Anthelmintic activity of praziquantel and Spilanthes acmella extract on an intestinal cestode parasite.

Spilanthes acmella Murr., popularised as toothache plant, is a well-known culinary and medicinal plant for different purposes, but its use as an anthelmintic is apparently exclusive to the Mizo people of India and Myanmar. A chloroform extract of Spilanthes acmella Murr. was analysed in a single quadrupole GC-MS system, from which it was found that the major compound was an alkylamide, N-isobutyl-(2E,4Z,8Z,10E)-dodecatetraenamide. A comparative study was performed on the anthelmintic activity of the plant extract and praziquantel (PZQ) against an intestinal cestode, Raillietina echinobothrida. In terms of efficacy, PZQ was more potent, but the plant extract was also effective at all concentrations tested. PZQ caused severe shrinkage and folds of the tegument, constriction of the suckers, dislocation of spines and erosion of microtriches. The plant extract caused shrinkage and folds on the main body but not on the scolex. Damage on the suckers is more pronounced than in PZQ-treated cestodes. The spines were completely removed. The current findings indicate that S. acmella is a good source of compounds with anthelmintic activity.

Matrine triggers colon cancer cell apoptosis and G0/G1 cell cycle arrest via mediation of microRNA-22.

Matrine (MAT) is an alkaloid in the dried roots of Sophora flavescens. The antitumor activity has been testified in colon cancer. Howbeit, the latent mechanism is still indistinct. The research probed the antitumor mechanism of MAT in colon cancer cells. MAT (0.25, 0.5, 0.75, 1, and 1.25 mM) was utilized to stimulate SW480 and SW620 cells for 24, 48, and 72 hr. Cell viability, apoptosis, cell cycle, and the correlative proteins were assessed via Cell Counting Kit-8, flow cytometry, and Western blot. microRNA-22 (miR-22) in MAT-treated or miR-22-silenced cells was estimated via real-time quantitative polymerase chain reaction. The functions of miR-22 inhibition were reassessed. Western blot was conducted for quantifying ß-catenin, MEK, and ERK. Luciferase reporter assay was done for confirming the targeting relationship between miR-22 and ERBB3 or MECOM. MAT prohibited cell viability, accelerated apoptosis, and triggered cells cycle stagnation at G0/G1 phase. Additionally, miR-22 was elevated by MAT; meanwhile, the influences of MAT were all inverted by miR-22 inhibitor. MAT enhanced the expression of miR-22, thereby obstructing Wnt/ß-catenin and MEK/ERK pathways. miR-22 had a potential to target mRNA 3'UTR of ERBB3 and MECOM. These discoveries manifested that MAT could evoke colon cancer cell apoptosis and G0/G1 cell cycle arrest via elevating miR-22.

In vitro effects of Artemisia sieberi on Echinococcus granulosus protoscolices.

Hydatidosis is a parasitic zoonotic disease. Surgery is one of its treatment modalities during which protoscolices are likely to be released into the peritoneal cavity and cause recurrence of the disease. Given the above problem and the complications associated with conventional anti-parasitic agents, it is imperative to find an effective and natural protoscolicidal agent. The present study was conducted to evaluate effects of Artemisia sieberi on Echinococcus granulosus protoscolices. Protoscolices were collected from slaughtered livestock in Kerman abattoir and the effect of three concentrations of aqueous extract of A. sieberi (25 mg ml-1, 50 mg ml-1 and 75 mg ml-1) was assessed over three different exposure periods. Results showed that scolicidal effect of this extract at exposure periods of 2, 5 and 10 min was 76 ±â€¯1.4, 76.8 ±â€¯1.41 and 85.7 ±â€¯3.29 percent at concentration of 25 mg ml-1 and 76.8 ±â€¯1.4, 78 ±â€¯3.18 and 86.4 ±â€¯24.9 percent at concentration of 50 mg ml-1 and finally 80 ±â€¯2.73, 90 ±â€¯0.79 and 92.6 ±â€¯1.27 percent at concentration of 75 mg ml-1, respectively. It can be concluded that the aqueous extract of A. sieberi has a protoscolicidal activity and can be considered a natural agent against hydatid cyst protoscolices.

Efficacy and Safety of Bunium Persicum (Boiss) to Inactivate Protoscoleces during Hydatid Cyst Operations.

