Okuyama Satoshi, Semba Tomoki, Toyoda Nobuki, Epifano Francesco, Genovese Salvatore, Fiorito Serena, Taddeo Vito Alessandro, Sawamoto Atsushi, Nakajima Mitsunari, Furukawa Yoshiko
Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan.
Department of Pharmacy, University "G. D'Annunzio", Chieti-Pescara Via dei Vestini 31, Chieti Scalo 66100, Italy.
Int J Mol Sci. 2016 Oct 17;17(10):1716. doi: 10.3390/ijms17101716.
In patients with Parkinson's disease (PD), hyperactivated inflammation in the brain, particularly microglial hyperactivation in the substantia nigra (SN), is reported to be one of the triggers for the delayed loss of dopaminergic neurons and sequential motor functional impairments. We previously reported that (1) auraptene (AUR), a natural prenyloxycoumain, suppressed inflammatory responses including the hyperactivation of microglia in the ischemic brain and inflamed brain, thereby inhibiting neuronal cell death; (2) 7-isopentenyloxycoumarin (7-IP), another natural prenyloxycoumain, exerted anti-inflammatory and neuroprotective effects against excitotoxicity; and (3) 4'-geranyloxyferulic acid (GOFA), a natural prenyloxycinnamic acid, also exerted anti-inflammatory effects. In the present study, using an intranigral lipopolysaccharide (LPS)-induced PD-like mouse model, we investigated whether AUR, 7-IP, and GOFA suppress microglial activation and protect against dopaminergic neuronal cell death in the SN. We successfully showed that these prenyloxyphenylpropanoids exhibited these prospective abilities, suggesting the potential of these compounds as neuroprotective agents for patients with PD.
在帕金森病（PD）患者中，据报道大脑中炎症过度激活，尤其是黑质（SN）中的小胶质细胞过度激活，是多巴胺能神经元延迟丧失和相继出现运动功能障碍的触发因素之一。我们之前报道过：（1）奥勒巴替尼（AUR），一种天然的异戊烯氧基香豆素，可抑制包括缺血性脑和炎症性脑中的小胶质细胞过度激活在内的炎症反应，从而抑制神经元细胞死亡；（2）7-异戊烯氧基香豆素（7-IP），另一种天然的异戊烯氧基香豆素，对兴奋性毒性具有抗炎和神经保护作用；（3）4'-香叶氧基阿魏酸（GOFA），一种天然的异戊烯氧基肉桂酸，也具有抗炎作用。在本研究中，我们使用黑质内注射脂多糖（LPS）诱导的帕金森病样小鼠模型，研究了AUR、7-IP和GOFA是否能抑制小胶质细胞激活并保护SN中的多巴胺能神经元细胞免于死亡。我们成功表明，这些异戊烯氧基苯丙烷类化合物具有这些预期的能力，表明这些化合物作为PD患者神经保护剂的潜力。
