Search Results (99)

Rafoxanide, originally developed as a veterinary anthelmintic for the treatment of parasitic infections in livestock, has recently emerged as a promising therapeutic prospect in oncology. This compound has demonstrated notable antineoplastic effects against a variety of cancers, including skin, gastric, colorectal, and lung cancers, as well as hematological malignancies such as multiple myeloma. Rafoxanide exerts its anticancer activity through multiple complementary mechanisms, including the induction of endoplasmic reticulum stress, cell cycle arrest, apoptosis, and immunogenic cell death. Furthermore, the drug has been reported to inhibit key oncogenic signaling pathways (e.g., STAT3, NF-κB, c-FLIP, survivin) that contribute to tumor growth and metastasis. Preclinical studies in murine models have demonstrated significant reductions in tumor volume of up to 50% and a tumor-free rate exceeding 80%, with effective doses ranging from 7.5 to 40 mg/kg. This multitargeted mode of action distinguishes rafoxanide from conventional therapies and may help overcome resistance mechanisms that often limit the efficacy of cancer treatments. In this review, we summarize and discuss the growing body of evidence supporting rafoxanide’s therapeutic potential in oncology, as well as its possible applications in cancer treatment. Full article

Background: Parasitic worm infections remain among the most prevalent and neglected health issues worldwide, affecting both humans and animals. Toxocariasis, caused by Toxocara spp., is a widespread zoonosis with significant public health and economic implications. Current anthelmintic treatments show limited efficacy, particularly against tissue-migrating larvae, underscoring the urgent need for new therapeutic options. This study aimed to evaluate the anthelmintic potential of H₁ antihistamines as repurposed drug candidates against Toxocara canis. Methods: Twenty-two H₁ antihistamines were screened for larvicidal activity against infective third-stage (L3) larvae of T. canis. Larval motility and morphology were assessed, and compounds with the highest efficacy were further investigated using density functional theory (DFT) to explore their electronic properties. Molecular docking simulations were also performed to predict interactions with T. canis β-tubulin. Results: Promethazine and rupatadine exhibited significant larvicidal effects, surpassing albendazole in reducing larval motility and inducing a distinct contorted morphology not observed in control or albendazole-treated larvae. DFT analyses suggested a strong electron-acceptor capacity, indicating a potential redox-based mechanism of action. Docking studies revealed favorable binding to the colchicine site of T. canis β-tubulin. Conclusions: This is the first report of larvicidal activity of antihistamines against T. canis, supporting their potential as repurposed therapeutic agents for the treatment of zoonotic helminthiases, particularly those caused by tissue-migrating nematodes. Full article

Multi-anthelmintic resistance in hookworms poses a significant challenge to both human and veterinary health, underscoring the need for novel treatment strategies. In this study, we evaluated the in vitro efficacy of three anthelmintics—pyrantel, ivermectin, and emodepside—against L3 larvae of drug-susceptible (WMD) and triple-anthelmintic-resistant (BCR) isolates of Ancylostoma caninum. While pyrantel was largely ineffective and ivermectin induced high mortality in both isolates, emodepside displayed a surprising trend: the drug-resistant BCR isolate was more susceptible than the drug-susceptible WMD isolate. To explore the underlying mechanism, we performed survival assays in the presence of penitrem A, a BK channel (SLO-1) inhibitor. The addition of penitrem A reversed the enhanced emodepside sensitivity in BCR, implicating elevated basal expression of SLO-1 channels as a potential factor. These findings suggest that emodepside, via its action on SLO-1, may offer a promising therapeutic avenue to combat multidrug-resistant hookworm infections. Full article

Parasitic nematodes, such as the zoonotic rat lungworm Angiostrongylus cantonensis, pose a significant global health burden, with current anthelmintics like albendazole showing limited efficacy. Here, we report the isolation of piplartine from Piper truncatum Vell. (Piperaceae) and its potent in vitro activity against A. cantonensis larvae. Piplartine demonstrated superior efficacy to albendazole, with EC₅₀ values of 8.3 µM for first-stage larvae (L1) and 10.4 µM for infective third-stage larvae (L3), compared to 14.2 µM (L1) and 15.6 µM (L3) for albendazole. Notably, piplartine exhibited no toxicity in the Caenorhabditis elegans model at therapeutic concentrations, underscoring its selective antiparasitic action. In silico profiling further revealed favorable drug-likeness and pharmacokinetic properties, including high gastrointestinal absorption and blood–brain barrier permeability, which are critical for targeting neurotropic infections. As the first study to characterize the activity of piplartine against A. cantonensis, our work highlights its potential as a structurally novel anthelmintic lead. Based on the obtained results, piplartine may be considered a promising and accessible candidate for combating angiostrongyliasis and related helminthic infections. Full article

