Bioguided isolation of N-malonyl-(+)-tryptophan from the fruit of Pithecellobium dulce (Roxb.) Benth. that showed high activity against Hymenolepis nana.

Pithecellobium dulce is distributed in America and Asia where is widely used in traditional medicine. This study describes the bioguided fractionation of the methanol extract (ME) obtained from the P. dulce fruit that showed in vitro activity against Hymenolepis nana; Artemia salina assay was used to determine toxicity; and the purified compound was computationally analysed to obtain its absorption-distribution-metabolism-excretion-and-toxicity properties (ADMET). The ME and its fractions were more active than praziquantel (PZQ), and the purified compound was characterized as N-malonyl-(+)-tryptophan (NMT). Parasites treated with NMT showed shorter paralysis and death times (5 and 7 min) than those treated with PZQ (15 and 30 min), both used at 20 mg/mL. Toxicity and ADMET prediction results supported the slight-hazardousness and efficacy of the assayed fractions/compound. This is the first report of the antiparasitary activity of both the P. dulce ME and NMT, showing their potential to treat human H. nana infections.

Novel Linezolid analogues with antiparasitic activity against Hymenolepis nana.

The stereoselective synthesis and anti- Hymenolepis nana activity of six Linezolid-type compounds, obtained by chemical modification of l-Alanine, are reported in this work. The synthetic strategy was to prepare diasteromeric N,N-dibenzylamino oxazolidinones 1 and 2, and coupling with 4-(4-bromophenyl)morpholine (3) to obtain N,N-dibenzylamino Linezolid analogues 4 and 5. A hydrogenolysis reaction over 4 and 5 resulted in amino-free Linezolid analogues 6 and 7, which were acetylated to reach diasteromeric Linezolid analogues 8 and 9. The six Linezolid analogues 4-9 show in vitro antiparasitic activity against Hymenolepis nana cestode, but not against several bacterial strains. Interestingly, compounds 6, 7 and 9 exhibit high potency, having shorter paralysis and death times after exposure (6-10 and 18-21 min, respectively), shorter than those found with antihelmintic compound Praziquantel (20 and 30 min) at 20 mg/mL. In addition, a cytocompatibility assay of 6-9 with human cells (ARPE-19 cells) demonstrate a non-cytotoxic effect at 0.4 mM. These results show the pharmacological potential of the newly reported Linezolid-type analogues as antiparasitic agents against Hymenolepis nana.

Anthelmintic Potential of Cucurbita pepo Seeds on Hymenolepis nana.

OBJECTIVE: The main drug used against Hymenolepis nana is praziquantel (PZQ), which causes side effects and toxicity. In contrast, natural extracts have limited side effects and are safer. Past researches have proved that pumpkin seeds are effective as natural antimicrobial and antiparasitic treatment. The present study investigates a natural alternative and less expensive treatment against H. nana using pumpkin seeds. MATERIALS AND METHODS: Healthy female albino mice were divided into four groups: normal control, infected control with H. nana, infected and treated with PZQ, and lastly, the group infected and treated with pumpkin seeds' extract. RESULTS: Pumpkin seeds aqueous extract showed a significant reduction (P < 0.05) in the number and length of H. nana adult worms, number and viability of eggs in comparison to the infected control group and PZQ group. Pumpkin seed aqueous extract is proven to be an effective anthelmintic against H. nana. CONCLUSION: We recommend pumpkin seed extract as a natural alternative, less expensive and safe therapy for H. nana. This is the first study in Saudi Arabia to investigate the therapeutic effect of pumpkin seeds' extract on H. nana.

Albendazole in the treatment of Hymenolepiasis in school children.

Hymenolepiasis is a helminthic and occasionally fatal disease of human imposing heavy economic losses to human society. Present study was aimed to diagnose the school children for the prevalence and control of Hymenolepiasis. A school based cross-sectional analysis of stool samples collected from 188 children aged 06-15 years was carried out (February to June 2016). Two stool samples were collected from each student before diagnosing and after treatment. The samples were fixed in 10% formalin and observed under the light microscope using the methods of direct smear in Lugol's solution, normal saline and flotation techniques. On the basis of drugs accessibility all the H. nana infected children were divided in to 2- groups. Children in group A were treated with albendazole (bendazol) 400mg once orally, group B was treated with albendazole (zentel) 200mg orally. Eggs per gram of faeces were counted in each group before and after treatment. Of the 188 children, current study reveals only 6.08% (n=18/296) infection with H.nana and 10.5% (n=16/151) were diagnosed with co infections. The % efficacy of albendazole (Zentel) and albendazole (bendazol) against Hymenolepis nana infection was reported as 83% and 75% respectively. Present study was concluded that albendazole (zentel) is the drug of choice for the treatment of hymenolepiasis in children.

