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Human helminthiasis affects approximately one in five people in the world and disproportionally affects the poorest and most deprived communities. Human angiostrongyliasis, caused by nematode Angiostrongylus cantonensis , is a neglected emerging disease with escalating importance worldwide. Chemotherapy is the main control method for helminthiasis, but the therapeutic arsenal is limited. This study aimed to evaluate the antiparasitic and molecular properties of the major available anthelmintic drugs against A. cantonensis in vitro. The first-stage larvae (L1), isolated from feces of an A. cantonensis -infected rat, were exposed to a set of 12 anthelmintic drugs in vitro. The larvae were monitored, and the concentration- and time-dependent viability alterations were determined. From 12 anthelmintic drugs, six (ivermectin, salamectin, moxidectin, pyrantel pamoate, albendazole and levamisole) were identified to affect the viability of A. cantonensis. The macrocyclic lactones (ivermectin, salamectin, moxidectin) and the imidazothiazole levamisole, were the most effective drugs, with IC50 ranging from 2.2 to 2.9 µM and a rapid onset of action. Albendazole, the most widely used anthelmintic in humans, had a slower onset of action, but an IC50 of 11.3 µM was achieved within 24 h. Molecular properties studies suggest that a less lipophilic character and low molecular weight could be favorable for the biological activity of the non-macrocyclic molecules. Collectively, our study revealed that macrocyclic lactones, levamisole, pyrantel pamoate, and albendazole are important anthelmintic agents against A. cantonensis. The results of this in vitro study also suggest that A. cantonensis L1 may be a particularly sensitive and useful model for anthelmintic studies. [ABSTRACT FROM AUTHOR]

Neglected tropical diseases affect the world's poorest populations with soil-transmitted helminthiasis and schistosomiasis being among the most prevalent ones. Mass drug administration is currently the most important control measure, but the use of the few available drugs is giving rise to increased resistance of the parasites to the drugs. Different approaches are needed to come up with new therapeutic agents against these helminths. Fungi are a source of secondary metabolites, but most fungi remain largely uninvestigated as anthelmintics. In this report, the anthelmintic activity of Albatrellus confluens against Caenorhabditis elegans was investigated using bio-assay guided isolation. Grifolin (1) and neogrifolin (2) were identified as responsible for the anthelmintic activity. Derivatives 4–6 were synthesized to investigate the effect of varying the prenyl chain length on anthelmintic activity. The isolated compounds 1 and 2 and synthetic derivatives 4–6, as well as their educts 7–10, were tested against Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum. Prenyl-2-orcinol (4) and geranylgeranyl-2-orcinol (6) showed promising activity against newly transformed schistosomula. The compounds 1, 2, 4, 5, and 6 were also screened for antiproliferative or cytotoxic activity against two human cancer lines, viz. prostate adenocarcinoma cells (PC-3) and colorectal adenocarcinoma cells (HT-29). Compound 6 was determined to be the most effective against both cell lines with IC50 values of 16.1 µM in PC-3 prostate cells and 33.7 µM in HT-29 colorectal cells. [ABSTRACT FROM AUTHOR]

Human helminthiasis affects approximately one in five people in the world and disproportionally affects the poorest and most deprived communities. Human angiostrongyliasis, caused by nematode Angiostrongylus cantonensis, is a neglected emerging disease with escalating importance worldwide. Chemotherapy is the main control method for helminthiasis, but the therapeutic arsenal is limited. This study aimed to evaluate the antiparasitic and molecular properties of the major available anthelmintic drugs against A. cantonensis in vitro. The first-stage larvae (L1), isolated from feces of an A. cantonensis-infected rat, were exposed to a set of 12 anthelmintic drugs in vitro. The larvae were monitored, and the concentration- and time-dependent viability alterations were determined. From 12 anthelmintic drugs, six (ivermectin, salamectin, moxidectin, pyrantel pamoate, albendazole and levamisole) were identified to affect the viability of A. cantonensis. The macrocyclic lactones (ivermectin, salamectin, moxidectin) and the imidazothiazole levamisole, were the most effective drugs, with IC50 ranging from 2.2 to 2.9 µM and a rapid onset of action. Albendazole, the most widely used anthelmintic in humans, had a slower onset of action, but an IC50 of 11.3 µM was achieved within 24 h. Molecular properties studies suggest that a less lipophilic character and low molecular weight could be favorable for the biological activity of the non-macrocyclic molecules. Collectively, our study revealed that macrocyclic lactones, levamisole, pyrantel pamoate, and albendazole are important anthelmintic agents against A. cantonensis. The results of this in vitro study also suggest that A. cantonensis L1 may be a particularly sensitive and useful model for anthelmintic studies.

