Didepsid atranorin shows selective cytotoxic effect on flatworm Mesocestoides vogae in vitro and in vivo whereas exerting immunomodulatory and protective effects in vivo in experimental mouse infection.

A member of a group of secondary lichen metabolites, didepsid atranorin (ATR, MW 372) has been shown to exert anti-cancer, antioxidant and anti-inflammatory effects in vitro. In the present study we examined its effect on the infection with proliferating larval stage of model cestode Mesocestoides vogae. Significant larvicidal effect of ATR in vitro was seen at concentration 100 ?M, as was demonstrated by motility and viability tests and disruption of metabolic homeostasis. Reduction of larvae was observed after total dose of 300 mg/kg b.w. given in 10 daily doses. Intensity of oxidative stress in the liver was diminished after ATR administration indicated from elevated glutathione levels and decreased lipid peroxides what correlated with decreased hydroxyproline concentrations used as fibrosis marker. We also assessed time- and dose-dependent cytotoxic and immunomodulatory activity of ATR on na?ve and mitogen-stimulated splenocytes and macrophages in vitro and in vivo using the following tests: MTT and lymphocyte proliferation test, ELISA assays for cytokine profile (IFN-g, TNF-?, IL-4, IL-10, IL-17, TGF-?), western blot analysis for quantification of pro- and anti-apoptotic proteins BAX and Bcl-xL, resp. Level of apoptosis was examined by Flow cytometry using annexin/PI Kit and fluorescent microscopy. ATR was cytotoxic for naive immune cells at concentrations ? 50 ?M and incubation time ? 24 h in vitro, whereby in vivo it showed imunomodulating and anti-apoptotic effect on immune cells. We also have demonstrated for the first time its antiparasitic and anti-fibrotic effect.

(Support to this work was given by Grant Agency VEGA, project no. 2/0150/13).