Laccase-mediated functionalization of natamycin by gallic acids for the therapeutic effect on Aspergillus fumigatus keratitis
Laccase-mediated functionalization of natamycin by gallic acids for the therapeutic effect on Aspergillus fumigatus keratitis
复制标题
没食子酸漆酶介导的那他霉素功能化对烟曲霉角膜炎的治疗作用
DOI：
10.1016/j.ejphar.2022.175041
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发表时间：
2022
影响因子：
5
通讯作者：
Guiqiu Zhao
中科院分区：
文献类型：
--
作者：
Xiaoyue Ji;Xudong Peng;Xiaojing Long;Yingxue Zhang;Jing Lin;Jiao Yin;Ranran Zhang;Guiqiu Zhao
为提高纳他霉素治疗真菌性角膜炎(FK)的疗效，制备了纳他霉素和没食子酸的接枝衍生物，并研究了其对烟曲霉菌角膜炎的影响。用FT-IR和UV-Vis表征了纳他霉素与没食子酸的接枝产物的结构，证明了没食子酸-纳他霉素(GA-NAT)的成功合成。CCK-8和Draize目测结果表明GA-NAT具有较低的细胞毒性。通过最低抑菌浓度(MIC)、黏附力、生物被膜形成、钙荧光染色等体外抗菌实验和临床评分、平板计数等体内实验，结果表明GA-NAT的抗真菌活性与纳他霉素相近，但治疗效果优于纳他霉素。髓过氧化物酶活性测定和免疫荧光染色也显示GA-NAT明显抑制中性粒细胞募集和活性。此外，还发现GA-NAT可抑制LOX-1、肿瘤坏死因子-α和IL-1β的基因和蛋白表达。这些结果表明，GA-NAT抑制了真菌的生长，减少了中性粒细胞向角膜的渗透，下调了皮损中炎症因子的表达，为FK的治疗提供了新的选择。
To improve the therapeutic effect of natamycin on fungal keratitis (FK), the grafted derivatives of natamycin and gallic acid were obtained, and the effects of the grafted derivatives on Aspergillus fumigatus ( A. fumigatus ) keratitis were investigated. The structure of natamycin grafted with gallic acid was identified by FT-IR and UV–Vis, and the successful synthesis of Gallic-Natamycin (GA-NAT) was proved. CCK-8 and the Draize eye test showed that GA-NAT had less cytotoxicity. Then, through in vitro antibacterial experiments such as minimum inhibitory concentration (MIC), adhesion, biofilm formation, and calcium fluorescence staining and in vivo experiments such as clinical score and plate counting, the results showed that GA-NAT had similar antifungal activity to natamycin, but had a better therapeutic effect than natamycin. Myeloperoxidase assay and immunofluorescence staining also showed that GA-NAT significantly inhibited neutrophil recruitment and activity. Moreover, It was further found that GA-NAT could inhibit the mRNA and protein expressions of LOX-1, TNF-α, and IL-1β. These results indicated that GA-NAT inhibited the fungal growth, reduced the neutrophil infiltration into cornea, and down-regulated the expression of inflammatory factors in lesions, which provides a new choice for FK treatment.