Gastrointestinal anthelmintic plants used on small ruminants in Benin: Traditional use and scientific results - Review.

In Benin, livestock breeders frequently use medicinal plants to treat gastrointestinal diseases in small ruminants. The aim of this review is to list the plants traditionally used in this context and to present the scientific findings on the efficacy of these plants. An extensive search was carried out using PubMed, Scopus, ScienceDirect, Biomed Central and Google Scholar databases to collect data, with combinations of relevant french and english keywords such as "ethnobotanical survey", "anthelmintic properties", "medicinal plants", "gastrointestinal parasites", "digestive strongyles", "Haemonchus", "Trichostrongylus", "small ruminants", "sheep", "goats" and "Benin". A total of 45 published articles met the eligibility criteria. This review listed 123 plants used by breeders to treat gastrointestinal ailments in small ruminants. The most commonly used parts are leaves and barks, and the most common forms are decoction, maceration and powder. Scientific studies have demonstrated the anthelmintic properties of 18 plants, including Zanthoxylum zanthoxyloides, Newbouldia laevis, Mitragyna inermis and Combretum glutinosum. The powders or leaf extracts of these plants showed in vivo significant reductions of over 50% in egg excretion, larval establishment, viability and fertility of gastrointestinal strongyles in small ruminants. Extracts of these plants also revealed in vitro inhibitory activity of over 50% on egg hatching, larval migration and motility of gastrointestinal strongyles. This manuscript highlights the traditional use of anthelmintic plants in small ruminants in Benin and provides scientific results supporting the efficacy of these plants.

The effectiveness of albendazole against hookworm infections and the impact of bi-annual treatment on anaemia and body mass index of school children in the Kpandai district of northern Ghana.

The impact of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) (initiated in 2000 in Ghana and ran for 12 years) in mitigating soil-transmitted helminth (STH) infections in LF-endemic areas is unknown. During a 1-year hiatus which ensued between 2011 and 2012, a longitudinal study was conducted to determine GPELF effect on hookworm infections in selected communities involved in the programme since its inception, while measuring the effectiveness of biannual ALB treatments on schoolchildren living in such communities. A total of 399 school children aged 3 to 18 years were randomly selected from four communities in the Kpandai district of northern Ghana. Each presented a single stool sample at baseline, 21 days post-treatment, at the 3rd and 6th months, 21 days post-second intervention (i.e. following sample collection and treatment with ALB in the 6th month), and in the ninth month of the study period. Haemoglobin (hb) levels were also measured at all time points using finger prick blood samples and a URIT digital test kit. Each participant submitting a sample, was treated with a single-dose ALB (400mg) at baseline and in the sixth month. Stool samples were processed by preparing duplicate Kato-Katz slides per sample, and examined by microscopy. The Body Mass Index-for-age z-scores (BAZ) of participants were assessed following the determination of BMIs at each time point by measuring their height and weight with a stadiometer and weighing scale. Overall hookworm prevalences were 25.68% (95% CI = 20.51-31.75) at baseline, 11.18% (95% CI = 7.87-15.41) 21 days post-treatment, 11.78% (95% CI = 8.38-16.11) and 6.95% (95% CI = 4.41-10.43) in the 3rd and 6th months, 0.91% (95% CI = 0.19-2.65) 21 days post-second intervention, and 8.46% (95% CI = 5.62-12.23) in the ninth month. Observed overall faecal egg count reduction rates (ERRs) were 94.21% (95% CI = 81.50%- 100.00%) 21 days after baseline treatment, 97.70% (95% CI = 85.08-100.00) and 96.95% (95% CI = 84.18%- 100.00%) in the 3rd and 6th months, 99.98% (95% CI = 86.42%- 100.00%) 21 days post-second intervention, and 17.18% (95% CI = 14.07%- 20.67%) in the 9th month. Respective cure rates (CRs) were 62.35% (95% CI = 46.71-81.56%), 85.88% (95% CI = 67.32-100.00%), 87.06% (95% CI = 68.36%- 100.00%), 98.82% (95% CI = 78.83%- 100.00%), and 36.36% (95% CI = 9.91%- 93.11%). Additionally, increases in the percent frequency of 'normal hb' (p < 0.01) were observed across the study time points, whilst 'normal BAZ' cases remained high (from 94.87% to 98.87%) throughout the study period. These findings primarily indicate satisfactory effectiveness of ALB which may be maintainable in mass drug administration programmes by the modification of treatment strategies from annual to bi-annual regimes. This could minimize the likelihood of emerging poorly-responding hookworm phenotypes in Ghana. Additionally, a positive impact of bi-annual treatment on participant anaemia status is herein indicated with particular regard to the school children in our cohort.

