Co-administration of silymarin elevates the therapeutic effect of praziquantel through modulation of specific antibody profiles, Th1/Th2/Tregs cytokines and down-regulation of fibrogenesis in mice with Mesocestoides vogae (Cestoda) infection

Silymarin (SIL) represents a natural mixture of polyphenols showing an array of health benefits. The present study, carried out on a model cestode infection induced by Mesocestoides vogae tetrathyridia in the ICR strain of mice, was aimed at investigating the impact of SIL as adjunct therapy on the activity of praziquantel (PZQ) in relation to parasite burden, immunity and liver fibrosis within 20 days post-therapy. In comparison with PZQ alone, co-administration of SIL and PZQ stimulated production of total IgG antibodies to somatic and excretory-secretory antigens of metacestodes and modified the expression patterns of immunogenic molecules in both antigenic preparations. The combined therapy resulted in the elevation of IFN-gamma and a decline of TNF-alpha and TGF-beta 1 in serum as compared to untreated group; however, SIL attenuated significantly the effect of PZQ on IL-4 and stimulated PZQ-suppressed phagocytosis of peritoneal macrophages. In the liver, SIL boosted the effect of PZQ on gene expression of the same cytokines in a similar way as was found in serum, except for down-regulation of PZQ-stimulated TNF-alpha. Compared to PZQ therapy, the infiltration of mast cells into liver after SIL co-administration was nearly abolished and correlated with suppressed activities of genes for collagen I, collagen III and alpha-SMA. In conclusion, co-administration of SIL modified the effects of PZQ therapy on antigenic stimulation of the immune system and modulated Th1/Th2/Tregs cytokines. In liver this was accompanied by reduced fibrosis, which correlated with significantly higher reduction of total numbers of tetrathyridia after combined therapy as compared with PZQ treatment.