Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia
別タイトル
抑肝散はミクログリアに抗炎症作用を示し、脳梁におけるクプリゾン誘発性脱髄を抑制する
著者
野村, 太一
(Nomura, Taichi)
上位タイトル
Neurochemical Research
Vol.42,
No.12
(2017.
12)
,p.3525-
3536
識別番号
ISSN
0364-3190
DOI
10.1007/s11064-017-2400-z
その他
PMID：28929408
博士論文情報
学位授与番号
10107A533
学位授与年月日
2019-3-25
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
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 the corpora callosa of cuprizone-fed mice. In addition, yokukansan significantly decreased the number of activated microglial cells in the corpora callosa of 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.