Chicory (Cichorium intybus) reduces cyathostomin egg excretion and larval development in grazing horses.

Cyathostomins are the most prevalent parasitic nematodes of grazing horses. They are responsible for colic and diarrhea in their hosts. After several decades of exposure to synthetic anthelmintics, they have evolved to become resistant to most compounds. In addition, the drug-associated environmental side-effects question their use in the field. Alternative control strategies, like bioactive forages, are needed to face these challenges. Among these, chicory (Cichorium intybus, Puna II cultivar (cv.)) is known to convey anthelmintic compounds and may control cyathostomins in grazing horses. To challenge this hypothesis, we measured fecal egg counts and the rate of larval development in 20 naturally infected young saddle horses (2-year-old) grazing either (i) a pasture sown with chicory (n = 10) or (ii) a mesophile grassland (n = 10) at the same stocking rate (2.4 livestock unit (LU)/ha). The grazing period lasted 45 days to prevent horse reinfection. Horses in the chicory group mostly grazed chicory (89% of the bites), while those of the control group grazed mainly grasses (73%). Cyathostomins egg excretion decreased in both groups throughout the experiment. Accounting for this trajectory, the fecal egg count reduction (FECR) measured in individuals grazing chicory relative to control individuals increased from 72.9% at day 16 to 85.5% at the end of the study. In addition, larval development in feces from horses grazed on chicory was reduced by more than 60% from d31 compared to control individuals. Using a metabarcoding approach, we also evidenced a significant decrease in cyathostomin species abundance in horses grazing chicory. Chicory extract enriched in sesquiterpenes lactones was tested on two cyathostomins isolates. The estimated IC50 was high (1 and 3.4 mg/ml) and varied according to the pyrantel sensitivity status of the worm isolate. We conclude that the grazing of chicory (cv. Puna II) by horses is a promising strategy for reducing cyathostomin egg excretion and larval development that may contribute to lower the reliance on synthetic anthelmintics. The underpinning modes of action remain to be explored further.

In Vitro anthelmintic efficacy of medicinal plant essential oils against Marshallagia marshalli: Evidence on oxidative/nitrosative stress biomarkers, DNA damage, and egg hatchability.

One of the major public health problems is drug resistance in parasitic diseases. It is therefore important to find new active ingredients to combat parasites. Herbal products such as essential oils (EOs) may show promise in treating infections caused by gastrointestinal nematodes (GINs). This study investigated the in vitro anthelmintic activity of the EOs of Lavandula angustifolia and Quercus infectoria against Marshallagia marshalli. The in vitro study was based on an egg hatch test (EHT), adult and larval motility inhibition tests, DNA damage, and several biomarkers of oxidative/nitrosative stress, including superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSH -Px], protein carbonylation [PCO], malondialdehyde [MDA], total antioxidant status [TAS], and nitric oxide levels [NO]. Different concentrations of Lavandula angustifolia and Quercus infectoria EOs (1, 5, 10, 25 and 50 mg/ml) were used to determine the anthelmintic effect on three stages of the life cycle of M. marshalli, i.e. eggs, larvae and adult parasites, for 24 hr. The results showed that EOs of L. angustifolia and Q. infectoria play an important role as anthelmintics. These essential oils significantly reduced the egg hatching and motility of larval and adult worms. This anthelmintic effect is dependent on concentration and time. Furthermore, the EOs of L. angustifolia and Q. infectoria caused oxidative/nitrosative stress (reduced SOD, GSH-Px and CAT and increased MDA, PCO and NO) and DNA damage, thereby providing significant antihelminthic effects. Based on the results, it seems that the EOs extracted from L. angustifolia and Q. infectoria may be effective in the control and treatment of M. marshalli infections. Further research is needed to investigate their potential for in vivo use in the treatment of parasitic infections.

