Protective effects of lichen metabolites evernic and usnic acids against redox impairment-mediated cytotoxicity in central nervous system-like cells

- SH-SY5Y and U373-MG cell lines are valid in vitro models for neurotoxicity studies.
- Exogenous H2O2 provokes oxidative stress and induces cytotoxicity in both models.
- Evernic acid pre-treatment protected against H2O2-mediated toxicity and apoptosis.
- Its redox modulatory effect is mediated by ROS scavenging and enhancement of antioxidant defenses.
- Antioxidant effects and cytoprotection displayed by usnic acid were more moderate.

Lichens species produce unique secondary metabolites that attract increasing pharmacological interest, including their redox modulatory activities. Current work evaluated for the first time the in vitro cytoprotective properties, based on the antioxidant activities, of the Parmeliaceae lichens Evernia prunastri and Usnea ghattensis and the mechanism of action of their major phenolic constituents: the evernic and usnic acids, respectively. In two models of central nervous system-like cells (U373-MG and SH-SY5Y cell lines), exogenous H2O2 induced oxidative stress-mediated cytotoxicity. We first assessed their radical scavenging capacities (ORAC and DPPH tests) and the phenolic content of the extracts. At the optimal concentrations, pretreatments with evernic acid displayed significant protection against H2O2-induced cytotoxic damage in both models. It reversed the alterations in oxidative stress markers (including ROS generation, glutathione system and lipid peroxidation levels) and cellular apoptosis (caspase-3 activity). Such effects were in part mediated by a notable enhancement of the expression of intracellular phase-II antioxidant enzymes; a plausible involvement of the Nrf2 cytoprotective pathway is suggested. Usnic acid exerted similar effects, to some extent more moderate. Results suggest that lichen polyketides evernic and usnic acids merit further research as promising antioxidant candidates in the therapy of oxidative stress-related diseases, including the neurodegenerative disorders.