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

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

  • Eur J Pharmacol. 2025 Dec 15:1009:178387. doi: 10.1016/j.ejphar.2025.178387.
Lihua Chen 1,  Xueping Wei 2,  Zhuo Zhang 2,  Yuxin Lu 1,  Long Shuang Huang 3,  Haijiang Zhang 4
Affiliations

Affiliations

  • 1 The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, China; The Department of Ophthalmology, Yichang Central People's Hospital, Yichang, 443003, China.
  • 2 Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai, China.
  • 3 Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai, China. Electronic address: [email protected].
  • 4 The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, China; The Department of Ophthalmology, Yichang Central People's Hospital, Yichang, 443003, China. Electronic address: [email protected].
PMID: 41271148 DOI: 10.1016/j.ejphar.2025.178387
Abstract

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.

Keywords

Dry eye disease; Inflammation; Macrophage; NF-κB; Rosarin.

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