Kaempferol ameliorate the prognosis of Aspergillus fumigatus keratitis by reducing fungal load and inhibiting the Dectin-1 and p38 MAPK pathway. (March 2022)

• Record Type: Journal Article
• Authors: Jia, Yiyi; Li, Cui; Yin, Min; Lin, Jing; Zhang, Lina; Li, Na; Jiang, Nan; Xu, Qiang; Wang, Qian; Gu, Lingwen; Yu, Bing; Zhao, Guiqiu
• Is Part Of: Experimental eye research. Volume 216(2022)
• Publication Date: 2022-03
• Subjects: Kaempferol -- Aspergillus fumigatus keratitis -- Dectin-1 -- p38 MAPK; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2022.108960
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Fungal keratitis is one of leading reasons for blindness in the world, which causes corneal blindness mainly due to excessive inflammatory responses. Kaempferol (KAE) is a natural flavonoid which has potent anti-inflammatory effects. However, whether KAE plays protective roles in fungal keratitis and the potentially protective mechanisms are unrevealed. Here we first investigated the anti-inflammatory and antifungal effects of KAE on Aspergillus fumigatus ( A. fumigatus ) keratitis in C57BL/6 mice. We found that treatment of KAE ameliorated the severity of keratitis, inhibited macrophages and neutrophils recruitment, depressed corneal fungal load, and declined the expression of TLR4 and Dectin-1 in A. fumigatus infected mice corneas. And in activated hyphae or Curdlan stimulated macrophages, pretreatment of KAE also significantly decreased the mRNA and protein expression of IL-1β, TNF-α, MIP-2 and the phosphorylated-p38 (p-p38)/p38 MAPK ratio. In summary, KAE ameliorated the prognosis of fungal keratitis in C57BL/6 mice by reducing corneal fungal load, depressing the inflammatory cells recruitment, and downregulating the expression of inflammatory factors, and those effects depended on the inhibition of Dectin-1 and p38 MAPK pathway. Highlights: Kaempferol decreased clinical score and fungal load in infected corneas of mice. Kaempferol reduced macrophages and neutrophils infiltration in A. fumigatus keratitis. Kaempferol attenuated the expression of inflammatory factors in vitro and in vivo. Kaempferol inhibited the activation of Dectin-1 mediated p38 MAPK pathway.