Challenges and opportunities for reducing anthelmintic use in ruminant livestock systems: Insights from a sheep farmer survey in France.

Today's level of anthelmintic use in livestock production is a major threat to both the livestock industry and the environment. In this context, the research community is looking for ways to equip farmers with preventive and treatment strategies that can decrease livestock-industry dependence on anthelmintics. Production practices for a sustainable control of parasites have been advocated for almost forty years, but farmers' uptake of these practices has been too slow to address the issues at stake. In this paper, we examine the rationales behind the under-adoption of sustainable worm control practices in grassland-based livestock systems. This research builds on 25 semi-structured interviews with dairy sheep farmers in southwestern France. The interview material was analysed via qualitative discourse analysis. We highlight farmers' social representations and rationales underpinning adoption or non-adoption of the 'low anthelmintics use' strategy. We identify six profiles for nematode control according to the way each farmer included treatment and coprology in their on-farm practice. We identify that the low-use strategy has low adoption potential due to its low perceived relative advantage; low perceived trialability; unclear compatibility with previous experiences, needs, and values; and higher complexity than the status quo option. We show that holistic, pro-environmental, and collaborative attitudes are associated with adoption of the low-use strategy. We then discuss ways to improve uptake, such as increased communication, trainings, and farm visits involving farmers, extension agents and veterinarians.

Bioactive compounds from the parasitic plant Arceuthobium vaginatum inhibit Haemonchus contortus egg hatching.

The aim of this study was to assess the in vitro ovicidal activity of an ethyl acetate extract from Arceuthobium vaginatum (EtOAc-E) and their subfractions (AvR5-AvR14) against Haemonchus contortus using the egg hatching inhibition (EHI) test. The EtOAc-E and subfractions were tested at 0.12-2.00 and at 0.015-2.0 mg/mL, respectively. Distilled water and methanol (2%) were used as negative controls and Thiabendazole (0.10 mg/mL) as a positive control. Treatments with a dependent effect on concentration were subjected to regression analysis to determine the effective concentrations (EC50 and EC90). The major secondary compounds present in the extract and subfractions were identified by high performance liquid chromatography (HPLC). The EtOAc-E and AvR9 exhibited the best ovicidal effect recording 97.5 and 100% of EHI at 0.25 mg/mL, respectively. The EtOAc-E and AvR9 displayed an EC50= 0.12 and 0.08 mg/mL, respectively. The HPLC analysis in the EtOAc-E and bioactive fractions indicated the presence of a polyphenol, glycosylated flavanones, quercetin glucoside, cinnamates, coumarin, cinnamic acid derivative, ferulic acid, coumarate, naringenin, protocatechuic acid and naringin. Results demonstrated that A. vaginatum extract and fraction is able to inhibit the egg hatch process of H. contortus and could be a viable option for the control of small ruminant haemonchosis.

Evaluation of the ovicidal activity and fasciolicidal activity of the extract of ethyl acetate from Artemisia ludoviciana Nutt. spp. mexicana and of artemisinin against adult parasites of Fasciola hepatica.

The objective of this work was to evaluate the effect of the ethyl acetate extract from A. ludoviciana (EALM) and artemisinin against adult parasites and eggs of F. hepatica. For the ovicidal assay, cell culture plates with 24 wells were used, and 90 to 110 F. hepatica eggs were placed in each well. The eggs were exposed to concentrations of 100, 200, 300, 400, and 500 mg/L EALM and incubated for 16 days. Additionally, triclabendazole (TCBZ) was used as a reference drug at concentrations of 10 and 50 mg, and the response of artemisinin at concentrations of 10 and 20 mg was simultaneously assessed. Adult flukes were exposed to concentrations of 125, 250, 375, and 500 mg/L EALM. The results of the ovicidal action of EALM on the eggs showed that concentrations greater than 300 mg/L were significant, with ovicidal percentages greater than 60% observed on day 16 of incubation (p < 0.05). The maximum efficiency of EALM on adult flukes was reached 72 h post-exposure at a concentration of 125 mg/L (p < 0.05).