BACKGROUND: Current scolicidal agents, which have been used for inactivation of protoscoleces during surgical procedures, are associated with adverse side effects including sclerosing cholangitis. This investigation aimed to evaluate the scolicidal effects of Bunium persicum (Boiss) essential oil against protoscoleces of hydatid cysts and also its toxicity in a mice model. METHODS: Protoscoleces were aseptically aspirated from sheep livers having hydatid cysts. Various concentrations of the essential oil (3.125-50 mcL/mL) were used for 5-30 min. The viability of protoscoleces was confirmed using the eosin exclusion test (0.1% eosin staining). Further, 48 male NMRI mice were used to determine the acute and sub-acute toxicity of B. persicum essential oil. RESULTS: The obtained results revealed that the B. persicum essential oil at the concentrations of 25 and 50 mcL/mL after 5 min of exposure killed 100% protoscoleces. The mean mortality rate of protoscoleces after 10 min of exposure to the concentration of 12.5 mcL/mL was 100%. Lower concentrations (6.25 and 3.125 mcL/mL) of B. persicum essential oil, however, indicated a delayed protoscolicidal effects. The LD50 value of intra-peritoneal injection of the B. persicum essential oil was 1.96 mL/kg body wt. No significant difference (p > 0.05) was observed in the clinical chemistry and hematologic parameters after oral administrations of B. persicum essential oil at the doses 0.05, 0.1, 0.2, and 4 mL/kg for 14 d. CONCLUSION: Our findings demonstrated the potent scolicidal activity of B. persicum with no significant toxicity; it might be used as a natural scolicidal agent in hydatid cyst surgery.

In vitro and in vivo action of Piptadenia viridiflora (Kunth) Benth against Haemonchus contortus in sheep.

Anthelminthic resistant populations of Haemonchus contortus are a major problem in sheep rearing, but plant extracts may offer viable alternative treatments. In our preliminary studies, Piptadenia viridiflora was frequently selected by sheep grazing in the Cerrado. The present research evaluated its in vitro and in vivo anthelmintic activity. The HPLC chromatograms of P. viridiflora aqueous extract (AE) and ethanolic extract (EE) showed the presence of flavonoids. The total condensed tannin (proanthocyanidin) was 0.2 and 1.01% in AE and EE, respectively. In an egg hatching inhibition (EHI) test, the LC90 of AE was 2.4mg/mL, and, of EE, was 2.1mg/mL. After tannin extraction, higher EHI and lower LC90 were observed. In a larval development inhibition test, the LC90 of AE was 13.66mg/g of fecal culture. The highest dose of AE administered to mice (203.0mg/kg bw) was well tolerated, suggesting low toxicity. In vivo, AE was orally administered to lambs at 283mg/kg bw, and, at weeks one, two, and three post-treatment, the mean fecal egg count (FEC) was significantly lower than in untreated lambs (P<0.05). Blood parameters were normal and similar in untreated and treated sheep. For all lamb groups, the mean total serum protein was significantly higher at week two post-treatment than at other evaluated periods (P<0.05). Piptadenia viridiflora extracts had low condensed tannin content and exhibited high anthelminthic efficacy in vitro and significantly reduced FEC. Tannins were not shown to be the principal components affecting EHI, hence it is necessary to isolate and characterize the principal active P. viridiflora compounds, and to assess their possible synergism.

The Comparative Double-Blind Clinical Study in Antihelmintic Efficacy Between Thai Traditional Herbal Formulae and Mebendazole.

This study was carried out in Mahasarakham Primary Healthcare Centre, Mahasarakham province in the area of Northeastern of Thailand. The experiment was randomized controlled trial in the clinical study to examine the efficacy of Thai Traditional Herbal Formula (TTHF) in the treatment of antihelmintic activity of mixed worm infections in human. The 2 experimental groups consisted of 10 patients, and 5 patients for control group with inclusion and exclusion criteria, who were screened by the selection of mixed worm infection symptom samples. The investigation and extraction of worm eggs per gram (EPG) of patient feces method were performed with Ether-Formalin Sedimentation test. The percentage of reduction of EPG of patient feces were collected, counted, and confirmed by parasitologist, and the clinical efficacy was investigated by the physician and the pharmacist. The percent EPG data were collected before and after the treatment with TTHF and with mebendazole. The result showed that TTHF had higher efficacy in antihelmintic activity than mebendazole and placebo, which had the percent reduction of EPG of feces as 93.69 in TTHF and percent reduction of EPG of feces as 87.50 in mebendazole. The suggestion of this study should increase the number of samples of worm-infected patients, which the samples can be identified with the specific helminths genus and species to obtain the efficacy by the treatment using TTHF and mebendazole comparatively.

