In vitro killing effect of berberine and niclosamide on ocular Demodex folliculorum

Shujia Guo; Yuqian Wang; Jiani Li; Yuwen Liu; Yi Han; Caihong Huang; Huping Wu; Jiaoyue Hu; Zuguo Liu

doi:10.1016/j.clae.2024.102336

In vitro killing effect of berberine and niclosamide on ocular Demodex folliculorum

Cont Lens Anterior Eye. 2024 Nov 29:102336. doi: 10.1016/j.clae.2024.102336. Online ahead of print.

Authors

Shujia Guo¹, Yuqian Wang¹, Jiani Li¹, Yuwen Liu¹, Yi Han², Caihong Huang¹, Huping Wu¹, Jiaoyue Hu³, Zuguo Liu⁴

Affiliations

¹ Xiamen University affiliated Xiamen Eye Center, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Fujian Engineering and Research Center of Eye Regenerative Medicine, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China.
² Department of Ophthalmology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China.
³ Xiamen University affiliated Xiamen Eye Center, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Fujian Engineering and Research Center of Eye Regenerative Medicine, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China. Electronic address: mydear_22000@163.com.
⁴ Xiamen University affiliated Xiamen Eye Center, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Fujian Engineering and Research Center of Eye Regenerative Medicine, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China; Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Xiamen, Fujian 361005, China; Department of Ophthalmology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China. Electronic address: zuguoliu@xmu.edu.cn.

PMID: 39616005
DOI: 10.1016/j.clae.2024.102336

Abstract

Purpose: To explore the in vitro killing effect of water-soluble berberine and lipid-soluble niclosamide against ocular Demodex folliculorum.

Methods: Demodex with good vigor were collected from patients' eyelashes. These mites were randomly distributed into different groups with 20 mites in each group. Saline, Double Distilled Water (DDW), Polysorbate 80 (TWEEN 80), Polyethylene glycol 300 (PEG 300) and Castor Oil were used to screen solvents and cosolvents. 20 % Tea Tree Oil (TTO) and Anhydrous Ethanol (EtOH) were used as positive controls. 0.2 % Berberine, 0.25 % Niclosamide and 0.5 % Niclosamide, were designated as experimental groups. Following treatment, the analysis of Kaplan-Meier survival curves and survival time of mites and safety of drugs were then performed.

Results: The survival of Demodex in vitro in Saline and DDW, was not significant different. Therefore, DDW, which was more conducive to the dissolution of berberine, was chosen as the solvent for berberine. 0.2 % Berberine significantly inhibited the survival distribution and survival time (P < 0.001) of Demodex in vitro compared with the DDW group. Through the evaluation of several cosolvents, PEG300 had milder effects on Demodex. Hence, the proportion of PEG300 in the niclosamide solvent group was increased to reduce the irritability of the vehicle. Furthermore, niclosamide could significantly inhibit the survival of Demodex compared with the vehicle group, and the effect of 0.5 % Niclosamide was more obvious (P < 0.001), and was better than 20 %TTO (P < 0.001). In addition, after niclosamide administration, Demodex bodies exhibited gradual distortion along with increased transparency and the presence of blurred dark particles compared to those in the vehicle group. Moreover, both drugs showed good subjective tolerability and safety in a mouse model.

Conclusion: 0.2 % berberine and 0.5 % niclosamide effectively inhibited Demodex survival in vitro, with 0.5 % niclosamide superior to 20 % TTO. These two drugs, with anti-Demodex, anti-bacterial, and anti-inflammatory properties, may offer alternative treatment for Demodex blepharitis.

Keywords: Berberine; Blepharitis; Demodex; Niclosamide.