Licochalcone A Ameliorates Aspergillus fumigatus Keratitis by Reducing Fungal Load and Activating the Nrf2/HO-1 Signaling Pathway.

Fungal keratitis (FK) is a blinding corneal infectious disease. The prognosis is frequently unfavorable due to fungal invasion and an excessive host inflammatory response. Licochalcone A (Lico A) exhibits a broad spectrum of pharmacological activities, encompassing antifungal, anti-inflammatory, antioxidation, and antitumor properties. However, the role of Lico A has not yet been studied in FK. In this study, we discovered that Lico A could disrupt Aspergillus fumigatus ( A. fumigatus ) biofilms, inhibit fungal growth and adhesion to host cells, induce alterations of hyphal morphology, and impair the cell membrane and cell wall integrity and mitochondrial structure of A. fumigatus . Lico A can alleviate the severity of FK in mice, reduce neutrophil infiltration and fungal load, and significantly decrease the pro-inflammatory cytokines in mouse corneas infected with A. fumigatus . In vitro, we also demonstrated that Lico A increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) around the nucleus in human corneal epithelial cells (HCECs) stimulated with A. fumigatus . We verified that the anti-inflammatory effect of Lico A is associated with the activation of the Nrf2/HO-1 axis. These results indicated that Lico A could provide a protective role in A. fumigatus keratitis through its anti-inflammatory and antifungal activities.