This preclinical study investigated the efficacy and safety of fenbendazole, a broad-spectrum benzimidazole anthelmintic, for the treatment of Gyrodactylus kobayashii in goldfish (Carassius auratus). In vivo bath treatments demonstrated potent, dose-dependent anthelmintic efficacy, achieving 98.58% efficacy at a concentration of 0.02 mg/L and a 48 h EC₅₀ of 0.006 mg/L. A short-duration (6 h) bath at 0.06 mg/L, followed by an 18 h recovery period in dechlorinated water, resulted in complete parasite elimination. However, acute toxicity assay indicated a relatively narrow safety margin for prolonged bath treatments, with a 96 h LC₅₀ of 0.039 mg/L, highlighting the need for caution when employing extended bath treatments. Oral administration of fenbendazole at 20 mg/kg body weight for three consecutive days resulted in an efficacy of 83.35%, which increased to 96.28% by seven days post-treatment. Safety evaluations revealed this regimen induced transient oxidative stress and mild, reversible histopathological alterations in the liver and gills. Biochemical and histological markers indicated a recovery trend, approaching baseline levels by 15 days post-treatment. These findings suggested that oral fenbendazole is an effective and relatively safe anthelmintic treatment against G. kobayashii in goldfish. This study underscores the potential of drug repurposing as an effective strategy for developing novel anthelmintic agents in aquaculture. Full article

Background: Vaccination represents an efficient way to control communicable diseases. Reliable vaccines would reduce the use of anthelmintics drugs and fight against the concern of anthelmintics resistances. Unfortunately, anthelmintic vaccines face many difficulties in their development. One of the most innovative vaccine models in this field is multiepitope vaccines since, based on advances in immunoinformatics, they facilitate immunization against parasites at different stages of their cycles. Objective: In this study, we evaluate the published efficacy of multiepitope vaccines against helminths. Methods: Independent reviewers conducted a comprehensive search of multiple databases until September 20th 2024, following PRISMA 2020 guidelines. The review included original in vivo protection studies using chimeric vaccines with antigenic epitopes in experimental models. Key information was summarized, tabulated, and analyzed, and risk of bias was assessed using the SYRCLE risk tool. Results: A total of 15 preclinical studies were included. In those immunization experiments, parasite load reductions varied from 12.4% to 100%. Conclusions: Overall, this study shows protections in parasite load or lesion in 50–80% and significant survival rates using experimental vaccines including B- and T-cell epitopes in a wide range of helminthic infections. Given the variability of the experiments and the limited available data, there was not a clear correlation between protections and immune responses. Confirmation trials are needed to corroborate the protection and immunological mechanisms reached not only in this initial valuable study but also with other multiepitope candidates. Full article

Gastrointestinal nematode infections are due to a wide number of helminthic genera and species, representing a major concern in goat and sheep farming and leading to different health issues and a general economic loss. Traditional diagnostic tools do not allow for a specific identification and, although a shift towards molecular diagnostic techniques is ongoing, species or genus-specific diagnosis is still poorly implemented. This study describes the development of a novel real-time PCR method for diagnosing Haemonchus sp. and its relative abundance in mixed infections in grazing ruminants. The method employs two primer/probe sets targeting the 18S-rRNA-ITS1-5.8S-ITS2 region: one shared by all strongylids (GEN) and another specific to Haemonchus sp. (HAEM). The method demonstrated optimal efficiency and determination coefficients when applied to serial dilutions of DNA extract. It was then applied in Faecal Egg Count Reduction Test (FECRT) trials conducted on five sheep and five goat farms in northeastern Italy. Seven farms were suspected of overall resistance and only one farm of Heamonchus-related resistance. The results proved the genus-specific approach as valuable in interpreting treatment outcomes and showing concerning levels of anthelmintic treatment ineffectiveness. Further research and sensitization activity is required to encourage the adoption of the method by local farmers and veterinarians. Full article

