芹菜素对 1-甲基-4-苯基吡啶离子诱导的 PC12 细胞神经毒性的保护作用。

Protective effects of apigenin against 1-methyl-4-phenylpyridinium ion‑induced neurotoxicity in PC12 cells.

机构信息

Guangdong Food and Drug Vocational College, Guangzhou, Guangdong 510520, P.R. China.

College of Science, Guangdong Ocean University, Zhanjiang, Guangdong 524088, P.R. China.

出版信息

Int J Mol Med. 2015 Mar;35(3):739-46. doi: 10.3892/ijmm.2014.2056. Epub 2014 Dec 30.

Abstract

Parkinson's disease is recognized as the second most common neurodegenerative disorder after Alzheimer's disease, characterized by the loss of dopominergic neurons in the substantia nigra pars compacta and can be experimentally mimicked by the use of the neurotoxin, 1‑methyl‑4‑phenylpyridinium ion (MPP(+)), in in vitro models. In this study, we investigated the potential protective effects of apigenin (AP), galangin and genkwanin, naturally occurring plant flavonoids, on the MPP(+)‑induced cytotoxicity in cultured rat adrenal pheochromocytoma cells (PC12 cells). The PC12 cells were pre-treated with various concentrations of the test compounds for 4 h, followed by the challenge with 1,000 µM MPP(+) for 48 h. We found that only pre-treatment with AP (3, 6 and 12 µM) before injury significantly increased cell viability, decreased the release of lactate dehydrogenase, reduced the level of intracellular reactive oxygen species and elevated mitochondrial membrane potential in the MPP(+)‑treated PC12 cells. In addition, AP markedly suppressed the increased rate of apoptosis and the reduced Bcl‑2/Bax ratio induced by MPP(+) in the PC12 cells. Taken together, the findings of this study demonstrate that AP exerts neuroprotective effects against MPP(+)‑induced neurotoxicity in PC12 cells, at least in part, through the inhibition of oxidative damage and the suppression of apoptosis through the mitochondrial pathway.

摘要

帕金森病是仅次于阿尔茨海默病的第二大常见神经退行性疾病,其特征是黑质致密部多巴胺能神经元丧失,可以通过使用神经毒素 1-甲基-4-苯基吡啶离子(MPP(+))在体外模型中模拟。在这项研究中,我们研究了芹菜素 (AP)、姜黄素和根皮素这三种天然植物类黄酮对培养的大鼠肾上腺嗜铬细胞瘤细胞 (PC12 细胞) 中 MPP(+)诱导的细胞毒性的潜在保护作用。PC12 细胞用不同浓度的测试化合物预处理 4 小时,然后用 1000µM MPP(+) 处理 48 小时。结果发现,只有在损伤前用 AP(3、6 和 12µM)预处理才能显著提高细胞活力,降低乳酸脱氢酶的释放,减少细胞内活性氧水平,并提高 MPP(+) 处理的 PC12 细胞中线粒体膜电位。此外,AP 显著抑制了 MPP(+)诱导的 PC12 细胞中凋亡率的增加和 Bcl-2/Bax 比值的降低。总之,这项研究的结果表明,AP 通过抑制氧化损伤和通过线粒体途径抑制细胞凋亡,对 MPP(+)诱导的 PC12 细胞神经毒性具有神经保护作用。

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