Activities of pumpkin seed oil against Biomphalaria alexandrina snails and the infective stages of Schistosoma mansoni with special emphasis on genotoxic and histopathological alterations.

Schistosomiasis is a serious health issue in tropical regions, and natural compounds have gained popularity in medical science. This study investigated the potential effects of pumpkin seed oil (PSO) on Biomphalaria [B.] alexandrina snails (Ehrenberg, 1831), Schistosoma [S.] mansoni (Sambon, 1907) miracidium, and cercariae. The chemical composition of PSO was determined using gas chromatography/mass spectrometry. A bioassay was performed to evaluate the effects of PSO on snails, miracidia, and cercariae. The results showed no significant mortality of B. alexandrina snails after exposure to PSO, but it caused morphological changes in their hemocytes at 1.0 mg/ml for 24 hours. PSO exhibited larvicidal activity against miracidia after 2 hours of exposure at a LC50 of 618.4 ppm. A significant increase in the mortality rate of miracidia was observed in a dose- and time-dependent manner, reaching a 100% death rate after 10 minutes at LC90 and 15 minutes at LC50 concentration. PSO also showed effective cercaricidal activity after 2 hours of exposure at a LC50 of 290.5 ppm. Histological examination revealed multiple pathological changes in the digestive and hermaphrodite glands. The PSO had genotoxic effects on snails, which exhibited a significant increase [p≤0.05] in comet parameters compared to the control. The findings suggest that PSO has potential as a molluscicide, miracidicide, and cercaricide, making it a possible alternative to traditional molluscicides in controlling schistosomiasis.

Field validation of different intervention modes for the potential transmission risk of schistosomiasis during post-transmission interruption phase.

OBJECTIVE: Precision interventions have been proposed in transmission-interrupted areas to further reduce the potential transmission risk of schistosomiasis. This study aimed to evaluate the effects of different interventions modes for potential transmission risk control. METHODS: Three groups of schistosomiasis-endemic villages were selected in Jiangling county, Hubei province. After baseline surveys in 2020, three intervention models were employed in 2021 and 2022. In Model 1, Oncomelania hupensis snail control in key settings and an integrated strategy with an emphasis on the infectious sources managing was employed. In Model 2, an integrated health education-led strategy with an emphasis on infectious source management was employed. In Model 3, only the integrated strategy with an emphasis on infectious source management was employed. The effects of the different intervention models were examined with multiple indicators after 2 years of intervention using the entropy-weighted technique for order of preference by similarity to ideal solution (TOPSIS), rank-sum ratio (RSR) and fuzzy combination model of entropy-weighted TOPSIS and RSR. RESULTS: Entropy-weighted TOPSIS modeling showed that the Ci values of Model 2 were 0.4434, 0.2759, and 0.3069 in the three pilot villages, Ci values were larger, with top comprehensive ranking. The results of the RSR method showed that the RSR values of Model 2 were 0.75, 0.708, and 0.736 in the three pilot villages, with top comprehensive ranking. The results from the fuzzy combination model of entropy-weighted TOPSIS and RSR showed that implementation of Model 2 resulted in the highest comprehensive ranking among the three models in the three pilot villages under Ci: RSR = 0.1: 0.9, Ci: RSR = 0.5: 0.5 and Ci: RSR = 0.9: 0.1. CONCLUSION: The integrated health education-led strategy with an emphasis on infectious source management was the optimal model to manage the risk of transmission of schistosomiasis during the post-transmission interruption phase.

Potential of pharmaceutical formulation based on Morinda citrifolia extract for the treatment of schistosomiasis.