Benzimidazole derivatives are well known for their anthelmintic activity. Investigating the potential efficacy of new derivatives of this class against various parasites is essential to identify novel drug candidates. For this purpose, an in-house molecular database was screened, and four benzimidazole-based molecules were chosen to evaluate antiprotozoal activity. The compounds (K1–K4) had been previously synthesized through a four-step procedure. The potential in vitro cytotoxic properties of the compounds were assessed against the Leishmania (L.) major strain and L929 mouse fibroblast cells. The tests indicated that K1 (3-Cl phenyl) demonstrated an antileishmanial effect (IC₅₀ = 0.6787 µg/mL) and cytotoxicity at elevated concentrations (CC₅₀ = 250 µg/mL) in healthy cells. These findings were comparable to those of AmpB. The antileishmanial activity values were determined as follows: K2; 8.89 µg/mL, K3; 45.11 µg/mL, K4; and 69.19 µg/mL. The CC₅₀ values were determined as follows: K2, 63 µg/mL; K3; 0.56 µg/mL; and K4, 292 µg/mL. Molecular docking and dynamic simulations were conducted to elucidate the potential mechanisms of action of the test substances. In silico investigations indicated interactions between the compounds and the active site of pteridine reductase 1 (PTR1), which is a biosynthetic enzyme essential for parasite proliferation. N-alkyl benzimidazole-based compounds exhibit potential inhibitory activity against L. (L.) major promastigotes. Therefore, these findings suggest that in vivo evaluation is warranted, and structural modifications may lead to the identification of more effective antileishmanial agents. Full article

Cervical cancer remains a major threat to women’s health, with advanced cases often exhibiting recurrence and metastasis due to cancer stem cells driving therapy resistance. This study evaluated fenbendazole (FBZ), a repurposed veterinary anthelmintic, for its antitumor activity dual targeting cervical cancer cells (CCCs) and cervical cancer stem cells (CCSCs). CD133⁺CD44⁺ CCSCs were isolated from HeLa and C-33 A cell lines via immunomagnetic sorting and validated for stemness. Cell proliferation, cell cycle and apoptosis, and protein expression were detected by MST assay, flow cytometry, and Western blot analysis, respectively. FBZ dose-dependently inhibited proliferation, induced G2/M arrest, and triggered apoptosis in both CCCs and CCSCs. Mechanistically, FBZ upregulated cyclin B1 and phosphorylation of cdc25C-Ser198, while downregulating Wee1, phosphorylation of CDK1, and phosphorylation of cdc25C-Ser216, collectively enforcing G2/M blockade. In vivo, FBZ (100 mg/kg) significantly suppressed tumor growth in xenograft models without weight loss, contrasting with cisplatin-induced toxicity. Survival analysis revealed 100% survival in FBZ-treated mice versus 40% in cisplatin and 0% in untreated controls. These findings demonstrate FBZ’s unique ability to simultaneously target bulk tumor cells and therapy-resistant CCSCs via cell cycle disruption, supported by its preclinical safety and efficacy, positioning it as a promising therapeutic candidate for cervical cancer. Full article

Thelazia callipaeda (T. callipaeda) is a zoonotic ocular parasite that poses a public health risk. Current treatment depends on mechanical parasite extraction and specific prophylactic anthelmintics, but direct ocular deworming agents are limited and expensive, and mechanical removal is often incomplete, causing animal stress and ocular injury. Levamisole eye drops have been applied; however, their efficacy and safety remain undefined. We established a standardized T. callipaeda viability assessment system (TVAS) and an animal infection model to evaluate candidate drugs. In vivo, 5 mg/mL levamisole was administered at escalating frequencies. Ocular symptoms, complete blood count (CBC), and serum biochemistry were measured, and cytotoxicity was assessed using Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays on rabbit conjunctival epithelial cells (RCECs).Four doses of 5 mg/mL levamisole applied at 30 min intervals cleared T. callipaeda from infected eyes within 2 h without significant changes in CBC, serum biochemistry, or ocular symptom scores. CCK-8 and LDH assays indicated minimal cytotoxicity in RCECs within 4 h. However, prolonged exposure (6–12 h) led to a significant decrease in RCEC viability, suggesting potential cytotoxicity with extended use and highlighting the need for further safety evaluation. A regimen of four topical administrations of 5 mg/mL levamisole at 30 min intervals cleared T. callipaeda from infected eyes with minimal cytotoxicity, supporting its safety and efficacy as a topical treatment. Full article

