Nobiletin

Nobiletin是ERK抑制剂，具有浓度依赖特征[1]。

Nobiletin是一种从柑橘类水果中分离的柑橘多甲氧基黄酮，在体外和动物研究的抗炎、抗肿瘤侵袭、增殖和癌转移中扮演重要角色。

Nobiletin具有抑制肿瘤生长和癌转移的功能。在人类鼻咽癌细胞系（HONE-1和NPC-BM）中，nobiletin处理可抑制ERK1/2磷酸化，显著抑制细胞侵袭[2]。在大鼠C6胶质瘤细胞中，nobiletin可抑制ERK活性，从而抑制细胞增殖[1]。

在5-min BCCAO诱导脑缺血的小鼠模型中，nobiletin（50 mg/kg）腹腔内给药连续7天可显著抑制海马CA1神经元中迟发性神经元死亡，改善情景记忆[3]。在MPTP诱导的帕金森氏症小鼠模型中，Nobiletin（50 mg/kg i.p.）腹腔内给药连续2周可改善运动和认知缺陷[4]。

在人类单核THP-1细胞中，nobietin在100 μM浓度时可阻断TPA增强的ERK1/2活化[5]。

参考文献：
[1].  Aoki, K., et al., Nobiletin induces inhibitions of Ras activity and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling to suppress cell proliferation in C6 rat glioma cells. Biol Pharm Bull, 2013. 36(4): p. 540-7.
[2].  Chien, S.Y., et al., Nobiletin inhibits invasion and migration of human nasopharyngeal carcinoma cell lines by involving ERK1/2 and transcriptional inhibition of MMP-2. Expert Opin Ther Targets, 2015: p. 1-14.
[3].  Yamamoto, Y., et al., Nobiletin improves brain ischemia-induced learning and memory deficits through stimulation of CaMKII and CREB phosphorylation. Brain Res, 2009. 1295: p. 218-29.
[4].  Yabuki, Y., et al., Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice. Neuroscience, 2014. 259: p. 126-41.
[5].  Eguchi, A., A. Murakami, and H. Ohigashi, Nobiletin, a citrus flavonoid, suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP-1 human monocytic cells. FEBS Lett, 2006. 580(13): p. 3321-8.