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

2021 ◽  
Vol 8 ◽  
Author(s):  
Yongchang Li ◽  
Mohamed Abdo Rizk ◽  
Eloiza May Galon ◽  
Mingming Liu ◽  
Jixu Li ◽  
...  
Keyword(s):  
Natural Product ◽  
Intraperitoneal Administration ◽  
Babesia Bovis ◽  
Babesia Microti ◽  
Mice Model ◽  
Diminazene Aceturate ◽  
Hematology Parameters ◽  
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 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.

scholarly journals Myrrh Oil in Vitro Inhibitory Growth on Bovine and Equine Piroplasm Parasites and Babesia microti of Mice

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 173 ◽  
Author(s):  
Mahmoud AbouLaila ◽  
Shimaa Abd El-Salam El-Sayed ◽  
Mosaab A. Omar ◽  
Mohammad Saleh Al-Aboody ◽  
Amer R. Abdel Aziz ◽  
...  
Keyword(s):  
Small Subunit ◽  
Babesia Bovis ◽  
Babesia Microti ◽  
Small Subunit Rrna ◽  
Theileria Equi ◽  
Diminazene Aceturate ◽  
Nested Polymerase Chain Reaction ◽  
Polymerase Chain

The present experimental study was conducted for the assessment of the efficacy of in vitro inhibition of myrrh oil on the propagation of Babesia bovis, B. divergens, B. bigemina, Theileria equi, and B. caballi and in vivo efficacy on B. microti in mice through fluorescence assay based on SYBR green I. The culture of B. divergens B. bovis and was used to evaluate the in vitro possible interaction between myrrh oil and other commercial compound, such as pyronaridine tetraphosphate (PYR), diminazene aceturate (DA), or luteolin. Nested-polymerase chain reaction protocol using primers of the small-subunit rRNA of B. microti was employed to detect any remnants of DNA for studied parasitic species either in blood or tissues. Results elucidated that; Myrrh oil significantly inhibit the growth at 1% of parasitic blood level for all bovine and equine piroplasm under the study. Parasitic regrowth was inhibited subsequently by viability test at 2 µg/mL for B. bigemina and B. bovis, and there was a significant improvement in the in vitro growth inhibition by myrrh oil when combined with DA, PYR, and luteolin. At the same time; mice treated with a combination of myrrh oil/DA showed a higher inhibition in emitted fluorescence signals than the group that challenged with 25 mg/kg of diminazene aceturate at 10 and 12 days post-infection. In conclusion, this study has recommended the myrrh oil to treat animal piroplasmosis, especially in combination with low doses of DA.

scholarly journals Evaluation of The In Vitro And In Vivo Inhibitory Effects of Enrofloxacin On the Growth of Babesia Species and Theileria Equi

2019 ◽  
pp. 1-6
Author(s):  
Ikuo Igarashi ◽  
Naoaki Yokoyama ◽  
Akram Salama ◽  
Amer AbdEl-Aziz ◽  
Mahmoud AbouLaila ◽  
...  
Keyword(s):  
Dose Rate ◽  
Inhibitory Effect ◽  
Babesia Microti ◽  
Babesia Species ◽  
Mice Model ◽  
Inhibitory Effects ◽  
Theileria Equi ◽  
Diminazene Aceturate

Objectives: Enrofloxacin, a fluoroquinolone antibiotic, is an inhibitor of prokaryotic topoisomerase II with antibacterial and antiparasitic activities. The study aimed to evaluate the inhibitory effect of enrofloxacin on Babesia species and Theileria equi in vitro and in vivo. Methods: The inhibitory effects of enrofloxacin were evaluated in vitro cultures using in vitro inhibition assay of three Babesia species and Theileria equi; furthermore, the in vivo inhibitory effect of enrofloxacin was evaluated in the mice model of Babesia microti. Results: The IC50 values of enrofloxacin were 4.9, 4.5, 4, and 3.9 nM for B. bovis, B. bigemina, B. caballi, and B. equi, respectively. Enrofloxacin at a dose rate of 10 mg/kg resulted in a 92.9 % inhibition of Babesia microti growth in BALB/c mice. Combination therapy of enrofloxacin at a dose rate of 5 mg/kg with diminazene aceturate at a dose rate of 12.5 mg/kg resulted in 93.83 % inhibition of Babesia microti growth in BALB/c mice. Conclusions: Enrofloxacin might be used for drug therapy in babesiosis.

scholarly journals The Comparative Analysis of Antiviral Activity of Native and Modified Fucoidans from Brown Algae Fucus evanescens In Vitro and In Vivo

