Rosarin alleviates dry eye disease via suppressing NF-κB signal mediated inflammation and M1 polarization in macrophage.

Local chronic inflammation is critical to the pathogenesis of dry eye disease (DED). Rosarin is a natural bioactive compound isolated from Rhodiola rosea L., which has shown significant antioxidant and neuroprotective properties in various preclinical researches. However, its role and mechanism of action in DED remains unclear. Thus, we aimed to investigate the protective role of Rosarin in a preclinical mouse model of DED, and to address the molecular mechanism of Rosarin in the regulation of inflammation and polarization in macrophages. The results showed that treatment using Rosarin increased tear production, mitigated corneal and conjunctival tissue disruption, suppressed phosphorylation of IκBα and NF-κB, and inhibited the expression of downstream inflammatory and macrophage M1 polarization marker genes (IL-1β, IL-6, TNF-α), CD86 and iNOS in Benzalkonium Chloride (BAC)-induced DED mice. By using network pharmacology screening, molecular docking and in vitro molecular biology studies we determined that Rosarin inhibited macrophage M1 polarization and inflammatory response by inhibiting NF-κB signals. In conclusion, Rosarin treatment alleviates BAC-induced DED in mice by inhibiting NF-κB mediated inflammation and M1 polarization in macrophages. Our findings not only provide a theoretical foundation for the clinical application of Rosarin but also open new avenues for targeted therapy of DED.