Apoptosis mediated leishmanicidal activity of Azadirachta indica bioactive fractions is accompanied by Th1 immunostimulatory potential and therapeutic cure in vivo.

BACKGROUND: Exploration of immunomodulatory antileishmanials of plant origin is now being strongly recommended to overcome the immune suppression evident during visceral leishmaniasis (VL) and high cost and toxicity associated with conventional chemotherapeutics. In accordance, we assessed the in vitro and in vivo antileishmanial and immunomodulatory potential of ethanolic fractions of Azadirachta indica leaves (ALE) and seeds (ASE). METHODS: A. indica fractions were prepared by sequential extraction of the powdered plant parts in hexane, ethanol and water. Erythrosin B staining was employed to appraise the anti-promastigote potential of ALE and ASE. Cytostatic or cytocidal mode of action was ascertained and alterations in parasite morphology were depicted under oil immersion light microscopy. Study of apoptotic correlates was performed to deduce the mechanism of induced cell death and anti-amastigote potential was assessed in Leishmania parasitized RAW 264.7 macrophages. In vivo antileishmanial effectiveness was evaluated in L. donovani infected BALB/c mice, accompanied by investigation of immunomodulatory potential of ALE and ASE. Adverse toxicity of the bioactive fractions against RAW macrophages was studied by MTT assay. In vivo side effects on the liver and kidney functions were also determined. Plant secondary metabolites present in ALE and ASE were analysed by Gas chromatography-mass spectrometry (GC-MS). RESULTS: ALE and ASE (500 µg ml(-1)) exhibited leishmanicidal activity in a time- and dose-dependent manner (IC50 34 and 77.66 µg ml(-1), respectively) with alterations in promastigote morphology and induction of apoptosis. ALE and ASE exerted appreciable anti-amastigote potency (IC50 17.66 and 24.66 µg ml(-1), respectively) that was coupled with profound in vivo therapeutic efficacy (87.76% and 85.54% protection in liver and 85.55% and 83.62% in spleen, respectively). ALE exhibited minimal toxicity with selectivity index of 26.10 whereas ASE was observed to be non-toxic. The bioactive fractions revealed no hepato- and nephro-toxicity. ALE and ASE potentiated Th1-biased cell-mediated immunity along with upregulation of INF-γ, TNF-α and IL-2 and decline in IL-4 and IL-10 levels. GC-MS analysis revealed several compounds that may have contributed to the observed antileishmanial effect. CONCLUSION: Dual antileishmanial and immunostimulatory efficacy exhibited by the bioactive fractions merits their use alone or as adjunct therapy for VL.

Fear of birth defects is a major barrier to soil-transmitted helminth treatment (STH) for pregnant women in the Philippines.

The World Health Organization recommends anthelminthic treatment for pregnant women after the first trimester in soil-transmitted helminth (STH) endemic regions to prevent adverse maternal-fetal consequences. Although studies have shown the high prevalence of infection in the Philippines, no research has evaluated deworming practices. We hypothesized that pregnant women are not receiving deworming treatment and we aimed to identify barriers to World Health Organization guideline implementation. We conducted key informant interviews with local Department of Health (DOH) administrators, focus group discussions with nurses, midwives, and health care workers, and knowledge, attitudes, and practices surveys with women of reproductive age to elicit perspectives about deworming during pregnancy. Key informant interviews revealed that healthcare workers were not deworming pregnant women due to inadequate drug supply, infrastructure and personnel as well as fear of teratogenicity. Focus group discussions showed that healthcare workers similarly had not implemented guidelines due to infrastructure challenges and concerns for fetal malformations. The majority of local women believed that STH treatment causes side effects (74.8%) as well as maternal harm (67.3%) and fetal harm (77.9%). Women who were willing to take anthelminthics while pregnant had significantly greater knowledge as demonstrated by higher Treatment Scores (mean rank 146.92 versus 103.1, z = -4.40, p<0.001) and higher Birth Defect Scores (mean rank 128.09 versus 108.65, z = -2.43, p = 0.015). This study concludes that World Health Organization guidelines are not being implemented in the Philippines. Infrastructure, specific protocols, and education for providers and patients regarding anthelminthic treatment are necessary for the successful prevention of STH morbidity and mortality among pregnant women.

