Lichen-Derived Compounds and Extracts as Biologically Active Substances with Anticancer and Neuroprotective Properties.

Elżbieta Studzińska-Sroka,Barbara Kaproń,Aleksandra Majchrzak-Celińska,Ewa Baranowska-Wójcik,Judyta Cielecka-Piontek,Przemysław Zalewski,Marcin Żarowski,Tomasz Plech,Dominik Szwajgier

doi:10.3390/ph14121293

Abstract

Lichens are a source of chemical compounds with valuable biological properties, structurally predisposed to penetration into the central nervous system (CNS). Hence, our research aimed to examine the biological potential of lipophilic extracts of Parmelia sulcata, Evernia prunastri, Cladonia uncialis, and their major secondary metabolites, in the context of searching for new therapies for CNS diseases, mainly glioblastoma multiforme (GBM). The extracts selected for the study were standardized for their content of salazinic acid, evernic acid, and (−)-usnic acid, respectively. The extracts and lichen metabolites were evaluated in terms of their anti-tumor activity, i.e., cytotoxicity against A-172 and T98G cell lines and anti-IDO1, IDO2, TDO activity, their anti-inflammatory properties exerted by anti-COX-2 and anti-hyaluronidase activity, antioxidant activity, and anti-acetylcholinesterase and anti-butyrylcholinesterase activity. The results of this study indicate that lichen-derived compounds and extracts exert significant cytotoxicity against GBM cells, inhibit the kynurenine pathway enzymes, and have anti-inflammatory properties and weak antioxidant and anti-cholinesterase properties. Moreover, evernic acid and (−)-usnic acid were shown to be able to cross the blood-brain barrier. These results demonstrate that lichen-derived extracts and compounds, especially (−)-usnic acid, can be regarded as prototypes of pharmacologically active compounds within the CNS, especially suitable for the treatment of GBM.

Highlights

In this study we evaluated the cytotoxic, anti-inflammatory, antioxidant, and anticholinergic properties of lichen acetone extracts from P. sulcata, E. prunastri, and C. uncialis as well as their most important components, salazinic acid, evernic acid and (−)-usnic acid (Figure 1), respectively
Blood-Brain Barrier (PAMPA-blood-brain barrier (BBB)) we evaluated if lichen-derived compounds, both used as pure substances and as the components of extracts, can cross the BBB and reach the central nervous system (CNS)
The HPLC method applied in order to determine the content of the dominant active compounds detected the major secondary metabolites; in P. sulcata extract it was salazinic acid, in E. prunastri extract it was evernic acid, and in C

Summary

Introduction

Secondary metabolites of lichens are polyphenolic compounds, constituting a group of natural substances with unique chemical structures and interesting biological properties. Phenolic compounds are effective against different neoplasms, which are one of the most important medical problems. Central nervous system (CNS) tumors are especially challenging, with glioblastoma multiforme (GBM) being one of the most deadly cancers. A growing body of evidence shows that natural bioactive molecules may serve well as an alternative 4.0/).

Methods

Results

Discussion

Conclusion