Antihydatic and immunomodulatory effects of Punica granatum peel aqueous extract in a murine model of echinococcosis

Objective: To investigate the effect of pomegranate peel aqueous extract (PGE) on the development of secondary experimental echinococcosis and on the viability of Echinococcus granulosus protoscoleces, and the immunomodulatory properties of PGE. Methods: Swiss mice were inoculated intraperitoneally with viable protoscoleces. Then, PGE was orally administered daily during cystic echinococcosis development. Cyst development and hepatic damage were macroscopically and histologically analyzed. The production of nitric oxide and TNF-alpha was assessed in plasma and the hepatic expression of iNOS, TNF-alpha, NF-kappa B and CD68 was examined. Moreover, protoscoleces were cultured and treated with different concentrations of PGE. Results: It was observed that in vitro treatment of protoscoleces caused a significant decrease in viability in a PGE-dose-dependent manner. In vivo, after treatment of cystic echinococcosis infected mice with PGE, a significant decrease in nitric oxide levels (P<0.000 1) and TNF-alpha levels (P<0.001) was observed. This decline was strongly related to the inhibition of cyst development (rate of hydatid cyst growth inhibition=63.08%) and a decrease in CD68 expression in both the pericystic layer of hepatic hydatid cysts and liver tissue (P<0.000 1). A significant diminution of iNOS, TNF-alpha and NF-kappa B expression was also observed in liver tissue of treated mice (P<0.000 I). Conclusions: Our results indicate an antihydatic scolicidal effect and immunomodulatory properties of PGE, suggesting its potential therapeutic role against Echinococcus granulosus infection.