Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan.
Nutrients. 2019 Jul 19;11(7):1655. doi: 10.3390/nu11071655.
Vasicinone is a quinazoline alkaloid isolated from the plant. In this study, we explored the neuroprotective effect and underlying molecular mechanism of vasicinone against paraquat-induced cellular apoptosis in SH-SY5Y cells. Vasicinone reduced the paraquat-induced loss of cell viability, rescued terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL)-positive apoptotic nuclei, and suppressed generation of reactive oxygen species (ROS) in a dose-dependent manner. Western blotting analysis revealed that vasicinone increased the phosphorylation of IGF1R/PI3K/AKT cell survival signaling molecules and downregulated the paraquat-induced, mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK)-mediated apoptotic pathways compared to that observed in cells not treated with vasicinone. This protection depended critically on the activation of IGF1R, and the silencing of IGF1R by siRNA completely abrogated the protective effect of vasicinone in SH-SY5Y cells. Our findings indicated that vasicinone is a potential candidate for the treatment of Parkinson's disease and possibly other oxidative stress-related neurodegenerative disorders.
蝙蝠葛新碱是一种从蝙蝠葛植物中分离得到的喹唑啉生物碱。在这项研究中，我们探讨了蝙蝠葛新碱对百草枯诱导的 SH-SY5Y 细胞凋亡的神经保护作用及其潜在的分子机制。蝙蝠葛新碱可降低百草枯诱导的细胞活力丧失，挽救末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）阳性凋亡核，并呈剂量依赖性抑制活性氧（ROS）的产生。Western blot 分析显示，与未用蝙蝠葛新碱处理的细胞相比，蝙蝠葛新碱增加了 IGF1R/PI3K/AKT 细胞存活信号分子的磷酸化，并下调了百草枯诱导的丝裂原活化蛋白激酶（MAPK）/c-Jun N 端激酶（JNK）介导的凋亡途径。这种保护作用严重依赖于 IGF1R 的激活，而 IGF1R 的 siRNA 沉默完全消除了蝙蝠葛新碱对 SH-SY5Y 细胞的保护作用。我们的研究结果表明，蝙蝠葛新碱可能是治疗帕金森病和其他氧化应激相关神经退行性疾病的潜在候选药物。
