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使用高通量筛选系统鉴定出的伊维菌素在大鼠中表现出抗活性。

Ivermectin Identified Using a High-Throughput Screening System Exhibits Anti- Activity in Rats.

作者信息

Lee Soon-Ok, Lee Hyeryon, Chu Ki Back, Li Jianhua, Hong Sung-Jong, Kim Sung Soo, No Joo Hwan, Quan Fu-Shi

机构信息

Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.

Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

出版信息

Antibiotics (Basel). 2025 Aug 19;14(8):837. doi: 10.3390/antibiotics14080837.

DOI:10.3390/antibiotics14080837
PMID:40868031
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12382626/
Abstract

Clonorchiasis, caused by the parasite , remains a public health concern in East Asian countries. In this study, high-throughput screening was used to analyze 320 compounds for potential inhibitory activity against . To ensure the selection of high-confidence hits, a stringent inhibition threshold of 80% was applied, leading to the identification of three active compounds: moxifloxacin, hexachlorophene, and ivermectin (IVM). Ivermectin emerged as a hit compound and was assessed for its anti- efficacy. Ivermectin demonstrated dose-dependent trematocidal activity against metacercariae (CsMC) and newly excysted juveniles (CsNEJs), showing superior efficacy against CsMC and CsNEJs compared to praziquantel. To assess in vivo efficacy, rats were infected with CsMC and treated with ivermectin at 1 and 4 weeks post-infection (wpi) to target larval and adult stages, respectively. A significant worm burden reduction was observed compared to untreated control when treatment was administered at 1 wpi, showing an antiparasitic effect against larvae. Parasite-specific IgG levels and ALT/AST responses were comparable to those of the infection control group. These findings suggest that ivermectin may serve as a potential alternative drug targeting larvae.

摘要

由该寄生虫引起的华支睾吸虫病在东亚国家仍然是一个公共卫生问题。在本研究中,采用高通量筛选方法分析了320种化合物对该寄生虫的潜在抑制活性。为确保筛选出高可信度的活性化合物,应用了80%的严格抑制阈值,从而鉴定出三种活性化合物:莫西沙星、六氯酚和伊维菌素(IVM)。伊维菌素成为一种活性化合物,并对其抗该寄生虫的效果进行了评估。伊维菌素对华支睾吸虫囊蚴(CsMC)和新脱囊幼虫(CsNEJs)表现出剂量依赖性杀吸虫活性,与吡喹酮相比,对CsMC和CsNEJs显示出更高的疗效。为评估体内疗效,将大鼠感染CsMC,并分别在感染后1周和4周用伊维菌素进行治疗,以分别针对幼虫期和成虫期。在感染后1周进行治疗时,与未治疗的对照组相比,观察到虫负荷显著降低,显示出对幼虫的抗寄生虫作用。寄生虫特异性IgG水平和ALT/AST反应与感染对照组相当。这些发现表明,伊维菌素可能作为一种针对该寄生虫幼虫的潜在替代药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/ebf50c5c835d/antibiotics-14-00837-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/988ce3426ed4/antibiotics-14-00837-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/e045c748cd53/antibiotics-14-00837-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/0d04d8dd5dd5/antibiotics-14-00837-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/8d48567dfa82/antibiotics-14-00837-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/11d730813109/antibiotics-14-00837-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/ebf50c5c835d/antibiotics-14-00837-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/988ce3426ed4/antibiotics-14-00837-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/e045c748cd53/antibiotics-14-00837-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/0d04d8dd5dd5/antibiotics-14-00837-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/8d48567dfa82/antibiotics-14-00837-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/11d730813109/antibiotics-14-00837-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2a/12382626/ebf50c5c835d/antibiotics-14-00837-g006.jpg

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本文引用的文献

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PLoS Negl Trop Dis. 2024 Oct 11;18(10):e0012574. doi: 10.1371/journal.pntd.0012574. eCollection 2024 Oct.
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Ovicidal activity of diaryl dichalcogenides and ivermectin on Fasciola hepatica: A novel candidate for a blending-based therapeutic strategy.二芳基二硫代膦酸盐和伊维菌素对肝片形吸虫的杀卵活性:一种基于混合的治疗策略的新候选药物。
Acta Trop. 2024 Oct;258:107363. doi: 10.1016/j.actatropica.2024.107363. Epub 2024 Aug 15.
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Virus-like particles expressing microneme-associated antigen of Plasmodium berghei confer better protection than those expressing apical membrane antigen 1.表达伯氏疟原虫微线体相关抗原的病毒样颗粒比表达顶膜抗原 1 的病毒样颗粒具有更好的保护效果。
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