关键词: A. fumigatus Antifungal treatment Eugenol Fungal keratitis Nrf2 A. fumigatus Antifungal treatment Eugenol Fungal keratitis Nrf2

Mesh : Animals Anti-Inflammatory Agents / pharmacology therapeutic use Antifungal Agents / pharmacology therapeutic use Aspergillosis / drug therapy metabolism microbiology Aspergillus fumigatus / physiology Cytokines / metabolism Eugenol / pharmacology therapeutic use Keratitis / drug therapy metabolism microbiology Mice Mice, Inbred C57BL

来  源:   DOI:10.1016/j.ejphar.2022.174955

Abstract:
Fungal keratitis is a corneal infection, which severely impairs vision. The fungal pathogen provokes host immune response, but the excessive inflammatory response causes significant collateral damage to the cornea. Eugenol, the main component of clove oil, has been found to have a broad range of pharmacological activities including anti-microbial, antioxidation and anti-inflammation. However, the role of eugenol in Aspergillus fumigatus (A. fumigatus) keratitis is unknown. In this study, we demonstrated that eugenol reduced mice keratitis severity, inflammatory cells infiltration, pro-inflammatory cytokine expression, and the fungal load. Eugenol also decreased the expressions of pro-inflammatory cytokines in human corneal epithelial cells (HCECs). We confirmed that the anti-inflammatory effects of eugenol were related to activating nuclear factor erythroid 2-related factor 2/Heme Oxygenase-1 (Nrf2/HO-1) signaling pathway. Moreover, we demonstrated that eugenol could inhibit the A. fumigatus growth and adhesion to host cells, as well as damage the fungal biofilm. The antifungal mechanism seemed to be disrupting the integrity of the fungal membrane and reducing the biosynthesis of ergosterol. Taken together, our research suggested that eugenol exerted protective effects on mouse A. fumigatus keratitis, due to its anti-inflammatory and antifungal activity.
摘要:
真菌性角膜炎是一种角膜感染,严重损害视力。真菌病原体引起宿主免疫反应,但是过度的炎症反应会对角膜造成严重的附带损害。丁香酚,丁香油的主要成分,已发现具有广泛的药理活性,包括抗微生物,抗氧化和抗炎。然而,丁香酚在烟曲霉中的作用(A.烟曲霉)角膜炎未知。在这项研究中,我们证明了丁香酚降低小鼠角膜炎的严重程度,炎性细胞浸润,促炎细胞因子表达,和真菌负荷。丁香酚还可以降低人角膜上皮细胞(HCECs)中促炎细胞因子的表达。我们证实丁香酚的抗炎作用与激活核因子-红细胞相关因子2/血红素氧合酶-1(Nrf2/HO-1)信号通路有关。此外,我们证明丁香酚可以抑制烟曲霉的生长和与宿主细胞的粘附,以及破坏真菌生物膜。抗真菌机制似乎破坏了真菌膜的完整性并减少了麦角甾醇的生物合成。一起来看,我们的研究表明,丁香酚对小鼠烟曲霉角膜炎具有保护作用,由于其抗炎和抗真菌活性。
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