Schistosomiasis is a parasitic disease that can be asymptomatic, but it can progress and cause serious damage, such as hospitalization and death. This work aimed to characterize and carry out the in vivo pharmacological test of the dry extract of Morinda citrifolia and obtain a pharmaceutical dosage form based on this extract for the treatment of schistosomiasis. The aqueous extract was characterized based on the evaluation of pH, dry residue and density. The aqueous extract was dried through the freeze-drying process. The obtained dry extract was characterized through phytochemical screening, rheological analysis, acute toxicity and in vivo pharmacology. Additionally, the pre-formulation development of a pharmaceutical dosage form was pursued with the dry extract. Through the HPLC chromatogram, characteristic rutin peaks were identified. The rheological behavior of the dry extract did not show good characteristics. Acute toxicity, at a dose of 2000 mg/kg, showed excitatory activity in the central and autonomous nervous system. The in vivo pharmacological test of the dry extract showed that, at a dose of 400 mg/kg, it was possible to reduce 67.5% of the total adult worms, 66% of female worms and 60% of the number of eggs. The pharmaceutical dosage form obtained was an oral solution that was clear, transparent, without the presence of lumps and precipitates, having a density of 1.1276 g mL-1 and pH of 5.92. The results obtained will provide parameters for the production of suitable pharmaceutical formulations, as well as for the quality control of products based on M. citrifolia, with promising schistosomicidal activity.

Therapeutic Potential of Natural Products in the Treatment of Schistosomiasis.

It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are Schistosoma Mansoni, S. japonicum, and S. haematobium, each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.

Human schistosomiasis in Nigeria: present status, diagnosis, chemotherapy, and herbal medicines.

Schistosomiasis is a neglected tropical disease caused by a parasitic, trematode blood fluke of the genus Schistosoma. With 20 million people infected, mostly due to Schistosoma haematobium, Nigeria has the highest burden of schistosomiasis in the world. We review the status of human schistosomiasis in Nigeria regarding its distribution, prevalence, diagnosis, prevention, orthodox and traditional treatments, as well as snail control strategies. Of the country's 36 states, the highest disease prevalence is found in Lagos State, but at a geo-political zonal level, the northwest is the most endemic. The predominantly used diagnostic techniques are based on microscopy. Other methods such as antibody-based serological assays and DNA detection methods are rarely employed. Possible biomarkers of disease have been identified in fecal and blood samples from patients. With respect to preventive chemotherapy, mass drug administration with praziquantel as well as individual studies with artemisinin or albendazole have been reported in 11 out of the 36 states with cure rates between 51.1 and 100%. Also, Nigerian medicinal plants have been traditionally used as anti-schistosomal agents or molluscicides, of which Tetrapleura tetraptera (Oshosho, aridan, Aidan fruit), Carica papaya (Gwanda, Ìbépe, Pawpaw), Borreria verticillata (Karya garma, Irawo-ile, African borreria), and Calliandra portoricensis (Tude, Oga, corpse awakener) are most common in the scientific literature. We conclude that the high endemicity of the disease in Nigeria is associated with the limited application of various diagnostic tools and preventive chemotherapy efforts as well as poor knowledge, attitudes, and practices (KAP). Nonetheless, the country could serve as a scientific base in the discovery of biomarkers, as well as novel plant-derived schistosomicides and molluscicides.

[Historical review of schistosomiasis prevention and treatment in southern Anhui from 1950 to 1970].

From 1950 to 1970, under the leadership of the central government, workstations for the prevention and control of schistosomiasis were established in the southern Anhui region. In terms of controlling the source of the disease, light and severe epidemic areas were scientifically divided. By opening new ditches to replace old ones, changing paddy fields to dry fields, and using traditional Chinese medicine and Western medicine to prevent the intermediate host of schistosomiasis, oncomelania from surviving. By managing the feces from human and animals and controlling the water source, the transmission route of schistosome eggs has been effectively cut off. At the same time, the education of hygiene awareness among susceptible populations were strengthened. In terms of diagnosis, modern physical and biochemical detection were used to improve the accuracy of diagnosis. In terms of treatment, by combining traditional Chinese medicine and Western medicine, together with the splenectomy, the cure rates were improved. In the process of preventing and controlling schistosomiasis, the governments of Anhui Province and the southern region of Anhui Province achieved good results, providing useful reference for the prevention and control of other diseases.

Anti-angiogenic and anti-proliferative activity of ziziphus leaf extract as a novel potential therapeutic agent for reducing hepatic injury in experimental hamster schistosomiasis.

