Fernández-Moriano Carlos, Divakar Pradeep Kumar, Crespo Ana, Gómez-Serranillos M Pilar
Department of Pharmacology, Faculty of Pharmacy, University Complutense of Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain.
Department of Plant Biology II, Faculty of Pharmacy, University Complutense of Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain.
Food Chem Toxicol. 2017 Jul;105:262-277. doi: 10.1016/j.fct.2017.04.030. Epub 2017 Apr 24.
Lichens species produce unique secondary metabolites that attract increasing pharmacological interest, including their redox modulatory activities. Current work evaluated for the first time the in vitro cytoprotective properties, based on the antioxidant activities, of the Parmeliaceae lichens Evernia prunastri and Usnea ghattensis and the mechanism of action of their major phenolic constituents: the evernic and usnic acids, respectively. In two models of central nervous system-like cells (U373-MG and SH-SY5Y cell lines), exogenous HO induced oxidative stress-mediated cytotoxicity. We first assessed their radical scavenging capacities (ORAC and DPPH tests) and the phenolic content of the extracts. At the optimal concentrations, pretreatments with evernic acid displayed significant protection against HO-induced cytotoxic damage in both models. It reversed the alterations in oxidative stress markers (including ROS generation, glutathione system and lipid peroxidation levels) and cellular apoptosis (caspase-3 activity). Such effects were in part mediated by a notable enhancement of the expression of intracellular phase-II antioxidant enzymes; a plausible involvement of the Nrf2 cytoprotective pathway is suggested. Usnic acid exerted similar effects, to some extent more moderate. Results suggest that lichen polyketides evernic and usnic acids merit further research as promising antioxidant candidates in the therapy of oxidative stress-related diseases, including the neurodegenerative disorders.
地衣物种产生独特的次生代谢产物，这些产物引起了越来越多的药理学关注，包括它们的氧化还原调节活性。目前的研究首次评估了梅衣科地衣扁枝衣和喜马拉雅松萝基于抗氧化活性的体外细胞保护特性，以及它们主要酚类成分（分别为扁枝衣酸和松萝酸）的作用机制。在两种中枢神经系统样细胞模型（U373-MG和SH-SY5Y细胞系）中，外源性过氧化氢诱导氧化应激介导的细胞毒性。我们首先评估了它们的自由基清除能力（氧自由基吸收能力和二苯基苦味酰基自由基测试）以及提取物中的酚类含量。在最佳浓度下，扁枝衣酸预处理在两种模型中均显示出对过氧化氢诱导的细胞毒性损伤的显著保护作用。它逆转了氧化应激标志物（包括活性氧生成、谷胱甘肽系统和脂质过氧化水平）的改变以及细胞凋亡（半胱天冬酶-3活性）。这些作用部分是由细胞内II期抗氧化酶表达的显著增强介导的；提示核因子E2相关因子2细胞保护途径可能参与其中。松萝酸也有类似作用，程度上稍弱。结果表明，地衣聚酮化合物扁枝衣酸和松萝酸作为氧化应激相关疾病（包括神经退行性疾病）治疗中有前景的抗氧化候选物值得进一步研究。