Therapeutic efficacy of Artemisia absinthium against Hymenolepis nana: in vitro and in vivo studies in comparison with the anthelmintic praziquantel.

Hymenolepis nana is a common intestinal tapeworm that affects humans. Drugs are available for the treatment of this infection, including praziquantel (PZQ), nitazoxanide and niclosamide. Although the drug of choice is praziquantel, due to its high cure rates, indicators of the development of PZQ resistance by different parasites have begun to appear over recent decades. Therefore, this study was a trial to find an alternative to PZQ by assessing the activity of the crude aqueous extract of the medicinal herb Artemisia absinthium against H. nana. In vitro, the extract was used against adult worms at concentrations of 1 and 5 mg/ml, in comparison with 1 mg/ml of PZQ. The times of worm paralysis and death were determined. Ultrastructural morphological changes were studied using transmission electron microscopy (TEM). For the in vivo study, infected mice were divided into untreated, PZQ-treated and A. absinthium-treated groups (400 mg/kg and 800 mg/kg). Pre- and post-treatment egg counts per gram of faeces (EPG) were performed; then, the reduction percentages of the EPG and worm burden were calculated. The best results were obtained with praziquantel. Artemisia absinthium induced worm paralysis, death and ultrastructural alterations, such as tegumental damage, lipid accumulation, and destruction of the nephridial canal and the intrauterine eggs, in a dose-dependent manner. Additionally, significant reductions in the EPG and worm burden were recorded in A. absinthium-treated mice. Although the results obtained with A. absinthium were promising and comparable to PZQ, further studies using different extracts, active ingredients and concentrations against different parasites should be conducted.

Immunoprotective Effect of Chitosan Particles on Hymenolepis nana - Infected Mice.

Hymenolepis nana is the most commonly known intestinal cestode infecting mainly human. This study aimed to investigate the potential effect of chitosan particles (CSP) to enhance the immune system against H. nana infection. Determination of worm burden, egg output, histopathological changes, oxidative stress markers (lipid peroxidation and reduced glutathione), goblet (GCs) and mucosal mast cells (MMCs) counts in intestinal ileum was performed. In addition, levels of intestinal mRNA expression of interleukin (IL)-4, IL-9, stem cell factor (SCF), type I and II interferons (IFN)-α/ γ, tumour necrosis factor (TNF)-α, mucin 2 (MUC2) and inducible nitric oxide synthase (iNOs) were investigated using real-time PCR. The results indicated induced reductions in adult worm and egg counts in infected mice after CSP treatment. This was associated with improvement in tissue morphometric measurements and oxidative stress which were altered after infection. Expression levels of iNOs, IFN-α, IFN-γ, TNF-α and IL-9 were decreased by CSP. Conversely, expression levels of MUC2, IL-4 and SCF increased compared to infected untreated group. In addition, GCs and MMCs counts were normalized by CSP. In conclusion, this study could indicate the immunoprotective effect of CSP against H. nana infection. This was characterized with Th2 anti-inflammatory responses.

Coinfection with Hymenolepis nana, Hymenolepis diminuta, Giardia intestinalis, and Human Immunodeficiency Virus: A Case Report with Complex Immunologic Interactions.

AbstractWe describe the case of a 43-year-old human immunodeficiency virus-infected man receiving combined antiretroviral therapy and coinfected with Hymenolepis nana, Hymenolepis diminuta, and Giardia intestinalis, presenting as chronic diarrhea and critical weight loss. Immunological aspects of these interactions are reviewed.

[STEROIDAL GENINS AND GLYCOSIDES OF SPIROSTAN AND FUROSTAN SERIES AS ANTHELMINTHIC AGENTS].

It was established that steroidal genins and their glycosides of the spirostan series and (especially) furostan series show anticestodal activity against Hymeiolepis nana species. Search for anthelminthic agents in the indicated series of compounds is a promising direction of research.

