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| 標題: | Neurotrophic Action of 5-Hydroxylated Polymethoxyflavones: 5-Demethylnobiletin and Gardenin A Stimulate Neuritogenesis in PC12 Cells |
| 作者: | Chiu, Szu-Ping
Wu, Ming-Jiuan
Chen, Pei-Yi
Ho, Yi-Ru
Tai, Mi-Hsueh
Ho, Chi-Tang
Yen, Jui-Hung |
| 貢獻者: | 生物科技系 |
| 關鍵字: | Polymethoxyflavones
5-Demethylnobiletin
Gardenin A
Pc12 Cells
Neurite Outgrowth |
| 日期: | 2013-10 |
| 上傳時間: | 2014-05-26 10:47:54 (UTC+8) |
| 出版者: | Amer Chemical Soc |
| 摘要: | Polymethoxyflavones (PMFs) exhibit a broad spectrum of biological properties, including anticancer, antiatherogenic, and neuroprotective effects. The aim of this study is to investigate the neurotrophic effects of 5-demethylnobiletin, a hydroxylated PMF found in citrus plants, and gardenin A, a synthetic PMF analogue, on neurite outgrowth and neuronal differentiation in PC12 cells. The results of this study showed that 5-demethylnobiletin and gardenin A (10-20 mu M) potently induce neurite outgrowth in PC12 cells, accompanied by the expression of neuronal differentiation and synapse formation marker proteins, growth associated protein-43 (GAP-43), and synaptophysin. We observed that the addition of K252a, a TrKA antagonist, significantly inhibited NGF-induced neurite outgrowth in PC12 cells, but 5-demethylnobiletin- or gardenin A-induced neurite outgrowth was not affected. Treatment with 5-demethylnobiletin and gardenin A markedly induced the phosphorylation of both cyclic AMP response element-binding protein (CREB) and CRE-mediated transcription, which was suppressed through the administration of the inhibitor 2-naphthol AS-E phosphate (KG-501) or. using CREB siRNA. Furthermore, our results showed that MAPK/ERK kinase 1/2 (MEK1/2), protein kinase A (PKA), and protein kinase C (PKC) inhibitors blocked the CRE transcription activity and neurite outgrowth induced through 5-demethylnobiletin or gardenin A. Consistently, increased ERK phosphorylation and PKA and PKC activities were observed in PC12 cells treated with 5-demethylnobiletin or gardenin A. These results reveal for the first time that 5-demethylnobiletin and gardenin A promote neuritogenesis through the activation of MAPK/ERK-, PKC-, and PICA dependent, but not TrkA-dependent, CREB signaling pathways in PC12 cells. |
| 關聯: | Journal of Agricultural And Food Chemistry, v.61 n.39 pp.9453-9463 |
| 顯示於類別: | [生物科技系(所)] 期刊論文
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