Neglected tropical diseases affect the world’s poorest populations with soil-transmitted helminthiasis and schistosomiasis being among the most prevalent ones. Mass drug administration is currently the most important control measure, but the use of the few available drugs is giving rise to increased resistance of the parasites to the drugs. Different approaches are needed to come up with new therapeutic agents against these helminths. Fungi are a source of secondary metabolites, but most fungi remain largely uninvestigated as anthelmintics. In this report, the anthelmintic activity of Albatrellus confluens against Caenorhabditis elegans was investigated using bio-assay guided isolation. Grifolin (1) and neogrifolin (2) were identified as responsible for the anthelmintic activity. Derivatives 4–6 were synthesized to investigate the effect of varying the prenyl chain length on anthelmintic activity. The isolated compounds 1 and 2 and synthetic derivatives 4–6, as well as their educts 7–10, were tested against Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum. Prenyl-2-orcinol (4) and geranylgeranyl-2-orcinol (6) showed promising activity against newly transformed schistosomula. The compounds 1, 2, 4, 5, and 6 were also screened for antiproliferative or cytotoxic activity against two human cancer lines, viz. prostate adenocarcinoma cells (PC-3) and colorectal adenocarcinoma cells (HT-29). Compound 6 was determined to be the most effective against both cell lines with IC50 values of 16.1 µM in PC-3 prostate cells and 33.7 µM in HT-29 colorectal cells.

Ozoroa insignis Del. is an ethnobotanical plant widely used in traditional medicine for various ailments, including schistosomiasis, tapeworm, and hookworm infections. From the so far not investigated fruits of Ozoroa insignis, the anthelmintic principles could be isolated through bioassay-guided isolation using Caenorhabditis elegans and identified by NMR spectroscopic analysis and mass spectrometric studies. Isolated 6-[8(Z)-pentadecenyl] anacardic (1), 6-[10(Z)-heptadecenyl] anacardic acid (2), and 3-[7(Z)-pentadecenyl] phenol (3) were evaluated against the 5 parasitic organisms Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum, which mainly infect humans and other mammals. Compounds 1–3 showed good activity against Schistosoma mansoni, with compound 1 showing the best activity against newly transformed schistosomula with 50% activity at 1µM. The isolated compounds were also evaluated for their cytotoxic properties against PC-3 (human prostate adenocarcinoma) and HT-29 (human colorectal adenocarcinoma) cell lines, whereby compounds 2 and 3 showed antiproliferative activity in both cancer cell lines, while compound 1 exhibited antiproliferative activity only on PC-3 cells. With an IC50 value of 43.2 µM, compound 3 was found to be the most active of the 3 investigated compounds.

Objective: To evaluate the anthelmintic property of Saba senegalensis (A.DC) Pichon (Apocynaceae) (S. senegalensis) on Haemonchus contortus that is traditionally used in Burkina Faso for its gastrointestinal parasites treatment. Methods: The lyophilized aqueous decoction of leaves of S. senegalensis at concentrations of 0.10, 1.00, 3.00, 10.00 and 15.00 mg/mL was used on eggs and adult worms of Haemonchus contortus collected from gastrointestinal tract of small ruminant. Results: The LC50 on adult worms was 6.79 mg/mL and 3.25 mg/mL for the leaves of S. senegalensis and the levamisole (reference drug), respectively. Inhibition of hatching assay showed a concentration-dependent manner with an inhibition of 93.63% at the concentration of 15.00 mg/mL of S. senegalensis. Conclusions: These results indicate that the aqueous extract of S. senegalensis possesses an anthelmintic property and may justify its use in traditional medicine for the treatment of gastrointestinal parasites.

