Kim Sang Min, Park Yong Joo, Shin Myoung-Sook, Kim Ha-Ryong, Kim Min Jae, Lee Sang Hun, Yun Seung Pil, Kwon Seung-Hwan
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, Baltimore, MD 21205, USA.
Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Bioorg Med Chem Lett. 2017 Dec 1;27(23):5207-5212. doi: 10.1016/j.bmcl.2017.10.048. Epub 2017 Oct 20.
Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound isolated from Flos Chrysanthemi Indici, chrysanthemum, safflower, and Calamintha and Linaria species has been shown to have anti-cancer activity, indicating its potential clinical value in cancer treatment. In this study, we sought to study the potentials of acacetin in preventing human dopaminergic neuronal death via inhibition of 6-hydroxydopamine (6-OHDA)-induced neuronal cell death in the SH-SY5Y cells. Our results suggest that acacetin was effective in preventing 6-OHDA-induced neuronal cell death through regulation of mitochondrial-mediated cascade apoptotic cell death. Pretreatment with acacetin significantly inhibited neurotoxicity and neuronal cell death through reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) dysfunction. Acacetin also markedly acted on key molecules in apoptotic cell death pathways and reduced phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3beta (GSK-3β). These results suggested that acacetin could inhibit 6-OHDA-induced neuronal cell death originating from ROS-mediated cascade apoptosis pathway. Thus, the results of our study suggest that acacetin is a potent therapeutic agent for PD progression.
刺槐素（5,7-二羟基-4'-甲氧基黄酮）是一种从野菊花、菊花、红花以及风轮菜属和柳穿鱼属植物中分离出的黄酮类化合物，已被证明具有抗癌活性，这表明其在癌症治疗中具有潜在的临床价值。在本研究中，我们试图通过抑制6-羟基多巴胺（6-OHDA）诱导的SH-SY5Y细胞神经元死亡，来研究刺槐素预防人类多巴胺能神经元死亡的潜力。我们的结果表明，刺槐素可通过调节线粒体介导的级联凋亡细胞死亡，有效预防6-OHDA诱导的神经元细胞死亡。刺槐素预处理可通过活性氧（ROS）生成和线粒体膜电位（MMP）功能障碍，显著抑制神经毒性和神经元细胞死亡。刺槐素还可显著作用于凋亡细胞死亡途径中的关键分子，并减少c-Jun氨基末端激酶（JNK）、p38丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇3-激酶（PI3K）/Akt和糖原合酶激酶-3β（GSK-3β）的磷酸化。这些结果表明，刺槐素可抑制源自ROS介导的级联凋亡途径的6-OHDA诱导的神经元细胞死亡。因此，我们的研究结果表明，刺槐素是一种治疗帕金森病进展的有效治疗剂。
