Resveratrol has neuroprotective effects and plays an anti-inflammatory role through Dectin-1/p38 pathway in Aspergillus fumigatus keratitis

• Published in: Cytokine (Philadelphia, Pa.) Vol. 179; p. 156626
• Main Authors: Diao, Weilin, Yin, Min, Qi, Yinghe, Fu, Yudong, Gu, Lingwen, Lin, Jing, Zhang, Lina, Jiang, Nan, Wang, Qian, Wang, Yuwei, Yi, Wendan, Chi, Menghui, Li, Cui, Zhao, Guiqiu
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2024
• Subjects: A. fumigatus; Antifungal; Dectin-1; Keratitis; Resveratrol; Dectin-1; Keratitis; Antifungal; A. fumigatus; Resveratrol
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2024.156626

•Resveratrol exertsantifungal activitiesagainst Aspergillus fumigatus (A. fumigatus)•Resveratrol alleviates the severity of mouse fungal keratitis.•Resveratrol suppressesA. fumigatus-induced inflammatory responses through inhibiting Dectin-1 /p38 MAPK pathway.•Resveratrol has protective effect on cornea nerves after A. fumigatus infection.
To determine the antifungal, anti-inflammatory and neuroprotective effects of resveratrol (RES) in Aspergillus fumigatus (A. fumigatus) keratitis.
Cytotoxicity assay and Draize eye assay were performed to assess the toxicity of RES. The antifungal effect of RES was assessed by minimal inhibitory concentration, scanning or transmission electron microscopy, propidium iodide uptake assay, and Calcofluor white staining. Phosphorylation of p38 MAPK, mRNA and protein levels of Dectin-1 and related inflammatory factors were measured by qRT-PCR, ELISA and Western blot in vitro and in vivo. Clinical score, HE staining, plate count, and myeloperoxidase test were used to observe the progress of fungal keratitis. IF staining, qRT-PCR, and the Von Frey test were selected to assess the neuroprotective effects of RES.
RES suppressed A. fumigatus hyphae growth and altered hyphae morphology in vitro. RES decreased the expression of Dectin-1, IL-1β and TNF-α, as well as p38 MAPK phosphorylation expression, and also decreased clinical scores, reduced inflammatory cell infiltration and neutrophil activity, and decreased fungal load. RES also protected corneal basal nerve fibers, down-regulated mechanosensitivity thresholds, and increased the mRNA levels of CGRP and TRPV-1..
These evidences revealed that RES could exert antifungal effects on A. fumigatus and ameliorate FK through suppressing the Dectin-1/p38 MAPK pathway to down-regulate IL-1β, IL-6, etc. expression and play protective effect on corneal nerves.