Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia
Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia
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Yokukansan 通过对小胶质细胞的抗炎作用减少铜宗诱导的胼胝体脱髓鞘
DOI：
10.1007/s11064-017-2400-z
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发表时间：
2017-09
影响因子：
4.4
通讯作者：
Yoshida Shigetaka
中科院分区：
文献类型：
--
作者：
Nomura Taichi;B;o Yoshio;You Hua;Tanaka Tatsuhide;Yoshida Shigetaka
多发性硬化症（MS）是一种中枢神经系统（CNS）的炎症性脱髓鞘疾病。炎性细胞因子和促氧化分子从小胶质细胞的释放已被证明在ms的病理中起关键作用，因此，抑制小胶质细胞活化是一种有吸引力的治疗选择。日本传统草药Yokukansan已被证明可以抑制中枢神经系统的小胶质细胞活动。然而，是否yokukansan减少脱髓鞘观察到的中枢神经系统在多发性硬化症仍不清楚。本实验用含0.2%铜酮（双环己酮草醛二腙）的饲粮诱导雌性C57BL/6小鼠胼胝体脱鞘。我们用免疫组织化学分析研究了横坎山是否能减少铜酮诱导的脱髓鞘。此外，我们还研究了yokukan对lps刺激的小鼠小胶质细胞系BV2细胞的体外抗炎作用。Luxol快速蓝染色和髓鞘碱性蛋白免疫染色表明，横kan可减少铜酮喂养小鼠胼胝体脱髓鞘的发生。此外，yokukansan显著降低了铜酮喂养小鼠胼胝体中活化的小胶质细胞的数量。此外，500 μg/ml yokukansan可抑制lps刺激的BV2细胞中白细胞介素-1β和诱导型一氧化氮合酶mRNA和蛋白的表达。这些发现表明，由于对小胶质细胞的抗炎作用，yokukan减少了脱髓鞘。由于yokukansan几乎没有副作用，yokukansan有可能成为治疗多发性硬化症的新选择。
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). The release of inflammatory cytokines and pro-oxidant molecules from microglia has been shown to play a key role in the pathology of MS. Thus, suppression of microglial cell activation is an attractive therapeutic option. Yokukansan, a traditional Japanese herbal medicine, has been shown to suppress microglial activity in the CNS. However, whether or not yokukansan reduces demyelination observed in the CNS during MS remains unknown. In this study, female C57BL/6 mice were fed a diet containing 0.2% cuprizone (bis-cyclohexanone oxaldihydrazone) to induce demyelination in the corpus callosum. We investigated whether or not yokukansan reduces cuprizone-induced demyelination using immunohistochemical analyses. Furthermore, we examined the in vitro anti-inflammatory effects of yokukansan on LPS-stimulated BV2 cells, a murine microglial cell line. Luxol fast blue staining and immunostaining for myelin basic protein demonstrated that yokukansan reduces demyelination of thecorpora callosaof cuprizone-fed mice. In addition, yokukansan significantly decreased the number of activated microglial cells in thecorpora callosaof cuprizone-fed mice. Furthermore, treatment with 500 μg/ml yokukansan suppressed the expression of interleukin-1β and inducible nitric-oxide synthase mRNA and protein in LPS-stimulated BV2 cells. These findings suggest that yokukansan reduces demyelination owing to anti-inflammatory effects on microglia. As yokukansan has few adverse effects, yokukansan has the potential to be a novel option to treat MS.
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DOI：
10.1093/brain/aws012
发表时间：
2012-03
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Fischer MT;Sharma R;Lim JL;Haider L;Frischer JM;Drexhage J;Mahad D;Bradl M;van Horssen J;Lassmann H
通讯作者：
Lassmann H
影响因子：
2.9
作者：
Taichi Nomura;Y. Bando;H. Bochimoto;D. Koga;Tsuyoshi Watanabe;S. Yoshida
通讯作者：
Taichi Nomura;Y. Bando;H. Bochimoto;D. Koga;Tsuyoshi Watanabe;S. Yoshida
影响因子：
168.9
作者：
Cagnin, A;Brooks, DJ;Banati, RB
通讯作者：
Banati, RB
影响因子：
2.5
作者：
Han, IO;Kim, KW;Kim, WK
通讯作者：
Kim, WK
影响因子：
4.4
作者：
Clarner, Tim;Janssen, Katharina;Kipp, Markus
通讯作者：
Kipp, Markus