Exposure of Heligmosomoides polygyrus and Trichuris muris to albendazole, albendazole sulfoxide, mebendazole and oxantel pamoate in vitro and in vivo to elucidate the pathway of drug entry into these gastrointestinal nematodes

Cysteine proteinases from the fruit and latex of plants, including papaya, pineapple and fig, were previously shown to have a rapid detrimental effect,in vitro, against the rodent gastrointestinal nematodes,Heligmosomoides polygyrus(which is found in the anterior small intestine) andTrichuris muris(which resides in the caecum). Proteinases in the crude latex of papaya also showed anthelmintic efficacy against both nematodesin vivo. In this paper, we describe thein vitroandin vivoeffects of these plant extracts against the rodent nematode,Protospirura muricola, which is found in the stomach. As in earlier work, all the plant cysteine proteinases examined, with the exception of actinidain from the juice of kiwi fruit, caused rapid loss of motility and digestion of the cuticle, leading to death of the nematodein vitro. In vivo, in contrast to the efficacy againstH. polygyrusandT. muris, papaya latex only showed efficacy againstP. muricolaadult female worms when the stomach acidity had been neutralized prior to administration of papaya latex. Therefore, collectively, our studies have demonstrated that, with the appropriate formulation, plant cysteine proteinases have efficacy against nematodes residing throughout the rodent gastrointestinal tract.

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Benzimidazole and Aminoalcohol Derivatives Show in Vitro Anthelmintic Activity Against Trichuris Muris and Heligmosomoides Polygyrus

10.21203/rs.3.rs-1250014/v1 ◽

2022 ◽

Author(s):

Elora Valderas-García ◽

Cécile Häberli ◽

María Álvarez Bardón ◽

Nerea Escala ◽

Verónica Castilla Gómez de Agüero ◽

...

Keyword(s):

Adult Stage ◽

Anthelmintic Activity ◽

Gastrointestinal Nematodes ◽

Economic Losses ◽

Parasitic Infections ◽

Trichuris Muris ◽

Heligmosomoides Polygyrus ◽

Derivatives Of

Abstract Background: Infections by gastrointestinal nematodes cause significant economic losses and disease in both human and animals worldwide. The discovery of novel anthelmintic drugs is a crucial point in maintaining control of these parasitic infections.Methods: For this purpose, the aim of the present study was to evaluate the potential anthelmintic activity of three series of compounds against the gastrointestinal nematodes Trichuris muris and Heligmosomoides polygyrusin vitro. The compounds tested are derivatives of benzimidazole, lipidic aminoalcohols and diamines. A primary screening was performed to select those compounds with an ability to inhibit T. muris L1 motility by more than 90% at a single concentration of 100 µM, and then, their respective IC50s were calculated. Those compounds with IC50 lower than 10 µM were also tested against the adult stage of T. muris and H. polygyrus at a single concentration of 10µM.Results: Of the 41 initial compounds screened, only compounds AO14, BZ6 and BZ12 had IC50s lower than 10 µM on T. muris L1 assay, showing IC50 values of 3.30, 8.89 and 4.17 µM, respectively. However, only two of them displayed activity against the adult stage of the parasites: BZ12 killed 81% of adults of T. muris (IC50 of 8.1 µM) and 53% of H. polygyrus while BZ6 killed 100% of H. polygyrus adults (IC50 of 5.3 µM) but only 17% of T. muris. Conclusions: BZ6 and BZ12 could be considered as potential candidates for further in vivo efficacy testing.

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In vitro anthelmintic effects of cysteine proteinases from plants against intestinal helminths of rodents

Journal of Helminthology ◽

10.1017/s0022149x0786408x ◽

2007 ◽

Vol 81 (4) ◽

pp. 353-360 ◽

Cited By ~ 19

Author(s):

Gillian Stepek ◽

Ann E. Lowe ◽

David J. Buttle ◽

Ian R. Duce ◽

Jerzy M. Behnke

Keyword(s):

Rapid Development ◽

Intestinal Helminths ◽

Cysteine Proteinases ◽

Trichuris Muris ◽

Heligmosomoides Polygyrus ◽

Development Of Resistance ◽

Taxonomic Groups ◽

Gi Helminths

AbstractInfections with gastrointestinal (GI) nematodes are amongst the most prevalent worldwide, especially in tropical climates. Control of these infections is primarily through treatment with anthelmintic drugs, but the rapid development of resistance to all the currently available classes of anthelmintic means that alternative treatments are urgently required. Cysteine proteinases from plants such as papaya, pineapple and fig are known to be substantially effective against three rodent GI nematodes, Heligmosomoides polygyrus, Trichuris muris and Protospirura muricola, both in vitro and in vivo. Here, based on in vitro motility assays and scanning electron microscopy, we extend these earlier reports, demonstrating the potency of this anthelmintic effect of plant cysteine proteinases against two GI helminths from different taxonomic groups – the canine hookworm, Ancylostoma ceylanicum, and the rodent cestode, Rodentolepis microstoma. In the case of hookworms, a mechanism of action targeting the surface layers of the cuticle indistinguishable from that reported earlier appears to be involved, and in the case of cestodes, the surface of the tegumental layers was also the principal location of damage. Hence, plant cysteine proteinases have a broad spectrum of activity against intestinal helminths (both nematodes and cestodes), a quality that reinforces their suitability for development as a much-needed novel treatment against GI helminths of humans and livestock.