BACKGROUND: Schistosomiasis is one of the most prevalent helminthic infections worldwide. Praziquantel (PZQ) resistance poses a possible danger to the disease's ability to be controlled. Little is known about the role of Ziziphus spina-christi leaf extract (ZLE) in the treatment of hepatic schistosomiasis. However, no study has explored ZLE's anti-angiogenic and anti-proliferative activity as a possible mechanism for reducing hepatic injury in this context. Therefore, this study aimed to evaluate the therapeutic potential of ZLE as an anti-angiogenic, and anti-proliferative agent in hamsters infected with S. mansoni. METHODS: Fifty hamsters were used and divided into 5 groups (10 hamsters each); noninfected untreated (controls), noninfected treated with ZLE, infected untreated, infected treated with PZQ- and infected treated with ZLE. Anti-angiogenic and anti-fibrotic effects of the drugs were assessed pathologically through the immunohistochemical expression of VEGF, Ki-67, and TGF ß1 in liver sections. Some oxidative stress parameters were measured in hepatic homogenates (NO, GSH, GST, and SOD), and serum liver enzymes were also assessed. RESULTS: A significant decrease in worm burden, granuloma size, granuloma area, and numbers in the ZLE- and PZQ-treated groups compared to the infected untreated group, and the decrease in granulomas number and tissue egg load was significantly lower in PZQ treated group compared to ZLE treated group (p<0.05). ZLE exhibited significant anti-angiogenic and anti-fibrotic effects on granulomas, illustrated by significantly lower expression of VEGF and TGF-ß1 than infected untreated and PZQ-treated groups. ZLE exhibits antiproliferative activity evidenced by a significant reduction of positive Ki-67 hepatocytes percentage compared to the infected untreated group. Moreover, ZLE exhibits potent antioxidant effects evidenced by a significantly lowered NO and conservation of hepatic GSH, GST, and SOD in hepatic homogenates compared to infected untreated and PZQ-treated groups (p<0.05). CONCLUSION: Our results point to ZLE as a promising hepatoprotective therapeutic tool in the treatment of schistosome hepatic fibrosis as it has anti-angiogenic, anti-proliferative, anti-fibrotic, and antioxidant effects in hamsters infected with S. mansoni, providing scientific support for its use in conventional medicine.

Antiparasitic properties of 4-nerolidylcatechol from Pothomorphe umbellata (L.) Miq. (Piperaceae) in vitro and in mice models with either prepatent or patent Schistosoma mansoni infections.

ETHNOPHARMACOLOGICAL RELEVANCE: Roots of Pothomorphe umbellata (L.) Miq. are used in traditional medicine of Africa and South America for the treatment of malaria and helminthiasis. However, neither P. umbellata nor its isolated compounds have been evaluated against Schistosoma species. AIMS OF THIS STUDY: To investigate the antischistosomal effects of P. umbellata root extracts and the isolated compound 4-nerolidylcatechol (4-NC) against Schistosoma mansoni ex vivo and in murine models of schistosomiasis. MATERIALS AND METHODS: The crude hydroalcoholic (PuE) and hexane (PuH) extracts of P. umbellata roots were prepared and initially submitted to an ex vivo phenotypic screening against adult S. mansoni. PuH was analyzed by HPLC-DAD, characterized by UHPLC-HRMS/MS, and submitted to chromatographic fractionation, leading to the isolation of 4-NC. The anthelmintic properties of 4-NC were assayed ex vivo against adult schistosomes and in murine models of schistosomiasis for both patent and prepatent S. mansoni infections. Praziquantel (PZQ) was used as a reference compound. RESULTS: PuE (EC50: 18.7 µg/mL) and PuH (EC50: 9.2 µg/mL) kill adult schistosomes ex vivo. The UHPLC-HRMS/MS analysis of PuH, the most active extract, revealed the presence of 4-NC, peltatol A, and peltatol B or C. After isolation from PuH, 4-NC presented remarkable in vitro schistosomicidal activity with EC50 of 2.9 µM (0.91 µg/mL) and a selectivity index higher than 68 against Vero mammalian cells, without affecting viability of nematode Caenorhabditis elegans. In patent S. mansoni infection, the oral treatment with 4-NC decreased worm burden and egg production in 52.1% and 52.3%, respectively, also reducing splenomegaly and hepatomegaly. 4-NC, unlike PZQ, showed in vivo efficacy against juvenile S. mansoni, decreasing worm burden in 52.4%. CONCLUSIONS: This study demonstrates that P. umbellata roots possess antischistosomal activity, giving support for the medicinal use of this plant against parasites. 4-NC was identified from P. umbellata roots as one of the effective in vitro and in vivo antischistosomal compound and as a potential lead for the development of novel anthelmintics.

