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Formononetin protects against Aspergillus fumigatus Keratitis: Targeting inflammation and fungal load.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2024 May 10; Vol. 132, pp. 112046. Date of Electronic Publication: 2024 Apr 09. - Publication Year :
- 2024
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Abstract
- Purpose: To investigate the potential treatment of formononetin (FMN) on Aspergillus fumigatus (A. fumigatus) keratitis with anti-inflammatory and antifungal activity.<br />Methods: The effects of FMN on mice with A. fumigatus keratitis were evaluated through keratitis clinical scores, hematoxylin-eosin (HE) staining, and plate counts. The expression of pro-inflammatory factors was measured using RT-PCR, ELISA, or Western blot. The distribution of macrophages and neutrophils was explored by immunofluorescence staining. The antifungal properties of FMN were assessed through minimum inhibitory concentration (MIC), propidium iodide (PI) staining, fungal spore adhesion, and biofilm formation assay.<br />Results: In A. fumigatus keratitis mice, FMN decreased the keratitis clinical scores, macrophages and neutrophils migration, and the expression of TNF-α, IL-6, and IL-1β. In A. fumigatus-stimulated human corneal epithelial cells (HCECs), FMN reduced the expression of IL-6, TNF-α, IL-1β, and NLRP3. FMN also decreased the expression of thymic stromal lymphopoietin (TSLP) and thymic stromal lymphopoietin receptor (TSLPR). Moreover, FMN reduced the levels of reactive oxygen species (ROS) induced by A. fumigatus in HCECs. Furthermore, FMN inhibited A. fumigatus growth, prevented spore adhesion and disrupted fungal biofilm formation in vitro. In vivo, FMN treatment reduced the fungal load in mice cornea at 3 days post infection (p.i.).<br />Conclusion: FMN demonstrated anti-inflammatory and antifungal properties, and exhibited a protective effect on mouse A. fumigatus keratitis.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Humans
Mice
Cytokines metabolism
Antifungal Agents therapeutic use
Antifungal Agents pharmacology
Neutrophils immunology
Neutrophils drug effects
Disease Models, Animal
Reactive Oxygen Species metabolism
Female
Macrophages drug effects
Macrophages immunology
Biofilms drug effects
Mice, Inbred C57BL
Cornea pathology
Cornea drug effects
Cornea microbiology
Aspergillus fumigatus drug effects
Keratitis drug therapy
Keratitis microbiology
Keratitis immunology
Aspergillosis drug therapy
Aspergillosis immunology
Isoflavones pharmacology
Isoflavones therapeutic use
Anti-Inflammatory Agents therapeutic use
Anti-Inflammatory Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 132
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38593508
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.112046