Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
Icelandic Institute of Natural History, Akureyri Division, IS-600 Akureyri, Iceland.
Phytomedicine. 2016 May 15;23(5):441-59. doi: 10.1016/j.phymed.2016.02.012. Epub 2016 Mar 2.
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.
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.
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.
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.
地衣作为光合生物和真菌共生体的共生体，表现出无与伦比的环境适应性和巨大的化学多样性。作为一个重要的形态群体，Cetrarioid 地衣是研究最多的地衣类群之一，其系统发育、次生化学、生物活性以及在民间医学中的用途，特别是地衣 Cetraria islandica。然而，在一些研究中发现，结构解析不充分和生物活性结果存在差异。
本综述旨在以批判性的方式更详细和更新地介绍 Cetrarioid 地衣次生代谢产物的知识，强调其在药物以及其他应用方面的潜力。在这里，我们还强调了分子系统发育、代谢组学和 ChemGPS-NP 模型在未来生物勘探、分类和药物筛选中的应用，以加速这些地衣物质的应用。
本文首先对地衣次生代谢产物的研究、Cetrarioid 地衣的生物分类以及目标进行了简短介绍。鉴于 Cetrarioid 地衣在治疗方面的民族用途，分子系统发育被提议作为未来 Cetrarioid 地衣生物勘探的工具，随后简要讨论了地衣物质的分类学价值。然后，详细描述了生物活性、专利、更新的化学结构和地衣来源，其中地衣物质按化学结构分组，并与参考化合物进行了生物活性比较。为了加速地衣物质生物活性和潜在药物靶点的发现，强调了 ChemGPS NP 模型的应用。最后展示了地衣物质的安全性问题（即毒性和免疫原性）以及该领域的未来前景。
虽然 Cetrarioid 地衣的民族用途和其次生代谢产物的药用潜力已经得到认可，但对具有有趣结构的大量地衣物质的了解仍然局限于各种缺乏生物学注释的体外测定，这一领域仍需要更多的生物活性、药物靶点和筛选研究。在进一步应用时，应注意准确解释其生物活性，避免各种体外生物测定的过度解释。
