
International Eye Science
2025;25(11):1728-1734
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the protective effect of β-sitosterol on retinal structure and function and its underlying molecular mechanism in a sodium iodate(NaIO3)-induced mouse model of dry age-related macular degeneration(ARMD).METHODS: A dry ARMD mouse model was established by NaIO3 injection. The therapeutic effect of β-sitosterol intervention was evaluated using fundus photography, histopathology(HE staining), and electroretinography(ERG). Network pharmacology was employed to screen potential targets of β-sitosterol in ARMD, and molecular docking was used to validate the binding ability between β-sitosterol and these targets. The impact of β-sitosterol on ARPE-19 cell viability and apoptosis pathways was analyzed using CCK-8 assay, Hoechst staining, and Western blotting.RESULTS: The β-sitosterol significantly alleviated structural damage in the retinas of model mice(increased retinal and outer nuclear layer thickness, reduced yellowish-white drusen-like deposits)and functional impairment(partial restoration of a-wave and b-wave amplitudes). Network pharmacology identified PON1 as a key target of β-sitosterol; molecular docking demonstrated that β-sitosterol binds to PON1 via hydrophobic interactions and hydrogen bonds. In vitro experiments showed that β-sitosterol(10 μmol/L)significantly increased ARPE-19 cell viability(P<0.01), reduced apoptosis(P<0.01), upregulated PON1 expression(P<0.01), and concurrently suppressed cleaved-Caspase3 expression(P<0.01).CONCLUSION: The β-sitosterol likely protects against oxidative stress-induced retinal damage by modulating PON1 to suppress the Caspase3-dependent apoptotic pathway. These findings provide experimental evidence supporting the development of β-sitosterol as a novel therapeutic agent for dry ARMD.
