Human toxocariasis is a neglected anthropozoonosis with global distribution. Treatment is based on the administration of anthelmintics; however, their effectiveness at the tissue level is low to moderate, necessitating the discovery of new drug candidates. Several groups of synthetic compounds, including coumarin derivatives, have demonstrated bioactivity against fungi, bacteria, and even parasites, such as Dactylogyrus intermedius, Leishmania major, and Plasmodium falciparum. The aim of this study was to evaluate the effect of ten coumarin-derived compounds against Toxocara canis larvae using in vitro, cytotoxicity, and in silico tests for selecting new drug candidates for preclinical tests aimed at evaluating the treatment of visceral toxocariasis. The compounds were tested in vitro in duplicate at a concentration of 1 mg/mL, and compounds with larvicidal activity were serially diluted to obtain concentrations of 0.5 mg/mL; 0.25 mg/mL; 0.125 mg/mL; and 0.05 mg/mL. The tests were performed in a microculture plate containing 100 T. canis larvae in RPMI-1640 medium. One compound (COU 9) was selected for cytotoxicity analysis using J774.A1 murine macrophages and it was found to be non-cytotoxic at any concentration tested. The in silico analysis was performed using computational models; the compound presented adequate results of oral bioavailability. To confirm the non-viability of the larvae, the contents of the microplate wells of COU 9 were inoculated intraperitoneally (IP) into female Swiss mice at 7-8 weeks of age. This confirmed the larvicidal activity of this compound. These results show that COU 9 exhibited larvicidal activity against T. canis larvae, which, after exposure to the compound, were non-viable, and that COU 9 inhibited infection in a murine model. In addition, COU 9 did not exhibit cytotoxicity and presented adequate bioavailability in silico, similar to albendazole, an anthelmintic, which is the first choice for treatment of human toxocariasis, supporting the potential for future investigations and preclinical tests on COU 9.

This study conducted a literature review to investigate the immunomodulatory effect of levamisole in both humans and farm animals. The following procedure was followed for database searching: PubMed, Google Scholar, Web of Science, and Cochrane Library. All research works were updated to September 2022. The terms used in the literature search were included: (\"levamisole\" OR \"immunity\" OR \"immune system\") AND (\"adjuvant\" OR \"fish\" OR \"poultry\" OR \"farm animal\" OR \"cattle\" OR \"sheep\"). The current review enlightens the extensive potential of levamisole as an adjuvant immunotherapeutic agent and explains its divergent applications beyond its antiparasitic use as an adjuvant, dietary supplement, immunostimulant, antiviral, and anti-cancer drug in humans and farm animals. In the articles examined, various mechanisms have been proposed for levamisole immunoprotective effects, but hormonal alteration and stress hormone reduction are indicated as the main mechanisms in various animal species.

We evaluated the effect of 4 anthelmintic treatments on the viability of Trichinella spiralis encysted muscle larvae (ML) 55 days post infection (PI) in experimentally infected pigs. Muscle larvae were isolated from pig muscle by artificial digestion after oral treatment of pigs with Levamisole (8 mg/kg, daily for 5 days) and Mebendazole (50 mg/kg, daily for 5 days); Doramectin (0.3 mg/kg, single IM injection), and Moxidectin (0.5 mg/kg, single pour on). Isolated larvae from treated pigs were orally inoculated into mice to assess viability of ML from each treatment. Only Mebendazole treatment of pigs significantly reduced ML viability in mice. The effect of timing of the effective Mebendazole treatment on ML from a longer term infection was then examined in a second experiment. Analysis revealed that Mebendazole treatment of pigs with 250 mg/kg over 3 days (83 mg/kg/day) or 5 days (50 mg/kg/day) reduced numbers of ML recovered from pig tissues compared to untreated, infected controls, and rendered ML non-infective to mice; Mebendazole treatment of pigs with 250 mg/kg in a single dose was not effective in reducing ML numbers recovered from pigs or in impacting ML infectivity to mice. An examination of the lowest effective dose of Mebendazole on encysted ML was determined in a third experiment. Mebendazole of pigs with 5, 50, or 100 mg/kg over 3 days demonstrated that 5 or 50 mg/kg over 3 days insufficient to reduce infectivity in recovered ML, while 100 mg/kg (and 83 g from experiment 2) over 3 days significantly reduces infectivity of ML. This procedure provides a means to evaluate the efficacy of various anthelmintic treatments on the viability of Trichinella spiralis ML in pig tissues, and identified Mebendazole, at 83-100 mg/kg administered over a 3-5 day period as an anthelmintic which renders encysted Trichinella spiralis ML from pig tissues non-infective. As risk from Trichinella significantly impacts acceptance of pork from pasture-raised pigs, these data provide a method, especially for producers of these high-risk pigs, to eliminate the potential of Trichinella transmission from infected pork.

