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Molecules (Basel, Switzerland) Jun 2020Soil-transmitted nematodes (STN) infect 1-2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many...
Soil-transmitted nematodes (STN) infect 1-2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many instances of reduced activity. Terpenes are a class of compounds with anthelmintic activity. Thymol, a natural monoterpene phenol, was used to help eradicate hookworms in the U.S. South circa 1910. However, the use of terpenes as anthelmintics was discontinued because of adverse side effects associated with high doses and premature stomach absorption. Furthermore, the dose-response activity of specific terpenes against STNs has been understudied. Here we used hollow, porous yeast particles (YPs) to efficiently encapsulate (>95%) high levels of terpenes (52% ) and evaluated their anthelmintic activity on hookworms (, a rodent parasite (), and whipworm (. We identified YP-terpenes that were effective against all three parasites. Further, YP-terpenes overcame albendazole-resistant . These results demonstrate that terpenes are broad-acting anthelmintics. Terpenes are predicted to be extremely difficult for parasites to resist, and YP encapsulation provides water-suspendable terpene materials without surfactants and sustained terpene release that could lead to the development of formulations for oral delivery that overcome fast absorption in the stomach, thus reducing dosage and toxic side effects.
Topics: Albendazole; Ancylostoma; Ancylostomatoidea; Animals; Anthelmintics; Benzimidazoles; Humans; Nematoda; Nematode Infections; Saccharomyces cerevisiae; Terpenes
PubMed: 32605043
DOI: 10.3390/molecules25132958 -
British Journal of Pharmacology Dec 2021The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat...
BACKGROUND AND PURPOSE
The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat psoriasis.
EXPERIMENTAL APPROACH
Psoriasis-like skin inflammation was induced in mice (C57 and Balb/C) by topical application of imiquimod or intradermal injection of recombinant IL-23. Praziquantel was either orally or topically administered during the psoriasis induction period.
KEY RESULTS
Mice treated with either oral or topical praziquantel exhibited markedly improved psoriasiform skin symptoms when compared with control mice, as judged by disease severity score, epidermal thickening, inflammatory cell infiltration and spleen size. Flow cytometric analysis of infiltrating immune cells from mouse skin displayed reduced infiltration of Th17 cells. In vitro experiments revealed that praziquantel inhibited STAT3 phosphorylation and RORγt expression in splenic CD4 T-cells. Praziquantel also decreased STAT3 phosphorylation in HEK-A/F cells. Down-regulation of STAT3 phosphorylation in these cells accounts for the decreased number of Th17 cells and keratinocytes.
CONCLUSION AND IMPLICATIONS
These results provide the first preclinical evidence that praziquantel may effectively treat psoriasis, and suggest that praziquantel alleviates symptoms in mice by inhibiting STAT3 phosphorylation, thereby suppressing Th17 immune responses.
Topics: Animals; Anthelmintics; Disease Models, Animal; Drug Repositioning; Mice; Mice, Inbred BALB C; Praziquantel; Psoriasis; Skin; Th17 Cells
PubMed: 34363611
DOI: 10.1111/bph.15652 -
Veterinary Parasitology, Regional... Dec 2021Cyathostomins are the most common parasites of adult horses worldwide. Currently, the three classes of anthelmintics used to treat cyathostomin infections includes...
Cyathostomins are the most common parasites of adult horses worldwide. Currently, the three classes of anthelmintics used to treat cyathostomin infections includes benzimidazoles, pyrimidines and macrocyclic lactones. However, due to widespread overuse, cyathostomins have developed varying degrees of resistance to all classes of anthelmintics. Fecal egg count reduction tests (FECRT) are currently used to determine the presence of anthelmintic resistance (AR), while egg reappearance periods (ERP) are used to investigate early macrocyclic lactone resistance. The objective of this study was to investigate the prevalence of cyathostomin pyrantel pamoate and ivermectin resistance, and to determine ERP at Prince Edward Island (PEI), Canada horse farms. In addition, fecal cultures and larval identification were performed to evaluate the prevalence of small and large strongyle egg shedding in PEI. Fecal egg counts (FEC) were performed on 270 horses on 14 horse farms across PEI. Horses with≥ 200 eggs per gram (EPG) met the inclusion criteria and were enrolled in the study (n = 101). The median (range) horses per farm was 7.5 (4-11) and 6.0 (4-8) for pyrantel pamoate and ivermectin groups, respectively. Horses were initially treated with 6.6 mg/kg of pyrantel pamoate orally (n = 101). Fecal egg counts were conducted every two weeks for 8 weeks post treatment. Once individual FEC were ≥ 200 EPG, horses were dewormed with 0.2 mg/kg of ivermectin orally (n = 80), and FEC were performed every 2-3 weeks for seven weeks. In this study the ERP was defined as the week the mean FECR were 10% below the initial mean two-week post treatment FECR. Fecal egg count reduction tests and ERP were used to evaluate the efficacy of each anthelmintic. Fecal culture was performed to confirm the shedding of cyathostomin eggs. Fecal egg count reduction tests detected pyrantel pamoate resistance on 5/14 farms. No signs of ivermectin AR were detected, while reappearance of eggs occurred at 4-6 weeks and 7-9 weeks for pyrantel pamoate and ivermectin, respectively. Fecal culture detected large strongyles on 5/14 farms, which accounted for 0.3% of strongyle type eggs cultured. The prevalence of Strongylus vulgaris among individual horses in this study was 2.8% and was detected on 2/14 farms. These findings will allow us to educate owners and veterinarians on appropriate anthelmintic protocols in PEI and can be used as a baseline for continued monitoring of ERP and anthelmintic resistance in this region.
