In Silico Comparison of Bioactive Compounds Characterized from Azadirachta indica with an FDA-Approved Drug against Schistosomal Agents: New Insight into Schistosomiasis Treatment.

The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from A. indica were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors (Schistosoma mansoni Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of -10.19 and -45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug.

In vitro Evaluation of the Antileishmanial and Antischistosomal Activities of p-Coumaric Acid Prenylated Derivatives.

We have evaluated eight p-coumaric acid prenylated derivatives in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC50=45.92 µM) and S. mansoni (IC50=64.25 µM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives.

Synthesis and antischistosomal activity of linker- and thiophene-modified biaryl alkyl carboxylic acid derivatives.

Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus Schistosoma and causes severe morbidity in infected patients. In 2018, 290.8 million people required treatment, and 200,000 deaths are reported per year. Treatment of this disease depends on a single drug, praziquantel (PZQ). However, in the past few years, reduced sensitivity of the parasites toward PZQ has been reported. Therefore, there is an urgent need for new drugs against this disease. In the past few years, we have focused on a new substance class called biaryl alkyl carboxylic acid derivatives, which showed promising antischistosomal activity in vitro. Structure-activity relationship (SAR) studies of the carboxylic acid moiety led to three promising carboxylic amides (morpholine, thiomorpholine, and methyl sulfonyl piperazine) with an antischistosomal activity down to 10 µM (morpholine derivative) and no cytotoxicity up to 100 µM. Here, we show our continued work on this substance class. We investigated, in extended SAR studies, whether modification of the linker and the thiophene ring could improve the antischistosomal activity. We found that the exchange of the alkyl linker by a pentadienyl or benzyl linker was tolerated and led to similar antischistosomal effects, whereas the exchange of the thiophene ring was not tolerated. Our data suggest that the thiophene ring is important for the antischistosomal activity of this compound class.

The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species.

Treatment and control of schistosomiasis depends on a single drug, praziquantel, but this is not ideal for several reasons including lack of potency against the juvenile stage of the parasite, dose size, and risk of resistance. We have optimised the properties of a series of compounds we discovered through high throughput screening and have designed candidates for clinical development. The best compounds demonstrate clearance of both juvenile and adult S. mansoni worms in a mouse model of infection from a single oral dose of < 10 mg/kg. Several compounds in the series are predicted to treat schistosomiasis in humans across a range of species with a single oral dose of less than 5 mg/kg.

New evidence for tamoxifen as an antischistosomal agent: in vitro, in vivo and target fishing studies.

Background: Praziquantel is the only drug available to treat schistosomiasis, and there is an urgent demand for new anthelmintic agents. Methodology & results: We conducted in-depth in vitro and in vivo studies and report a target fishing investigation. In vitro, tamoxifen was active against adult and immature worms at low concentrations (<5 µM). Tamoxifen at a single dose (400 mg/kg) or once daily for five consecutive days (100 mg/kg/day) in mice harboring either adult (patent infection) or juvenile (prepatent infection) significantly reduced worm burden (30-70%) and egg production (70-90%). Target fishing studies revealed propionyl-CoA carboxylase as a potential target for tamoxifen in Schistosoma mansoni and glucose uptake by S. mansoni was also significantly reduced. Conclusion: Our results provide news evidence of antiparasitic effect of tamoxifen and reveal propionyl-CoA carboxylase as a potential target.

In vitro and in vivo evaluation of cnicin from blessed thistle (Centaurea benedicta) and its inclusion complexes with cyclodextrins against Schistosoma mansoni.

