Ginkgolide B alleviates dry eye in a Sjögren syndrome mouse model

Sjögren syndrome is an autoimmune disease characterized by inflammation of the exocrine glands, leading to dry eye disease. Current treatments have limited efficacy, indicating the need for novel therapeutic strategies. We aimed to investigate the therapeutic potential of ginkgolide B (GB) using a mouse model of Sjögren syndrome and explored the underlying molecular mechanisms. Female MRL/lpr mice were treated with 0.05% GB, 0.05% cyclosporine A (CsA), or saline for 3 weeks. Treatment efficacy was evaluated by assessing tear secretion, ocular surface inflammation, and histological analysis of the cornea and lacrimal gland. Mechanistically, mRNA expression levels of immune-regulated genes, including Il-4, Il-8, Tlr4, Nos2, Mmp9, Muc5ac, Tnf, Ifng, Il-1β, and Il-6 in the lacrimal glands were also determined. Our results demonstrated that GB treatment significantly alleviated dry eye disease symptoms by increasing tear secretion and reducing ocular surface inflammation. Histological analyses revealed that GB protected both the corneal epithelium and lacrimal gland from pathological changes. RT-PCR results showed a significant downregulation of nine inflammation-related molecules ( Il-4, Il-8, Tlr4, Nos2, Muc5ac, Tnf, Ifng, Il-1β and Il-6 ), and upregulation of Mmp9 following GB treatment. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified IL-17 signalling pathway as the most enriched pathway. These findings suggest that GB effectively alleviates dry eye symptoms and may serve as a promising alternative to current treatments, possibly through modulation of IL-17 signalling pathway. Graphical abstract