PRESCRIBING PATTERNS AND THE USE OF ANTHELMINTIC DRUGS IN COLOMBIAN PATIENTS: A CROSS-SECTIONAL STUDY.

Intestinal parasites continue to be a public health problem in low- and middle-income countries. Broad use of anthelmintics during deworming programs is still necessary in many regions. However, description of the usage of these medications in general medical practice has been limited. The objective of this study was to determine the use of anthelmintic drugs and their indications in a group of Colombian patients. This was a descriptive study from a drug-dispensing database, identifying patients with prescriptions for anthelmintic drugs. A total of 381 cases were randomly selected, and their medical records were reviewed, analyzing sociodemographic, clinical, and pharmacological variables (indication of use). The lack of diagnosis registration or clinical manifestations of parasites was determined as a prescription without indication. In total, 50.9% (n = 194) of patients were female, and 67.4% of all patients were under 18 yr of age. The diagnosis of helminthiases was clearly stated in 114 (29.9%) patients, and only 4.2% (n = 16) of these had microbiological confirmation. The most commonly used anthelmintic drug was albendazole (70.4% of all prescriptions). The use of anthelmintics was not indicated in 266 cases (69.8%). Nutritional supplements or vitamin prescriptions were associated with using anthelmintics without indication (odds ratio: 2.25; 95% confidence interval: 1.26-4.03). A high proportion of patients lacked symptoms or diagnoses in their clinical records that supported the use of anthelmintic drugs.

Therapeutic Potential of Natural Products in the Treatment of Schistosomiasis.

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 Schistosoma Mansoni, S. japonicum, and S. haematobium, 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.

Emerging alternatives to traditional anthelmintics: the in vitro antiparasitic activity of silver and selenium nanoparticles, and pomegranate (Punica granatum) peel extract against Haemonchus contortus.

Haemonchus contortus (H. contortus) is one of the most prevalent gastrointestinal nematodes, causing health problems and economic losses in ruminants. Nanotechnology holds great promise as a field of science, with potential applications in veterinary medicine. This study investigated the in vitro anthelmintic activity of silver nanoparticles (AgNPs), selenium nanoparticles (SeNPs), and pomegranate peel extract (Punica granatum; PPE) on different stages of H. contortus: eggs, larvae, and adults. The in vitro anthelmintic efficacy was evaluated using the egg hatching inhibition assay (EHA), the third larval stage paralysis assay (LPA), and the adult worm motility inhibition assay (WMI). Six dilutions of PPE were utilized for EHA, LPA, and WMI, ranging from 0.25 to 6 mg/ml. AgNPs dilutions ranged from 0.00001 to 1.0 µg/ml for EHA and LPA and 1 to 25 µg/ml for WMI. SeNPs were utilized at dilutions of 1, 5, 10, and 15 µg/ml for EHA, LPA, and WMI. The results showed that the lowest concentration of AgNPs, SeNPs, and PPE significantly inhibited egg hatching. To further assess larvicidal activity, AgNPs at the highest concentration of 1 µg/ml induced a strong larvicidal effect, as did SeNPs at the lowest concentration. On the contrary, PPE displayed a significant larvicidal effect at 1 mg/ml compared to the control. The percentage mortality of adult H. contortus was measured as follows (mortality (%) = the number of dead adult H. contortus/total number of adult H. contortus per test × 100). The death of the adult H. contortus was determined by the absence of motility. Adult H. contortus mortality percentage was also significantly affected by all three agents when compared to the control. The AgNPs, SeNPs, and PPE have effective antiparasitic activity on gastrointestinal parasitic nematodes. These results provide evidence of the excellent antiparasitic properties of AgNPs, SeNPs, and PPE, demonstrating their effectiveness in controlling eggs, larvae, and adult H. contortus in vitro.

Supplementation of minerals and vitamins influences optimal targeted selective treatment thresholds for the control of gastro-intestinal nematodes in lambs.

