Sanguinarine attenuates Aspergillus fumigatus keratitis by exerting antifungal and anti-inflammatory effects.

Abstract

Fungal keratitis (FK) is a severe infectious disease of the cornea that can cause significant visual impairment or even blindness. The poor prognosis of FK is primarily attributed to fungal invasion and excessive host inflammatory responses. Sanguinarine (SAN) is a natural quaternary benzophenanthridine alkaloid that exhibits potent anti-inflammatory and antimicrobial properties. However, its therapeutic potential in FK remains unclear. In this study, we initially evaluated the safety of various concentrations of SAN in human corneal epithelial cells (HCECs) and in mice. We demonstrated that SAN exerts both antifungal and anti-inflammatory effects during Aspergillus fumigatus (A. fumigatus) keratitis. SAN not only inhibited the germination of A. fumigatus spores and hyphal growth but also disrupted the integrity of the fungal cell wall and membrane. SAN suppressed biofilm formation and reduced the adhesion of fungal elements to HCECs. In the mouse model of A. fumigatus keratitis, SAN decreased the corneal fungal burden, reduced the recruitment of neutrophils and macrophages, and downregulated the mRNA and protein expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and C-C motif chemokine ligand 2 (CCL2). In addition, SAN exerted anti-inflammatory effects in HCECs by downregulating both mRNA and protein expression of the IL-6 and CCL2. In conclusion, SAN improves the prognosis of A. fumigatus keratitis by inhibiting fungal growth, disrupting hyphal morphology, reducing neutrophil and macrophage infiltration, and suppressing the expression of inflammatory mediators.