This study aimed to assess the anthelmintic activity of methanol extracts from Merremia vitifolia stems using a combination approach encompassing experimental, in vitro, and in silico evaluations. Despite the well-recognized pharmacological properties of M. vitifolia, its potential as an anthelmintic agent remained unexplored. This plant\'s anthelmintic potential was assessed on adult earthworms (Pheretima posthuma), revealing a dose-dependent reduction in spontaneous motility leading to paralysis and eventual mortality. The most effective dose of M. vitifolia (200 mg/ml) for anthelmintic effects on Pheretima posthuma was identified. Complementary in silico investigations were also conducted, employing Autodock PyRx 0.8 for docking studies of reported M. vitifolia compounds. Notably, quercetin emerged as a promising candidate with superior binding energies against β-tubulin (-8.3 Kcal/mol). Moreover, this comprehensive research underlines the anthelmintic potential of Merremia vitifolia stem extract and highlights quercetin as a noteworthy compound for further investigation in the quest for novel anthelmintic agents.

BACKGROUND: Roots of Pothomorphe umbellata (L.) Miq. are used in traditional medicine of Africa and South America for the treatment of malaria and helminthiasis. However, neither P. umbellata nor its isolated compounds have been evaluated against Schistosoma species.
OBJECTIVE: To investigate the antischistosomal effects of P. umbellata root extracts and the isolated compound 4-nerolidylcatechol (4-NC) against Schistosoma mansoni ex vivo and in murine models of schistosomiasis.
METHODS: The crude hydroalcoholic (PuE) and hexane (PuH) extracts of P. umbellata roots were prepared and initially submitted to an ex vivo phenotypic screening against adult S. mansoni. PuH was analyzed by HPLC-DAD, characterized by UHPLC-HRMS/MS, and submitted to chromatographic fractionation, leading to the isolation of 4-NC. The anthelmintic properties of 4-NC were assayed ex vivo against adult schistosomes and in murine models of schistosomiasis for both patent and prepatent S. mansoni infections. Praziquantel (PZQ) was used as a reference compound.
RESULTS: PuE (EC50: 18.7 μg/mL) and PuH (EC50: 9.2 μg/mL) kill adult schistosomes ex vivo. The UHPLC-HRMS/MS analysis of PuH, the most active extract, revealed the presence of 4-NC, peltatol A, and peltatol B or C. After isolation from PuH, 4-NC presented remarkable in vitro schistosomicidal activity with EC50 of 2.9 μM (0.91 μg/mL) and a selectivity index higher than 68 against Vero mammalian cells, without affecting viability of nematode Caenorhabditis elegans. In patent S. mansoni infection, the oral treatment with 4-NC decreased worm burden and egg production in 52.1% and 52.3%, respectively, also reducing splenomegaly and hepatomegaly. 4-NC, unlike PZQ, showed in vivo efficacy against juvenile S. mansoni, decreasing worm burden in 52.4%.
CONCLUSIONS: This study demonstrates that P. umbellata roots possess antischistosomal activity, giving support for the medicinal use of this plant against parasites. 4-NC was identified from P. umbellata roots as one of the effective in vitro and in vivo antischistosomal compound and as a potential lead for the development of novel anthelmintics.

Biopesticides are generally considered a safer and more environmentally friendly alternative to conventional pesticides. Plant metabolites display a range of pest specific activity ranging from antimicrobial to larvicidal and nematocidal. We herein describe the evaluation of a Guyanese collection of Vismia guianensis (Clusiaceae) for anthelmintic activity. The bioassay-guided evaluation of the hexane extract yielded the new prenylated benzophenone 8,9-epoxyvismiaphenone F (1). The final structures were elucidated based on spectral analysis and comparison to the known metabolite. To evaluate the anthelmintic efficacy of these compounds, Caenorhabditis elegans were exposed to the compounds via a ring assay model. Post-exposure, the numbers of live C. elegans in the compound (middle), bacteria ring were recorded for 3 d, as well as the total number of live worms for each plate. Compound 1 reduced C. elegans\' overall growth and reproduction, suggesting that these prenylated benzophenones may hold some promise as natural pesticides.