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Essential Oils and Their Bioactive Compounds in the Control of Gastrointestinal Nematodes of Small Ruminants

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.81804 ◽

2018 ◽

Vol 46 (1) ◽

pp. 14 ◽

Cited By ~ 1

Author(s):

Weibson Paz Pinheiro André ◽

Wesley Lyeverton Correia Ribeiro ◽

Lorena Mayana Beserra de Oliveira ◽

Iara Tersia Freitas Macedo ◽

Fernanda Cristina Macedo Rondon ◽

...

Keyword(s):

Natural Products ◽

Essential Oils ◽

Bioactive Compounds ◽

Small Ruminant ◽

Anthelmintic Activity ◽

Gastrointestinal Nematodes ◽

In Vivo Tests ◽

Anthelmintic Effect

Background: Gastrointestinal nematodes are one of the major health and economic problem of sheep and goats in the world. The control of these nematodes is carried out conventionally with synthetic anthelminths, which favored the selection of gastrointestinal nematode (GIN) populations multiresistant to anthelmintics. The emergence of anthelmintic resistance has stimulated the search for new alternatives to control small ruminant GIN, standing out the use of plants and their bioactives compounds, such as essential oils (EO). The objective of this review was to present the main characteristics and anthelmintic activity of EO, their isolated compounds and drug delivery systems in the control of GIN.Review: Essential oils are a complex blend of bioactive compounds with volatile, lipophilic, usually odoriferous and liquid substances. EO are composed of terpenes, terpenoids, aromatic and aliphatic constituents. EO has various pharmacological activities of interest in preventive veterinary medicine such as antibacterials, antifungals, anticoccicids, insecticides and anthelmintics. In vitro and in vivo tests are used to validate the anthelmintic activity of EO on GIN. In vitro tests are low cost screening tests that allow the evaluation of the anthelmintic activity of a large amount of bioactive compounds on eggs, first (L1) and third stage larvae (L3), and adult nematodes. The antiparasitic effect of EO is related to its main compound or to the interaction of the compounds. These bioactive compounds penetrate the cuticle of the nematodes by transcuticular diffusion, altering the mechanisms of locomotion, besides causing cuticular lesions. Following in vitro evaluation, the acute and sub-chronic toxicity test should be performed to assess the toxicity of the bioactive compounds and to define the dose to be used in in vivo tests. In vivo tests are more reliable because the anthelmintic effectiveness of bioactive compounds is evaluated after the metabolization process. The metabolization process of the bioactive compounds can generate metabolites that exhibit or not anthelmintic effectiveness. The in vivo tests assessing the anthelmintic effectiveness of bioactive compounds in sheep and goats are the fecal egg count reduction test and the controlled test. OE promoted reduction of egg elimination in faeces which may be related to cuticular and reproductive alterations in GIN, and reduction of parasite burden in in vivo tests. Due to the promising results obtained with OE in the in vivo tests, interest has been aroused in using nanotechnology as an alternative to increase the bioavailability of OE and consequently, potentializing its anthelmintic effect, reducing the dose and toxicity of the biocompounds. In addition to nanotechnology, the isolation and chemical modification of compounds isolated from OE have been employed to obtain new molecules with anthelmintic action and understand the mechanism of action of EO on the small ruminant GIN.Conclusion: The use of EO and their compound bioactive in the control of resistant populations of GIN is a promising alternative. The adoption of strategies in which natural products can replace synthetic anthelmintics, such as in dry periods and use synthetic anthelmintics in the rainy season when the population in refugia in the pasture is high, thus reducing the dissemination of GIN resistant populations. As perspective, the evaluation of pharmacokinetics and pharmacodynamics of these natural products should be performed so that one defines treatment protocols that optimize the anthelmintic effect.

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In vitro and in vivo anthelmintic activity of extracts from Artemisia parviflora and A. sieversiana

Helminthologia ◽

10.1515/helm-2017-0028 ◽

2017 ◽

Vol 54 (3) ◽

pp. 218-224 ◽

Cited By ~ 5

Author(s):

S. Irum ◽

H. Ahmed ◽

B. Mirza ◽

K. Donskow-Łysoniewska ◽

A. Muhammad ◽

...

Keyword(s):

Adult Worm ◽

Plant Extracts ◽

Small Ruminants ◽

Anthelmintic Activity ◽

Gastrointestinal Nematodes ◽

Economic Losses ◽

Egg Hatching ◽

Infective Larvae

SummaryIn the northern areas of Pakistan, the use of Artemisia based therapeutics is a common practice. Plants of genus Artemisia are known to possess anthelmintic and therapeutic effect. Infections caused by gastrointestinal nematodes are major threat to livestock industry across the world resulting in loss of production and indirect economic losses due to high cost of anthelmintic drugs. Present study was carried out to evaluate in vitro and in vivo effect of Artemisia sieversiana and Artemisia parviflora on Haemonchus contortus, a parasitic nematode of small ruminants. Methanolic plant extract was tested against three different developmental stages using an egg hatch assay, infective larvae and adult worm motility assay. Different concentrations were used for the bioassays and post exposure mortality was recorded after 8 hr for adult worms and infective larvae, while egg inhibition percentage was observed after 27 hr. A highly significant ability to inhibit the egg hatching (100 %) was recorded for both plant extracts while, the highest activity for adult worm assay and larvicidal assay was 90 % for A. sieversiana. The highest activity for adult motility and larvicidal assay for A. parviflora was 89 % and 86.6 % respectively. For in vivo trials maximum parentage reduction was 77.0 % for A. sieversiana and 73.6 % for A. parviflora. It is concluded that selected plant extracts were effective in reducing worm burden in animals.

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