Objective To evaluate the anthelmintic property of Saba senegalensis (A.DC) Pichon (Apocynaceae) ( S. senegalensis ) on Haemonchus contortus that is traditionally used in Burkina Faso for its gastrointestinal parasites treatment. Methods The lyophilized aqueous decoction of leaves of S. senegalensis at concentrations of 0.10, 1.00, 3.00, 10.00 and 15.00 mg/mL was used on eggs and adult worms of Haemonchus contortus collected from gastrointestinal tract of small ruminant. Results The LC 50 on adult worms was 6.79 mg/mL and 3.25 mg/mL for the leaves of S. senegalensis and the levamisole (reference drug), respectively. Inhibition of hatching assay showed a concentration-dependent manner with an inhibition of 93.63% at the concentration of 15.00 mg/mL of S. senegalensis . Conclusions These results indicate that the aqueous extract of S. senegalensis possesses an anthelmintic property and may justify its use in traditional medicine for the treatment of gastrointestinal parasites. [ABSTRACT FROM AUTHOR]

The Onobrychis genus comprises a few agronomically important forage legume species, with sainfoin (Onobrychis viciifolia) being the most widespread. O. viciifolia has a long history of traditional culture worldwide, but its use has declined in western countries over the last decades. It suffers from low productivity and is more difficult to maintain than other legumes but is known to have valuable characteristics such as palatability and drought tolerance. Recent studies suggest that it has several other highly beneficial properties due to its unique tannin and polyphenol composition. Condensed tannins present in Onobrychis species have been shown to confer anthelmintic properties, increase protein utilization and prevent bloating; they may also have the potential to reduce greenhouse gas emissions. Positive effects on wildlife and honey production could also be advantageous in the context of sustainable farming. Modern breeding programmes have not been a priority, leading to a lack of genetic knowledge in comparison to extensively used forage legumes. It is expected that potential for O. viciifolia improvements could be achieved by rigorous characterization of the available germplasm and utilization of characters derived from close relatives of the genus. Breeding priorities for the future would include enhanced germination and improved early establishment, allied to the best anthelmintic properties observed in some varieties. [ABSTRACT FROM PUBLISHER]

Abstract: The effects of feeding wilted cassava foliage (WCF) on the growth of Martinik lambs and the parasite Haemonchus contortus (Hc) were evaluated. Thirty 6-month-old Martinik lambs (body weight: 20.3±1.6kg) were allocated to one of the three treatments. The basal diet consisted of Dichanthium spp. hay ad libitum plus cassava tuber (450g/lamb/day). In addition, depending on the experimental treatment, they received alfalfa pellets (450g/lamb/day) or WCF (650g/lamb/day) or WCF (650g/lamb/day)+PEG (25g/lamb/day). At the beginning of the trial, each lamb was inoculated with a single dose of 10,000 third-stage larvae of Hc. The mean faecal egg count decreased by 41% in lamb fed WCF relative to the lucerne control level. Egg development to third-stage larvae was reduced by 60% when excreted by lambs fed on WCF compared to those fed on lucerne. Given the results obtained with animals receiving PEG, the positive effect of WCF on the reduction of Hc parasites may be explained by the action of condensed tannins. The action of the latter on worm fertility is suspected. Due to the high fill value (ADL) relative to the lucerne diet, the consumption of WCF provides limited total energy intake (48.0g vs. 57.6g of digestible dry matter per kg of metabolic weight) and has a depressive effect on lamb growth (120.8g/d vs. 163.5g/d). [ABSTRACT FROM AUTHOR]

Abstract: Two successive completely randomised feeding trials were performed to test the nutritional value and anthelmintic properties of banana foliage in lambs. In the first trial, 40 five-month-old Martinik lambs (body weight: 17.3±4.1kg) were divided into four groups: artificially infected with Haemonchus contortus or non-infected lambs consuming a Dichantium hay or banana foliage diet. In the second trial, 20 lambs fed with a Dichantium hay diet were divided into two groups (Dichantium hay or banana foliage diet) 21days after being infected with H. contortus. Low growth rates were recorded in lambs, which were linked to the low intake of digestible dry matter. The first trial indicated a lack of effect of banana foliage against H. contortus in lambs. In the second trial, a significant positive effect of banana foliage on faecal egg count was observed, illustrating the probable effect of banana foliage on the fecundity of adult worms. [Copyright &y& Elsevier]

