Kecheng Zhou1, Jiayu Wu1, Jie Chen1, Ye Zhou1, Xiaolong Chen1, Qiaoyun Wu1, Yangxinzi Xu2, Wenzhan Tu1, Xinfa Lou3, Guanhu Yang3, Songhe Jiang4. 1. Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Integrative & Optimized Medicine Research Center, China-USA Institute for Acupuncture and Rehabilitation, Wenzhou Medical University, Wenzhou, Zhejiang, China. 2. Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada. 3. Integrative & Optimized Medicine Research Center, China-USA Institute for Acupuncture and Rehabilitation, Wenzhou Medical University, Wenzhou, Zhejiang, China. 4. Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Integrative & Optimized Medicine Research Center, China-USA Institute for Acupuncture and Rehabilitation, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: jshwz@126.com.
Abstract
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-1β, TNF-α, 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.
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-1β, TNF-α, 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.