Efficacy and safety of oral praziquantel against Dicrocoelium dendriticum in llamas.

Dicrocoelium dendriticum can cause severe pathological changes of the liver and bile system in camelids, and therapeutic options for treatment are limited. To address this problem, the efficacy of two different dose rates of praziquantel was investigated in llamas suffering from natural D. dendriticum infections. 53 llamas were examined under field conditions on two occasions: before and two weeks after treatment. At the beginning of the study, the animals were weighed, randomly allocated to one of the treatment groups (n=21 each) or the control group (n=11) and dosed orally using a praziquantel-containing paste (250 mg/ml) at a dose of either 25 mg (group 1) or 50 mg (group 2) per kg of body weight. Criteria for efficacy were faecal egg count reduction (FECR) and extensity effect. Animals treated with 25 mg/kg of body weight showed a FECR of 85%. Therapy with 50 mg/kg led to a FECR of 91%. Almost twice the number of animals of group 1 (33%) still shed eggs two weeks after treatment compared with group 2. The results of this study indicate that 50 mg/kg oral praziquantel is required for efficacious dosing and that this dose rate is safe in llamas and thus is recommended for the treatment of camelids naturally infected with D. dendriticum.

The effect of three-monthly albendazole treatment on malarial parasitemia and allergy: a household-based cluster-randomized, double-blind, placebo-controlled trial.

BACKGROUND: Helminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially. We evaluated the effects of albendazole treatment, every three months for 21 months, on STH, malarial parasitemia and allergy. METHODS AND FINDINGS: A household-based cluster-randomized, double-blind, placebo-controlled trial was conducted in an area in Indonesia endemic for STH. Using computer-aided block randomization, 481 households (2022 subjects) and 473 households (1982 subjects) were assigned to receive placebo and albendazole, respectively, every three months. The treatment code was concealed from trial investigators and participants. Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test (SPT) to allergens as well as reported symptoms of allergy in children aged 5-15 years. The general impact of treatment on STH prevalence and body mass index (BMI) was evaluated. Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen. Analysis was by intention to treat. At 9 and 21 months post-treatment 80.8% and 80.1% of the study subjects were retained, respectively. The intensive treatment regiment resulted in a reduction in the prevalence of STH by 48% in albendazole and 9% in placebo group. Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment (OR 4.16(1.35-12.80)) and no statistically significant increase in SPT reactivity (OR 1.18(0.74-1.86) at 9 months or 1.37 (0.93-2.01) 21 months). No effect of anthelminthic treatment was found on BMI, reported malaria-like- and allergy symptoms. No adverse effects were reported. CONCLUSIONS: The study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH. This degree of reduction appears safe without any increased risk of malaria or allergies. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN83830814.

Integrated community-directed intervention for schistosomiasis and soil transmitted helminths in western Kenya - a pilot study.

BACKGROUND: Schistosome and soil-transmitted helminth (STH) infections are recognized as major global public health problems, causing severe and subtle morbidity, including significant educational and nutritional effects in children. Although effective and safe drugs are available, ensuring access to these drugs by all those at risk of schistosomiasis and STHs is still a challenge. Community-directed intervention (CDI) has been used successfully for mass distribution of drugs for other diseases such as onchocerciasis and lymphatic filariasis. A national control programme is yet to be instituted in Kenya and evidence for cost-effective strategies for reaching most affected communities is needed. This study evaluated the effectiveness and feasibility of the CDI strategy in the control of schistosomiasis and STHs, in East Uyoma location, Rarieda district, a community of western Kenya that is highly endemic for both infections. RESULTS: Pre-treatment prevalence of S. mansoni averaged 17.4% (range 5-43%) in the entire location. Treatment coverage in different villages ranged from 54.19 to 96.6% by community drug distributor (CDD) records. Assessment from a household survey showed coverage of 52.3 -91.9% while the proportion of homesteads (home compounds) covered ranged from 54.9-98.5%. Six months after one round of drug distribution, the prevalence levels of S. mansoni, hookworm and Trichuris trichura infections were reduced by 33.2%, 69.4% and 42.6% respectively. CONCLUSIONS: This study shows that CDI is an accepted and effective strategy in the mass treatment of schistosomiasis and STH infections in resource constrained communities in Kenya and may be useful in similar communities elsewhere. A controlled trial comparing CDI and school based mass drug administration to demonstrate their relative advantages is ongoing.

