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[川崎柑橘(川崎蜜柑)果皮及奥瑞烯对高血糖小鼠海马和全脑缺血/再灌注损伤小鼠的神经保护作用]

[Neuroprotective effects of the peel of Citrus kawachiensis (Kawachi Bankan) and auraptene in the hippocampus of hyperglycemia mice and global cerebral ischemia/reperfusion injury mice].

作者信息

Okuyama Satoshi, Sawamoto Atsushi, Nakajima Mitsunari, Furukawa Yoshiko

机构信息

Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University.

出版信息

Nihon Yakurigaku Zasshi. 2020;155(4):214-219. doi: 10.1254/fpj.20022.

Abstract

The peel of Citrus kawachiensis (Kawachi Bankan), a citrus species grown in Ehime, Japan, is abundant in auraptene. Auraptene, a coumarin compound, have been shown to exert anti-inflammatory effects in peripheral tissues, but it was still unclear of the effect in the brain. Hyperglycemia and brain ischemia induce inflammation and oxidative stress and cause massive damage in the brain; therefore, we examined the anti-inflammatory and other effects of the dried peel powder of C. kawachiensis and auraptene in a hyperglycemia and global cerebral ischemia models. The C. kawachiensis treatment inhibited astroglial activation in the hippocampus and the hyperphosphorylation of tau protein in hippocampal neurons, and also relieved the suppression of neurogenesis in the dentate gyrus of the hippocampus in the type 2 diabetic db/db mice. The C. kawachiensis treatment inhibited microglial and astroglial activation, and neuronal cell death in the hippocampus of transient global cerebral ischemia mice. It was suggested that the dried peel powder of C. kawachiensis exerts anti-inflammatory and neuroprotective effects in the brain. We attempted to demonstrate the effect of auraptene in the brains in streptozotocin-induced hyperglycemic mice and transient global cerebral ischemia mice. Auraptene administration showed the similar effects as the peel of C. kawachiensis in the hippocampus of these mice models. These results suggested that auraptene have potential effects as a neuroprotective agent in the peel of C. kawachiensis.

摘要

香川县柑橘(香川蜜柑)是一种生长在日本爱媛县的柑橘品种,其果皮富含金松双黄酮。金松双黄酮是一种香豆素化合物,已被证明在外周组织中具有抗炎作用,但在大脑中的作用仍不清楚。高血糖和脑缺血会引发炎症和氧化应激,并对大脑造成巨大损伤;因此,我们在高血糖和全脑缺血模型中研究了香川县柑橘干皮粉和金松双黄酮的抗炎及其他作用。在2型糖尿病db/db小鼠中,香川县柑橘处理可抑制海马体中的星形胶质细胞激活以及海马神经元中tau蛋白的过度磷酸化,还可缓解海马齿状回中神经发生的抑制。香川县柑橘处理可抑制短暂性全脑缺血小鼠海马体中的小胶质细胞和星形胶质细胞激活以及神经元细胞死亡。提示香川县柑橘干皮粉在大脑中具有抗炎和神经保护作用。我们试图在链脲佐菌素诱导的高血糖小鼠和短暂性全脑缺血小鼠中证明金松双黄酮在大脑中的作用。在这些小鼠模型的海马体中,给予金松双黄酮显示出与香川县柑橘果皮相似的效果。这些结果表明,金松双黄酮作为香川县柑橘果皮中的一种神经保护剂具有潜在作用。

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