PMID- 32114357 OWN - NLM STAT- MEDLINE DCOM- 20210203 LR - 20210203 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 126 DP - 2020 Jun TI - Luteolin alleviates neuroinflammation via downregulating the TLR4/TRAF6/NF-kappaB pathway after intracerebral hemorrhage. PG - 110044 LID - S0753-3322(20)30235-3 [pii] LID - 10.1016/j.biopha.2020.110044 [doi] AB - The activation of microglia and in fl ammatory responses is essential for the process of intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). In this study, we investigated the effects of luteolin on ICH-induced SBI and the potential mechanisms. Autologous blood was injected to establish the ICH model in vivo, and oxyhemoglobin (OxyHb) was used to mimic the ICH model in vitro. We found that the administration of luteolin significantly improved motor and sensory impairments and inhibited neuronal cell degeneration in vivo. In the in vitro study, the decrease of the neuronal cell viability induced by activated microglia was alleviated by luteolin treatment. Furthermore, by antagonizing the activation of the Toll-like receptor 4 (TLR4)/TNF receptor-associated factor 6 (TRAF6)/nuclear transcription factor-kappaB (NF-kappaB) signaling pathway, the ICH-induced elevation of cytokine release was decreased after treatment with luteolin, which was confirmed both in vivo and in vitro. Additionally, we found that luteolin engaged with TRAF6 and inhibited the ubiquitination of TRAF6. Taken together, our findings demonstrate the neuroprotective effects of luteolin after ICH and the potential mechanisms, which suggest that luteolin is a potential therapeutic candidate for ICH treatment. CI - Copyright (c) 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Yang, Yi AU - Yang Y AD - Department of Neurology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China. FAU - Tan, Xin AU - Tan X AD - Department of Neurology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China. FAU - Xu, Jianguo AU - Xu J AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. FAU - Wang, Tianyi AU - Wang T AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. FAU - Liang, Tianyu AU - Liang T AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. FAU - Xu, Xiang AU - Xu X AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. FAU - Ma, Cheng AU - Ma C AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. FAU - Xu, Zhongmou AU - Xu Z AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. FAU - Wang, Wenjie AU - Wang W AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. FAU - Li, Haiying AU - Li H AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. FAU - Shen, Haitao AU - Shen H AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. FAU - Li, Xiang AU - Li X AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. Electronic address: xiangli2017@suda.edu.cn. FAU - Dong, Wanli AU - Dong W AD - Department of Neurology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China. Electronic address: wanli_dong@126.com. FAU - Chen, Gang AU - Chen G AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China. LA - eng PT - Journal Article DEP - 20200227 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (NF-kappa B) RN - 0 (Neuroprotective Agents) RN - 0 (TNF Receptor-Associated Factor 6) RN - 0 (Tlr4 protein, rat) RN - 0 (Toll-Like Receptor 4) RN - KUX1ZNC9J2 (Luteolin) SB - IM MH - Animals MH - *Brain/drug effects/immunology MH - Cells, Cultured MH - Cerebral Hemorrhage/*drug therapy/immunology MH - Disease Models, Animal MH - Down-Regulation MH - Inflammation MH - Luteolin/*therapeutic use MH - Male MH - Microglia/drug effects/immunology MH - NF-kappa B/genetics/*metabolism MH - Neurons/drug effects/immunology MH - Neuroprotective Agents/*therapeutic use MH - Rats MH - Rats, Sprague-Dawley MH - Rotarod Performance Test MH - Signal Transduction/genetics/immunology MH - TNF Receptor-Associated Factor 6/genetics/*metabolism MH - Toll-Like Receptor 4/genetics/*metabolism OTO - NOTNLM OT - Intracerebral hemorrhage OT - Luteolin OT - NF-kappaB OT - Neuroinflammation OT - TRAF6 COIS- Declaration of Competing Interest The authors declared that there were no conflict of interest exists. EDAT- 2020/03/03 06:00 MHDA- 2021/02/04 06:00 CRDT- 2020/03/02 06:00 PHST- 2019/11/27 00:00 [received] PHST- 2020/02/19 00:00 [revised] PHST- 2020/02/23 00:00 [accepted] PHST- 2020/03/03 06:00 [pubmed] PHST- 2021/02/04 06:00 [medline] PHST- 2020/03/02 06:00 [entrez] AID - S0753-3322(20)30235-3 [pii] AID - 10.1016/j.biopha.2020.110044 [doi] PST - ppublish SO - Biomed Pharmacother. 2020 Jun;126:110044. doi: 10.1016/j.biopha.2020.110044. Epub 2020 Feb 27.