Targeted Selective Treatment (TST) is a gastrointestinal nematode (GIN) control strategy where anthelmintic treatment decisions are made at an individual animal level. TST has been proven to reduce anthelmintic use and subsequently slow down anthelmintic resistance development, however questions remain regarding optimal TST methods and their applicability across farms. In this study, the influence of Mineral and Vitamin (MV) supplementation on optimal energy utilisation (EU) TST thresholds was assessed on three Welsh farms. In total, 360 lambs were split into two groups, MV supplemented and control, and were treated with an anthelmintic against GIN at the midway point of the experiment. Lambs that improved their EU efficiency post treatment were deemed to have benefited from anthelmintic treatment. Optimal EU TST thresholds was determined for each treatment group per farm using Youden's J statistic where the treatment threshold retrospectively exhibiting the greatest combined sensitivity and specificity in correctly identifying lambs benefiting from treatment was deemed to be optimal. Results demonstrated that the optimal EU TST threshold was higher in MV supplemented groups at 0.72, 0.71 and 0.56 versus 0.58, 0.67, 0.51 for control groups on each respective farm. Identification of lambs for TST was more effective when using an optimised EU TST threshold, compared to when using the standard EU TST threshold of 0.66. The study highlights that applying standard EU TST thresholds may not be appropriate on all commercial farms with factors including MV status as noted in this study likely to influence optimal EU TST thresholds. Additional refinement of TST systems can further strengthen their applicability across sheep flocks.

Anthelmintic activity of European fern extracts against Haemonchus contortus.

Most drugs used in the treatment of helminthiasis in humans and animals have lost their efficacy due to the development of drug-resistance in helminths. Moreover, since anthelmintics, like many pharmaceuticals, are now recognized as hazardous contaminants of the environment, returning to medicinal plants and their products represents an environmentally friendly way to treat helminthiasis. The goal of the present study was to test the anthelminthic activity of methanol extracts of eight selected European ferns from the genera Dryopteris, Athyrium and Blechnum against the nematode Haemonchus contortus, a widespread parasite of small ruminants. Eggs and adults of H. contortus drug-susceptible strain ISE and drug-resistant strain WR were isolated from experimentally infected sheep. The efficacy of fern extracts was assayed using egg hatch test and adults viability test based on ATP-level measurement. Among the ferns tested, only Dryopteris aemula extract (0.2 mg/mL) inhibited eggs hatching by 25% in comparison to control. Athyrium distentifolium, Dryopteris aemula and Dryopteris cambrensis were effective against H. contortus adults. In concentration 0.1 mg/mL, A. distentifolium, D. aemula, D. cambrensis significantly decreased the viability of females from ISE and WR strains to 36.2%, 51.9%, 32.9% and to 35.3%, 27.0%, 23.3%, respectively in comparison to untreated controls. None of the extracts exhibited toxicity in precise cut slices from ovine liver. Polyphenol's analysis identified quercetin, kaempferol, luteolin, 3-hydroxybenzoic acid, caffeic acid, coumaric acid and protocatechuic acid as the major components of these anthelmintically active ferns.

Anti-angiogenic and anti-proliferative activity of ziziphus leaf extract as a novel potential therapeutic agent for reducing hepatic injury in experimental hamster schistosomiasis.

