*Article* **Lichen Extracts from Cetrarioid Clade Provide Neuroprotection against Hydrogen Peroxide-Induced Oxidative Stress**

**Isabel Ureña-Vacas, Elena González-Burgos \*, Pradeep Kumar Divakar and María Pilar Gómez-Serranillos**

Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain

**\*** Correspondence: elenagon@ucm.es

**Abstract:** Oxidative stress is involved in the pathophysiology of many neurodegenerative diseases. Lichens have antioxidant properties attributed to their own secondary metabolites with phenol groups. Very few studies delve into the protective capacity of lichens based on their antioxidant properties and their action mechanism. The present study evaluates the neuroprotective role of *Dactylina arctica*, *Nephromopsis stracheyi*, *Tuckermannopsis americana* and *Vulpicida pinastri* methanol extracts in a hydrogen peroxide (H2O2) oxidative stress model in neuroblastoma cell line "SH-SY5Y cells". Cells were pretreated with different concentrations of lichen extracts (24 h) before H2O2 (250 μM, 1 h). Our results showed that *D. arctica* (10 μg/mL), *N. stracheyi* (25 μg/mL), *T. americana* (50 μg/mL) and *V. pinastri* (5 μg/mL) prevented cell death and morphological changes. Moreover, these lichens significantly inhibited reactive oxygen species (ROS) production and lipid peroxidation and increased superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) levels. Furthermore, they attenuated mitochondrial membrane potential decline and calcium homeostasis disruption. Finally, high-performance liquid chromatography (HPLC) analysis revealed that the secondary metabolites were gyrophoric acid and lecanoric acid in *D. artica*, usnic acid, pinastric acid and vulpinic acid in *V. pinastri*, and alectoronic acid in *T. americana*. In conclusion, *D. arctica* and *V. pinastri* are the most promising lichens to prevent and to treat oxidative stress-related neurodegenerative diseases.

**Keywords:** lichens; neuroprotection; cetrarioid clade; oxidative stress