Schistosomiasis, caused by a blood fluke of the genus Schistosoma, afflicts over 230 million people worldwide. Treatment of the disease relies on just one drug, praziquantel. Cnicin (Cn) is the sesquiterpene lactone found in blessed thistle (Centaurea benedicta) that showed antiparasitic activities but has not been evaluated against Schistosoma. However, cnicin has poor water solubility, which may limit its antiparasitic activities. To overcome these restrictions, inclusion complexes with cyclodextrins may be used. In this work, we evaluated the in vitro and in vivo antischistosomal activities of cnicin and its complexes with ß-cyclodextrin (ßCD) and 2-hydroxypropyl-ß-cyclodextrin (HPßCD) against Schistosoma mansoni. Cnicin were isolated from C. benedicta by chromatographic fractionation. Complexes formed by cnicin and ßCD (Cn/ßCD), as well as by cnicin and HPßCD (Cn/HPßCD), were prepared by coprecipitation and characterized. In vitro schistosomicidal assays were used to evaluate the effects of cnicin and its complexes on adult schistosomes, while the in vivo antischistosomal assays were evaluated by oral and intraperitoneal routes. Results showed that cnicin caused mortality and tegumental alterations in adult schistosomes in vitro, also showing in vivo efficacy after intraperitoneal administration. The oral treatment with cnicin or Cn/ßCD showed no significant worm reductions in a mouse model of schistosomiasis. In contrast, Cn/HPßCD complex, when orally or intraperitoneally administered to S. mansoni-infected mice, decreased the total worm load, and markedly reduced the number of eggs, showing high in vivo antischistosomal effectiveness. Permeability studies, using Nile red, indicated that HPßCD complex may reach the tegument of adult schistosomes in vivo. These results demonstrated the antischistosomal potential of cnicin in preparations with HPßCD.

A multi-dimensional, time-lapse, high content screening platform applied to schistosomiasis drug discovery.

Approximately 10% of the world's population is at risk of schistosomiasis, a disease of poverty caused by the Schistosoma parasite. To facilitate drug discovery for this complex flatworm, we developed an automated high-content screen to quantify the multidimensional responses of Schistosoma mansoni post-infective larvae (somules) to chemical insult. We describe an integrated platform to process worms at scale, collect time-lapsed, bright-field images, segment highly variable and touching worms, and then store, visualize, and query dynamic phenotypes. To demonstrate the methodology, we treated somules with seven drugs that generated diverse responses and evaluated 45 static and kinetic response descriptors relative to concentration and time. For compound screening, we used the Mahalanobis distance to compare multidimensional phenotypic effects induced by 1323 approved drugs. Overall, we characterize both known anti-schistosomals and identify new bioactives. Apart from facilitating drug discovery, the multidimensional quantification provided by this platform will allow mapping of chemistry to phenotype.

Identification of annotated bioactive molecules that impair motility of the blood fluke Schistosoma mansoni.

Neglected tropical diseases are of growing worldwide concern and schistosomiasis, caused by parasitic flatworms, continues to be a major threat with more than 200 million people requiring preventive treatment. As praziquantel (PZQ) remains the treatment of choice, an urgent need for alternative treatments motivates research to identify new lead compounds that would complement PZQ by filling the therapeutic gaps associated with this treatment. Because impairing parasite neurotransmission remains a core strategy for control of parasitic helminths, we screened a library of 708 compounds with validated biological activity in humans on the blood fluke Schistosoma mansoni, measuring their effect on the motility on schistosomulae and adult worms. The primary phenotypic screen performed on schistosomulae identified 70 compounds that induced changes in viability and/or motility. Screening different concentrations and incubation times identified molecules with fast onset of activity on both life stages at low concentration (1 µM). To complement this study, similar assays were performed with chemical analogs of the cholinomimetic drug arecoline and the calcilytic molecule NPS-2143, two compounds that rapidly inhibited schistosome motility; 17 arecoline and 302 NPS-2143 analogs were tested to enlarge the pool of schistosomicidal molecules. Finally, validated hit compounds were tested on three functionally-validated neuroregulatory S. mansoni G-protein coupled receptors (GPCRs): Sm5HTR (serotonin-sensitive), SmGPR2 (histamine) and SmD2 (dopamine), revealing NPS-2143 and analogs as potent inhibitors of dopamine/epinine responses on both human and S. mansoni GPCRs. This study highlights the potential for repurposing known human therapeutic agents for potential schistosomicidal effects and expands the list of hits for further progression.

