REQUIMTE/Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, n°. 228, 4050-313 Porto, Portugal.
CEBAS (CSIC) Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, P.O. Box 164, 30100 Campus University Espinardo, Murcia, Spain.
J Steroid Biochem Mol Biol. 2014 Mar;140:106-15. doi: 10.1016/j.jsbmb.2013.12.013. Epub 2013 Dec 24.
Several evidences suggest that enhanced oxidative stress is involved in the pathogenesis and/or progression of several neurodegenerative diseases. The aim of this study was to investigate for the first time whether both extracts from tomato plant (Lycopersicon esculentum Mill.) leaves and their isolated steroidal alkaloids (tomatine and tomatidine) afford neuroprotective effect against glutamate-induced toxicity in SH-SY5Y neuroblastoma cells and to elucidate the mechanisms underlying this protection. Steroidal alkaloids from tomato are well known for their cholinesterases' inhibitory capacity and the results showed that both purified extracts and isolated compounds, at non-toxic concentrations for gastric (AGS), intestinal (Caco-2) and neuronal (SH-SY5Y) cells, have the capacity to preserve mitochondria membrane potential and to decrease reactive oxygen species levels of SH-SY5Y glutamate-insulted cells. Moreover, the use of specific antagonists of cholinergic receptors allowed observing that tomatine and tomatidine can interact with nicotinic receptors, specifically with the α7 type. No effect on muscarinic receptors was noticed. In addition to the selective cholinesterases' inhibition revealed by the compounds/extracts, these results provide novel and important insights into their neuroprotective mechanism. This work also demystifies the applicability of these compounds in therapeutics, by demonstrating that their toxicity was overestimated for long time.
有几项证据表明，氧化应激增强与几种神经退行性疾病的发病机制和/或进展有关。本研究的目的是首次研究番茄植物（Lycopersicon esculentum Mill.）叶片的提取物及其分离的甾体生物碱（番茄碱和番茄啶）是否对谷氨酸诱导的 SH-SY5Y 神经母细胞瘤细胞毒性具有神经保护作用，并阐明这种保护作用的机制。番茄中的甾体生物碱以其对胆碱酯酶的抑制能力而闻名，结果表明，在对胃（AGS）、肠（Caco-2）和神经元（SH-SY5Y）细胞无毒的浓度下，两种纯化提取物和分离化合物都具有保持线粒体膜电位和降低 SH-SY5Y 谷氨酸损伤细胞中活性氧水平的能力。此外，使用特定的胆碱能受体拮抗剂可以观察到番茄碱和番茄啶可以与烟碱型受体相互作用，特别是与α7 型受体。没有观察到对毒蕈碱型受体的影响。除了这些化合物/提取物所揭示的选择性胆碱酯酶抑制作用外，这些结果还为它们的神经保护机制提供了新的重要见解。这项工作还通过证明这些化合物的毒性长期以来被高估，消除了它们在治疗中的应用的神秘感。
