PMID- 36523959 OWN - NLM STAT- MEDLINE DCOM- 20221223 LR - 20221223 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2022 DP - 2022 TI - Amentoflavone Exerts Anti-Neuroinflammatory Effects by Inhibiting TLR4/MyD88/NF-kappaB and Activating Nrf2/HO-1 Pathway in Lipopolysaccharide-Induced BV2 Microglia. PG - 5184721 LID - 10.1155/2022/5184721 [doi] LID - 5184721 AB - BACKGROUND: Amentoflavone, a natural biflavone, exerts anti-inflammation, antioxidation, and antiapoptosis effects on many diseases. However, the mechanism of amentoflavone on neuroinflammation-related diseases has not been comprehensively examined clearly. METHODS: BV2 microglial cells were treated with amentoflavone (10 muM), followed by lipopolysaccharide (LPS). Microglial activation and migration ability and the expression of proinflammatory cytokines and other signaling proteins were determined using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and wound-healing assays. RESULTS: Amentoflavone restored LPS-induced microglia activation, migration, and inflammation response which depends on regulating toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-kappaB) pathway. In addition, amentoflavone also enhanced nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) levels in LPS-treated BV2 microglial cells. CONCLUSIONS: Amentoflavone ameliorated LPS-induced neuroinflammatory response and oxidative stress in BV2 microglia. These data provide new insight into the mechanism of amentoflavone in the treatment of neuroinflammation-related diseases. Therefore, amentoflavone may be a potential therapeutic option for neurological disorders. CI - Copyright (c) 2022 Shikuo Rong et al. FAU - Rong, Shikuo AU - Rong S AUID- ORCID: 0000-0001-7904-0096 AD - Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China. AD - Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China. AD - Ningxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia 750004, China. FAU - Yang, Chunrong AU - Yang C AUID- ORCID: 0000-0003-0533-8302 AD - Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China. FAU - Wang, Feng AU - Wang F AUID- ORCID: 0000-0001-7841-5028 AD - Ningxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia 750004, China. AD - Department of Neurosurgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310003, China. FAU - Wu, Yiyang AU - Wu Y AUID- ORCID: 0000-0003-1446-0174 AD - Ningxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia 750004, China. FAU - Sun, Kuishen AU - Sun K AUID- ORCID: 0000-0003-2755-572X AD - Ningxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia 750004, China. FAU - Sun, Tao AU - Sun T AUID- ORCID: 0000-0002-8847-6972 AD - Ningxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia 750004, China. FAU - Wu, Zeyu AU - Wu Z AUID- ORCID: 0000-0003-0066-0378 AD - Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China. AD - Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China. LA - eng PT - Journal Article DEP - 20221206 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 9I1VC79L77 (amentoflavone) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - 0 (Lipopolysaccharides) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (Biflavonoids) SB - IM MH - Humans MH - Cell Line MH - Heme Oxygenase-1/drug effects/metabolism MH - Lipopolysaccharides/pharmacology/metabolism MH - *Microglia/drug effects/metabolism MH - Myeloid Differentiation Factor 88/antagonists & inhibitors/metabolism MH - Neuroinflammatory Diseases/drug therapy MH - NF-E2-Related Factor 2/agonists/metabolism MH - NF-kappa B/antagonists & inhibitors/metabolism MH - Toll-Like Receptor 4/antagonists & inhibitors/metabolism MH - *Biflavonoids/pharmacology/therapeutic use PMC - PMC9747320 COIS- The authors declare that they have no conflicts of interest. EDAT- 2022/12/17 06:00 MHDA- 2022/12/20 06:00 PMCR- 2022/12/06 CRDT- 2022/12/16 02:30 PHST- 2022/01/21 00:00 [received] PHST- 2022/09/27 00:00 [revised] PHST- 2022/10/17 00:00 [accepted] PHST- 2022/12/16 02:30 [entrez] PHST- 2022/12/17 06:00 [pubmed] PHST- 2022/12/20 06:00 [medline] PHST- 2022/12/06 00:00 [pmc-release] AID - 10.1155/2022/5184721 [doi] PST - epublish SO - Mediators Inflamm. 2022 Dec 6;2022:5184721. doi: 10.1155/2022/5184721. eCollection 2022.