Perillaldehyde Protects Against Aspergillus fumigatus Keratitis by Reducing Fungal Load and Inhibiting Inflammatory Cytokines and LOX-1

Abstract

Purpose

The purpose of this research was to explore the antifungal and anti-inflammatory effects of perillaldehyde (PAE) in Aspergillus fumigatus (A. fumigatus) keratitis and the underlying mechanism.

Methods

The biofilm formation, adherence assay, and propidium iodide uptake test were used to determine the possible mechanism of PAE in terms of antifungal effects in vitro. The severity of corneal infection was evaluated by clinical scores. The immunofluorescence staining (IFS) was adopted to detect the number of macrophages in infected corneas. Draize test was performed to assess the ocular toxicity of PAE. Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot reflected the expression of inflammatory cytokines and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in mice corneas and RAW264.7 cells.

Results

PAE was able to inhibit the formation of biofilm, reduce conidial adhesion, and damage the integrity of membranes to exert antifungal activity. In C57BL/6 mice models, PAE alleviated the severity of infected corneas, reduced the recruitment of macrophages and had low ocular toxicity. In addition, the mRNA and protein levels of TNF-α, CCL-2, and LOX-1 could be significantly decreased by the application of PAE after A. fumigatus infection in vivo and in vitro.

Conclusion

Our study indicated that PAE protected against A. fumigatus keratitis by reducing fungal load, accumulation of macrophages, and inhibiting the expression of inflammatory cytokines.

Keywords:

• Perillaldehyde
• Aspergillus fumigatus
• keratitis
• macrophage
• fungal inflammation
• LOX-1

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data for this study are available upon request to the corresponding author.

Additional information

Funding

This work was supported by the Natural Science Foundation of Shandong Province [grant numbers ZR2017BH025], Key Research and Development Plan of Shandong Province [grant numbers 2019GSF107022], Taishan Scholar Project of Shandong Province [grant numbers tsqn201812151], and the Youth National Natural Science Foundation of China [grant numbers 81500695].