BACKGROUND: Schistosomiasis is one of the most prevalent helminthic infections worldwide. Praziquantel (PZQ) resistance poses a possible danger to the disease's ability to be controlled. Little is known about the role of Ziziphus spina-christi leaf extract (ZLE) in the treatment of hepatic schistosomiasis. However, no study has explored ZLE's anti-angiogenic and anti-proliferative activity as a possible mechanism for reducing hepatic injury in this context. Therefore, this study aimed to evaluate the therapeutic potential of ZLE as an anti-angiogenic, and anti-proliferative agent in hamsters infected with S. mansoni. METHODS: Fifty hamsters were used and divided into 5 groups (10 hamsters each); noninfected untreated (controls), noninfected treated with ZLE, infected untreated, infected treated with PZQ- and infected treated with ZLE. Anti-angiogenic and anti-fibrotic effects of the drugs were assessed pathologically through the immunohistochemical expression of VEGF, Ki-67, and TGF ß1 in liver sections. Some oxidative stress parameters were measured in hepatic homogenates (NO, GSH, GST, and SOD), and serum liver enzymes were also assessed. RESULTS: A significant decrease in worm burden, granuloma size, granuloma area, and numbers in the ZLE- and PZQ-treated groups compared to the infected untreated group, and the decrease in granulomas number and tissue egg load was significantly lower in PZQ treated group compared to ZLE treated group (p<0.05). ZLE exhibited significant anti-angiogenic and anti-fibrotic effects on granulomas, illustrated by significantly lower expression of VEGF and TGF-ß1 than infected untreated and PZQ-treated groups. ZLE exhibits antiproliferative activity evidenced by a significant reduction of positive Ki-67 hepatocytes percentage compared to the infected untreated group. Moreover, ZLE exhibits potent antioxidant effects evidenced by a significantly lowered NO and conservation of hepatic GSH, GST, and SOD in hepatic homogenates compared to infected untreated and PZQ-treated groups (p<0.05). CONCLUSION: Our results point to ZLE as a promising hepatoprotective therapeutic tool in the treatment of schistosome hepatic fibrosis as it has anti-angiogenic, anti-proliferative, anti-fibrotic, and antioxidant effects in hamsters infected with S. mansoni, providing scientific support for its use in conventional medicine.

Antiparasitic properties of 4-nerolidylcatechol from Pothomorphe umbellata (L.) Miq. (Piperaceae) in vitro and in mice models with either prepatent or patent Schistosoma mansoni infections.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIMS OF THIS STUDY: 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. MATERIALS AND 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.

Ethnobotanical knowledge on native Brazilian medicinal plants traditionally used as anthelmintic agents - A review.

Intestinal helminthiasis is a neglected disease that affects a significant portion of the global population, specifically in developing countries, where medicinal plants are widely used for therapeutic purposes. With the purpose to identify the native species used in traditional Brazilian medicine for the management of helminthiasis, ethnopharmacological books edited in Brazil documenting the folk use of medicinal plants were analyzed. The native species cited in at least three studies were selected, and bibliographic research was performed using electronic databases to identify their scientifically validated anthelmintic properties. The search retrieved 133 native species belonging to 88 genera and 43 families from all six Brazilian biomes. Fabaceae (14 Genera and 25 Species) and Asteraceae (7 Genera and 8 Species) were the most frequently cited families. The most reported native species were Baccharis crispa Spreng., Hymenaea courbaril L., Senna occidentalis (L.) Link, Carapa guianensis Aubl., Stachytarpheta cayennensis (Rich.) Vahl, Annona glabra L., Hymenaea stigonocarpa Mart. ex Hayne, Spigelia anthelmia L., Simarouba versicolor A.St.-Hil. and Anacardium occidentale L. Bark (19%) and leaves (17%) were the most commonly used plant parts, and decoction (27%) was the most preferred method of preparation. Evidence of the anthelmintic properties of most species was confirmed using in vitro assays for key human and animal parasites, including Haemonchus contortus, Hymenolepis diminuta, Schistosoma mansoni and Trichostrongylus spp. The species S. alata, S. occidentalis, A. occidentale, and S. anthelmia have been the subject of many biological studies, supporting their use as vermicides. The overall results obtained in this review revealed that Brazil is rich in traditional herbal medicines used to manage helminthiasis; however pharmacological investigations are lacking to confirm their therapeutic properties. Thus, this study could serve as a baseline to validate their use and encourage further clinical investigation of their vermifuge potential.

Evaluation of a combination of Citrus aurantium var. Dulcis essential oil and albendazole for the treatment of sheep gastrointestinal nematodes.

