Isoimperatorin alleviates fungal keratitis by regulating NF-κB pathway and macrophage immune response.

Purpose: The purpose of this research study was to investigate the impact of isoimperatorin on Aspergillus fumigatus (A. fumigatus) keratitis and elucidate its underlying mechanisms via the TLR4/MyD88/IKK/NF-κB signaling pathway. Materials and methods: The targets of the active ingredient isoimperatorin were identified via network pharmacology. Key interactions between isoimperatorin and its predicted targets were validated using molecular docking. Results: Isoimperatorin inhibited TLR4/MyD88 complex formation and IKK/NF-κB phosphorylation, downregulated pro-inflammatory cytokines, reduced neutrophil infiltration, and promoted macrophage polarization from the M1 to the M2 phenotype. Additionally, it inhibited cell apoptosis and alleviated corneal epithelial damage. Conclusion: This study demonstrates that isoimperatorin exerts a protective effect against A. fumigatus keratitis primarily by modulating the host immune response. The mechanism is mediated through the multi-target inhibition of the TLR4/MyD88/IKK/NF-κB pathway, leading to a coordinated reduction in inflammation and tissue damage. These findings highlight the therapeutic potential of isoimperatorin as a novel immunomodulatory strategy for managing fungal keratitis.