Topics: Animals; Anthelmintics; Drug Resistance; Horse Diseases; Horses; Parasite Egg Count; Prevalence; Prince Edward Island
PubMed: 34879940
DOI: 10.1016/j.vprsr.2021.100629 -
BMC Complementary Medicine and Therapies Jan 2023Trichinellosis, a zoonosis caused by the genus Trichinella, is a widespread foodborne disease. Albendazole, one of the benzimidazole derivatives, is used for treating...
BACKGROUND
Trichinellosis, a zoonosis caused by the genus Trichinella, is a widespread foodborne disease. Albendazole, one of the benzimidazole derivatives, is used for treating human trichinellosis, but with limited efficacy in killing the encysted larvae and numerous adverse effects. Cyperus rotundus L. is a herbal plant with a wide range of medicinal uses, including antiparasitic, and is frequently used in traditional medicine to treat various illnesses.
METHODS
LC-ESI-MS was used to identify the active phytoconstituents in the methanol extract (MeOH ext.) of the aerial parts of C. rotundus and its derivate fractions ethyl acetate (EtOAc fr.), petroleum ether (pet-ether fr.), and normal butanol (n-BuOH fr.). The in vivo therapeutic effects of C. rotundus fractions of the extracts were evaluated using the fraction that showed the most promising effect after detecting their in vitro anti-Trichinella spiralis potential.
RESULTS
C. rotundus extracts are rich in different phytochemicals, and the LC-ESI-MS of the 90% methanol extract identified 26 phenolic compounds classified as phenolic acids, flavonoids, and organic acids. The in vitro studies showed that C. rotundus extracts had a lethal effect on T. spiralis adults, and the LC were 156.12 µg/ml, 294.67 µg/ml, 82.09 µg/ml, and 73.16 µg/ml in 90% MeOH ext., EtOAc fr., pet-ether fr. and n-BuOH fr., respectively. The n-BuOH fr. was shown to have the most promising effects in the in vitro studies, which was confirmed by scanning electron microscopy. The in vivo effects of n-BuOH fr. alone and in combination with albendazole using a mouse model were evaluated by counting adults in the small intestine and larvae in the muscles, in addition to the histopathological changes in the small intestine and the muscles. In the treated groups, there was a significant decrease in the number of adults and larvae compared to the control group. Histopathologically, treated groups showed a remarkable improvement in the small intestine and muscle changes. Remarkably, maximal therapeutic effects were detected in the combination therapy compared to each monotherapy.
CONCLUSION
Accordingly, C. rotundus extracts may have anti-T. spiralis potential, particularly when combined with albendazole, and they may be used as synergistic to anti-T. spiralis medication therapy.
Topics: Humans; Albendazole; Plant Extracts; Cyperus; Methanol; Anthelmintics; Ethers
PubMed: 36658562
DOI: 10.1186/s12906-023-03839-7 -
International Journal For Parasitology.... Dec 2018Ion channels are membrane protein complexes that underlie electrical excitability in cells, allowing ions to diffuse through cell membranes in a regulated fashion. They... (Review)
Review
Ion channels are membrane protein complexes that underlie electrical excitability in cells, allowing ions to diffuse through cell membranes in a regulated fashion. They are essential for normal functioning of the neuromusculature and other tissues. Ion channels are also validated targets for many current anthelmintics, yet the properties of only a small subset of ion channels in parasitic helminths have been explored in any detail. Transient receptor potential (TRP) channels comprise a widely diverse superfamily of ion channels with important roles in sensory signaling, regulation of ion homeostasis, organellar trafficking, and other functions. There are several subtypes of TRP channels, including TRPA1 and TRPV1 channels, both of which are involved in, among other functions, sensory, nociceptive, and inflammatory signaling in mammals. Several lines of evidence indicate that TRPA1-like channels in schistosomes exhibit pharmacological sensitivities that differ from their mammalian counterparts and that may signify unique physiological properties as well. Thus, in addition to responding to TRPA1 modulators, schistosome TRPA1-like channels also respond to compounds that in other organisms modulate TRPV1 channels. Notably, TRPV channel genes are not found in schistosome genomes. Here, we review the evidence leading to these conclusions and examine potential implications. We also discuss recent results showing that praziquantel, the current drug of choice against schistosomiasis, selectively targets host TRP channels in addition to its likely primary targets in the parasite. The results we discuss add weight to the notion that schistosome TRP channels are worthy of investigation as candidate therapeutic targets.