In vivo studies of the effect of PPQ-6, a quinoline-based agent against Schistosoma mansoni in mice.

Schistosomiasis is still a public health problem. Praziquantel is the only drug available for treatment of all forms of human schistosomiasis. Although praziquantel is an effective drug against all species of human schistosomes, concerns about resistance have been raised, especially in endemic areas. A hybrid compound containing several pharmacophore within a single molecule is a promising strategy. Here, we described the anti-schistosomal effect of 4-(2-Chloroquinolin-3-yl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (PPQ-6), a hybrid drug based on quinoline and pyridine. PPQ-6 was given as two regimens (20 or 40 mg/kg). In both regimens, PPQ-6 significantly reduced liver and spleen indices, nitric oxide production, tissue egg load, hepatic granuloma size and count, immature eggs and total worm burden especially females. Our findings suggested that PPQ-6 is a promising anti-schistosomal agent; however more research is needed to elucidate its mechanism of action and report its activity on juvenile schistosomes and other species of human schistosomes.

Vanillin-Related N-Acylhydrazones: Synthesis, Antischistosomal Properties and Target Fishing Studies.

BACKGROUND: Schistosomiasis is a neglected disease, which affects millions of people in developing countries. Its treatment relies on a single therapeutic alternative, the praziquantel. This situation may lead to drug resistance which, in turn, made urgent the need for new antischistosomal agents. Nacylhydrazones are usually explored as good antimicrobial agents, but the vanillin-related N-acylhydrazones have never been tested by their antiparasitic potential. OBJECTIVE: Herein, we report the synthesis of seven analogues, three of them unpublished, their biological investigation against Schistosoma mansoni and Target Fishing studies. METHODS: The compounds were synthesized following classical synthetical approaches. The anthelmintic potential was assessed as well as their cytotoxicity profile. Confocal laser scanning microscopy and target fishing study were performed to better understand the observed antischistosomal activity. RESULTS: Compound GPQF-407 exhibited good antischistosomal activity (47.91 µM) with suitable selectivity index (4.14). Confocal laser scanning microscopy revealed that it triggered severe tegumental destruction and tubercle disintegration. Target fishing studies pointed out some probable targets, such as the serine-threonine kinases, dihydroorotate dehydrogenases and carbonic anhydrase II. CONCLUSION: The GPQF-407 was revealed to be a promising antischistosomal agent which, besides presenting the N-acylhydrazone privileged scaffold, also could be easily synthesized on large scales from commercially available materials.

In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum.

BACKGROUND: Schistosomiasis is a debilitating neglected tropical disease that affects approximately 190 million people around the world. Praziquantel (PZQ) is the only drug available for use against all Schistosoma species. Although PZQ has a high efficacy, recognized concerns have prompted the development of new, alternative drugs for repeated use in endemic areas where PZQ efficacy against strains of Schistosoma is reduced. A hybrid drug containing different pharmacophores within a single molecule is a promising strategy. Our earlier in vivo studies showed the significant antiparasitic activity of a praziquantel derivative, DW-3-15, against Schistosoma japonicum. In the present study, DW-3-15 was synthesized in large amounts by a pharmaceutical company and its schistosomicidal efficacy and stability were further confirmed. Parameters such as parasite viability, pairing and oviposition were evaluated in vitro. An in vivo study was conducted to assess the effect of commercial DW-3-15 on worm burden, egg production and diameter of granulomas. Additionally, to gain insight into the mechanism of action for DW-3-15, morphological changes in the tegument of S. japonicum were also examined. RESULTS: The in vitro study showed the antiparasitic activity of DW-3-15 against S. japonicum, with significant reductions in viability of adult and juvenile worms, worm pairings and egg output. Compared to PZQ, DW-3-15 induced similar ultrastructural changes and evident destruction of the tegument surface in male worms. In vivo, the oral administration of DW-3-15 at a dose of 400 mg/kg per day for five consecutive days in mice significantly reduced the total worm burden and number of eggs in the liver. Histological analysis of the livers showed a marked reduction in the average diameter of the egg granuloma. CONCLUSIONS: Our findings suggest that DW-3-15, a PZQ derivative with the prospect of commercial production, can be developed as a potential promising schistosomicide.