Usefulness of pumpkin seeds combined with areca nut extract in community-based treatment of human taeniasis in northwest Sichuan Province, China.

Taeniasis refers to the infection with adult tapeworms of Taenia spp. in the upper small intestine of humans, which is also a cause of cysticercosis infection in either both humans and/or animals. Currently the most commonly applied anthelminthics for treatment of taeniasis are praziquantel and niclosamide. Praziquantel is very effective, but has the risk of induction of epileptic seizures or convulsions in carriers with asymptomatic concurrent neurocysticercosis. In contrast, niclosamide is safe and effective, but is not readily available in many endemic countries including China. In the current community-based study, we assessed the curative effect of either pumpkin seeds or areca nut extract alone in taeniasis, and also looked at synergistic effects of these two herb drugs on tapeworms. In the study group with the pumpkin seed/areca nut extract treatment, 91 (79.1%) of 115 suspected taeniasis cases (with a history of expulsion of proglottids within the previous one year) released whole tapeworms, four (3.5%) expelled incomplete strobila, and no tapeworms or proglottids were recovered in the remaining 20 cases. In these 115 persons, 45 were confirmed as taeniasis before treatment by microscopy and/or coproPCR. Forty (88.9%) of 45 confirmed cases eliminated intact worms following treatment. The mean time period for complete elimination of tapeworms in 91 taeniasis cases was 2 h (range 20 min to 8 h 30 min), and 89.0% (81) of 91 patients discharged intact worms within 3h after drug administration. In Control Group A with treatment of pumpkin seeds alone, 75.0% (9/12) of confirmed taeniasis cases expelled whole tapeworms, but the mean time period for complete elimination was about 14 h 10 min (range 3 h 20 min to 21 h 20 min), which was much longer than that (2 h) for the study group, whereas in Control Group B treated with areca nut extract alone, only 63.6% (7/11) of taeniasis cases discharged whole tapeworms, and the mean time period was 6 h 27 min (range 1-22 h). Mild side effects included nausea and dizziness in about 46.3% of patients with the pumpkin seeds/areca nut extract treatment, but all discomforts were transient and well tolerated. In conclusion, a synergistic effect of pumpkin seed and areca nut extract on Taenia spp. tapeworms was confirmed in the current study, primarily in producing an increased rate of effect on tapeworm expulsion (average time 2 h for combination vs 6-21 h for individual extracts). The pumpkin seed/areca combined treatment was indicated to be safe and highly effective (89%) for human taeniasis.

Anthelminthic efficacy of banana crop residues on gastrointestinal nematodes of sheep: in vitro and in vivo tests.

Resistance to anthelminthics is common due to intensive and incorrect use. In searching for alternatives, extracts of banana plant were evaluated for egg hatching inhibition and fecal egg count reduction of sheep nematodes. Aqueous extracts of the leaf, pseudostem, and heart of the banana plant cv. Prata anã were tested at concentrations of 0.31, 0.62, 1.25, 2.5, 5.0, and 10.0 mg ml(-1) in egg hatching inhibition tests. For in vivo analysis, aqueous extracts were evaluated at dosages calculated according to the 10% lethal dose derived from acute toxicity testing in mice. Efficacy was evaluated at two time periods following oral administration. For the banana extracts at 2.5 mg ml(-1), egg hatching was significantly fewer than the negative control, with an LC(50) and LC(90) of 0.19 and 0.84 mg ml(-1), respectively. In vivo analysis for weeks 1 and 2 following a single treatment with aqueous leaf extract showed 33.1% and 32.5% anthelminthic efficacy, respectively. Further research on higher dosages with more frequent administration is needed to evaluate the potential for utilizing banana plant residues in gastrointestinal nematode control.

In vitro and in vivo efficacy of aqueous extract of Caryocar brasiliense Camb. to control gastrointestinal nematodes in sheep.

A major problem faced in sheep rearing has been the rapid acquisition of anthelminthic-resistant populations of gastrointestinal nematodes. In the search for alternatives, aqueous extract of the peel of Caryocar brasiliense was evaluated for larval development inhibition, egg-hatching inhibition, and fecal nematode egg count reduction in sheep. For in vivo analysis, the doses were calculated according to a 10% lethal dose derived from acute toxicity tests in mice, and the efficacy was evaluated for two periods following oral administration of the extract. Egg-hatching inhibition at concentrations of 15 and 7.5 mg/ml was significantly higher than observed in negative controls with distilled water. For larval development inhibition, all concentrations showed anthelminthic activity significantly higher than controls and were not significantly different from ivermectin treatment. The LC(90) of larval development inhibition was 53.19 mg/ml. In vivo analysis for first and second weeks after treatment found 32.2% and 33% anthelminthic efficacy, respectively.