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 224 ◽  
Author(s):  
Natalya V. Krylova ◽  
Svetlana P. Ermakova ◽  
Vyacheslav F. Lavrov ◽  
Irina A. Leneva ◽  
Galina G. Kompanets ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Brown Algae ◽  
Biological Activities ◽  
Intraperitoneal Administration ◽  
In Vivo Studies ◽  
Mice Model ◽  
Dna And Rna ◽  
Antiviral Activities

The enzymatic depolymerization of fucoidans from brown algae allowed the production of their standardized derivatives with different biological activities. This work aimed to compare the antiviral activities of native (FeF) and modified with enzyme (FeHMP) fucoidans from F. evanescens. The cytotoxicity and antiviral activities of the FeF and FeHMP against herpes viruses (HSV-1, HSV-2), enterovirus (ECHO-1), and human immunodeficiency virus (HIV-1) in Vero and human MT-4 cell lines were examined by methylthiazolyltetrazolium bromide (MTT) and cytopathic effect (CPE) reduction assays, respectively. The efficacy of fucoidans in vivo was evaluated in the outbred mice model of vaginitis caused by HSV-2. We have shown that both FeF and FeHMP significantly inhibited virus-induced CPE in vitro and were more effective against HSV. FeF exhibited antiviral activity against HSV-2 with a selective index (SI) > 40, and FeHMP with SI ˃ 20, when they were added before virus infection or at the early stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that after intraperitoneal administration (10 mg/kg), both FeF and FeHMP protected mice from lethal intravaginal HSV-2 infection to approximately the same degree (44–56%). Thus, FeF and FeHMP have comparable potency against several DNA and RNA viruses, allowing us to consider the studied fucoidans as promising broad-spectrum antivirals.

scholarly journals Clofazimine Inhibits the Growth of Babesia and Theileria ParasitesIn VitroandIn Vivo

2016 ◽  
Vol 60 (5) ◽  
pp. 2739-2746 ◽  
Author(s):  
Bumduuren Tuvshintulga ◽  
Mahmoud AbouLaila ◽  
Batdorj Davaasuren ◽  
Aki Ishiyama ◽  
Thillaiampalam Sivakumar ◽  
...  
Keyword(s):  
Subcutaneous Administration ◽  
Blood Analysis ◽  
Babesia Bovis ◽  
Babesia Microti ◽  
Control Group ◽  
Blood Transfusions ◽  
Inhibitory Effects ◽  
Diminazene Aceturate ◽  
Content Type

ABSTRACTThe present study evaluated the growth-inhibitory effects of clofazimine, currently used for treating leprosy, againstBabesia bovis,B. bigemina,B. caballi, andTheileria equiinin vitroculture and againstBabesia microtiin mice. The 50% inhibitory concentrations (IC50s) of clofazimine against thein vitrogrowth ofB. bovis,B. bigemina,B. caballi, andT. equiwere 4.5, 3, 4.3, and 0.29 μM, respectively. In mice infected withB. microti, treatment with 20 mg/kg of body weight of clofazimine administered orally resulted in a significantly lower peak parasitemia (5.3%) than that in the control group (45.9%), which was comparable to the subcutaneous administration of 25 mg/kg diminazene aceturate, the most widely used treatment for animal piroplasmosis. Although slight anemia was observed in both clofazimine- and diminazene aceturate-treated infected mice, the level and duration of anemia were lower and shorter, respectively, than those in untreated infected mice. Using blood transfusions and PCR, we also examined whether clofazimine completely killedB. microti. On day 40 postinfection, when blood analysis was performed, parasites were not found in blood smears; however, the DNA ofB. microtiwas detected in the blood of clofazimine-treated animals and in several tissues of clofazimine- and diminazene aceturate-treated mice by PCR. The growth of parasites was observed in mice after blood transfusions from clofazimine-treated mice. In conclusion, clofazimine showed excellent inhibitory effects againstBabesiaandTheileria in vitroandin vivo, and further study on clofazimine is required for the future development of a novel chemotherapy with high efficacy and safety against animal piroplasmosis and, possibly, human babesiosis.

scholarly journals Apicoplast-Targeting Antibacterials Inhibit the Growth of Babesia Parasites

2012 ◽  
Vol 56 (6) ◽  
pp. 3196-3206 ◽  
Author(s):  
Mahmoud AbouLaila ◽  
Tserendorj Munkhjargal ◽  
Thillaiampalam Sivakumar ◽  
Akio Ueno ◽  
Yuki Nakano ◽  
...  
Keyword(s):  
Growth Cycle ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Babesia Bovis ◽  
Babesia Microti ◽  
Babesia Bigemina ◽  
Content Type ◽  
Babesia Equi

