scholarly journals Effects of Callistemon citrinus aqueous extract on prepatent and patent infections with Schistosoma mansoni in experimentally infected mice

2018 ◽  
Vol 93 (04) ◽  
pp. 424-433
Author(s):  
S.A. El-Refai ◽  
A.F. Atia ◽  
S.F. Mahmoud
Keyword(s):  
Schistosoma Mansoni ◽  
Aqueous Extract ◽  
Worm Burden ◽  
Total Bilirubin ◽  
Liver Enzymes ◽  
Control Strategies ◽  
Chemotherapeutic Agents ◽  
Egg Load ◽  
Hepatic Granuloma

AbstractSchistosomiasis is a chronic debilitating parasitic disease that causes hepatic damage and is known to be endemic in developing countries. Recent control strategies for schistosomiasis depend exclusively on chemotherapeutic agents, specifically praziquantel. Unfortunately, praziquantel has low efficacy in the early phase of infection, and resistance to treatment is increasingly reported. The aim of this work was to find an alternative treatment by assessing the in vivo activity of aqueous extract of Callistemon citrinus against Schistosoma mansoni in both prepatent and patent phases in experimentally infected mice. The study was conducted on 80 male BALB/c albino mice divided into eight groups. Callistemon was administered at a dose of 200 mg/kg on days 14 and 45 post infection as a single therapy and in combination with praziquantel. Porto-mesenteric worm burden, hepatic and intestinal egg counts, hepatic granuloma number and diameter, and oogram pattern were assessed to evaluate the anti-schistosomal properties of C. citrinus. Liver enzymes and total bilirubin were tested to assess hepatoprotective effects. Results revealed that the use of C. citrinus was associated with a significant decrease in worm burden and tissue egg load together with an increased percentage of dead eggs. In addition, there was a significant reduction in granuloma formation. Callistemon also led to a significant improvement in liver function. The best results were obtained when C. citrinus was given in the prepatent phase of infection and when combined with praziquantel. Although the effects of C. citrinus are considered to be promising, further studies using different extracts, active ingredients and doses are needed.

scholarly journals Praziquantel in a Clay Nanoformulation Shows More Bioavailability and Higher Efficacy against Murine Schistosoma mansoni Infection

2015 ◽  
Vol 59 (6) ◽  
pp. 3501-3508 ◽  
Author(s):  
Gina S. El-Feky ◽  
Wael S. Mohamed ◽  
Hanaa E. Nasr ◽  
Naglaa M. El-Lakkany ◽  
Sayed H. Seif el-Din ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Rate Constant ◽  
Elimination Rate ◽  
New Drugs ◽  
Egg Load ◽  
Potential Cost ◽  
Time Curve ◽  
Content Type ◽  
Mmt Clay

ABSTRACTConsideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and itsin vivoefficacy againstSchistosoma mansoniwere investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61- and 1.96-fold and 2.16- and 1.94-fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC0–8) and maximum concentration of drug in serum (Cmax), with a decrease in elimination rate constant (kel) by 2.84- and 1.35-fold and increases in the absorption rate constant (ka) and half-life (t1/2e) by 2.11- and 1.51-fold and 2.86- and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED50] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different between groups receiving the test PZQ-clay nanoformulation and conventional PZQ.

scholarly journals In VivoActivity of Aryl Ozonides against Schistosoma Species

2011 ◽  
Vol 56 (2) ◽  
pp. 1090-1092 ◽  
Author(s):  
Jennifer Keiser ◽  
Katrin Ingram ◽  
Mireille Vargas ◽  
Jacques Chollet ◽  
Xiaofang Wang ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Worm Burden ◽  
Female Worm ◽  
Lead Compound ◽  
Content Type ◽  
Total Worm Burden

ABSTRACTWe evaluated thein vivoantischistosomal activities of 11 structurally diverse synthetic peroxides. Of all compounds tested, ozonide (1,2,4-trioxolane) OZ418 had the highest activity against adultSchistosoma mansoni, with total and female worm burden reductions of 80 and 90% (P< 0.05), respectively. Furthermore, treatment ofS. haematobium-infected mice with OZ418 reduced the total worm burden by 86%. In conclusion, OZ418 is a promising antischistosomal lead compound.

scholarly journals Safety of Aqueous Extract of Calea ternifolia Used in Mexican Traditional Medicine