Screening of 42 medicinal plants for in vivo anthelmintic activity against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus).

In the present study, methanol extracts of 42 traditional medicinal plants with potent anthelmintic activity against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus) were investigated. Cinnamomum cassia, Lindera aggregata, and Pseudolarix kaempferi exhibited 100% activity and were selected for further evaluation by applying five solvents (petroleum ether, chloroform, ethyl acetate, methanol, and water) for the extraction of the samples, followed by the in vivo bioassay. Among the extracts tested, water and methanol extracts of C. cassia showed the highest efficacies with EC(50) values of 13.2 and 12.3 mg L(-1), showing 100% efficacy against D. intermedius at 30.0 and 40.0 mg L(-1), followed by methanol extract of L. aggregata which demonstrated 100% efficacy at 60.0 mg L(-1) with EC(50) value of 17.1 mg L(-1) after 48 h of exposure. Methanol and ethyl acetate extract of P. kaempferi, which exhibited a 100% efficacy against D. intermedius at 60.0 and 50.0 mg L(-1), revealed similar activity with EC(50) values of 23.5 and 23.3 mg L(-1), respectively. Acute toxicity of these active extracts was investigated on goldfish for 48 h and the corresponding median lethal concentrations (LC(50)) of 56.9, 31.3, 88.7, 168.2, and 165.7 mg L(-1), respectively. These findings indicated that these extracts of the three plants can be developed as preferred natural antiparasitic agents for the treatment of D. intermedius.

Anthelmintic activity of medicinal plants used in Côte d'Ivoire for treating parasitic diseases.

Natural products play an important role in the discovery and development of new pharmaceuticals. In the present study, we assessed the anthelmintic properties of medicinal plants used in Cote d'Ivoire. Ethanolic extracts from 50 medicinal plants were tested in vitro against trematodes (Echinostoma caproni, Schistosoma mansoni) and nematodes (Ancylostoma ceylanicum, Heligmosomoides bakeri, Trichuris muris). Active extracts were evaluated for their cytotoxicity and followed up in vivo in mice harbouring adult S. mansoni, E. caproni and T. muris at single oral doses of 400 or 800 mg/kg. All extracts tested were active against at least one helminths species. Ten of the 65 extracts tested (15.4%) in vitro revealed activity against all helminths tested. Of 65 extracts tested in vitro at a concentration of 2 mg/ml, all caused death of schistosomula and 34.4% and 39.1% were lethal against adult S. mansoni and E. caproni 72 h post-incubation, respectively. The highest activity against A. ceylanicum in vitro was observed with Sclerocarya birrea at 2 mg/ml, which resulted in death of adult worms and inhibition of activity of third-stage larvae (L3). Of the extracts, 41.5% completely inhibited movement of H. bakeri L3 at minimal lethal concentration (MLC) values of 20-200 µg/ml 48 h post-incubation, and 15.4% paralysed adult H. bakeri at 200 µg/ml 72 h after incubation. Of the extracts, 19% resulted in death of adult T. muris at MLC values of 10-100 µg/ml. In vivo, none of the extracts tested revealed activity against E. caproni. Olax subscorpioidea achieved total and female worm burden reductions of 60% and 84%, respectively in S. mansoni-infected mice. Combretum mucronatum was the most active extracts in vivo against T. muris with a worm burden reduction of 85.3%. In conclusion, several of the medicinal plants used in Côte d'Ivoire are active against different helminths, hence might play a role in the treatment of helminthiases. Further studies are necessary to isolate the active components from these extracts.

Anthelmintic activity of ripe fruit extract of Solanum myriacanthum Dunal (Solanaceae) against experimentally induced Hymenolepis diminuta (Cestoda) infections in rats.

