Studzińska-Sroka Elżbieta, Majchrzak-Celińska Aleksandra, Zalewski Przemysław, Szwajgier Dominik, Baranowska-Wójcik Ewa, Kaproń Barbara, Plech Tomasz, Żarowski Marcin, Cielecka-Piontek Judyta
Department of Pharmacognosy, Poznan University of Medical Sciences, Święcickiego 4, 60-781 Poznan, Poland.
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Święcickiego 4, 60-781 Poznan, Poland.
Pharmaceuticals (Basel). 2021 Dec 10;14(12):1293. doi: 10.3390/ph14121293.
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 , , , 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.
地衣是具有宝贵生物学特性的化合物来源，其结构有利于穿透中枢神经系统（CNS）。因此，我们的研究旨在研究[此处原文缺失地衣名称]、[此处原文缺失地衣名称]、[此处原文缺失地衣名称]和[此处原文缺失地衣名称]的亲脂性提取物及其主要次生代谢产物在寻找中枢神经系统疾病（主要是多形性胶质母细胞瘤，GBM）新疗法背景下的生物学潜力。所选用于研究的提取物分别针对其柳酸、扁枝衣酸和（-）-松萝酸的含量进行了标准化。对提取物和地衣代谢产物的抗肿瘤活性，即对A-172和T98G细胞系的细胞毒性以及抗吲哚胺2,3-双加氧酶1（IDO1）、吲哚胺2,3-双加氧酶2（IDO2）、色氨酸2,3-双加氧酶（TDO）活性、通过抗环氧化酶-2（COX-2）和抗透明质酸酶活性发挥的抗炎特性、抗氧化活性以及抗乙酰胆碱酯酶和抗丁酰胆碱酯酶活性进行了评估。本研究结果表明，地衣衍生的化合物和提取物对GBM细胞具有显著的细胞毒性，抑制犬尿氨酸途径酶，具有抗炎特性以及较弱的抗氧化和抗胆碱酯酶特性。此外，扁枝衣酸和（-）-松萝酸能够穿过血脑屏障。这些结果表明，地衣衍生的提取物和化合物，尤其是（-）-松萝酸，可被视为中枢神经系统内具有药理活性化合物的原型，特别适合用于治疗GBM。