Could we expect new praziquantel derivatives? A meta pharmacometrics/pharmacoinformatics analysis of all antischistosomal praziquantel derivatives found in the literature.

Praziquantel (PZQ) is the first line drug for the treatment of human Schistosoma spp. worm infections. However, it suffers from low activity towards immature stages of the worm, and its prolonged use induces resistance/tolerance. During the last 40 years, 263 PZQ analogues have been synthesized and tested against Schistosoma spp. worms, but less than 10% of them showed significant activity. Here, we propose a rationalization of the chemical space of the PZQ derivatives by a ligand-based approach. First, we constructed an in-house database with all PZQ derivatives available in the literature. This analysis shows a high heterogeneity in the data. Fortunately, all studies include PZQ as a reference, permitting the classification of compounds into three classes according to their activities. Models involving ligand-based pharmacophore and logistic regression were performed. Five physicochemical parameters were identified as the best to explain the biological activity. In the end, we proposed new PZQ derivatives with modifications at positions 1 and 7, we analysed them with our models, and we observed that they can be more active than the previously synthesized derivatives. The main goal of this work was to conduct the most valuable meta-pharmacometrics/pharmacoinformatics analysis with all Praziquantel medicinal chemistry data available in the literature.

Life cycle maintenance and drug-sensitivity assays for early drug discovery in Schistosoma mansoni.

Drug discovery for schistosomiasis is still limited to a handful of academic laboratories worldwide, with only a few novel antischistosomal lead compounds being actively researched. Despite recent international mobilization against the disease to stimulate and promote antischistosomal drug discovery, setting up a drug-screening flow with schistosome parasites remains challenging. Whereas numerous different protocols to obtain and cultivate schistosomes have been published, those describing the drug-screening process are scarce, and none gather together parasite cultivation and early drug discovery procedures. To help overcome this hurdle, we provide here a set of integrated methods either adapted from already-published protocols or based on our long-term experience in schistosomiasis research. Specifically, we detail the establishment and maintenance of the complex and several-week-long Schistosoma mansoni life cycle in a laboratory setting, as well as the means of retrieving and culturing the parasites at their relevant life stages. The in vitro and in vivo assays that are performed along the drug-screening cascade are also described. In these assays, which can be performed within 5 d, the effect of a drug is determined by phenotypic assessment of the parasites' viability and morphology, for which stage-specific scoring scales are proposed. Finally, the modalities for testing and evaluating a compound in vivo, constituting a procedure lasting up to 10 weeks, are presented in order to go from in vitro hit identification to the selection of early lead candidates.

Niosomes for enhanced activity of praziquantel against Schistosoma mansoni: in vivo and in vitro evaluation.

Praziquantel (PZQ) is recommended by the WHO as the first line in treatment of schistosomiasis. Unfortunately, it exhibits low oral bioavailability which can compromise its efficacy. Nanostructures showed promising potential to overcome this problem. Accordingly, the aim of this study was to investigate the effect of niosomal encapsulation of PZQ on its activity on Schistosoma mansoni in vitro and in vivo. PZQ was encapsulated in niosomal formulation comprising span 60, cholesterol with peceol being included as absorption enhancer. The in vitro work determined the schistosomicidal activity and morphological changes after incubation with drug solution or PZQ-niosomes. The in vivo study utilized infected mice which received PZQ orally as solution or as niosomes. The activity was assessed by monitoring egg and worm count in addition to histopathological and immunohistochemical studies. The in vitro studies revealed that niosomes alone caused a 30% death of adult parasites and caused completely coiled body, destruction, and peeling of tubercles and spines, with flattening and effacement of gynecophoric canal, blebbing with niosomes vesicles attached to it. Niosomes containing PZQ at a concentration of 0.001 µg/ml increased the death from 30 to 50% with the corresponding PZQ solution causing only 10% death. The in vivo study reflected of niosome-PZQ over PZQ solution as indicated from significant reduction of adult worm count, hepatic and intestinal egg depositions, hepatic granuloma size, and numbers, with marked reduction of vascular endothelial growth factor expression. The study introduced niosomes as promising carriers for enhanced activity of PZQ.

