Schaftoside ameliorates oxygen glucose deprivation-induced inflammation associated with the TLR4/Myd88/Drp1-related mitochondrial fission in BV2 microglia cells

被引:69
作者
Zhou, Kecheng [1 ,2 ,3 ]
Wu, Jiayu [1 ,2 ,3 ]
Chen, Jie [1 ,2 ,3 ]
Zhou, Ye [1 ,2 ,3 ]
Chen, Xiaolong [1 ,2 ,3 ]
Wu, Qiaoyun [1 ,2 ,3 ]
Xu, Yangxinzi [4 ]
Tu, Wenzhan [1 ,2 ,3 ]
Lou, Xinfa [3 ]
Yang, Guanhu [3 ]
Jiang, Songhe [1 ,2 ,3 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Phys Med & Rehabil, 268 Xue Yuan Xi Rd, Wenzhou 325027, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Yuying Childrens Hosp, 268 Xue Yuan Xi Rd, Wenzhou 325027, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, China USA Inst Acupuncture & Rehabil, Integrat & Optimized Med Res Ctr, Wenzhou, Zhejiang, Peoples R China
[4] Univ Manitoba, Dept Physiol & Pathophysiol, Winnipeg, MB, Canada
基金
中国国家自然科学基金;
关键词
Mitochondrial fission; Microglia; TLR4; Stroke; Schaftoside; RECEPTOR; 4; STRESS; DRP1; INHIBITION; INJURY; AUTOPHAGY; EXTRACT; PATHWAY; MICE;
D O I
10.1016/j.jphs.2018.10.012
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: Neuroinflammation plays a major role in the development of ischemic stroke, and regulation of the proinflammatory TLR4 signaling pathway in microglia stands to be a promising therapeutic strategy for stroke intervention. Recently, the homeostasis of mitochondrial dynamics has also been raised as a vital component in maintaining neuronal health, but its relevance in microglia hasn't been investigated. Schaftoside, a natural flavonoid compound and a promising treatment for inflammation, has demonstrated potency against LPS-induced lung inflammation in mice; however, its action on TLR4-induced neuroinflammation and mitochondrial dynamics in microglia is still unknown. Methods: The effects of schaftoside in regulating inflammation and mitochondrial dynamics were investigated in vitro in oxygen glucose deprivation (OGD)-stimulated BV2 microglia cells. Results: Schaftoside inhibited mRNA and protein expressions of proinflammatory cytokines (IL-1 beta, TNF-alpha, and IL-6) after 4 h in OGD-stimulated BV2 microglia cells, similar to the effect of TAK242, an inhibitor of TLR4. TLR4/Myd88 signaling pathway was effectively suppressed by schaftoside. In addition, both schaftoside and TAK242 treatments significantly decreased Drp1 expression, phosphorylation, translocation and mitochondrial fission in OGD-stimulated BV2 cells. Conclusions: Our study suggested that schaftoside was able to reduce neuroinflammation, which is mediated in part by reducing TLR4/Myd88/Drp1-related mitochondrial fission in BV2 microglia cells. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
引用
收藏
页码:15 / 22
页数:8
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