A procedure to determine albendazole and ivermectin in veterinary formulations, like tablet, bolus, oral suspensions, and injections by micellar liquid chromatography, has been developed. Sample preparation was a batch solid-to-liquid extraction in mobile phase, consisting of a stirring step (15 min), followed by ultrasonication (15 min) and filtration of the obtained supernatant, to reach a target concentration of 2 mg/L for both analytes. Using a mobile phase of 0.15 M sodium dodecyl sulfate-6% 1-pentanol buffered at pH 3 with a 0.01 M phosphate salt, running at 1 mL/min through a C18 column, both drugs were resolved in less than 10 min. Absorbance detection wavelength was 292 nm. Procedure was validated by the guidelines of the International Council on Harmonization in terms of specificity, calibration range (0.025-5 mg/L), trueness (97.8%-102.6%), precision (<2.2%), and system suitability. The method was found easy-to-handle, low cost, safe, green, and with high sample-throughput, thus useful for routine analysis. Therefore, it represents a valuable alternative for quality control of veterinary formulations. It was applied to samples of veterinary formulations purchased from local chemists and veterinarians, and label claims were inside the acceptance criteria (95%-105%).

Trichinosis is a foodborne parasitic infection that results from ingestion of raw or under-cooked pork meat infected by parasitic nematode Trichinella spiralis with cosmopolitan distribution. Anthelmintic drugs are used to eliminate intestinal adult parasites and larvae as well as tissue-migrating newborn and in-turn encysted larvae. However, eliminating the infection or averting it from transmission is rarely possible using anthelmintic groups of benzimidazole derivatives. Eugenol (EO) is the main extracted constituent of clove oil (80−90%) and is responsible for its aroma. Therefore, this study aims to investigate the effect of eugenol on both adult and muscle larvae of Trichinella spiralis in vitro. IC50 for different concentrations of eugenol were calculated for both muscle larvae (187.5 µM) and adults (190.4 µM) to determine the accurate dose range. Both the nematode stages were cultured in the commonly used RPMI-1640 media in 24-well plates. Different concentrations of eugenol (122, 305, 609, 1218, and 3045 µM) were administered in different groups of larvae/adults. The parasitological parameters were monitored after 1, 3, 6, 10, 24 h for each EO concentration in concomitant with the control groups. Reference chemotherapeutic anthelminthic drug “albendazole” (at dose 377 µM) was experimentally grouped in triplicates as positive control and the untreated as negative control, respectively. Mortality was observed where time-dependent adult stages were less susceptible than muscle larvae. Eugenol achieved 100% efficacy against T. spiralis larvae and killed the total larvae after 10 and 24 h at concentrations of 1218 and 3045 µM, the same as albendazole’s effect on the positive control group. In regard to adults, resembling muscle larvae (ML), a significant effect of both concentrations at p < 0.0001 was obtained, and the concentration × time interaction was significant at p < 0.0001. Furthermore, the treated/untreated adult and muscle larvae were collected and processed for scanning electron microscopy (SEM). Massive destruction of parasite burden was observed, especially at high concentrations (1218 and 3045 µM). In addition, complete and mild loss in cuticular striation in both the treated and positive controls were confirmed by SEM, respectively, in comparison to the control untreated group.

Lactobacilli are GRAS organisms and are important members of gut microbiota. They have been strongly recommended as probiotics because of many benefits provided by them to overall human health. Human gut lactobacilli with salutary properties can provide additional advantages. Limosilactobacillus fermentumL1 MW600457, L. fermentumL3 MW600480, L. fermentumL4 MW600464, L. fermentumL5 MW600493, L. fermentumL6 MW600495, L. fermentumL7 MW600496, L. fermentumL8 MW485761, Lactiplantibacillus plantarumL9 MW485746, and Ligilactobacillus salivariusL10 MW600498 with in vitro probiotic properties were explored for salutogenic characteristics. Salutary properties like β-galactosidase activity, anthelminthic property assay, anti-inflammatory assay, antidiabetic study, cholesterol assimilation assay, and biofilm assay were performed. All the isolates were positive for β-galactosidase activity. The anthelminthic property with minimum paralysis time and death time between 16-25 min was shown by L.fermentumL8 MW485761. Anti-inflammatory activity with bovine serum albumin was maximum at 200 μg ml-1 concentration. α-amylase inhibitory activity was maximum for L. fermentumL8 MW485761 (51%). Maximum cholesterol assimilation was reported for L. fermentumL6 MW600495 (76%). Strong biofilm forming ability for all isolates improved the colonization and stability as probiotics. Human gut lactobacilli with salutary properties can make an efficient probiotic.

Strongyloides stercoralis and Trichuris trichiura parasitic infections are two of the many neglected tropical diseases. These parasitic infections are of considerable public health relevance, particularly in resource-limited countries. Moxidectin, a well-established drug in veterinary medicine, is now a Food and Drug Administration (FDA) approved medication for human onchocerciasis. For the past five years, this medication has been under clinical trials to evaluate its efficacy and safetiness in other helminthic infections. Moxidectin might complement the already existing treatment and control of soil-transmitted helminthiasis (STH). Therefore, we systematically reviewed existing human interventional studies to evaluate the efficacy and safety of this medication when administered alone or in combination with other antiparasitic medications in order to achieve a cure.