Structure-Activity Relationship and in Vitro Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) Studies of N-aryl 3-Trifluoromethyl Pyrido[1,2- a]benzimidazoles That Are Efficacious in a Mouse Model of Schistosomiasis.

We have previously reported on the antischistosomal activity of pyrido[1,2- a]benzimidazole (PBI) derivatives. As a follow-up, we designed and prosecuted further structure-activity relationship (SAR) studies that incorporate N-aryl substitutions on the PBI scaffold. Investigations into the in vitro antischistosomal activity against newly transformed schistosomula (NTS) and adult worms revealed several leads with promising potency. Active compounds with a good cytotoxicity profile were tested in vivo whereby 6 and 44 induced noteworthy reduction (62-69%) in the worm load in the Schistosoma mansoni mouse model. Pharmacokinetic analysis on 44 pointed to slow absorption, low volume of distribution, and low plasma clearance indicating the potential of these compounds to achieve a long duration of action. Overall, our work demonstrates that PBI chemotype is a promising scaffold in the discovery of new antischistosomal leads.

SAR of a new antischistosomal urea carboxylic acid.

Urea carboxylic acids, products of aryl hydantoin hydrolysis, were recently identified as a new antischistosomal chemotype. We now describe a baseline structure-activity relationship (SAR) for this compound series. With one exception, analogs of lead urea carboxylic acid 2 were quite polar with Log D7.4 values ranging from -1.9 to 1.8, had high aqueous solubilities in the range of 25-100 µg/mL, and were metabolically stable. None of the compounds had measurable in vitro antischistosomal activity or cytotoxicity, but four of these had moderate worm burden reduction (WBR) values of 42-70% when they were administered as single 100 mg/kg oral doses to S. mansoni-infected mice. These data indicate that with the exception of the gem-dimethyl substructure and the distal nitrogen atom of the urea functional group, the rest of the structure of 2 is required for in vivo antischistosomal activity.

Photoactivated water-disinfecting, and biological properties of Ag NPs@Sm-doped ZnO nanorods/cuttlefish bone composite: In-vitro bactericidal, cercaricidal and schistosomicidal studies.

Herein, eco-friendly composite was synthesized by embedding silver (Ag) nanospheres onto aragonitic cuttlefish bone (CB)-stabilized samarium doped zinc oxide (Sm-doped ZnO) nanorods. The operating interaction profile and the photoactive behavior of this nanocomposite were assessed via XRD, FTIR, Raman, TEM, FE-SEM, DLS, DRS and PL techniques. Locality of Sm-doped ZnO and its attaching modes to the cuttlefish bone lamella were highly dominated by embedding Ag NPs that encouraged Zn2+ Lewis acid sites to electrostatically interact with aragonite carbonates in the channeled porous CB system. Such interacting approach enhanced photoactivity of Sm-doped ZnO by lowering its energy band gap (from 3.26 eV for Sm-doped ZnO/CB to 2.12 eV for Ag@Sm-doped ZnO/CB). Besides, plasmon-induced silver electrons provided Sm-doped ZnO by extra photosensitivity. Ag@Sm-doped ZnO/CB nanocomposite exhibited pronounced photo-activated disinfection efficiencies for Staphylococcus aureus (80%), Pseudomonas aeruginosa (60%), and Schistosoma mansoni cercariae (100%) linked with progressive demolition in cercarial body. Such nanocomposite also possessed exterminating action against Schistosoma mansoni adult worms serving near 100% worm-mortality accompanied by significant disintegration of worm body. These findings were successfully drawn Ag@Sm-doped ZnO/CB as an efficient weapon in the biocides arsenal being even capable of destructing pathogenic bacteria and parasites in dark- and photo- conditions.

