Antiparasitic activity

Thymol is one of the most important phytochemical components because of its pharmacological and bioactive potential effects. This review focuses particularly on thymol as an alternative natural antiparasitic with potential use in the pharmaceutical industry. This is in line with the preferences of the natural products for treatment being safer and without side effects. The biosynthesis pathways of thymol and carvacrol have been discussed, and mechanism of action of thymol on parasites. Studies on thymol confirmed the activity of thymol as anti-parasite against anthelmintic, Trypanosoma ssp., Toxoplasma gondii, Leishmania spp., Plasmodium falciparum, Giardia duodenalis, Eimeria ssp., Cryptosporidium baileyi and Cryptosporidium galli.

Linearolactone (1) and kaempferol (2) have amebicidal activity in in vitro studies. The type of cell death induced by 1 and 2 and their effects on the virulence of E. histolytica were analyzed by transmission and confocal electron microscopy, reactive oxygen species (ROS) production, and apoptosis, detected by flow cytometry with dichlorofluorescein 2′,7′-diacetate and annexin-V binding, respectively, and confirmed by TUNEL. The interaction of 1 and 2 with actin was analyzed by docking, and the in vivo amoebicidal activity was established with the Mesocricetus auratus model; amebic liver abscess (ALA) development was evaluated by magnetic resonance (MR) and validated post mortem. In vitro, compounds 1 and 2 caused chromatin condensation, intracellular ROS, and loss of actin structures. Coupling analysis showed that they bind to the allosteric and catalytic sites of actin with binding energies of −11.30 and −8.45 kcal/mol, respectively. Treatments with 1 and 2 induced a decrease in ALA formation without toxic effects on the liver and kidney. Thus, compound 1, but not 2, was able to induce apoptosis-like effects in E. histolytica trophozoites by intracellular production of ROS that affected the actin cytoskeleton structuration. In vivo, compound 1 was more active than compound 2 to reduce the development of ALA. A mebiasis, caused by Entamoeba histolytica, is acquired after ingesting food or water contaminated with cysts, which excyst and give rise to trophozoites, which grow in the intestine. Once it is colonized, trophozoites invade the tissue and migrate to different organs, such as the liver. To date, the most commonly used treatment is metronidazole. However, studies have demonstrated the development of resistance to this drug, both in vitro and in vivo. 1 Therefore, there is a need to search for new, safer, and more effective antiamoebic drugs. Linearolactone (1) is a neo-clerodane diterpenoid isolated from Salvia polystachya, 2 and kaempferol (2) 3 is a flavonol isolated from Cuphea pinetorum, which have been characterized previously. Their antiprotozoal activities has been demonstrated in vitro, 2 where the half-maximal inhibitory concentrations (IC 50) of these compounds were established against Giardia lamblia and E. histolytica. Recently, it was reported that 2 inhibits the growth of E. histolytica by altering the functions of the cytoskeleton. 4 Based on these reports, 1 and 2 are considered good candidates to develop antiamoebic treatments. 3 However, the action mechanism of these specialized metabolites in animal models has not been described. In this work, we determined the type of death induced by 1 and 2 on E. histolytica trophozoites. The antiamoebic effect of both compounds on the development of amoebic liver abscess in a Mesocricetus auratus model was also analyzed, 5 and the potential toxic effects during the administration of the treatments were also examined.

The steady increase in the price of protein feed ingredients and the retraction of antibiotics from diets has encouraged nutritionists to search the alternatives for protein source and functional feedstuffs that can substitute the role of antibiotic growth promoters in poultry production. With crude protein of 24-30%, in vitro protein digestibility of 80% and proportion of essential amino acids of 47%, seed from ripe papaya may be exploited as the alternative protein feed ingredient for poultry. Moreover, the growth promoting effect, antimicrobial and antiparasitic activities, and immunomodulatory and antioxidative activities may confirm the potential of papaya seed as a functional feedstuff that could replace the role of antibiotic growth promoters for poultry. The in-depth study is needed to further elucidate the functionalities of papaya seed on poultry. This review provides the updates on the nutritional contents of papaya seed, the potential of papaya seed as an alternative to conventional protein-rich ingredient, the growth-promoting effect of feeding papaya seed, the antimicrobial and antiparasitic activities of papaya seed, antioxidative activities of papaya seed, and the immunomodulatory activity of papaya seed on poultry.

