Research and Development Division, IMG Pharma Biotech, 48160 Derio, Spain.
Instituto de Biomedicina y Biotecnología de Cantabria, IBBTEC, Consejo Superior de Investigaciones Centíficas (CSIC), University of Cantabria, 39011 Santander, Spain.
Int J Mol Sci. 2023 Jan 10;24(2):1315. doi: 10.3390/ijms24021315.
The development of strains with high cannabidiol (CBD) and low tetrahydrocannabinol (THC) content is a growing field of research, both for medical and recreational use. However, the mechanisms behind clinical actions of cannabinoids are still under investigation, although there is growing evidence that mitochondria play an important role in many of them. Numerous studies have described that cannabinoids modulate mitochondrial activity both through activation of mitochondrial cannabinoid receptors and through direct action on other proteins such as mitochondrial complexes involved in cellular respiration. Thus, the aim of this study was to determine the actions of a panel of extracts, isolated from high-CBD varieties of , on the activity of the mitochondrial electron transport chain complex IV, cytochrome c oxidase (CCO), in order to select those with a safer profile. After demonstrating that strains could be identified by cannabinoids content, concentration-response curves were performed with a collection of extracts from strains with high-CBD and low-THC content using bovine CCO. The CCO rate was clearly modified by specific extracts of plants compared to others. Half maximal inhibitory concentrations (IC50) of extracts and the inhibitory effects evoked at 1 × 10 g/mL displayed a significant correlation with the THC. Therefore, the screening of extracts based on CCO activity provides a powerful and rapid methodology to identify those plants with higher mitochondrial toxicity or even mito-protective actions.
高大麻二酚 (CBD) 和低四氢大麻酚 (THC) 含量菌株的开发是一个正在不断发展的研究领域，无论是用于医疗还是娱乐用途。然而，大麻素临床作用的机制仍在研究中，尽管越来越多的证据表明线粒体在其中许多作用中发挥着重要作用。许多研究表明，大麻素通过激活线粒体大麻素受体以及通过直接作用于其他蛋白质（如参与细胞呼吸的线粒体复合物）来调节线粒体活性。因此，本研究旨在确定一组从高 CBD 品种中分离出的提取物对线粒体电子传递链复合物 IV（细胞色素 c 氧化酶，CCO）活性的作用，以选择那些具有更安全特性的提取物。在证明可以根据大麻素含量鉴定 菌株后，使用牛 CCO 对高 CBD 和低 THC 含量的菌株的提取物进行了浓度反应曲线的测定。与其他提取物相比，特定的 植物提取物明显改变了 CCO 速率。提取物的半最大抑制浓度 (IC50) 和在 1 × 10 g/mL 时引起的抑制作用与 THC 呈显著相关。因此，基于 CCO 活性筛选提取物提供了一种强大而快速的方法，可以识别那些具有更高线粒体毒性甚至线粒体保护作用的植物。
