Discovering the Potent Inhibitors Against Babesia bovis in vitro and Babesia microti in vivo by Repurposing the Natural Product Compounds

In the present study, we screened 502 natural product compounds against the in vitro growth of Babesia (B.) bovis. Then, the novel and potent identified compounds were further evaluated for their in vitro efficacies using viability and cytotoxicity assays. The in vivo inhibitory effects of the selec...

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Autores principales: Yongchang Li, Mohamed Abdo Rizk, Eloiza May Galon, Mingming Liu, Jixu Li, Aaron Edmond Ringo, Shengwei Ji, Iqra Zafar, Maria Agnes Tumwebaze, Byamukama Benedicto, Naoaki Yokoyama, Ikuo Igarashi, Bayin Chahan, Xuenan Xuan
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:986906b003574c5ca593d357711b94142021-12-01T13:09:46ZDiscovering the Potent Inhibitors Against Babesia bovis in vitro and Babesia microti in vivo by Repurposing the Natural Product Compounds2297-176910.3389/fvets.2021.762107https://doaj.org/article/986906b003574c5ca593d357711b94142021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fvets.2021.762107/fullhttps://doaj.org/toc/2297-1769In the present study, we screened 502 natural product compounds against the in vitro growth of Babesia (B.) bovis. Then, the novel and potent identified compounds were further evaluated for their in vitro efficacies using viability and cytotoxicity assays. The in vivo inhibitory effects of the selected compounds were evaluated using B. microti “rodent strain” in mice model. Three potent compounds, namely, Rottlerin (RL), Narasin (NR), Lasalocid acid (LA), exhibited the lowest IC50 (half-maximal inhibitory concentration) as follows: 5.45 ± 1.20 μM for RL, 1.86 ± 0.66 μM for NR, and 3.56 ± 1.41 μM for LA. The viability result revealed the ability of RL and LA to prevent the regrowth of treated parasite at 4 × IC50 and 2 × IC50, respectively, while 4 × IC50 of NR was sufficient to stop the regrowth of parasite. The hematology parameters of B. microti in vivo were different in the NR-treated groups as compared to the infected/untreated group. Interestingly, intraperitoneal administration of NR exhibiting inhibition in the growth of B. microti in mice was similar to that observed after administration of the commonly used antibabesial drug, diminazene aceturate (DA) (76.57% for DA, 74.73% for NR). Our findings indicate the richness of natural product compounds by novel potent antibabesial candidates, and the identified potent compounds, especially NR, might be used for the treatment of animal babesiosis.Yongchang LiYongchang LiMohamed Abdo RizkMohamed Abdo RizkEloiza May GalonMingming LiuMingming LiuJixu LiJixu LiAaron Edmond RingoShengwei JiIqra ZafarMaria Agnes TumwebazeByamukama BenedictoNaoaki YokoyamaIkuo IgarashiBayin ChahanXuenan XuanFrontiers Media S.A.articlenatural product compoundsBabesia bovisin vitroBabesia microtiin vivoVeterinary medicineSF600-1100ENFrontiers in Veterinary Science, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic natural product compounds
Babesia bovis
in vitro
Babesia microti
in vivo
Veterinary medicine
SF600-1100
spellingShingle natural product compounds
Babesia bovis
in vitro
Babesia microti
in vivo
Veterinary medicine
SF600-1100
Yongchang Li
Yongchang Li
Mohamed Abdo Rizk
Mohamed Abdo Rizk
Eloiza May Galon
Mingming Liu
Mingming Liu
Jixu Li
Jixu Li
Aaron Edmond Ringo
Shengwei Ji
Iqra Zafar
Maria Agnes Tumwebaze
Byamukama Benedicto
Naoaki Yokoyama
Ikuo Igarashi
Bayin Chahan
Xuenan Xuan
Discovering the Potent Inhibitors Against Babesia bovis in vitro and Babesia microti in vivo by Repurposing the Natural Product Compounds
description In the present study, we screened 502 natural product compounds against the in vitro growth of Babesia (B.) bovis. Then, the novel and potent identified compounds were further evaluated for their in vitro efficacies using viability and cytotoxicity assays. The in vivo inhibitory effects of the selected compounds were evaluated using B. microti “rodent strain” in mice model. Three potent compounds, namely, Rottlerin (RL), Narasin (NR), Lasalocid acid (LA), exhibited the lowest IC50 (half-maximal inhibitory concentration) as follows: 5.45 ± 1.20 μM for RL, 1.86 ± 0.66 μM for NR, and 3.56 ± 1.41 μM for LA. The viability result revealed the ability of RL and LA to prevent the regrowth of treated parasite at 4 × IC50 and 2 × IC50, respectively, while 4 × IC50 of NR was sufficient to stop the regrowth of parasite. The hematology parameters of B. microti in vivo were different in the NR-treated groups as compared to the infected/untreated group. Interestingly, intraperitoneal administration of NR exhibiting inhibition in the growth of B. microti in mice was similar to that observed after administration of the commonly used antibabesial drug, diminazene aceturate (DA) (76.57% for DA, 74.73% for NR). Our findings indicate the richness of natural product compounds by novel potent antibabesial candidates, and the identified potent compounds, especially NR, might be used for the treatment of animal babesiosis.
format article
author Yongchang Li
Yongchang Li
Mohamed Abdo Rizk
Mohamed Abdo Rizk
Eloiza May Galon
Mingming Liu
Mingming Liu
Jixu Li
Jixu Li
Aaron Edmond Ringo
Shengwei Ji
Iqra Zafar
Maria Agnes Tumwebaze
Byamukama Benedicto
Naoaki Yokoyama
Ikuo Igarashi
Bayin Chahan
Xuenan Xuan
author_facet Yongchang Li
Yongchang Li
Mohamed Abdo Rizk
Mohamed Abdo Rizk
Eloiza May Galon
Mingming Liu
Mingming Liu
Jixu Li
Jixu Li
Aaron Edmond Ringo
Shengwei Ji
Iqra Zafar
Maria Agnes Tumwebaze
Byamukama Benedicto
Naoaki Yokoyama
Ikuo Igarashi
Bayin Chahan
Xuenan Xuan
author_sort Yongchang Li
title Discovering the Potent Inhibitors Against Babesia bovis in vitro and Babesia microti in vivo by Repurposing the Natural Product Compounds
title_short Discovering the Potent Inhibitors Against Babesia bovis in vitro and Babesia microti in vivo by Repurposing the Natural Product Compounds
title_full Discovering the Potent Inhibitors Against Babesia bovis in vitro and Babesia microti in vivo by Repurposing the Natural Product Compounds
title_fullStr Discovering the Potent Inhibitors Against Babesia bovis in vitro and Babesia microti in vivo by Repurposing the Natural Product Compounds
title_full_unstemmed Discovering the Potent Inhibitors Against Babesia bovis in vitro and Babesia microti in vivo by Repurposing the Natural Product Compounds
title_sort discovering the potent inhibitors against babesia bovis in vitro and babesia microti in vivo by repurposing the natural product compounds
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/986906b003574c5ca593d357711b9414
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