Although there are many effective drugs available to treat intestinal worms, the fact remains that they remain out of reach to a majority of the population in many areas of the world. On the other hand, traditional plant-based remedies continue to be an important therapeutic aid for treating worm infections throughout the world, especially in the developing nations. Solanum myriacanthum Dunal is a perennial shrub that is used in the folk medicine of Tangkhul Naga tribe of India for treating intestinal worms. This study evaluates the anthelmintic activity of its ripe fruit extract using experimental Hymenolepis diminuta (a zoonotic tapeworm) infections in albino rats. The efficacy of extract was adjudged by monitoring the eggs per gram (EPG) count of parasite as well as by the direct count of surviving worms in the intestine following treatment with methanol fruit extract of this plant to different groups of rats harbouring H. diminuta infections. The plant extract showed a dose-dependent reduction of both EPG as well as worm counts for all the developmental stages of H. diminuta in rats. However, the effects of the extract were more apparent on the adult stages than larval or immature stages of the parasite. Against the adult stage, a single oral dose of 800 mg/kg of extract, given for 3 days, showed 60.49% reduction in the EPG counts and 56.60% reduction in the worm counts in the extract-treated group as compared to untreated control. In comparison, the reference drug praziquantel (5 mg/kg) showed 51.81% and 70.00% reduction in the EPG and worm counts, respectively. The LD50 (oral) of the extract was determined to be 3,093.24 mg/kg in rats, and no significant changes were observed in the values of serum glutamate oxalate transaminase, serum glutamate pyruvate transaminase, cholesterol and total protein between the extract-treated and control groups of animals. These findings indicate that ripe fruits of S. myriacanthum possess significant anthelmintic property, without any adverse effects to the experimental animals. This may provide a scientific rationale for the traditional use of this plant against intestinal worms.

The acceptability and safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and soil-transmitted helminthiasis in children aged 1-4 years in Uganda.

OBJECTIVE: There is limited information on the acceptability and safety of praziquantel for treatment of schistosomiasis in children below the age of four years. In addition, although mebendazole has been extensively used together with praziquantel against infections with schistosomiasis and soil-transmitted helminthiasis (STH) in school-aged children, no specific acceptability or safety studies have been published on this drug combination in younger children. METHODS: A randomized clinical trial was conducted to determine the safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and STH in children aged 1 to 4 years. RESULTS: A total of 596 children from Bwondha fishing community in Mayuge district and Wang-Kado fishing community in Nebbi district were investigated using duplicate Kato-Katz thick smears of two stool samples and 130 (21·8%) were found infected with S. mansoni. Of these, 19·2% (25) had heavy intensity of infections. Of the infected children, 82 were included and randomised into praziquantel (40 mg/kg) + mebendazole (500 mg) or praziquantel (40 mg/kg) alone. CONCLUSION: Many symptoms were reported before treatment while very few were reported after treatment and all on treatment day. No serious adverse events were reported or observed after treatment. Praziquantel with or without mebendazole was well tolerated in small children in the study area.

Curcumin induces a nuclear factor-erythroid 2-related factor 2-driven response against oxidative and nitrative stress after praziquantel treatment in liver fluke-infected hamsters.

Praziquantel has been used for the treatment of liver fluke infection, but an oxidative/nitrative stress may occur after a short-term treatment and participate in side effects. In an attempt to reduce the adverse effects, we administered curcumin, an anti-inflammatory agent, to Opisthorchis viverrini-infected hamsters treated with praziquantel. At 12h after treatment, curcumin decreased eosinophil infiltration and increased mononuclear cell infiltration in parallel with nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 expression at the transcriptional and protein levels. Curcumin also enhanced the expression of genes involved in the Nrf2-regulated stress pathway (Kelch-like ECH-associated protein 1, NAD(P)H:quinine oxidoreductase 1, glutamate cysteine ligase, and activating transcription factor 3, peroxiredoxin 3, peroxiredoxin 6, manganese superoxide dismutase, and catalase), leading to increased ferric antioxidant capacity in the plasma. In contrast, curcumin decreased the level of oxidative and nitrative stress markers such as urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, plasma levels of malondialdehyde and nitrate/nitrite, and activity of plasma alanine transaminase, a liver injury marker. This correlated with the suppression of nuclear factor-kappaB (NF-κB) and related molecules (cyclooxygenase-2 and inducible nitric oxide synthase) and pro-inflammatory cytokines (IL-1ß and TNF-α). In conclusion, curcumin may be an effective chemopreventive agent against oxidative and nitrative stress derived from praziquantel treatment during O. viverrini infection via induction of Nrf2 and suppression of NF-κB-mediated pathways. Nrf2 may also be a novel therapeutic target for not only parasitic diseases but other types of inflammation-mediated diseases.