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姜黄素通过与微管蛋白α链相互作用作为蛋白靶点对Chilodonella uncinata 具有有效的治疗作用。

Curcumin is an efficacious therapeutic agent against Chilodonella uncinata via interaction with tubulin alpha chain as protein target.

机构信息

College of Animal Science and Technology, Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi, 712100, China.

College of Animal Science and Technology, Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi, 712100, China; Engineering Research Center of the Innovation and Development of Green Fishery Drugs, Universities of Shaanxi Province, Northwest A&F University, Yangling, Shaanxi, 712100, China.

出版信息

Fish Shellfish Immunol. 2024 Nov;154:109961. doi: 10.1016/j.fsi.2024.109961. Epub 2024 Oct 10.

DOI:10.1016/j.fsi.2024.109961
PMID:39395598
Abstract

Chilodonella, a parasitic ciliate that infects both cold water and warm water fish, can impede the growth of juvenile fish and cause considerable economic losses globally to freshwater aquaculture. In this study, the parasite was collected from both the gills and zygotes of largemouth bass (Micropterus salmoides). Isolated from diseased fish, the parasites were identified as Chilodonella uncinata based on morphological features and genetical diagnostic characterization using the partial small subunit ribosomal RNA gene. To develop an effective approach to treat chilodonellosis caused by C. uncinata in largemouth bass farming, we first developed an in vivo culture model for propagating C. uncinate and thus could use for morphological characterization, molecular analyses and antiparasitic drug screening. Curcumin was successfully identified as an efficacious anti-C. uncinata agent from 26 phytochemical compounds. When administered at a concentration of 6 mg/L, curcumin not only completely cured infected largemouth bass but also shielded uninfected fish from C. uncinata infections. The 24 h median effective concentration (EC) of curcumin against C. uncinata was 3.098 mg/L. Remarkably, the 96 h median lethal concentration (LC) of curcumin against largemouth bass was determined to be 17.143 mg/L, approximately 5.533 times higher than EC. The mechanism of action of curcumin was investigated by the cellular thermal shift assay, demonstrating that tubulin alpha chain was the binding target for curcumin. Moreover, SEM investigations further provided morphological evidence suggesting that curcumin induces parasite demise by disrupting the parasite's body surface and subsequently infiltrating its interior. These findings collectively emphasize the potential of curcumin as a safe and effective therapeutic agent for controlling C. uncinata in aquaculture.

摘要

寄生纤毛虫 Chilodonella 可感染冷水鱼和温水鱼,会阻碍幼鱼生长,并在全球范围内给淡水水产养殖造成巨大的经济损失。本研究从大口黑鲈(Micropterus salmoides)的鳃和受精卵中采集到该寄生虫。从患病鱼体中分离出的寄生虫,根据形态特征和使用部分小亚基核糖体 RNA 基因进行基因诊断特征,鉴定为卷曲Chilodonella。为了开发治疗大口黑鲈 Chilodonellosis 的有效方法,我们首先开发了一种体内培养模型来繁殖卷曲 Chilodonella,从而可以进行形态特征描述、分子分析和抗寄生虫药物筛选。从 26 种植物化学化合物中成功鉴定出姜黄素是一种有效的抗卷曲 Chilodonella 药物。当以 6mg/L 的浓度给药时,姜黄素不仅完全治愈了受感染的大口黑鲈,而且还使未感染的鱼免受卷曲 Chilodonella 感染。姜黄素对卷曲 Chilodonella 的 24 小时半数有效浓度(EC)为 3.098mg/L。值得注意的是,姜黄素对大口黑鲈的 96 小时半数致死浓度(LC)确定为 17.143mg/L,约为 EC 的 5.533 倍。细胞热转移试验研究了姜黄素的作用机制,表明微管蛋白 alpha 链是姜黄素的结合靶标。此外,SEM 研究进一步提供了形态学证据,表明姜黄素通过破坏寄生虫的体表并随后渗透其内部来诱导寄生虫死亡。这些发现共同强调了姜黄素作为一种安全有效的水产养殖中控制卷曲 Chilodonella 的治疗剂的潜力。

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