Evaluation of anthelmintic potential of the Ethiopian medicinal plant Embelia schimperi Vatke in vivo and in vitro against some intestinal parasites.

BACKGROUND: Embelia schimperi has been used for the treatment of intestinal parasites especially tapeworm infestations for centuries in Ethiopia. However, there is lack of scientific based evidences regarding the efficacy, safety and phytochemical analysis of this plant despite its frequent use as an anthelmintic. This study has therefore evaluated the efficacy and acute toxicity of E. schimperi thereby generating relevant preclinical information. METHODS: The anthelmintic activities of the crude hydroalcoholic extract of E. schimperi and the isolated compound, embelin, were conducted using in vivo and in vitro models against the dwarf tapeworm, Hymenolepis nana, and the hookworm, Necator americanus, respectively. LD50 of the crude hydroalcoholic extract was determined using Swiss albino mice following the OECD guidelines. Chemical characterization of the isolated embelin was conducted using UV-spectroscopy, HPLC and NMR. RESULTS: In the acute toxicity study no prominent signs of toxicity and mortality were recorded among the experimental animals at the highest administered dose. Hence the LD50 of the plant was found to be higher than 5000 mg/kg. In vivo cestocidal activity of the crude hydroalcoholic extract of E. schimperi showed 100% parasite clearance at 1000 mg/kg, while the diammonium salt of embelin showed 85.3% parasite clearance at 750 mg/kg. The in vitro anthelminthic activity study revealed that the LC50 value of the crude extract and albendazole were 228.7 and 51.33 µg/mL, respectively. CONCLUSION: The results clearly indicated that the hydroalcoholic extract of E. schimperi and the diammonium salt of the isolated compound embelin had anthelmintic activity against hookworm larva in vitro and H. nana in vivo. Hence the findings of this study showed Embelia schimperi appears to possess some anthelmintic activity that may support the usage of these plants by local traditional healers to treat helminthic infestations.

A Physicochemical and Pharmacological Study of the Newly Synthesized Complex of Albendazole and the Polysaccharide Arabinogalactan from Larch Wood.

Inclusion complexes of albendazole (ABZ) with the polysaccharide arabinogalactan from larch wood Larix sibirica and Larix gmelinii were synthesized using a solid-state mechanochemical technology. We investigated physicochemical properties of the synthesized complexes in the solid state and in aqueous solutions as well as their anthelmintic activity against Trichinella spiralis, Hymenolepis nаna, Fasciola hepatica, Opisthorchis felineus, and mixed nematodoses of sheep. Formation of the complexes was demonstrated by means of intrinsic solubility and the NMR relaxation method. The mechanochemically synthesized complexes were more stable in comparison with the complex produced by mixing solutions of the components. The complexes of ABZ showed anthelmintic activity at 10-fold lower doses than did free ABZ. The complexes also showed lower acute toxicity and hepatotoxicity. These results suggest that it is possible to design new drugs on the basis of the ABZ:arabinogalactan complex that are safer and more effective than albendazole.

Efficacy and security of ivermectin given orally to rats naturally infected with Syphacia spp., Giardia spp. and Hymenolepis nana.

The results of this study show that the oral administration of ivermectin (48 mg/L) repeatedly for 72 h used in accordance with the present protocol is a safe and highly effective treatment for Giardia spp. and Hymenolepis nana in laboratory rat colonies. The drug can be easily and safely administered using drinking water. This simple regimen should control pinworm infection (Syphacia muris), a problem that can be endemic in laboratory colonies. Experiments using healthy animals are likely to generate more consistent results, thereby requiring a reduced number of animals per group.

Anthelmintic constituents from ginger (Zingiber officinale) against Hymenolepis nana.