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Ma G. E. González-Yáñez ◽  
Catalina Rivas-Morales ◽  
María A. Oranday-Cárdenas ◽  
María J. Verde-Star ◽  
María A. Núñez-González ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Aqueous Extract ◽  
Histological Analysis ◽  
Liver Enzymes ◽  
Renal Tissue ◽  
Proximal Tubules ◽  
Hepatic Toxicity ◽  
Treatment Of Diabetes

There is a trend to use medicinal plants for primary medical care or as dietary supplements; however, the safety of many of these plants has not been studied. The objective of this work was to determine the toxic effect of the aqueous extract of Calea ternifolia (C. zacatechichi), known popularly as “dream herb” in vivo and in vitro in order to validate its safety. In vivo, the extract had moderate toxicity on A. salina. In vitro, the extract induced eryptosis of 73% at a concentration of 100 μg·mL−1 and it inhibited CYP3A by 99% at a concentration of 375 μg/mL. After administering 8.5 mg/kg of C. ternifolia to rats, we found a reduction in platelets and leukocytes and an increase in urea and the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Histological analysis showed spongiform changes in the proximal tubules of renal tissue and a lymphoid infiltrate in liver tissue. This plant is used in the treatment of diabetes, and it is commercialized as a dietary supplement in several countries. Our results show renal and hepatic toxicity; therefore, more profound research on the toxicity of this plant is needed.

scholarly journals Ginger (Zingiber Officinale)-derived nanoparticles in Schistosoma mansoni infected mice: Hepatoprotective and enhancer of etiological treatment

2021 ◽  
Vol 15 (5) ◽  
pp. e0009423
Author(s):  
Wegdan M. Abd El Wahab ◽  
Ayman A. El-Badry ◽  
Soheir S. Mohmoud ◽  
Yaser A. El-Badry ◽  
Mohamed A. El-Badry ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Therapeutic Effect ◽  
Worm Burden ◽  
Zingiber Officinale ◽  
Egg Load ◽  
Therapeutic Drug ◽  
Slight Reduction ◽  
Prophylactic Drug ◽  
Egg Density ◽  
Therapeutic Doses

Background Nanotechnology has been manufactured from medicinal plants to develop safe, and effective antischistosmal alternatives to replace today’s therapies. The aim of the study is to evaluate the prophylactic effect of ginger-derived nanoparticles (GNPs), and the therapeutic effect of ginger aqueous extract, and GNPs on Schistosoma mansoni (S. mansoni) infected mice compared to praziquantel (PZQ), and mefloquine (MFQ). Methodology/principal findings Eighty four mice, divided into nine different groups, were sacrificed at 6th, 8th, and 10th week post-infection (PI), with assessment of parasitological, histopathological, and oxidative stress parameters, and scanning the worms by electron microscope. As a prophylactic drug, GNPs showed slight reduction in worm burden, egg density, and granuloma size and number. As a therapeutic drug, GNPs significantly reduced worm burden (59.9%), tissue egg load (64.9%), granuloma size, and number at 10th week PI, and altered adult worm tegumental architecture, added to antioxidant effect. Interestingly, combination of GNPs with PZQ or MFQ gave almost similar or sometimes better curative effects as obtained with each drug separately. The highest therapeutic effect was obtained when ½ dose GNPs combined with ½ dose MFQ which achieved 100% reduction in both the total worm burden, and ova tissue density as early as the 6th week PI, with absence of detected eggs or tissue granuloma, and preservation of liver architecture. Conclusions/significance GNPs have a schistosomicidal, antioxidant, and hepatoprotective role. GNPs have a strong synergistic effect when combined with etiological treatments (PZQ or MFQ), and significantly reduced therapeutic doses by 50%, which may mitigate side effects and resistance to etiological drugs, a hypothesis requiring further research. We recommend extending this study to humans.

scholarly journals Activity of Praziquantel Enantiomers and Main Metabolites against Schistosoma mansoni

2014 ◽  
Vol 58 (9) ◽  
pp. 5466-5472 ◽  
Author(s):  
Isabel Meister ◽  
Katrin Ingram-Sieber ◽  
Noemi Cowan ◽  
Matthew Todd ◽  
Murray N. Robertson ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Significant Role ◽  
Worm Burden ◽  
Racemic Mixture ◽  
Content Type ◽  
Effector Molecule ◽  
Oral Doses ◽  
Newly Transformed Schistosomula