Background/Objectives: Taeniasis, a zoonotic infection, is a common foodborne disease. Niclosamide and praziquantel have proven to be effective in treating it, but the use of the same drugs can lead to resistance, so alternative drugs need to be explored. This study investigated the anthelmintic potential of derived fractions from hydroethanolic extracts (HEs) of Aframomum melegueta (AM) and Xylopia aethiopica (XA), two medicinal plants known for their diverse bioactive properties. Methods: AM-HE fractions (dichloromethane fraction (DCMF), ether fraction (EF), aqueous fraction (AF)) and XA-HE fractions (chloroform fraction (CF), ether fraction (EF), and aqueous fraction (AF)) were used, and in vitro anthelmintic activity was assessed against Taenia spp. by using an adult motility assay for the worm’s paralysis time determination. The parasiticidal and parasitostatic activity was also tested on Taenia spp. adult worms. Cell viability was further evaluated using propidium iodide (PI) staining, with albendazole (20 mg/mL) as the reference drug. Results: The three fractions of each plant exhibited significant, dose-dependent anthelmintic activity, with AM-HE and XA-CF showing the greatest effects at 20 mg/mL. AM-EF demonstrated significant activity at 0.4% and 0.8%. Irreversibility tests revealed that most of the treated worms remained paralysis, except those exposed to the AF of both plants. PI staining confirmed the dose-dependent mortality of Taenia cells treated with HE, DCMF, and AF of AM. Conclusions: These results underscore the potential of AM and XA extracts and fractions as alternative treatments for helminth infections. Further, in vivo studies are warranted to confirm their safety and therapeutic efficacy. Full article

Background: The COVID-19 pandemic necessitated the urgent exploration of therapeutic options, including drug repurposing. Anthelmintic drugs such as ivermectin and mebendazole have garnered interest due to their potential antiviral and immunomodulatory properties. However, conflicting evidence from randomized clinical trials (RCTs) necessitates a comprehensive meta-analysis to determine their efficacy and safety in COVID-19 management. Objective: This meta-analysis evaluates the clinical efficacy of ivermectin and mebendazole in treating COVID-19 by analyzing their impact on viral clearance, symptom resolution, hospitalization duration, and safety profiles. Methods: A systematic search of Scopus, PubMed, Embase, and the Cochrane Library was conducted following PRISMA guidelines to identify RCTs published up to February 2025. Eligible studies included adult patients with confirmed COVID-19 who received ivermectin or mebendazole compared with a placebo or standard of care. Data extraction and risk of bias assessment were performed using the Cochrane Risk of Bias Tool. Statistical heterogeneity was evaluated using the I² statistic, and pooled effect sizes were calculated for primary clinical outcomes. Results: Twenty-three RCTs (n = 12,345) were included, with twenty-one studies on ivermectin and two on mebendazole. The pooled analysis suggested no statistically significant improvement in viral clearance (p = 0.39), hospitalization duration (p = 0.15), or symptom resolution (p = 0.08) with ivermectin or mebendazole. However, individual studies indicated potential benefits, particularly for mebendazole, in reducing viral load and inflammation. Both drugs exhibited favorable safety profiles, with no significant increase in adverse events. Conclusions: The promising propensities observed in selected studies underscore the potential of ivermectin and mebendazole as adjunct therapies for COVID-19. With well-established safety profiles, immunomodulatory effects, and affordability, these drugs present strong candidates for further exploration. Advancing research through well-designed, large-scale RCTs will help unlock their full therapeutic potential and expand treatment options in the fight against COVID-19. Full article