Parasitic infestation of carp fish is a major challenge for commercial fish farmers of northwest Bangladesh. Commercial fish farmers of this region are using emamectin benzoate (a plant pesticide) for water treatment of parasite infested fish ponds. The study was conducted to know the practice of using emamectin benzoate (water treatment at the rate of 2µg/L pond water and feed at the rate of 50µg/kg fish for seven consecutive days) impact on zooplanktons, aquatic insects and benthos population in aquaculture ponds. Regular sampling of zooplanktons, aquatic insects and benthos were done and counted at pretreatment and after 1, 2, 5, 10, 15, 21 and 28 days of the treatment for both methods of treatment. Though both the feeding and water treatment with emamectin benzoate was found to be equally successful in killing the target fish parasites, however, the unintended impact of the water treatment was found to be huge on zooplanktons and benthos population. Aquatic insects were also found to be affected partially. Moreover, choice of application method creates a great difference (water treatment requires many times more) in amount of total emamectin benzoate required for the treatment and ultimately used in the water body.

Thymol is one of the most important phytochemical components because of its pharmacological and bioactive potential effects. This review focuses particularly on thymol as an alternative natural antiparasitic with potential use in the pharmaceutical industry. This is in line with the preferences of the natural products for treatment being safer and without side effects. The biosynthesis pathways of thymol and carvacrol have been discussed, and mechanism of action of thymol on parasites. Studies on thymol confirmed the activity of thy-mol as anti-parasite against anthelmintic, Trypanosoma ssp., Toxoplasma gondii, Leishmania spp., Plasmodium falciparum, Giardia duodenalis, Eime-ria ssp., Cryptosporidium baileyi and Cryptosporidium galli.

Chagas disease is caused by Trypanosoma cruzi, being considered a public health problem. An alternative
to combat this pathogen is the use of natural products isolated from fruits such as Eugenia uniflora, a plant
used by traditional communities as food and medicine due to its antimicrobial and biological activities.
Ethanolic extract from E. uniflora was used to evaluate in vitro anti-epimastigote and cytotoxic activity.
This is the first record of anti-Trypanosoma activity of E. uniflora, demonstrating that a concentration presenting
50% of activity (EC50) was 62.76 lg/mL. Minimum inhibitory concentration (MIC) was 61024 lg/
mL. Our results indicate that E. uniflora could be a source of plant-derived natural products with anti-epimastigote
activity with low toxicity.

Context: Scanning electron microscopy (SEM) has become a useful tool for the study of the ultrastructural changes of the surface of the Schistosoma worms in response to chemotherapy as well as evaluation of serum acetylcholinesterase (AChE) determine safety of the drug on
cholinergic function. Aims: The aim was to study the effect of Mirazid (MZD) on the teguments of Schistosoma mansoni worms recovered from infected mice and its effect on the cholinergic function of treated animals compared to praziquantel (PZQ). Materials and Methods: Forty
albino mice were enrolled in four groups of ten mice each: Group 1: normal group; Group II: infected control given only the vehicle; Group III: infected mice treated orally with MZD in a dose of 500 mg/kg for 5 days at 7‑week postinfection; and Group IV: infected mice treated
orally with PZQ 500 mg/kg for 2 days. Two‑week posttreatment, mice were sacrificed and Schistosoma worms were examined by SEM and blood samples were taken for estimation of serum AChE. Statistical Analysis Used: The data of serum AChE level were analyzed using Student’s t‑test for comparison of means. Results: PZQ caused extensive tegumental damages in male and female worms in the form of rupture of tubercles and loss of spines in male worms and ulceration in female worms. MZD showed tegumental damages with shrinkage of the outer surface of male tubercles with marked loss of spines and mild ulceration in female worms. The two drugs showed nonsignificant effect on serum AChE compared to the normal mice. Conclusions: MZD showed potent antischistosomal activity but lower than that of PZQ and the two drugs had no effect on cholinergic function at the studied dose.

