Flavonoid silymarin potentiates antiheimintic effect of praziquantel via down-regulation of oxidative stress and fibrogenesis in the liver

Silymarin, a mixture of bioactive flavonolignans isolated from Silybum marianum, exhibits anti-inflammatory, cytoprotective and anticarcinogenic effects. In this study impact of silymarin on larvicidal effect of praziquantel and on fibrogenesis in the liver of mice infected with Mesocestoide vogae (Cestoda) tetrathyridia was investigated.co-administration of bioactive flavonoid silymarin with antihelmintic drug praziquantel on the liver infection with Mesocestoides vogue larvae (Cestoda) was investigated In vitro experiments revealed no larvicidal effect of silymarin on M vogae larvae and demonstrated its powerful ROS-scavenging activity on peritoneal macrophages. Co-administration of praziquantel and silymarin to infected mice significantly enhanced the efficacy of the treatment in comparison with administration of the drug alone. In the light of the in vitro findings we believe that silymarin potentiated larvicidal effect of PZQ in the liver indirectly via suppression of oxidative stress and normalisation of GSH redox balance. Elimination of reactive oxygen species in the course of combined therapy resulted also in the significant decrease of total collagen synthesis as well as in decrease expression of genes for collagen type I and III in the liver. Thus, potentiation of larvicidal activity of praziquantel with silymarin is mediated via its antioxidant effect, resulting in the down-regulation of fibrogenesis and consequently in higher availability of drug for parasite.