PMID- 31476693 OWN - NLM STAT- MEDLINE DCOM- 20200303 LR - 20200303 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 76 DP - 2019 Nov TI - Eupatilin attenuates the inflammatory response induced by intracerebral hemorrhage through the TLR4/MyD88 pathway. PG - 105837 LID - S1567-5769(19)31447-X [pii] LID - 10.1016/j.intimp.2019.105837 [doi] AB - BACKGROUND: Intracranial hemorrhage (ICH) is one of the most common brain traumas, and inflammation caused by ICH seriously affects the quality of life and prognosis of patients. Eupatilin has been shown to have anti-inflammatory effects in various diseases. However, only one paper has reported that Eupatilin has a therapeutic effect on the inflammatory response caused by ICH and the underlying mechanism needs to be studied. METHODS: We used erythrocyte lysis stimulation (ELS) to induce mouse microglia BV2 as the inflammation model. CCK-8 and Transwell assays were used to detect cell viability and migration. RT-PCR, western blotting, and ELISA were used to detect the secretion of inflammatory factors and the expression of related mechanism proteins. HE staining was used to detect cell edema and death. RESULT: We found that ELS significantly increased protein and mRNA levels and secretion of inflammatory factors IL-1beta and TNF-alpha, which Eupatilin attenuated through the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) pathway. The anti-inflammatory effect of Eupatilin was significantly attenuated after siRNA was used to reduce TLR4 expression. The experimental results and mechanism were also verified in TLR4 knockout mice in vivo. CONCLUSION: Eupatilin has a therapeutic effect on inflammation caused by ICH. The underlying mechanism may be related to TLR4/MyD88, which brings new hope for clinical patients to improve symptoms and prognosis. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Fei, Xiaowei AU - Fei X AD - Department of Neurosurgery, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China, Chengdu 610072, China.; Dapartment of Physiology, Dalian Medical University, Dalian 116044, China.; Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China. FAU - Chen, Chen AU - Chen C AD - Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China. FAU - Kai, Sun AU - Kai S AD - Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China. FAU - Fu, Xiaojun AU - Fu X AD - Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China. FAU - Man, Weitao AU - Man W AD - Department of Neurosurgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China. FAU - Ding, Boyun AU - Ding B AD - Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China. FAU - Wang, Chongwu AU - Wang C AD - Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China.. Electronic address: darklordwcw@163.com. FAU - Xu, Ruxiang AU - Xu R AD - Department of Neurosurgery, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China, Chengdu 610072, China.; Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China.. Electronic address: 524727684@qq.com. LA - eng PT - Journal Article DEP - 20190830 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Flavonoids) RN - 0 (IL1B protein, mouse) RN - 0 (Interleukin-1beta) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Tlr4 protein, mouse) RN - 0 (Tnf protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 4D58O05490 (eupatilin) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology/*therapeutic use MH - Cell Line MH - Cell Movement/drug effects MH - Cell Survival/drug effects MH - Cerebral Hemorrhage/*drug therapy/genetics/immunology MH - Flavonoids/pharmacology/*therapeutic use MH - Interleukin-1beta/genetics/immunology MH - Mice, Knockout MH - Microglia/drug effects/physiology MH - Myeloid Differentiation Factor 88/genetics/immunology MH - Signal Transduction/drug effects MH - Toll-Like Receptor 4/genetics/immunology MH - Tumor Necrosis Factor-alpha/genetics/immunology OTO - NOTNLM OT - Eupatilin OT - IL-1beta OT - Inflammation OT - Intracranial hemorrhage OT - TLR4 OT - TNF-alpha EDAT- 2019/09/03 06:00 MHDA- 2020/03/04 06:00 CRDT- 2019/09/03 06:00 PHST- 2019/07/03 00:00 [received] PHST- 2019/08/09 00:00 [revised] PHST- 2019/08/18 00:00 [accepted] PHST- 2019/09/03 06:00 [pubmed] PHST- 2020/03/04 06:00 [medline] PHST- 2019/09/03 06:00 [entrez] AID - S1567-5769(19)31447-X [pii] AID - 10.1016/j.intimp.2019.105837 [doi] PST - ppublish SO - Int Immunopharmacol. 2019 Nov;76:105837. doi: 10.1016/j.intimp.2019.105837. Epub 2019 Aug 30.