Series of new metronidazole urea and thiourea derivatives have been prepared in good yields through reactions of 2-(2-methyl-5-nitroimidazolyl)ethyl amine hydrochloride with various cyanates and isothiocyanates. Similarly, metronidazole salicylic acid derivatives were synthesized by reacting 2-(2-methyl-5-nitro-1H-imidazol-1-yl) ethyl 4-methyl benzene sulfonate (98) with meta and para hydroxy benzoic acids. Structures of the newly prepared compounds were confirmed through different spectroscopic methods such as 1H-NMR, 13C-NMR, mass spectrometry and also by elemental analyses. The antigiardial and antitrichomonal activities of the prepared compounds were evaluated in vitro. Compounds 3a, 3b, 3c, 6a, and 6b exhibited remarkable antigiardial activitiy and were found to be more active than metronidazole with IC50 of 6.4, 5.25, 5.36, 5.90, and 4.95 µg/mL, respectively, while compounds 3a, 3d, and 3g displayed the most antitrichomonal activity with IC50 of 6.3, 6.3, and 5.2 µg/mL, respectively.

This study was performed on the derived fractions [chloroform (FT-C), ethyl acetate (FT-E) and n-butanol (FT-B)] of the 70% ethanol extract prepared from Frankenia thymifolia, endemic to North Africa. The fractions showed high total phenolic and flavonoid contents particularly FT-E. These results agreed with their antioxidant effects. Indeed, all the fractions were able to scavenge 1,1-diphenyl-2-picrylhydrazyl radical, with a better power of FT-E. These results were supported by the inhibition of β-carotene oxidation assay. The fractions showed moderate activity against Acanthamoeba castellanii and Leishmania amazonensis with a better activity of FT-E against A. castellanii. Moreover, FT-B exhibited an interesting antimicrobial activity against all tested bacteria. The phytochemical investigation of the most active fractions (FT-E and FT-B) led to the isolation and structural determination of six compounds. The observed biological activities may be associated with the presence of quercetin and its derivatives found in the chemical composition of these fractions.

A doença de Chagas e a leishmaniose são doenças que prevalecem em países pobres. Os fármacos disponíveis para o tratamento dessas doenças são altamente tóxicos, sendo este um dos motivos que dificulta à adesão terapêutica e, assim, levando à busca por novas drogas eficazes e seguras para seus tratamentos. A pesquisa utilizando produtos naturais tem se mostrado uma alternativa na procura de novos compostos com potencial clínico-terapêutico. O gênero Passiflora possui as seguintes atividades farmacológicas centrais como calmantes, sedativas, ansiolíticas e indutor do sono e atividades antiparasitarias. A Passiflora cincinnata possui ampla distribuição pelo Brasil sendo popularmente utilizada para distúrbios de sono. Neste estudo avaliamos sua atividade antiparasitária contra Leishmania brasiliensis, Leishmania infantum e Trypanosoma cruzi, bem como sua citotoxicidade em fibroblastos. Foram testados extratos hidroalcoólicos obtidos das folhas, casca, sementes e caule em diferentes concentrações. Os extratos das folhas, casca e sementes não foram eficazes contra L. brasiliensis e T. cruzi, porém, o extrato do caule promoveu uma inibição de 29,12 % contra T. cruzi numa concentração de 500 μg/mL, entretanto o extrato da casca de P. cincinnata foi o que apresentou a melhor atividade contra as formas parasitárias de L. infantum, causando um percentual de morte >20 % nas concentrações de 250 a 1000 μg/mL. Referente à toxicidade, o extrato das folhas foi o que apresentou maior citotoxicidade, quando comparado com os demais, causando a mortalidade de 68,63 % dos fibroblastos numa concentração de 1000 μg/mL. A baixa citotoxicidade revelada abre espaço para novos estudos biológicos

The treatment of leishmaniasis includes pentavalent antimony drugs but, because of the side effects, toxicity and cases of treatment failure or resistance, the search of new antileishmanial compounds are necessary. The aims of this study were to evaluate and compare the in vitro antileishmanial activity of four green tea catechins, and to assess the efficacy of topical (−)-epigallocatechin gallate in a cutaneous leishmaniasis model. The antileishmanial activity of green tea catechins was evaluated against intracellular amastigotes, and cytotoxicity was performed with human monocytic cell line. BALB/c mice were infected in the ear dermis with Leishmania (Leishmania) amazonensis and treated with topical 15% (−)-epigallocatechin gallate, intraperitoneal Glucantime, and control group. The efficacy of treatments was evaluated by quantifying the parasite burden and by measuring the lesions size. (−)-Epigallocatechin gallate and (−)-epigallocatechin were the most active compounds with IC 50 values <59.6 µg/mL and with a selectivity index >1. Topical treatment with (−)-epigallocatechin gallate decreased significantly both lesion size and parasite burden (80.4% inhibition) compared to control group (p < 0.05), and moreover (−)-epigallocatechin gallate showed a similar efficacy to Glucantime (85.1% inhibition), the reference drug for leishmaniasis treatment.