Citrus fruits are consumed all over the world and their by-products are used for animal feed and essential oils production. This study aimed to evaluate the in vitro and in vivo activity of Citrus aurantium var. Dulcis essential oil (CaEO) combined with ABZ against benzimidazole resistant Haemonchus contortus. In vitro egg hatching assays (EHA) were performed using CaEO and ABZ to estimate the effective concentration to achieve 50% egg death (EC50) values and calculate the test essential oil and drug combinations using a simplex-centroid mixture design. These concentrations were used for a second round of EHAs. Sixteen sheep were randomly allocated into two groups and treated with ABZ and the combination of CaEO and ABZ, and faecal egg count reduction tests were performed. In the first round of EHA, CaEO and ABZ showed EC50 values of 0.57 and 0.0048 mg mL-1, respectively. The H. contortus strain used in the study was shown to be highly benzimidazole resistant, with only 1.5% of parasites having susceptible ß-tubulin SNP genotypes. The ABZ reduced the shedding of nematode eggs by 78%, however, its combination with CaEO reduced faecal egg counts by only 9%. The present study is important to highlight the interferences of natural products in anthelmintic metabolism and consequently in drug efficacy.

Clinostomum complanatum: Anthelmintic potential of curcumin on the infective progenetic metacercarial stage.

The emerging resistance against commonly used antiparasitic drugs has driven investigators to explore alternative approaches using plant-derived active ingredients. These compounds have been tested for antiviral, antibacterial, and anthelmintic properties, particularly against adult worms. However, their effects on larval forms have been neglected. Curcumin is a polyphenol that is a significant constituent of the rhizome of Curcuma longa and possesses various biological activities, including antioxidant, anti-inflammatory, anti-infectious, and anti-carcinogenic. In the present study, the anthelmintic potential of curcumin was tested in vitro for its efficacy against the zoonotically important larval form, the progenetic metacercariae of Clinostomum complanatum, which were procured from the forage fish, Trichogaster fasciatus. Curcumin produced time and concentration-dependent inhibition in the motility of treated metacercarial worms, with the maximum inhibition of motility reported at 60 µM along with a significant increase of (36-92%) in ROS and (57-112%) in GSH levels at the end of a period of 6 h. In contrast, curcumin at the highest concentration significantly inhibited the activities of the antioxidant and detoxification enzymes SOD (36%) and GST (16%), respectively, in addition to altering the polypeptide profile and inhibiting cysteine proteases. The tegumental surface appeared to be highly disrupted in curcumin-treated worms, exhibiting severe blebbing, shearing of the tegument, and spine erosion. Such changes would affect the tegumental functions and survival of worms in the hostile microenvironment. This would render worms more susceptible to host-mediated rejection responses. Based on the results of the present study, it is inferred that C. complanatum could serve as an excellent model for screening novel anthelmintic drugs against larval trematodes of great economic significance. Furthermore, we conclude that curcumin could be exploited as an excellent phytotherapeutic agent against the virulent larval form under investigation.

Red palm olein-enriched biscuit supplementation lowers Ascaris lumbricoides reinfection at 6-month after anthelmintic treatment among schoolchildren with vitamin A deficiency (VAD).

Notwithstanding the global efforts made to control intestinal parasitic infections, soil-transmitted helminth (STH) infections are still one of the most prevalent infections globally, especially in developing countries. A double-blinded, randomized controlled trial was conducted on 343 primary schoolchildren (8-12 years old) with vitamin A deficiency (VAD) in rural areas of Malaysia to investigate the effects of red palm olein (RPO)-enriched biscuits on STH reinfection rates and infection intensities. The effects of the RPO-enriched biscuits (experimental group, n = 153) and palm olein (PO)-enriched biscuits (control group, n = 190), were assessed at 3- and 6-month after the administration of complete triple-dose albendazole (one dose of 400 mg for three consecutive days). The overall STH infection rate at baseline was recorded at 65.6%. At 6-month, a significantly lower reinfection rate of A. lumbricoides was observed in the experimental group (35.3%) compared to the control group (60.0%) (P< 0.05), and a significant reduction in fecal egg count (epg) of A. lumbricoides was observed in the experimental group from baseline (P< 0.001), but no significant reduction was observed in the control group. No significant differences in the reduction of infection intensities of T. trichiura and hookworm were observed between experimental and control groups at 3- and 6-month (P>0.05). These findings suggest the potential beneficial effects of RPO-enriched biscuit supplementation on the reinfection of A. lumbricoides, which could be attributed to its high carotenoids content by enhancing host immune response and mucosal epithelium integrity. However, further studies are warranted to confirm whether RPO supplementation could result in similar parasite-specific beneficial effects in other community settings, as well as to explore the underlying mechanisms.