ABSTRACT

Background: Lichens, as a symbiotic association of photobionts and mycobionts, display an unmatched environmental adaptability and a great chemical diversity. As an important morphological group, cetrarioid lichens are one of the most studied lichen taxa for their phylogeny, secondary chemistry, bioactivities and uses in folk medicines, especially the lichen Cetraria islandica. However, insufficient structure elucidation and discrepancy in bioactivity results could be found in a few studies.

Purpose: This review aimed to present a more detailed and updated overview of the knowledge of secondary metabolites from cetrarioid lichens in a critical manner, highlighting their potentials for pharmaceuticals as well as other applications. Here we also highlight the uses of molecular phylogenetics, metabolomics and ChemGPS-NP model for future bioprospecting, taxonomy and drug screening to accelerate applications of those lichen substances.

Chapters: The paper starts with a short introduction in to the studies of lichen secondary metabolites, the biological classification of cetrarioid lichens and the aim. In light of ethnic uses of cetrarioid lichens for therapeutic purposes, molecular phylogeny is proposed as a tool for future bioprospecting of cetrarioid lichens, followed by a brief discussion of the taxonomic value of lichen substances. Then a delicate description of the bioactivities, patents, updated chemical structures and lichen sources is presented, where lichen substances are grouped by their chemical structures and discussed about their bioactivity in comparison with reference compounds. To accelerate the discovery of bioactivities and potential drug targets of lichen substances, the application of the ChemGPS NP model is highlighted. Finally the safety concerns of lichen substances (i.e. toxicity and immunogenicity) and future-prospects in the field are exhibited. Conclusion: While the ethnic uses of cetrarioid lichens and the pharmaceutical potential of their secondary metabolites have been recognized, the knowledge of a large number of lichen substances with interesting structures is still limited to various in vitro assays with insufficient biological annotations, and this area still deserves more research in bioactivity, drug targets and screening. Attention should be paid on the accurate interpretation of their bioactivity for further applications avoiding over-interpretations from various in vitro bioassays.

Keywords:

Cetrarioid lichens

Chemotaxonomy

Ethnopharmacology

Lichen substances

Pharmaceutical potential

Phytogeny

Introduction

Lichens are in fact an ecosystem comprising of a photobiont that can either be a green alga (Chlorophyta) or a cyanobacterium and a mycobiont that in most cases belongs to the Ascomycetes. The nomenclature of a certain lichen taxon stems from its mycobiont partner and they are taxonomically classified within the fungi where majority of lichen-forming fungi belong to Lecanoromycetes (Tehler and Wedin 2008). With a special symbiotic lifestyle, a vast genetic diversity and interactions with various environmental factors, they produce lichen-unique profiles of primary and secondary metabolites (i.e. lichen substances) with interesting physiochemical properties, such as lipophilicity and UV filtration (Nguyen et al. 2013), and marked biological activities determined by a series of in vitro and in vivo assays (Boustie et al. 2011). In particular, antioxidant, antimicrobial, anti-inflammatory and anti-proliferative activities of certain lichen substances are well studied (Fernandez-Moriano et al. 2016; Haraldsdottir et al....