This work describes the techniques for industrial production of tablets with microspheres of flutamide. This study evaluates the pharmacotechnical characteristics of the present formulation using an appropiate experimental design. The operating technique chosen was coaservation-phase separation  process that was modified by means of the addition of as intermediate stage of emulsion formation. The in vitro dissolution of flutamide from the polyhydroxyetthylmethacrylate microspheres was proportional to the square root of the time according to the equation proposed by Higuchi.

Helminthiases, a group of neglected tropical diseases, affect more than one billion people mainly in tropical and subtropical regions. Albendazole (ABZ) is a broad‐spectrum anthelmintic recommended by the World Health Organisation (WHO). However, drug resistance is emerging due to its widespread use. In order to tackle this problem, taking into account the spectacular results obtained with the organometallic derivatization of the antimalarial drug chloroquine, we have prepared, in this study, a series of new ferrocenyl and ruthenocenyl derivatives of the organic drug ABZ and assessed their activity against different helminths but also protozoans, namely Trichuris muris adult, Heligmosomoides polygygrus adult, Schistosoma mansoni adult, Giardia lamblia, Haemonchus contortus xL3s and Toxoplasma gondii to determine the full potential of our new compounds. Worthy of note, the ferrocene‐containing ABZ analogue 2d exhibited over 70% activity against T. muris adult in vitro and no toxicity...

Chagas&#x27; disease, caused by Trypanosoma cruzi, is considered a public health problem. Nowadays, chemotherapy is the only available treatment for this disease, and the drugs currently used, nifurtimox and benzonidazole, present high toxicity levels. Alternatives for replacing these drugs are natural extracts from Eugenia jambolana, a plant used in traditional medicine because of its antimicrobial and biological activities. An ethanol extract from E. jambolana was prepared. To research in vitro anti-epimastigote activity, T. cruzi CL-B5 clone was used. Epimastigotes were inoculated at a concentration of 1×10(5)/mL in 200 μL of tryptose-liver infusion. For the cytotoxicity assay J774 macrophages were used. To examine antifungal activity, Candida albicans, Candida tropicalis, and Candida krusei were used. This is the first record of trypanocide activity for E. jambolana. The effective concentration capable of killing 50% of the parasites was 56.42 μg/mL. The minimum inhibitory conce...

Leishmaniasis is caused by parasites of the genus Leishmania. Recent reports
about leishmaniasis show a few number of drugs available, indicating the
necessity of new drugs. In this study, the ethanol extract and fractions of
Pityrogramma calomelanos (L.) link. (Pteridaceae) were assayed to verify the
cytotoxicity and in vitro leishmanicidal activity against promastigote forms of
Leishmania brasiliensis. The cytotoxic assay was performed using fibroblasts
NCTC929. The studies indicated a leishmanicidal effect of the ethanol extract and
the ethyl-acetate fraction. However, a high cytotoxic effect was observed. The
hexane and methanol fractions did not show leishmanicidal activity, nor cytotoxic
effect. The phytochemical screening detected the presence of alkaloids, a class of
secondary metabolites with a known leishmanicidal activity. This is the first study
reporting an anti-Leishmania and cytotoxic effect of P. calomelanos, being an
interesting approach in the search for drugs against this disease.

