The therapeutic effect and mechanism of carnosic acid in Aspergillus fumigatus keratitis

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research Pub Date : 2025-03-13 DOI:10.1016/j.exer.2025.110338

Menghui Chi, Lingwen Gu, Lina Zhang, Jing Lin, Qian Wang, Xueyun Fu, Xue Tian, Ziyi Wang, Bing Yu, Wenyao Liu, Cui Li, Guiqiu Zhao

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引用次数: 0

Abstract

Fungal keratitis is a vision-threatening corneal infectious disease. However, clinically therapeutic medicines cannot attain ideal efficacy due to limited control of fungal virulence and excessive inflammatory response. Carnosic acid (CA) is a phenolic diterpene, which has been reported to have multiple abilities including antibacterial, anti-inflammatory and antioxidant. The therapeutic efficacy and potential mechanism of CA in fungal keratitis remain unknown. This study aimed to confirm the therapeutic role and potential mechanism of CA in Aspergillus fumigatus (A. fumigatus)–caused keratitis. In this study, we demonstrated that CA markedly suppressed the growth of A. fumigatus hyphae, the generation of biofilms and the integrity of the hyphal membrane. A. fumigatus-related genes (RodA, RodB, FKs, Rho1, CshA-C and Cyp51A-B) levels were suppressed under CA treatment. CA at 5 μg/mL and 10 μg/mL obviously promoted cell proliferation. In A. fumigatus-infected mice cornea, CA relieved the severity of corneal impairment, inhibited neutrophil recruitment and fungal load. Compared with inactivated hyphae, CA down-regulated the mRNA and protein levels of inflammatory cytokines, Dectin-1, NLRP3, cleaved caspase-1, IL-18 and IL-1β. Moreover, Curdlan (a specific agonist of Dectin-1) stimulation could promote the expression of NLRP3, cleaved caspase-1, IL-18 and IL-1β, which could be down-regulated by CA treatment. In conclusion, CA displays antifungal function on A. fumigatus. CA ameliorates the prognosis of keratomycosis by suppressing inflammatory cytokines production, which is regulated by Dectin-1 and pyroptosis.

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鼠尾草酸治疗烟曲霉角膜炎的疗效及作用机制

真菌性角膜炎是一种威胁视力的角膜感染性疾病。然而，临床治疗药物由于对真菌毒力控制有限，炎症反应过度，不能达到理想的疗效。鼠尾草酸（CA）是一种酚类二萜，具有抗菌、抗炎、抗氧化等多种功能。CA治疗真菌性角膜炎的疗效和潜在机制尚不清楚。本研究旨在证实CA在烟曲霉性角膜炎中的治疗作用及其潜在机制。在本研究中，我们证明了CA显著抑制烟曲霉菌丝的生长、生物膜的生成和菌丝膜的完整性。CA处理抑制了烟曲霉相关基因（RodA、RodB、FKs、Rho1、CshA-C和Cyp51A-B）水平。CA浓度为5 μg/mL和10 μg/mL，对细胞增殖有明显促进作用。在烟曲霉感染的小鼠角膜中，CA减轻了角膜损伤的严重程度，抑制了中性粒细胞的募集和真菌负荷。与灭活菌丝相比，CA下调了炎症因子、Dectin-1、NLRP3、cleaved caspase-1、IL-18和IL-1β的mRNA和蛋白水平。此外，Curdlan （Dectin-1的特异性激动剂）刺激可促进NLRP3、cleaved caspase-1、IL-18和IL-1β的表达，这些表达可被CA处理下调。综上所述，CA对烟曲霉具有一定的抑菌作用。CA通过抑制由Dectin-1和焦亡调节的炎症细胞因子的产生来改善角化病的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental eye research 医学-眼科学

CiteScore

6.80

自引率

5.90%

发文量

323

审稿时长

66 days

期刊介绍： The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.