Licochalcone A Ameliorates <i>Aspergillus fumigatus</i> 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 <i>Aspergillus fumigatus</i> (<i>A. fumigatus</i>) 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 <i>A. fumigatus</i>. 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 <i>A. fumigatus</i>. 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 <i>A. fumigatus</i>. 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 <i>A. fumigatus</i> keratitis through its anti-inflammatory and antifungal activities.