Exploring the Therapeutic Effect and Mechanism of Luteolin on Experimental Autoimmune Uveitis Based on the Notch1/Jagged1/Hes1 Pathway

This study aimed to investigate the therapeutic effects of Lut (luteolin) on EAU (experimental autoimmune uveitis) and its impact on the Notch1/Jagged1/Hes1 signaling pathway. Rats were randomly divided into Control group (control group), Model group (model group), Lut-L, Lut-M, and Lut-H group (low-, medium-, and high-dose luteolin groups), as well as Lut-H+JFC group (high-dose luteolin plus Notch1 pathway activator group). Except for the Control group, EAU rat models were established in all other groups. After drug interven tion, ocular signs were observed and clinical scores were assessed using a slit-lamp microscope; histopathological changes in the eyeball were examined via HE staining; RT-qPCR was performed to measure the mRNA expression levels of IL-10, IL-17A, TNF-α, Arg1, iNOS, and IFN-γ in retinal tissues; the proportions of Treg and Th17 cells in the spleen were detected by flow cytometry; immunohistochemistry was used to evaluate the positive expression of Iba-1, Occludin, and Claudin-1 in ocular tissues; and Western blot was applied to determine the protein expression levels of the Notch1/Jagged1/Hes1 pathway in retinal tissues. The study found that EAU rats exhibited conjunctival vascular dilation, iris hyperemia, edema, and inflammatory damage in ocular tissues. The relative mRNA expression levels of IL-17A, TNF-α, iNOS, and IFN-γ in retinal tissues, the proportion of Th17 cells and the Th17/Treg ratio in the spleen, the positive expression of Iba-1, and the protein expression levels of the Notch1/Jagged1/Hes1 pathway were significantly increased (P<0.05). Conversely, the relative mRNA expression levels of Arg1 and IL-10, the pro portion of Treg cells in the spleen, and the positive expression of Occludin and Claudin-1 were decreased (P<0.05). Low-, medium-, and high-dose Lut administration ameliorated inflammatory damage in rat ocular tissues, reduced the relative mRNA expression levels of IL-17A, TNF-α, iNOS, and IFN-γ in retinal tissues, lowered the proportion of Th17 cells and the Th17/Treg ratio in the spleen, decreased the positive expression of Iba-1 and the protein ex pression levels of the Notch1/Jagged1/Hes1 pathway, and increased the relative mRNA expression levels of Arg1 and IL-10, elevated the proportion of Treg cells in the spleen, and enhanced the positive expression of Occludin and Claudin-1 (P<0.05). Compared with the Lut-H group, the Lut-H+JFC group showed aggravated inflammatory damage in ocular tissues, a higher proportion of Th17 cells and an increased Th17/Treg ratio in the spleen, polarization of microg lia toward the M1 phenotype, disruption of the blood-retinal barrier, and enhanced activity of the Notch1/Jagged1/Hes1 pathway (P<0.05). Based on the comprehensive results, Lut may alleviate inflammatory responses in the ocular tis sues of EAU rats, enhance the protective function of the blood-retinal barrier, and regulate immune homeostasis by modulating the Notch1/Jagged1/Hes1 signaling pathway.

CSTR: 32200.14.cjcb.2026.03.0012