Ma Jian, Gao Shan-Shan, Yang Hai-Jie, Wang Mian, Cheng Bin-Feng, Feng Zhi-Wei, Wang Lei
School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, China.
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
Front Neurosci. 2018 May 31;12:369. doi: 10.3389/fnins.2018.00369. eCollection 2018.
Proanthocyanidins (PA) are natural flavonoids widely present in many vegetables, fruits, nuts and seeds, and especially in grape seed. In the present study, we examined the neuroprotective effects of PA and the underlying molecular mechanism in rotenone model of Parkinson's disease (PD). We found that pretreatment with PA significantly reduced rotenone-induced oxidative stress in human neuroblastoma SH-SY5Y dopaminergic cells. In addition, PA markedly enhanced cell viability against rotenone neurotoxicity and considerably blocked rotenone-induced activation of caspase-9, caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP), biochemical features of apoptosis. Further study demonstrated that the anti-apoptotic effect of PA was mediated by suppressing p38, JNK, and ERK signaling, and inhibitors of these three signaling pathways reproduced the protective effect of PA separately. In summary, our results demonstrated that PA mitigated rotenone-induced ROS generation and antagonized apoptosis in SH-SY5Y cells by inhibiting p38, JNK, and ERK signaling pathways, and it may provide a new insight of PA in PD therapy.
原花青素（PA）是广泛存在于许多蔬菜、水果、坚果和种子中的天然黄酮类化合物，尤其是葡萄籽中含量丰富。在本研究中，我们研究了PA对帕金森病（PD）鱼藤酮模型的神经保护作用及其潜在的分子机制。我们发现，PA预处理可显著降低鱼藤酮诱导的人神经母细胞瘤SH-SY5Y多巴胺能细胞的氧化应激。此外，PA显著增强细胞活力，抵抗鱼藤酮的神经毒性，并显著阻断鱼藤酮诱导的半胱天冬酶-9、半胱天冬酶-3的激活以及聚（ADP-核糖）聚合酶（PARP）的裂解，这些都是细胞凋亡的生化特征。进一步研究表明，PA的抗凋亡作用是通过抑制p38、JNK和ERK信号通路介导的，这三种信号通路的抑制剂分别重现了PA的保护作用。总之，我们的结果表明，PA通过抑制p38、JNK和ERK信号通路减轻鱼藤酮诱导的SH-SY5Y细胞中活性氧的产生并拮抗细胞凋亡，这可能为PA在PD治疗中的应用提供新的见解。