ABSTRACTA racemic mixture ofRandSenantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though theSenantiomer and the metabolites are presumed to contribute only a little to the activity of the drug, in-depth side-by-side studies are lacking. The aim of this study was to investigate thein vitroactivities of PZQ and its main metabolites, namely,R- andS-cis- andR- andS-trans-4′-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored thein vivoactivity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations ofR-PZQ,S-PZQ, andR-trans- andR-cis-4′-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 μg/ml, respectively, for adultS. mansoniwere determinedin vitro. S-trans- andS-cis-4′-hydroxypraziquantel were not active at 100 μg/ml. These results are consistent with microcalorimetry data and studies with NTS.In vivo, single 400-mg/kg oral doses ofR-PZQ andS-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treatedin vivowithS-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm thatR-PZQ is the main effector molecule, whileS-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ.

scholarly journals Activities ofN,N′-Diarylurea MMV665852 Analogs against Schistosoma mansoni

2015 ◽  
Vol 59 (4) ◽  
pp. 1935-1941 ◽  
Author(s):  
Noemi Cowan ◽  
Philipp Dätwyler ◽  
Beat Ernst ◽  
Chunkai Wang ◽  
Jonathan L. Vennerstrom ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Schistosoma Mansoni ◽  
In Silico ◽  
Worm Burden ◽  
Unmet Need ◽  
Intestinal Wall ◽  
Content Type ◽  
Pharmacokinetic Properties

ABSTRACTThere is an unmet need to discover and develop novel antischistosomal drugs. As exemplified by MMV665852,N,N′-diarylureas have recently emerged as a promising antischistosomal chemotype. In this study, we evaluated the structure-activity relationships of 46 commercially available analogs of MMV665852 on newly transformed schistosomula (NTS) and adultSchistosoma mansoniwormsin vitro. Active compounds were evaluated with a cytotoxicity assay,in silicocalculations, metabolic stability studies, and anin vivoassay with mice harboring adultS. mansoniworms. Of the 46 compounds tested at 33.3 μM, 13 and 14 compounds killed NTS and adult worms, respectively, within 72 h. Nine compounds had 90% inhibitory concentrations (IC90s) of ≤10 μM against adult worms, with selectivity indexes of ≥2.8. Their physicochemical properties and permeation through an artificial membrane indicated good to moderate intestinal absorption. Their metabolic stabilities ranged from low to high. Despite satisfactoryin vitroresults andin silicopredictions, only one compound resulted in a statistically significant worm burden reduction (66%) after administration of a single oral dose of 400 mg/kg of body weight toS. mansoni-infected mice. Worm burden reductions of 0 to 43% were observed for the remaining eight compounds tested. In conclusion, several analogs of theN,N′-diarylurea MMV665852 had high efficacy againstS. mansoniin vitroand favorable physicochemical properties for permeation through the intestinal wall. To counteract the low efficacy observed in the mouse model, further investigations should focus on identifying compounds with improved solubility and pharmacokinetic properties.

The impact of cinnarizine and griseofulvin on juvenile and adult stages of Schistosoma mansoni

2019 ◽  
Vol 94 ◽  
Author(s):  
R.M. Sarhan ◽  
H.S. Thabet ◽  
J.T. Nazeer ◽  
S. William
Keyword(s):  
Schistosoma Mansoni ◽  
Worm Burden ◽  
Early Infection ◽  
Complete Disappearance ◽  
Late Infection ◽  
And Control ◽  
The Impact ◽  
Total Worm Burden

Abstract Schistosomiasis affects millions globally. There is no vaccine, and treatment depends entirely on praziquantel (PZQ). Field isolates exhibit reduced susceptibility to PZQ, and resistance has been experimentally induced, suggesting that reliance on a single treatment is particularly dangerous. The present study investigated the value of cinnarizine and griseofulvin against Schistosoma mansoni through their in vitro effects on adult worms and oviposition as well as in vivo evaluation in early and late infection, compared to PZQ, in a preliminary experimental model. In vitro, both cinnarizine and griseofulvin showed uncoupling, sluggish worm movement and complete absence of ova at 100 μg/ml. In early infection, cinnarizine showed a significant reduction in the number of porto-mesenteric couples compared to the griseofulvin and control groups, a finding similar to PZQ. Remarkably, cinnarizine significantly exceeded PZQ and griseofulvin in reducing the total worm burden. In late infection, cinnarizine and griseofulvin showed results similar to PZQ by significantly reducing the numbers of hepatic and porto-mesenteric couples and total worm burden compared to controls. Cinnarizine performed better than griseofulvin by reducing hepatic and intestinal ovum counts, and it led to complete disappearance of the first two immature stages. The current work suggests the possibility of using cinnarizine and griseofulvin, mainly in late S. mansoni infection, especially cinnarizine, which showed similar results to PZQ and surpassed it in early infection. Further studies are required to elucidate their exact mechanisms of action and particularly their synergistic effect with PZQ.