ABSTRACTThe apicoplast housekeeping machinery, specifically apicoplast DNA replication, transcription, and translation, was targeted by ciprofloxacin, thiostrepton, and rifampin, respectively, in thein vitrocultures of fourBabesiaspecies. Furthermore, thein vivoeffect of thiostrepton on the growth cycle ofBabesia microtiin BALB/c mice was evaluated. The drugs caused significant inhibition of growth from an initial parasitemia of 1% forBabesia bovis, with 50% inhibitory concentrations (IC50s) of 8.3, 11.5, 12, and 126.6 μM for ciprofloxacin, thiostrepton, rifampin, and clindamycin, respectively. The IC50s for the inhibition ofBabesia bigeminagrowth were 15.8 μM for ciprofloxacin, 8.2 μM for thiostrepton, 8.3 μM for rifampin, and 206 μM for clindamycin. The IC50s forBabesia caballiwere 2.7 μM for ciprofloxacin, 2.7 μM for thiostrepton, 4.7 μM for rifampin, and 4.7 μM for clindamycin. The IC50s for the inhibition ofBabesia equigrowth were 2.5 μM for ciprofloxacin, 6.4 μM for thiostrepton, 4.1 μM for rifampin, and 27.2 μM for clindamycin. Furthermore, an inhibitory effect was revealed for cultures with an initial parasitemia of either 10 or 7% forBabesia bovisorBabesia bigemina, respectively. The three inhibitors caused immediate death ofBabesia bovisandBabesia equi. The inhibitory effects of ciprofloxacin, thiostrepton, and rifampin were confirmed by reverse transcription-PCR. Thiostrepton at a dose of 500 mg/kg of body weight resulted in 77.5% inhibition ofBabesia microtigrowth in BALB/c mice. These results implicate the apicoplast as a potential chemotherapeutic target for babesiosis.

scholarly journals Trichostatin A, a potential drug for treatment of animal Babesia infections

2014 ◽  
Vol 11 (2) ◽  
pp. 24-26 ◽  
Author(s):  
T Nyamjargal ◽  
N Oshima ◽  
X Xuan ◽  
I Igarashi ◽  
T Munkhjargal ◽  
...  
Keyword(s):  
Trichostatin A ◽  
Inhibitory Effect ◽  
Babesia Bovis ◽  
Babesia Microti ◽  
Control Group ◽  
Babesia Bigemina ◽  
Theileria Equi ◽  
Babesia Gibsoni

In the present study, we evaluated the inhibitory effect of trichostatin A on the asexual growth of bovine, equine, and canine Babesia parasites in vitro as well as on the in vivo growth of Babesia microti (B.microti) in mice. The growth of Babesia bovis (B.bovis), Babesia bigemina (B.bigemina), Babesia caballi (B.caballi), Theileria equi (T.equi), and Babesia gibsoni (B.gibsoni) species was significantly inhibited (P < 0.05) by very low concentrations of trichostatin A (IC50 values = 2.6, 2.4, 2.3, 2.4, and 2.3 nM, respectively). Furthermore, in B.microti-infected mice, trichostatin A caused significant higher (P < 0.05) inhibition of the growth of B.microti at the dose of 2 mg/kg body weight than that in the control group. These results indicated the trichostatin A might be a chemotherapeutic agent for treatment of babesiosis. DOI: http://dx.doi.org/10.5564/mjas.v11i2.210 Mongolian Journal of Agricultural Sciences Vol.11(2) 2013 pp.24-26

scholarly journals Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Leonardo J. M. Carvalho ◽  
Bunduurem Tuvshintulga ◽  
Arifin B. Nugraha ◽  
Thillaiampalam Sivakumar ◽  
Naoaki Yokoyama
Keyword(s):  
Babesia Bovis ◽  
Babesia Microti

scholarly journals Probiotic and Functional Properties of Limosilactobacillus reuteri INIA P572

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1860
Author(s):  
Patricia Diez-Echave ◽  
Izaskun Martín-Cabrejas ◽  
José Garrido-Mesa ◽  
Susana Langa ◽  
Teresa Vezza ◽  
...  
Keyword(s):  
In Vitro Assays ◽  
Immunomodulatory Activity ◽  
Probiotic Properties ◽  
Protective Effects ◽  
Mice Model ◽  
In Vivo Models ◽  
Food Borne ◽  
Gastrointestinal Conditions

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.

scholarly journals Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

2021 ◽  
Vol 22 (1) ◽  
pp. 434
Author(s):  
Yuria Jang ◽  
Hong Moon Sohn ◽  
Young Jong Ko ◽  
Hoon Hyun ◽  
Wonbong Lim
Keyword(s):  
Nuclear Translocation ◽  
Critical Role ◽  
Osteoclast Differentiation ◽  
Point Mutations ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mice Model ◽  
Gsk 3Β ◽  
Rank Signaling

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.

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