Effect of Phenotypic Screening of Extracts and Fractions of<i> Erythrophleum ivorense</i> Leaf and Stem Bark on Immature and Adult Stages of<i> Schistosoma mansoni</i>

Kyere-Davies, Gertrude; Agyare, Christian; Boakye, Yaw Duah; Suzuki, Brian M.; Caffrey, Conor R.

doi:10.1155/2018/9431467

Cited by 15 publications

(15 citation statements)

References 29 publications

(41 reference statements)

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“…Phenotypic screening of parasites following dorsomorphin exposure and RNAi was performed according to a protocol adapted from Kyere-Davies et al (2018) . Briefly, single word descriptors for parasite phenotypic characteristics such as movement, shape, translucence, and orientation were used to characterize treatment effects that could be observed visually.…”

Section: Methodsmentioning

confidence: 99%

Schistosome AMPK Is Required for Larval Viability and Regulates Glycogen Metabolism in Adult Parasites

et al. 2021

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On entering the mammalian host, schistosomes transition from a freshwater environment where resources are scarce, to an environment where there is an unlimited supply of glucose, their preferred energy substrate. Adult schistosome glycolytic activity consumes almost five times the parasite’s dry weight in glucose per day to meet the parasite’s energy demands, and the schistosome glycolytic enzymes and mechanisms for glucose uptake that sustain this metabolic activity have previously been identified. However, little is known of the parasite processes that regulate schistosome glucose metabolism. We previously described the Schistosoma mansoni ortholog of 5′ AMP-Activated Protein Kinase (AMPK), which is a central regulator of energy metabolism in eukaryotes, and characterized the developmental regulation of its expression and activity in S. mansoni. Here we sought to explore the function of AMPK in schistosomes and test whether it regulates parasite glycolysis. Adult schistosomes mounted a compensatory response to chemical inhibition of AMPK α, resulting in increased AMPK α protein abundance and activity. RNAi inhibition of AMPK α expression, however, suggests that AMPK α is not required for adult schistosome viability in vitro. Larval schistosomula, on the other hand, are sensitive to chemical AMPK α inhibition, and this correlates with inactivity of the AMPK α gene in this life cycle stage that precludes a compensatory response to AMPK inhibition. While our data indicate that AMPK is not essential in adult schistosomes, our results suggest that AMPK regulates adult worm glycogen stores, influencing both glycogen utilization and synthesis. AMPK may therefore play a role in the ability of adult schistosomes to survive in vivo stressors such as transient glucose deprivation and oxidative stress. These findings suggest that AMPK warrants further investigation as a potential drug target, especially for interventions aimed at preventing establishment of a schistosome infection.

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Section: Methodsmentioning

confidence: 99%

Schistosome AMPK Is Required for Larval Viability and Regulates Glycogen Metabolism in Adult Parasites

et al. 2021

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“…The acetone fractions of both leaf and bark demonstrated the highest anti-schistosomal activity causing severe phenotypic alterations (immobility/inactivity, change in shape, translucence, surface disintegration) and death of schistosomules at all dilutions (except 0.31 g/mL) at 24 h and 48 h. For adult parasites, severe phenotypic changes specifically damage to the adult parasite's tegument (surface) was observed for the acetone fraction of the stem bark extract. The adult worms were observed to be uncoordinated by 5 h, darkened in color by 24 h and died at 48 h exhibiting tegumental damage [77].…”

Section: Erythrophleum Ivorense Afzel (Euphorbiaceae)mentioning

confidence: 99%

The Ghanaian Flora as a Potential Source of Anthelmintic and Anti-Schistosomal Agents

Asante-Kwatia¹,

Mensah²,

Gyimah³

et al. 2022

Natural Medicinal Plants

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Parasitic infections including schistosomiasis and soil transmitted helminthiasis are the most commonly encountered Neglected Tropical Diseases (NTDs) in the world. These diseases remain a major public health concern affecting millions of people especially those living in poor regions where access to effective conventional health care is a challenge. Interventions to control these infections in endemic areas have not been successful due to the high cost of drugs, limited availability as well as inequity of access to preventive chemotherapies. Another problem is the development resistance to the limited number of recommended medications due to their intensive use in both human and live-stock. There is an increasing awareness of the potential of natural products as chemotherapeutic agents to combat parasitic infections. Natural products may offer an unlimited source of chemically diverse drug molecules which may be safe, efficient, less toxic, less expensive and readily available for use especially in low-income countries. The Ghanaian flora provides such a ready source for new therapeutic interventions for the local population. Several researches have provided evidence of the anti-parasitic activity of Ghanaian medicinal plants. This chapter provides a review with special focus on medicinal plants collected from Ghana with anthelmintic and anti-schistosomal activity. Evidence of pharmacological activities of crude extracts, fractions and bioactive phytoconstituents as well as possible mechanisms of action where investigated are discussed.

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“…Schistosome phenotypic responses were recorded employing a series of 'descriptors, ' such as rounding, degeneration, overactivity, loss of translucency and changes in motility, as described previously 5,50,51,53 . To allow for comparisons of compound activity, each descriptor was awarded a value of 1 and these were added up to a maximum 'severity score' of 4.…”

Section: Cytotoxicity Assay On Bovine Spermatozoa Semen Samples Werementioning

confidence: 99%

Novel and selective inactivators of Triosephosphate isomerase with anti-trematode activity

Ferraro

Corvo

Bergalli

et al. 2020

Sci Rep

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Trematode infections such as schistosomiasis and fascioliasis cause significant morbidity in an estimated 250 million people worldwide and the associated agricultural losses are estimated at more than US$ 6 billion per year. Current chemotherapy is limited. Triosephosphate isomerase (TIM), an enzyme of the glycolytic pathway, has emerged as a useful drug target in many parasites, including Fasciola hepatica TIM (FhTIM). We identified 21 novel compounds that selectively inhibit this enzyme. Using microscale thermophoresis we explored the interaction between target and compounds and identified a potent interaction between the sulfonyl-1,2,4-thiadiazole (compound 187) and FhTIM, which showed an ic 50 of 5 µM and a K d of 66 nM. In only 4 hours, this compound killed the juvenile form of F. hepatica with an ic 50 of 3 µM, better than the reference drug triclabendazole (TCZ). Interestingly, we discovered in vitro inhibition of FhTIM by TCZ, with an IC 50 of 7 µM suggesting a previously uncharacterized role of FhTIM in the mechanism of action of this drug. Compound 187 was also active against various developmental stages of Schistosoma mansoni. The low toxicity in vitro in different cell types and lack of acute toxicity in mice was demonstrated for this compound, as was demonstrated the efficacy of 187 in vivo in F. hepatica infected mice. Finally, we obtained the first crystal structure of FhTIM at 1.9 Å resolution which allows us using docking to suggest a mechanism of interaction between compound 187 and TIM. In conclusion, we describe a promising drug candidate to control neglected trematode infections in human and animal health.

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Effect of Phenotypic Screening of Extracts and Fractions of Erythrophleum ivorense Leaf and Stem Bark on Immature and Adult Stages of Schistosoma mansoni

Cited by 15 publications

References 29 publications

Schistosome AMPK Is Required for Larval Viability and Regulates Glycogen Metabolism in Adult Parasites

Schistosome AMPK Is Required for Larval Viability and Regulates Glycogen Metabolism in Adult Parasites

The Ghanaian Flora as a Potential Source of Anthelmintic and Anti-Schistosomal Agents

Novel and selective inactivators of Triosephosphate isomerase with anti-trematode activity

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