Topics: Animals; Anthelmintics; Drug Delivery Systems; Host-Parasite Interactions; Humans; Mice; Praziquantel; Schistosoma; Schistosomiasis; TRPA1 Cation Channel; TRPV Cation Channels; Transient Receptor Potential Channels
PubMed: 30224169
DOI: 10.1016/j.ijpddr.2018.08.003 -
Parasite (Paris, France) 2021Anthelmintic overuse and failure to implement methods preventing the development and spread of anthelmintic resistance (AR) have led to an alarming increase of resistant...
Anthelmintic overuse and failure to implement methods preventing the development and spread of anthelmintic resistance (AR) have led to an alarming increase of resistant ovine trichostrongylids worldwide. The aim of the present study was to determine whether the routine anthelmintic treatment strategy was effective, to obtain insights into the frequency of AR in trichostrongylids of sheep in Austria, and to determine the presence of different trichostrongylid genera. On 30 sheep farms, the faecal egg count reduction test (FECRT) was performed with the Mini-FLOTAC technique in two consecutive studies. In study 1, only fenbendazole and moxidectin were tested, while different compounds and products were used in study 2. Overall, 33 treatment groups were formed: 11 groups were treated with benzimidazoles (fenbendazole and albendazole), 2 groups with avermectins (ivermectin, doramectin), 18 groups with moxidectin, and two groups with monepantel. Reduced efficacy was detected in 64%, 100%, 28% and 50% of these groups, respectively. The most frequently detected genus in larval cultures was Haemonchus, which had been barely detected in Austria previously, followed by Trichostrongylus. Multispecific resistance of trichostrongylids in Austria seems to be on the rise and H. contortus was detected unexpectedly frequently in comparison to previous studies. There is an urgent need to develop efficient communication strategies aimed at improving the engagement of farmers and veterinarians in sustainable parasite control.
Topics: Animals; Anthelmintics; Austria; Drug Resistance; Feces; Haemonchus; Ivermectin; Parasite Egg Count; Sheep; Sheep Diseases
PubMed: 34114948
DOI: 10.1051/parasite/2021048 -
Veterinary Parasitology May 2022This revision of the original poultry guidelines has been prepared to assist in the planning, conduct and interpretation of studies designed to assess the anthelmintic... (Review)
Review
This revision of the original poultry guidelines has been prepared to assist in the planning, conduct and interpretation of studies designed to assess the anthelmintic efficacy of drugs (newly discovered or currently used) against helminth parasites of chickens and turkeys. The original set of poultry guidelines was published in 2003. The current version provides an update on procedures to study and quantify the most important helminth parasites of chickens and turkeys, and to integrate these poultry guidelines with a new series of general, reflective and host-specific guidelines relative to assessing anthelmintic efficacy in production and companion animals. General considerations required for the conduct of studies designed to evaluate anthelmintics regardless of animal host such as the selection of study animals, animal housing, feeding, study design, record keeping and statistical analysis are for the most part provided in the newly published general guidelines. Taken together, the general and poultry guidelines should help investigators and others design and conduct studies and evaluate data concerned with determining the efficacy and safety of anthelmintics in chickens and turkeys. Additionally, this revision draws attention to several timely considerations inherent to anthelmintic evaluations such as the need to properly collect helminth specimens for subsequent determinations (e.g. species and stage verification, helminth genotyping). The investigations addressed herein, will most likely provide the very first public record of a new product's abilities to effectively reduce targeted, helminth infections in animals, and particular attention should be focused on study excellence and accuracy. Due to changes in consumer preferences, and new regulatory requirements, poultry husbandry, especially regarding laying hens, has changed immensely in many countries since the publication of the first poultry guidelines. These changes have generally allowed for a much greater exposure of birds to the source of helminth challenge (litter and fields as opposed to cages). Parasitic helminthiosis of poultry has therefore greatly increased in incidence and magnitude; changes that accentuate the need for more effective anthelmintic intervention and an update on the means of determining anthelmintic efficacy.
