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Inhibitory effect of morin on aldolase 2 from Eimeria tenella

文献类型： 外文期刊

作者： Hu, Junjing 1 ; Sun, Mingfei 2 ; Qi, Nanshan 2 ; Abuzeid, Asmaa M., I 1 ; Li, Juan 2 ; Cai, Haiming 2 ; Lv, Minna 2 ; Lin, Xuhui 2 ; Liao, Shenquan 2 ; Li, Guoqing 1 ;

作者机构： 1.South China Agr Univ, Coll Vet Med, Guangdong Prov Key Lab Zoonosis Prevent & Control, Guangzhou 510542, Peoples R China

2.Guangdong Acad Agr Sci, Inst Anim Hlth,Key Lab Livestock Dis Prevent Guan, Minist Agr & Rural Affairs,Sci Observat & Expt St, Key Lab Avian Influenza & Other Major Poultry Dis, Guangzhou 510640, Guangdong, Peoples R China

3.Suez Canal Univ, Fac Vet Med, Ismailia 41522, Egypt

关键词： Eimeria tenella; Fructose 1,6-bisphosphate aldolase 2; Molecular characterization; Biochemical characterization; Morin; Inhibitory effect

期刊名称：INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE （ 影响因子：4.284； 五年影响因子：4.04 ）

ISSN： 2211-3207

年卷期： 2022 年 20 卷

页码：

收录情况： SCI

摘要： Eimeria tenella (E. tenella) is a protozoal parasite that can cause severe cecal lesions and death in chickens, seriously harming the chicken industry. Conventional control strategies mainly rely on anticoccidial drugs. However, the emerging problems of anticoccidial resistance and drug residues necessitate exploring potential drug targets for developing new anticoccidial drugs. Fructose-1,6-bisphosphate aldolase (ALD) is an essential enzyme for parasite energy metabolism that has been considered a potential drug target. In this study, we analyzed the molecular and biochemical properties of E. tenella ALD2 (EtALD2). EtALD2 mRNA expression was highest in second-generation merozoites, whereas the protein level was highest in unsporulated oocysts. Indirect immunofluorescence showed that EtALD2 was mainly distributed in sporozoite' cytoplasm. The natural product inhibitor (morin) was screened by computer-aided drug screening. Enzyme kinetic and inhibition kinetic assays showed that morin had a good inhibitory effect on EtALD2 activity (IC50 = 10.37 mu M, Ki = 48.97 mu M). In vitro inhibition assay demonstrated that morin had an inhibitory effect on E. tenella development, with an IC50 value of 3.98 mu M and drug selection index of 177.49. In vivo, morin significantly improved cecal lesions (p < 0.05) and reduced oocyst excretion (p < 0.05) in E. tenella-infected chickens compared with the untreated group. The anticoccidial index of the group receiving 450 mg morin per kg feed was 162, showing a good anticoccidial effect. These findings suggest that EtALD2 could be a novel drug target for E. tenella treatment, and morin should be further evaluated as a therapeutic candidate for chicken coccidiosis.

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