Chemotherapy for Fighting Schistosomiasis: Past, Present and Future.

Chemotherapy based on repeated doses of praziquantel remains the most effective control strategy against schistosomiasis, a neglected tropical disease caused by platyhelminths of the genus Schistosoma spp. Its long-term use, however, raises serious concerns about drug resistance against praziquantel. Therefore, it is generally acknowledged that alternative treatment options are urgently needed. This Review summarizes data on relinquished drugs as well as recent advances in the area of antischistosomal compounds from a medicinal chemistry point of view. Furthermore, insights into the structure-activity relationships of each class of compounds are presented including in vitro and in vivo data, if available. Although many compounds have demonstrated good antischistosomal activity in vitro, they offer little promise to replace praziquantel. Nevertheless, the race to develop novel antischistosomal agents is ongoing.

[Development of a novel method for UPLC-QTOF-MS analysis of anti-schistosomiasis heterocyclic compounds].

OBJECTIVE: To develop an ultra-performance liquid chromatography/quadrupole-time of flight mass spectrometry (UPLC-QTOF-MS) method for the determination of an oxadiazole-2-oxide heterocyclic compound F-2015-14. METHODS: Mouse plasma and liver homogenate specimens were extracted with ethyl acetate and chromatographed on a Waters CORTECS column (C18, 1.6 µm, 2.1 mm × 150 mm) by using a mobile phase of 10% acetonitrile-0.1% formic acid with by a volume fractionation by gradient elution. Then, UPLC-QTOF-MS was performed to determine F-2015-14 in mouse plasma and liver homogenate specimens. RESULTS: The linearity of F-2015-14 in plasma ranged from 12.5 to 250 mg/mL with a correlation coefficient of 0.990 and a detection limit of 8.8 mg/mL. F-2015-14 in liver homogenates ranged from 12.5 to 250 mg/mL. The linearity was good with a correlation coefficient of 0.992 and a limit of detection of 5.6 mg/mL. If the concentration of plasma and liver homogenate specimens was 12.5 mg/mL, the accuracy and the matrix effect were 80% to 120%, and the inter-day and intra-day precision was within 20%. If the concentrations of plasma and liver homogenate specimens were 100 mg/mL and 200 mg/mL, the accuracy and the matrix effect were 85% to 115%, and the inter-day and intra-day precision was within 15%. CONCLUSIONS: The UPLC-QTOF-MS established in this study has a high sensitivity and good reproducibility for the determination of F-2015-14, which provides bases for the development of novel anti-schistosomiasis drugs.

Antischistosomal Properties of Hederacolchiside A1 Isolated from Pulsatilla chinensis.

Background: Schistosomiasis is a major neglected disease for which the current control strategy involves mass treatment with praziquantel, the only available drug. Hence, there is an urgent need to develop new antischistosomal compounds. Methods: The antischistosomal activity of hederacolchiside A1 (HSA) were determined by total or female worm burden reductions in mice harboring Schistosoma japonicum or S. mansoni. Pathology parameters were detected on HSA against 1-day-old S. japonicum-harboring mice. Moreover, we confirmed the antischistosomal effect of HSA on newly transformed schistosomula (NTS) of S. japonicum in vitro. Results: HSA, a natural product isolated from Pulsatilla chinensis (Bunge) Regel, was initially corroborated to possess promising antischistosomal properties. We demonstrated that HSA had high activity against S. japonicum and S. mansoni less in 11 days old parasites harbored in mice. The antischistosomal effect was even more than the currently used drugs, praziquantel, and artesunate. Furthermore, HSA could ameliorate the pathology parameters in mice harboring 1-day-old juvenile S. japonicum. We also confirmed that HSA-mediated antischistosomal activity is partly due to the morphological changes in the tegument system when NTS are exposed to HSA. Conclusions: HSA may have great potential to be an antischistosomal agent for further research.