Topics: Animals; Anthelmintics; Chickens; Female; Helminthiasis; Poultry; Turkeys
PubMed: 35487870
DOI: 10.1016/j.vetpar.2022.109711 -
Molecules (Basel, Switzerland) Sep 2023It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect... (Review)
Review
It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are , , and , each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.
Topics: Humans; Animals; Anthelmintics; Schistosoma haematobium; Biological Products; Schistosomiasis; Praziquantel; Schistosoma mansoni
PubMed: 37836650
DOI: 10.3390/molecules28196807 -
Journal of Global Antimicrobial... Jun 2023This study aimed to characterise compounds with activity against carbapenemase-expressing Gram-negative bacteria and nematodes and evaluate their cytotoxicity to...
OBJECTIVES
This study aimed to characterise compounds with activity against carbapenemase-expressing Gram-negative bacteria and nematodes and evaluate their cytotoxicity to non-cancerous human cells.
METHODS
The antimicrobial activity and toxicity of a series of phenyl-substituted urea derivatives were evaluated using broth microdilution, chitinase, and resazurin reduction assays.
RESULTS
The effects of different substitutions present on the nitrogen atoms of the urea backbone were investigated. Several compounds were active against Staphylococcus aureus and Escherichia coli control strains. Specifically, derivatives 7b, 11b, and 67d exhibited antimicrobial activity against Klebsiella pneumoniae 16, a carbapenemase-producing Enterobacteriaceae species, with minimum inhibitory concentration (MIC) values of 100, 50, and 72 µM (32, 64, and 32 mg/L), respectively. In addition, the MICs obtained against a multidrug-resistant E. coli strain were 100, 50, and 36 µM (32, 16, and 16 mg/L) for the same compounds, respectively. Furthermore, the urea derivatives 18b, 29b, 50c, 51c, 52c, 55c-59c, and 62c were very active towards the nematode Caenorhabditis elegans.
CONCLUSIONS
Testing on non-cancerous human cell lines suggested that some of the compounds have the potential to affect bacteria, especially helminths, with limited cytotoxicity to humans. Given the simplicity of synthesis for this class of compounds and their potency against Gram-negative, carbapenemase-expressing K. pneumoniae, aryl ureas possessing the 3,5-dichloro-phenyl group certainly warrant further investigation to exploit their selectivity.
Topics: Anthelmintics; Phenylurea Compounds; Anti-Bacterial Agents; Microbial Sensitivity Tests; Bacterial Proteins; beta-Lactamases; Humans; Cell Line; Bacteria; Helminths; Caenorhabditis elegans; Animals
PubMed: 36906171
DOI: 10.1016/j.jgar.2023.02.021 -
Acta Tropica Apr 2022Hyptis dilatata and Mesosphaerum suaveolens belong to Lamiaceae, are aromatic and medicinal subshrubs with antiparasitic potential and occurrence in the Amazon Region....
Hyptis dilatata and Mesosphaerum suaveolens belong to Lamiaceae, are aromatic and medicinal subshrubs with antiparasitic potential and occurrence in the Amazon Region. The essential oils of both species were extracted, analyzed, and identified by GC and GC-MS and then evaluated their anthelmintic activities against the nematode Caenorhabditis elegans. Primary constituents of the samples of H. dilatata oils were limonene (72.6%), myrcene (11.5%), and p-cymene (10.3%) to PAMA19 sample, and camphor (25.5%), α-pinene (25.4%), 1,8-cineole (18.8%), β-pinene (12.0%), and limonene (5.9%) to PAMA108 sample, while in the oil of M. suaveolens, PAMA131 sample, predominated bicyclogermacrene (23.5%, 1,8-cineole (23.0%), germacrene D (17.2%), and (E)-caryophyllene (10.4%). The sample oil of H. dilatata (PAMA108) exhibited the lower anthelmintic inhibitory concentration, with an IC value of 2.09 mg/mL for C. elegans Bristol N2 strain, while the oils of H. dilatata (PAMA19) and M. suaveolens (PAMA131) showed an IC up of 4 mg/mL for C. elegans IVR15 and Bristol N2 strains. These results suggest that the H. dilatata and M. suaveolens oils constituents' combination can be helpful as a nematicidal agent due to their synergistic action.
Topics: Animals; Anthelmintics; Caenorhabditis elegans; Gas Chromatography-Mass Spectrometry; Hyptis; Oils, Volatile; Plant Oils
PubMed: 35063413
DOI: 10.1016/j.actatropica.2022.106321