scholarly journals Activities of Quinoxaline, Nitroquinoxaline and [1,2,4]Triazolo[4,3-a]quinoxaline Analogs of MMV007204 against Schistosoma mansoni

2020 ◽  
Author(s):  
Stefan L. Debbert ◽  
Mikaela J. Hintz ◽  
Christian J. Bell ◽  
Kenya R. Earl ◽  
Grant E. Forsythe ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Worm Burden ◽  
New Drugs ◽  
Parasitic Disease ◽  
Quinoxaline Derivative ◽  
Pharmacokinetic Properties ◽  
Malaria Box ◽  
Newly Transformed Schistosomula

The reliance on one drug, praziquantel, to treat the parasitic disease schistosomiasis in millions of people a year shows the need to further develop a pipeline of new drugs to treat this disease. Recently, an antimalarial quinoxaline derivative (MMV007204) from the Medicines for Malaria Venture (MMV) Malaria Box demonstrated promise against Schistosoma mansoni. In this study, 47 synthesized compounds containing quinoxaline moieties were first assayed against the larval stage of this parasite, newly transformed schistosomula (NTS); of these, 16 killed over 70% NTS at 10 μM. Further testing against NTS and adult S. mansoni yielded three compounds with 50% inhibitory concentrations (IC50s) of ≤ 0.31 μM against adult S. mansoni and selectivity indices of ≥ 8.9. Administration of these compounds as a single oral dose of 400 mg/kg of body weight to S. mansoni-infected mice yielded only moderate worm burden reduction (WBR) (9.3% – 46.3%). The discrepancy between these compounds’ good in vitro activities and their poor in vivo activities indicates that optimization of their pharmacokinetic properties may yield compounds with greater bioavailabilities and better antischistosomiasis activities in vivo.

scholarly journals Hepatoprotective Effect of Pancha Lavana Dravagam Against Paracetamol induced Hepatotoxicity in Wistar Albino Rats - An in-Vivo Study

2021 ◽  
pp. 1-10
Author(s):  
G. Kaaruniya ◽  
A. Mariappan ◽  
V. Suba ◽  
R. Meenakumari
Keyword(s):  
Total Bilirubin ◽  
Liver Enzymes ◽  
Liver Toxicity ◽  
Hepatoprotective Effect ◽  
Control Group ◽  
Albino Rats ◽  
Standard Drug ◽  
Wistar Albino Rats ◽  
Serum Glutamate

Objective: To evaluate the liver protective effect of Pancha Lavana Dravagam (PLD) against Paracetamol induced hepatotoxicity in wistar albino rat models. Methods: The hepatoprotective activity of PLD was evaluated using paracetamol induced liver damage in rats. Wistar albino rats were divided into five groups of six animals each. Paracetamol 1gm/kg bw, p.o. was given to produce liver toxicity. The normal control was given the vehicle (water 1ml/kg bw, p.o). Two test groups with PLD 1ml/kg, 2ml/kg bw, p.o. were tested for hepatoprotective potential. Silymarin 50mg/kg bw, p.o. was given as standard drug. All these drugs were administered for 7 days. On 8th day, the animals were sacrificed and blood was collected from retro-orbital plexus and analyzed for serum enzymes like Serum Glutamate Pyruvate Transaminase (SGPT), Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Alanine Phosphate (ALP), Total Bilirubin, Total Proteins and liver was excised for histopathological analysis. Results: In toxicant control group, paracetamol produced liver toxicity due to decrease in glutathione (GSH) by oxidative stress and mitochondrial dysfunction of hepatic cells. It resulted in an increase of serum liver enzymes like SGPT, SGOT, ALP and Total Bilirubin. This increased serum liver enzymes were reduced significantly in the test drug PLD treated groups and Standard group. The histology of liver tissues was also improved in PLD treated groups when compared to the toxicant group. Conclusion: Since, no scientific evidence is available to claim the hepatoprotective effect of PLD, in vivo studies were conducted. It demonstrated that it has a potent hepatoprotective effect against the paracetamol induced hepatotoxicity by suppression of the reactive oxygen species and increasing the anti-oxidant glutathione in liver cells.

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