Evaluation of 43 species of Congolese medicinal plants used traditionally for the treatment of schistosomiasis leading to the isolation of an anti-schistosomal phaeophytin from Pseudolachnostylis maprouneifolia Pax.

ETHNOPHARMACOLOGICAL RELEVANCE: Schistosomiasis (bilharzia) is an important, prevalent and neglected tropical disease for which new treatments are urgently required. In the DR Congo and other sub- and tropical countries, traditional medicines are widely used for the control of schistosomiasis. AIM OF STUDY: To evaluate 43 Congolese plant species used traditionally for the treatment of urogenital schistosomiasis against Schistosoma mansoni. MATERIALS AND METHODS: Methanolic extracts were screened against S. mansoni newly transformed schistosomula (NTS). Three of the most active extracts were evaluated for acute oral toxicity in guinea pigs and activity guided fractionation of the least toxic was carried out using S. mansoni NTS and adult stages. An isolated compound was identified by means of spectroscopic techniques. RESULTS: Thirty-nine of 62 extracts killed S. mansoni NTS at 100 µg/mL and 7 extracts were active at ≥ 90% at 25 µg/mL; 3 extracts were selected for acute oral toxicity evaluation; the least toxic of these, Pseudolachnostylis maprouneifolia leaf was then subjected to activity-guided fractionation. 173-ethoxyphaeophorbide a (1) was isolated as an active compound with 56% activity against NTS at 50 µg/mL and 22.5% activity against adult S. mansoni at 100 µg/mL but these activities are significantly less than those of the parent fractions suggesting that other active compounds are also present and/or that synergistic interactions are taking place. CONCLUSION: This study has identified 39 plant extracts with activity against S. mansoni NTS lending support to their traditional use in the treatment of schistosomiasis for which new treatments are urgently needed. P. maprouneifolia leaf extract was found to have potent anti-schistosomal activity and low in vivo oral toxicity in guinea pigs; activity-guided fractionation resulted in the isolation of an active compound, 173-ethoxyphaeophorbide a. Phaeophorbides may merit exploration as potential anti-schistosomal agents and further work on plant species shown to have potent activity against S. mansoni NTS in this study would be worthwhile.

Molluscicidal activity of plant alkaloids.

Some snail species pose a serious threat for human health, economy, and the environment due to their widespread distribution and the transmission of dangerous parasites causing, among others, schistosomiasis and fascioliasis. Scientists from around the world have been studying the effects of plant extracts on snails for many years in order to find an alternative to molluscicides of synthetic origin. The main purpose of this study was to collect the results obtained so far on the effect of plant alkaloids on snails in the context of their molluscicidal properties. This work presents the results of publications on the effect of plant alkaloids on snails, which were published in the years 1974-2021. The Solanaceae, Papaveraceae, and Asteraceae are the plant families most frequently cited for containing alkaloids with molluscicidal activity. The alkaloids identified as molluscicidal belonged to various groups, of which the most numerous were pseudoalkaloids and tyrosine-derived alkaloids. Most of the tested alkaloids were characterized by a high mortality rate among the studied groups of snails. Based on the collected research results, it was found that plant alkaloids can be extremely useful in the fight against problematic species of snails and cause much lower harm to the environment than synthetic molluscicides.