Parasitic nematodes are among the most common and economically important infectious diseases of grazing livestock, especially in small ruminants in the tropics and subtropics in Kenya the control of gastrointestinal nematode infections in sheep and goats is usually made with synthetic anthelmintics but substantial levels of anthelmintic resistance have been recorded. A number of medicinal plants, that may provide possible alternatives, and are used by pastoralists and smallholder farmers in Kenya as deworming agents for their livestock and equines, namely Aframomum sanguineum, Dodonea angustifolia, Hildebrandtia sepalosa, Myrsine africana, Rapanea melanophloeos from Kenya, and Azadirachta indica from Kenya and Malaysia, together with the chemicals embelin and santonin that occur in some of these plants, were evaluated against Heligmosomoides polygyrus in mice. Commercial anthelmintics, namely ivermectin, pyrantel and piperazine, were also investigated, both to validate the mouse model system and to assess efficacy of these drugs against H. polygyrus. Pyrantel and ivermectin were highly effective in reducing the numbers of H. polygyrus worms as well as eggs in faeces of the mice, but piperazine had a lower activity. Application of santonin and M. africana significantly reduced the number of total worm counts (TWC) but not faecal egg counts (FEC). The use of embelin, R. melanophloeos and A. indica reduced FEC but not TWC. In all cases, however, reductions were well below the a priori level of 70% required for biological significance. A. sanguineum, D. angustifolia and H. sepalosa had no effect on either TWC or FEC. In conclusion, none of the plant preparations had any biologically significant anthelmintic effect in this monogastric host–parasite model system. [Copyright &y& Elsevier]

Ozoroa insignis Del. is an ethnobotanical plant widely used in traditional medicine for various ailments, including schistosomiasis, tapeworm, and hookworm infections. From the so far not investigated fruits of Ozoroa insignis, the anthelmintic principles could be isolated through bioassay-guided isolation using Caenorhabditis elegans and identified by NMR spectroscopic analysis and mass spectrometric studies. Isolated 6-[8(Z)-pentadecenyl] anacardic (1), 6-[10(Z)-heptadecenyl] anacardic acid (2), and 3-[7(Z)-pentadecenyl] phenol (3) were evaluated against the 5 parasitic organisms Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum, which mainly infect humans and other mammals. Compounds 1–3 showed good activity against Schistosoma mansoni, with compound 1 showing the best activity against newly transformed schistosomula with 50% activity at 1µM. The isolated compounds were also evaluated for their cytotoxic properties against PC-3 (human prostate adenocarcinoma) and HT-29 (human colorectal adenocarcinoma) cell lines, whereby compounds 2 and 3 showed antiproliferative activity in both cancer cell lines, while compound 1 exhibited antiproliferative activity only on PC-3 cells. With an IC50 value of 43.2 µM, compound 3 was found to be the most active of the 3 investigated compounds. [ABSTRACT FROM AUTHOR]

Praziquantel is currently the only drug available to treat schistosomiasis, a disease of enormous public health significance caused by a blood fluke of the genus Schistosoma Diminazene, a drug approved by the FDA, has been successfully used to treat diseases caused by blood protozoan parasites. In this study, we evaluated the antiparasitic properties of diminazene against Schistosoma mansoni ex vivo and in mice harboring either chronic or early S. mansoni infections. In vitro , we monitored phenotypic and tegumental changes as well as the effects of the drug on pairing and egg production. In mice infected with either adult (chronic infection) or immature (early infection) worms, diminazene was administered intraperitoneally (10 to 100 mg/kg of body weight) or by oral gavage (100 to 400 mg/kg), and we studied the influence of the drug on worm burden and egg production. Liver and spleen pathologies and serum aminotransferase levels were also analyzed. In vitro , 50% effective concentrations (EC 50 revealed that diminazene is able to kill both immature and adult parasites, and its effect was time and concentration dependent. In addition, confocal laser scanning microscopy showed morphological alterations in the teguments of schistosomes. In an animal model, the influence of the drug on worm burden, egg production, hepatomegaly, and splenomegaly depended on the dosing regimen applied and the route of administration. Diminazene also caused a significant reduction in aminotransferase levels. Comparatively, diminazene treatment was more effective in chronic infection than in early infection. In tandem, our study revealed that diminazene possesses anthelmintic properties and inhibits liver injury caused by 90 revealed that diminazene is able to kill both immature and adult parasites, and its effect was time and concentration dependent. In addition, confocal laser scanning microscopy showed morphological alterations in the teguments of schistosomes. In an animal model, the influence of the drug on worm burden, egg production, hepatomegaly, and splenomegaly depended on the dosing regimen applied and the route of administration. Diminazene also caused a significant reduction in aminotransferase levels. Comparatively, diminazene treatment was more effective in chronic infection than in early infection. In tandem, our study revealed that diminazene possesses anthelmintic properties and inhibits liver injury caused by Schistosoma eggs., (Copyright © 2020 American Society for Microbiology.)