Efficiency of Three Extracts of Carica papaya as Molluscicidal and Anti-schistosomal Agents against Biomphalaria alexandrina and Schistosoma mansoni by Flow Cytometry

Abstract

Schistosomias is a prevalent parasitic disease in tropical and sub-tropical areas, which comes in the second place in terms of socioeconomic and public health burden. Around 600 million people in 74 countries are infected yearly, predominantly in the developing world. The aim of this work was to assess the efficiency of three extracts from Carica papaya (methanol, ethanol and butanol extracts) for their molluscicidal and anti-schistosomal activities. The LC50 of methanol, ethanol and butanol extracts of Carica papaya against B. alexandrinea were 180, 499.3 and 509.1 mg/L while the respective LC90 values were 220.3, 700.6, 769.6 mg/L respectively. The effect of these extracts on Biomphalaria alexandrina snails and larval stages of Schistosma mansoni, for miracidia the LC50 of methanol, ethanol and butanol extracts of Carica papaya against miracidia were 3.4, 15.4 and 8.1 mg/L, respectively, while the respective LC90 values were 8.4, 38.2, 11.2 mg/L, and for  cercariae the LC50 of methanol, ethanol and butanol extracts of Carica papaya were 2, 20 and 4 mg/L, while the respective LC90 values were 13.5, 80.5, 18.5 mg/L respectively  was evaluated, in addition to flowcytometric analysis of CD4, CD25, FOXP3 and TGF-β levels during S. mansoni infection in mice. The in-vivo results showed that the three extracts have variable potential against snails and miracidia and cercariae of S. mansoni. The mortality rate in B. alexandrina snails for methanol, ethanol and butanol extracts of Carcia papay were 86%, 45% and 64%, respectively. While it was 83%, 35% and 66%, respectively in miracidia and 92%, 40% and 70%, respectively in cercariae. The results indicated that methanol extract from Carica papaya recorded higher activity against snails, miracidia and cercariae. The levels of CD4, CD25, FOXP3 regulatory T (Treg) cells were decreased significantly (p<0.001) in infected mice compared to healthy controls. However, there was a significant (p<0.001) increase in levels of TGF-β. A significant increase in the levels of CD4, CD25, and FOXP3 Treg in Carica papaya treated group compared to infected control group, with a significant (p<0.001) decrease in TGF-β level than infected group. In conclusion, methanol extract was more effective at concentration of LC50 180 and LC90 220.3 than ethanol and butanol extracts of Carica papaya therefore controlling B. alexandrina snails by methanol extract is a promising way as it is an eco-friendly strategy in rural areas of developing countries, where schistosomiasis is endemic. Moreover, the increased immune defense mechanism in treated group with the same extracts is a promising target for new immune modulatory strategies against schistosomiasis.