Introduction: Grazing dairy ewes are often heavily challenged by parasitic infections, which represent one of the most important concerns in sheep farming due to their impacts on dairy sheep production. Objectives: The objectives of the present study were (i) to compare the short (i.e., albendazole) and long (i.e., eprinomectin) persistent effect of these anthelmintics in reducing infections by gastrointestinal nematodes (GIN) in ewes and (ii) to determine these effects on milk yield and quality in naturally infected with GIN dairy ewes. Methods: On each farm, 40 selected ewes were divided into four similar groups on Day 0 based on their fecal egg counts (eggs per gram of feces; epg) as follows: Group 1—control group; Group 2—albendazole-treated group; Group 3—pour-on eprinomectin-treated group; Group 4—injectable eprinomectin-treated group. Fecal egg counts and coprocultures were performed on Days 0, 15, 30, 45, 60 and 75. The milk yield and milk quality (i.e., fat and protein concentration and somatic cell counts) were estimated on the aforementioned occasions. Results: Eprinomectin outperformed albendazole in treating gastrointestinal nematode infections in dairy ewes. Both pour-on and injectable eprinomectin formulations provided long-lasting protection by reducing fecal egg counts (i.e., from 92.1% to 99.9%). Furthermore, eprinomectin-treated ewes exhibited increased daily milk yield and improved milk composition in terms of fat and protein concentrations and somatic cell counts. Conclusions: These findings highlight the benefits of long-persistent efficacy of eprinomectin as a preferred anthelmintic treatment for lactating dairy ewes, offering enhanced productivity and milk quality, while addressing parasite resistance concerns. Full article

New alternatives for controlling resistant populations of gastrointestinal nematodes are being studied, including the use of plant compounds and biological control with nematophagous fungi. The objective of this study was to evaluate the in vitro anthelmintic effect of linalool and its association with the fungus Duddingtonia flagrans (isolated AC001) in controlling gastrointestinal nematodes in sheep. The ovicidal activity of linalool was assessed via the Egg Hatch Test (EHT), and the larvicidal activity of linalool, alone and in combination with D. flagrans conidia, was evaluated via the Larval Motility Inhibition Test (LMIT) on infective larvae (L3). In the EHT, 100% inhibition occurred (at 1.25 and 2.5 mg/mL), with an LC50 of 0.49 mg/mL. In the LMIT, linalool alone inhibited 100% of larval motility (at 4% and 8%), with an LC50 of 0.42% or 4.2 mg/mL. In the combination of linalool with D. flagrans, there was a significant reduction in larvae, starting at 24 h, with 100% reduction after 14 days, thus being more effective in reducing L3 compared to the use of the fungus alone. It is concluded that linalool exhibits ovicidal and larvicidal activity, and its association with D. flagrans enhances the fungal predation capacity and potentiates anthelmintic efficacy. Full article

For thousands of years, Vachellia nilotica has been widely used as an herbal medicine to treat some diseases and symptoms, including respiratory, gastrointestinal and urogenital ailments. The present study was adapted to document and assemble existing information about V. nilotica and its evidence-based ethnopharmacological activities, with brief reviews on the description, geographical distribution, ecology, medical uses and phytochemistry. A literature review and information up to 2024 was performed in various scientific databases, including PubMed, Science Direct and Google Scholar. The keywords were “Acacia nilotica”, “Botany”, “ecology”, “Traditional uses”, “Phytochemistry”, “Polyphenols”, “Molecular docking”, “Ethnopharmacological activities” and “toxicity”, among others. V. nilotica has a wide range of uses, with low toxicity, reported in different countries. It can be infused into oils or tea or incorporated into paste, poultice and biscuits, used as an emollient, antidiarrheal, astringent and as an antidote for bite poisons. Glucose and lipid-lowering, anti-inflammatory, analgesic, antipyretic, antioxidant, antihypertensive, antibacterial, antifungal, antiviral and anthelmintic activities are the most prominent. Over 150 chemical components have been identified from V. nilotica that could be associated with its potential actions. Quercetin, rutin, kaempferol, naringenin, catechin, epicatechin, gallic acid, ellagic acid, lupeol and niloticane are its main active constituents. From the research data, and despite the fact that human clinical trials and detailed methodological studies are scarce, V. nilotica has shown wide-ranging activities, though the most robust evidence is related to the treatment of microbial infections, diarrhea, wound and ulcer healing and for topical application. More pharmacological and toxicological studies are required to further elucidate the mechanisms of action, potential side effects, and optimal dosages for these treatments. Additionally, more clinical trials are needed to validate these traditional uses in human populations and to ensure the safety and efficacy of V. nilotica for these applications. This article offers an overview of therapeutic applications by utilizing traditional uses and recent findings on phytochemical studies, and clinical and pharmacological research. Full article