Tripanosomiasis or “Chagas disease”, caused by Trypanosoma cruzi, affect 10 million people in Latin America. Today, the chemotherapy is the only specific treatment against this disease, being the most used drugs the nifurtimox and benznidazole. Leishmaniasis is a disease caused by parasites of the genus Leishmania, mainly founded in regions with forests, as the Amazonia. Recent reports about the Leishmaniasis indicate a deficit of therapeutical drugs available against this disease and reinforce the necessity of the discovering of new drugs. An interesting approach against these diseases is the use of natural products, as the extracts of plants as Mentha arvensis and Turnera ulmifolia. For the in vitro assays against T. cruzi and Leishmania, was used the clone CL-B5 and promastigote forms, respectively. The cytotoxic assay was performed using fibroblasts. Our results indicated that M. arvensis was active against all strains assayed, inhibiting 65 e 47% of the assayed strains (IC50 = 192.3 and 531.9 μg/mL respectively), representing an interesting and alternative source of natural products with anti-kinetoplastida activity.

Toxoplasma gondii (T. gondii) is a highly prevalent parasite that has no gold standard treatment due to the poor action or the numerous side effects. Focused sulfonamide-1,2,3-triazole hybrids 3a–c were wisely designed and synthesized via copper catalyzed 1,3-dipolar cycloaddition approach between prop-2-yn-1-alcohol 1 and sulfa drug azides 2a–c. The newly synthesized click products were fully characterized using different spectroscopic experiments and were loaded onto chitosan nanoparticles to form novel nanoformulations for further anti-Toxoplasma investigation. The current study proved the anti-Toxoplasma effectiveness of all examined compounds in experimentally infected mice. Relative to sulfadiazine, the synthesized sulfonamide-1,2,3-triazole (3c) nanoformulae demonstrated the most promising result for toxoplasmosis treatment as it resulted in 100% survival, 100% parasite reduction along with the remarkable histopathological improvement in all the studied organs.

Leishmaniasis is caused by parasites of the genus Leishmania. Recent reports about leishmaniasis show a few number of drugs available, indicating the necessity of new drugs. In this study, the ethanol extract and fractions of Pityrogramma calomelanos (L.) link. (Pteridaceae) were assayed to verify the cytotoxicity and in vitro leishmanicidal activity against promastigote forms of Leishmania brasiliensis. The cytotoxic assay was

Trichomonas vaginitis is the most common non-viral disease that is transmitted sexually. Although metronidazole is the most effective medication for this disease, it has some adverse effects. Herbal medicines have fewer side effects and are more popular among people. This study aimed to review the plants, which are effective against Trichomonas vaginalis and their therapeutic effects. For this purpose, the databases of Scopus, PubMed, Medline, Google Scholar, SID, and Magiran were searched for the articles published during 2000-2019 by keywords, such as Trichomonas vaginalis, complimentary, complementary therapies, herbal medicine, medicinal plants, and their Persian equivalents. All in vivo and in vitro trial studies were included in the present review. The data indicated that some compounds, including eucalyptus, case, and garlic were effective in inhibiting the growth of T. vaginalis.

Chagas disease, caused by Trypanosoma cruzi, is a public health problem. Currently, chemotherapy is the only available treatment for this disease, and the drugs used, nifurtimox and benzonidazol, present high toxicity levels. An alternative for replacing these drugs are natural extracts from Momordica charantia L. (Cucurbitaceae) used in traditional medicine because of their antimicrobial and biological activities.

Chagas’ disease, caused by Trypanosoma cruzi, is considered a public health problem. Nowadays, chemotherapy
is the only available treatment for this disease, and the drugs currently used, nifurtimox and benzonidazole, present
high toxicity levels. Alternatives for replacing these drugs are natural extracts from Eugenia jambolana, a plant used in
traditional medicine because of its antimicrobial and biological activities. An ethanol extract from E. jambolana was prepared.
To research in vitro anti-epimastigote activity, T. cruzi CL-B5 clone was used. Epimastigotes were inoculated at a concentration
of 1 · 105/mL in 200 lL of tryptose-liver infusion. For the cytotoxicity assay J774 macrophages were used. To examine
antifungal activity, Candida albicans, Candida tropicalis, and Candida krusei were used. This is the first record of trypanocide
activity for E. jambolana. The effective concentration capable of killing 50% of the parasites was 56.42 lg/mL. The
minimum inhibitory concentration was £ 1,024 lg/mL. Metronidazole showed a potentiation of its antifungal effect when
combined with the ethanol extract of E. jambolana. Thus our results indicate that E. jambolana could be a source of plantderived
natural products with anti-epimastigote and antifungal modifying activity with moderate toxicity.