(2S)-5, 2′, 5′-Trihydroxy-7-Methoxyflavanone, a Natural Product from Abacopteris penangiana, Presents Neuroprotective Effects In Vitro and In Vivo
(2S)-5, 2′, 5′-Trihydroxy-7-Methoxyflavanone, a Natural Product from Abacopteris penangiana, Presents Neuroprotective Effects In Vitro and In Vivo
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DOI：
10.1007/s11064-013-1070-8
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发表时间：
2013-05
影响因子：
4.4
通讯作者：
Han Wei;Guanghua Wu;Jinglou Chen;Xuenong Zhang;C. Xiong;Yong-fang Lei;Wei Chen;J. Ruan
中科院分区：
文献类型：
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作者：
Han Wei;Guanghua Wu;Jinglou Chen;Xuenong Zhang;C. Xiong;Yong-fang Lei;Wei Chen;J. Ruan
本研究的目的是研究(2S)- 5,2 ', 5 ' -三羟基-7-甲氧基黄酮（TMF）的神经保护作用。在体外和体内氧化应激诱导的神经变性模型。在PC12细胞中，TMF （3-20 μM）预培养24 h可通过调节氧化应激敏感标志物还原性谷胱甘肽/氧化性谷胱甘肽（GSH/GSSG）的比例，降低多巴胺诱导的PC12细胞毒性，减轻PC12细胞氧化还原失衡。此外，长期腹腔注射TMF（4或8 mg/kg/天）2周，可显著改善d-半乳糖（d-gal）处理小鼠在Morris水迷宫试验中的行为表现。生化分析显示，TMF抑制了AP-1（激活蛋白-1）的激活，上调了d-gal处理小鼠海马中BDNF（脑源性神经因子）的水平以及GSH/GSSG的比值。此外，western blotting分析表明，TMF增加了camp反应元件结合蛋白（CREB）的磷酸化。因此，天然产物TMF具有治疗神经退行性疾病的潜力。
The aim of this study was to investigate the neuroprotective effects of (2S)-5, 2′, 5′-trihydroxy-7-methoxyflavanone (TMF), a natural product fromAbacopteris penangiana(Hook.) Ching, in oxidative stress-induced neurodegeneration models in vitro and in vivo. In PC12 cells, preincubation of TMF (3–20 μM) for 24 h decreased the dopamine-induced toxicity and attenuated the redox imbalance in PC12 cells through regulating the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG), which is a sensitive marker of oxidative stress. Additionally, long-term intraperitoneal (i.p.) injection of TMF (4 or 8 mg/kg/day) for 2 weeks significantly improved the behavioral performance ofd-galactose (d-gal) treated mice in a Morris water maze test. Biochemical analysis revealed that TMF inhibited the activation of AP-1 (activator protein-1) and upregulated the level of BDNF (brain derived neurophic factor) as well as the ratio of GSH/GSSG in the hippocampus ofd-gal treated mice. Furthermore, western blotting analysis indicated that TMF increased phosphorylation of cAMP-response element-binding protein (CREB). Therefore, the natural product TMF possessed a potential for the treatment of neurodegenerative diseases.