PMID- 30528467 OWN - NLM STAT- MEDLINE DCOM- 20190124 LR - 20210214 IS - 1347-8648 (Electronic) IS - 1347-8613 (Linking) VI - 139 IP - 1 DP - 2019 Jan TI - Schaftoside ameliorates oxygen glucose deprivation-induced inflammation associated with the TLR4/Myd88/Drp1-related mitochondrial fission in BV2 microglia cells. PG - 15-22 LID - S1347-8613(18)30209-3 [pii] LID - 10.1016/j.jphs.2018.10.012 [doi] AB - 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-1beta, 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. CI - Copyright (c) 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved. FAU - Zhou, Kecheng AU - Zhou K AD - 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. FAU - Wu, Jiayu AU - Wu J AD - 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. FAU - Chen, Jie AU - Chen J AD - 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. FAU - Zhou, Ye AU - Zhou Y AD - 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. FAU - Chen, Xiaolong AU - Chen X AD - 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. FAU - Wu, Qiaoyun AU - Wu Q AD - 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. FAU - Xu, Yangxinzi AU - Xu Y AD - Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Tu, Wenzhan AU - Tu W AD - 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. FAU - Lou, Xinfa AU - Lou X AD - Integrative & Optimized Medicine Research Center, China-USA Institute for Acupuncture and Rehabilitation, Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Yang, Guanhu AU - Yang G AD - Integrative & Optimized Medicine Research Center, China-USA Institute for Acupuncture and Rehabilitation, Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Jiang, Songhe AU - Jiang S AD - 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. LA - eng PT - Journal Article DEP - 20181125 PL - Japan TA - J Pharmacol Sci JT - Journal of pharmacological sciences JID - 101167001 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Glycosides) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 0 (schaftoside) RN - EC 3.6.5.5 (Dnm1l protein, mouse) RN - EC 3.6.5.5 (Dynamins) RN - IY9XDZ35W2 (Glucose) SB - IM EIN - J Pharmacol Sci. 2021 Jul;146(3):182. PMID: 33582002 MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Cell Line MH - Dynamins/physiology MH - Glucose/deficiency MH - Glycosides/*pharmacology MH - Hypoxia MH - Mice MH - Microglia/*drug effects/physiology MH - Mitochondrial Dynamics/*drug effects MH - Myeloid Differentiation Factor 88/physiology MH - Toll-Like Receptor 4/physiology OTO - NOTNLM OT - Microglia OT - Mitochondrial fission OT - Schaftoside OT - Stroke OT - TLR4 EDAT- 2018/12/12 06:00 MHDA- 2019/01/25 06:00 CRDT- 2018/12/12 06:00 PHST- 2018/08/11 00:00 [received] PHST- 2018/10/29 00:00 [revised] PHST- 2018/10/31 00:00 [accepted] PHST- 2018/12/12 06:00 [pubmed] PHST- 2019/01/25 06:00 [medline] PHST- 2018/12/12 06:00 [entrez] AID - S1347-8613(18)30209-3 [pii] AID - 10.1016/j.jphs.2018.10.012 [doi] PST - ppublish SO - J Pharmacol Sci. 2019 Jan;139(1):15-22. doi: 10.1016/j.jphs.2018.10.012. Epub 2018 Nov 25.