The flavonoid Baicalein attenuates cuprizone-induced demyelination via suppression of neuroinflammation.

The flavonoid Baicalein attenuates cuprizone-induced demyelination via suppression of neuroinflammation.
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DOI:
10.1016/j.brainresbull.2017.09.007
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发表时间:
2017-10
影响因子:
3.8
通讯作者:
Yoshikawa K
Yoshikawa K
中科院分区:
医学3区
文献类型:
--
作者:
Hashimoto M;Yamamoto S;Iwasa K;Yamashina K;Ishikawa M;Maruyama K;Bosetti F;Yoshikawa K

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多发性硬化(MS)是中枢神经系统的慢性脱髓鞘疾病,其特征在于复发性和进行性脱髓鞘/髓鞘再生周期、神经炎症、少突胶质细胞损失和轴突病理。从黄芩根中分离的黄芩素已被证明具有抗炎和抗氧化作用。铜腙模型是已建立的MS小鼠模型,其引起脱髓鞘和运动功能障碍,并诱导神经炎症,如神经胶质活化和促炎细胞因子产生。为了确定黄芩素是否减弱铜唑啉诱导的脱髓鞘,我们将黄芩素给予暴露于铜唑啉的小鼠。黄芩素可减轻铜腙模型小鼠体重减轻(P<0.05)和运动功能障碍(P<0.05)。黄芩素能有效抑制脱髓鞘(P<0.01)及CNP(P<0.05)、MBP(P<0.05)基因表达。黄芩素治疗组也能抑制铜唑酮诱导的小胶质细胞Iba 1阳性(P<0.001)、星形胶质细胞GFAP阳性(P<0.001)以及CD 11b(P<0.01)、GFAP(P <0.05)、TNFα(P <0.05)、IL-1β(P<0.05)和iNOS(P<0.01)基因表达的增加。我们发现黄芩素治疗减弱了铜唑酮诱导的脱髓鞘、神经胶质活化、促炎细胞因子表达和运动功能障碍。我们的研究结果表明,黄芩素可能是一个有用的治疗剂在脱髓鞘疾病,以抑制神经炎症。
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, and axonal pathology. Baicalein isolated from the roots of Scutellaria baicalensis has been shown to exert anti-inflammatory and antioxidant effects. The cuprizone model is an established mouse model of MS and causes demyelination and motor dysfunction and induces neuroinflammation, such as glial activation and pro-inflammatory cytokine production. To determine whether Baicalein attenuates cuprizone-induced demyelination, we administrated Baicalein to cuprizone-exposed mice. Baicalein attenuated weight loss (P<0.05) and motor dysfunction (P<0.05) in the cuprizone model mice. Baicalein treatment effectively suppressed the demyelination (P<0.01) and gene expressions of CNP (P<0.05) and MBP (P<0.05). Baicalein treatment also inhibited the cuprizone-induced increase in Iba1-positive microglia (P<0.001), GFAP-positive astrocytes (P<0.001), and the gene expressions of CD11b (P<0.01), GFAP (P<0.05), TNFα (P<0.05), IL-1β (P<0.05), and iNOS (p<0.01). We found that Baicalein treatment attenuated cuprizone-induced demyelination, glial activation, pro-inflammatory cytokine expression, and motor dysfunction. Our results suggest that Baicalein may be a useful therapeutic agent in demyelinating diseases to suppress neuroinflammation.
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