This study investigated the anthelmintic activity of gingerenone A, [6]-dehydrogingerdione, [4]-shogaol, 5-hydroxy-[6]-gingerol, [6]-shogaol, [6]-gingerol, [10]-shogaol, [10]-gingerol, hexahydrocurcumin, 3R,5S-[6]-gingerdiol and 3S,5S-[6]-gingerdiol, a constituent isolate from the roots of ginger, for the parasite Hymenolepis nana. The cestocidal activity or ability to halt spontaneous parasite movement (oscillation/peristalsis) in H. nana of above constituents was reached from 24 to 72h in a time- and dose-dependent manner, respectively. The [10]-shogaol and [10]-gingero1 have maximum lethal efficacy and loss of spontaneous movement than the others at 24-72h. In addition, worms treated with 1 and 10µM [10]-gingero1, more than 30% had spontaneous movement of oscillation at 72h but [10]-shogaol at 72h only about 15-20% of oscillation. This showing that [10]-gingero1 had less loss of spontaneous movement efficacy than [10]-shogaol. After exposure to 200µM [10]-shogaol, 100% of H. nana had died at 12h rather than died at 24h for [10]-gingerol, showing that [10]-gingero1 had less lethal efficacy than [10]-shogaol. In addition, these constituents of ginger showed effects against peroxyl radical under cestocidal activity. In order to evaluate the cestocidal activity and cytokine production caused by ginger's extract R0 in the H. nana infected mice, we carried out in vivo examination about H. nana infected mice BALB/c mice were inoculated orally with 500 eggs. After post-inoculation, R0 (1g/kg/day) was administered orally for 10 days. The R0 exhibited cestocidal activity in vivo of significantly reduced worms number and cytokines production by in vitro Con A-stimulated spleen cells showed that INF-γ and IL-2 were significantly increases by R0. IL-4, IL-5, IL-6, IL-10 and IL-13 were significantly decreases and Murine KC and IL-12 were not significantly changes by R0. Together, these findings first suggest that these constituents of ginger might be used as cestocidal agents against H. nana.

The effect of praziquantel and Carica papaya seeds on Hymenolepis nana infection in mice using scanning electron microscope.

Hymenolepis nana (H. nana) is the most common tapeworm infection worldwide. It is more prevalent in warm climates where sanitation is poor, particularly among children. The effect and mechanism of action of praziquantel (PZQ), given at a dose of 25-mg/kg BW, and Carica papaya dried seed crude aqueous extract (CAE), given at a dose of 1.2-g/kg BW, were assessed on H. nana worms in experimentally infected mice. Tegumental changes were studied using the scanning electron microscope (SEM) and different parasitological parameters were observed. Each group of infected mice was divided into two subgroups. The first subgroup received either treatment before the 4th day after infection to investigate their effects on the cysticercoid stage. The other subgroup received treatments after the development of the adult stage, confirmed by eggs detection in stool. Both PZQ and C. papaya dried seed CAE resulted in a significant reduction of worm burden, total egg output and viable egg count. Marked tegumental changes were evident in adult worms treated with either treatment including shrinkage of the scolex and neck region with rostellar edema and complete loss of its hooks. However, all previous effects were exerted more rapidly in the case of PZQ treatment. They both significantly reduced cysticercoid stage size. Nevertheless, C. papaya outstand PZQ in having a deforming effect on adults arising from treated cysticercoids. It was concluded that C. papaya has significant anti-cestodal properties that enable its seed extract to be a very effective alternative to PZQ against H. nana.

Anthelmintic activities of aporphine from Nelumbo nucifera Gaertn. cv. Rosa-plena against Hymenolepis nana.

Nelumbo nucifera Gaertn. cv. Rosa-plena (Nelumbonaceae), commonly known as lotus, is a perennial aquatic plant grown and consumed throughout Asia. All parts of N. nucifera have been used for various medicinal purposes in oriental medicine. From the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena (an aquatic plant), liriodenine (1), lysicamine (2), (-)-anonaine (3), (-)-asimilobine (4), (-)-caaverine (5), (-)-N-methylasimilobine (6), (-)-nuciferine (7), (-)-nornuciferine (8), (-)-roemerine (9), 7-hydroxydehydronuciferine (10) and cepharadione B (11) were isolated and identification and anthelmintic activities of aporphine was evaluated against Anisakis simplex and Hymenolepis nana. This study found that the above constituents killed H. nana or reduced their spontaneous movements (oscillation/peristalsis). However, the above constituents at various concentrations demonstrated no larvicidal effect or ability to halt spontaneous parasite movement for 72 h against A. simplex, respectively. In addition, according to an assay of cestocidal activity against H. nana and nematocidal activity against A. simplex, we found that the above compounds showed greater lethal efficacy on H. nana than against A. simplex. Further investigation showed that these above constituents have effects against peroxyl radicals under cestocidal effect. Together, these findings suggest that these constituents of Nelumbo nucifera Gaertn. cv. Rosa-plena might be used as anthelmintic agents against H. nana.