2. Academic Validation
  3. 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

  • Eur J Pharmacol. 2022 Jul 5;926:175041. doi: 10.1016/j.ejphar.2022.175041.
Xiaoyue Ji 1,  Xudong Peng 2,  Xiaojing Long 3,  Yingxue Zhang 4,  Jing Lin 5,  Jiao Yin 6,  Ranran Zhang 7,  Guiqiu Zhao 8
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The Affiliated Hospital of Qingdao University NO. 16 Jiangsu Road, Qingdao, Shandong Province, 266000, China. Electronic address: jxyyk923@163.com.
  • 2 Department of Ophthalmology, The Affiliated Hospital of Qingdao University NO. 16 Jiangsu Road, Qingdao, Shandong Province, 266000, China; Department of Ophthalmology, University of Washington, Seattle, WA, 98104, USA. Electronic address: drpxd@uw.edu.
  • 3 State Key Laboratory of Bio-fibers and Eco-textiles, Institute of Marine Biobased Materials, College of Materials Science and Engineering, Qingdao University, Qingdao, Shandong Province, 266071, China. Electronic address: longxj@qdu.edu.cn.
  • 4 Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, 40201, USA. Electronic address: yingxue@wayne.edu.
  • 5 Department of Ophthalmology, The Affiliated Hospital of Qingdao University NO. 16 Jiangsu Road, Qingdao, Shandong Province, 266000, China. Electronic address: linjing_yk@126.com.
  • 6 Department of Ophthalmology, The Affiliated Hospital of Qingdao University NO. 16 Jiangsu Road, Qingdao, Shandong Province, 266000, China. Electronic address: yankeyinjiao@126.com.
  • 7 Department of Ophthalmology, The Affiliated Hospital of Qingdao University NO. 16 Jiangsu Road, Qingdao, Shandong Province, 266000, China. Electronic address: zrr_0102@163.com.
  • 8 Department of Ophthalmology, The Affiliated Hospital of Qingdao University NO. 16 Jiangsu Road, Qingdao, Shandong Province, 266000, China. Electronic address: zhaoguiqiu_good@126.com.
PMID: 35597265 DOI: 10.1016/j.ejphar.2022.175041
Abstract

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.

Keywords

Fungal keratitis; Gallic acid; Laccase; Natamycin; Therapeutic effect.

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