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Microglia-mediated neuroinflammation is an important contributor to the pathogenesis of neurodegenerative diseases. Inhibition of neuroinflammation has been proved to be effective in neurodegenerative diseases treatment. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key mediator of endogenous inducible defense systems in the body. In response to oxidative stress, Nrf2 translocates to the nucleus and binds to specific DNA sites termed as anti-oxidant response elements to initiate transcription of cytoprotective genes, such as hemeoxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase-1 (NQO1). However, insufficient Nrf2 activation has been closely associated with the progress of neurodegenerative diseases. New findings have linked activation of Nrf2 signaling to anti-inflammatory effects. Icariin (ICA), a natural compound derived from Herba Epimedii, possesses amounts of pharmacological activities, such as anti-aging, anti-oxidation and anti-inflammatory effects. Recent studies have confirmed that ICA exerted neuroprotection against neurodegenerative diseases. However, the mechanisms underlying ICA-mediated neuroprotection were not fully understood. In the present study, microglia BV-2 cell lines were performed to investigate the anti-neuroinflammatory effects of ICA and the mechanisms of actions. Results showed that ICA suppressed lipopolysaccharide (LPS)-induced microglial pro-inflammatory factors production. In addition, activation of Nrf2 signaling pathway participated in ICA-mediated anti-neuroinflammation, as evidenced by the following observations. First, Nrf2 siRNA reversed ICA-reduced microglial activation and pro-inflammatory factors release. Second, a selective inhibitor of HO-1 abolished ICA-mediated anti-neuroinflammatory actions. This study will give us an insight into the potential of Nrf2 and neuroinflammation in terms of opening up an alternative therapeutic strategy for neurodegenerative diseases.

Titel:	Icariin targets Nrf2 signaling to inhibit microglia-mediated neuroinflammation.
Autor/in / Beteiligte Person:	Zheng, Y ; Zhu, G ; He, J ; Wang, G ; Li, D ; Zhang, F
Link:	Zum Volltext
Zeitschrift:	International immunopharmacology, Jg. 73 (2019-08-01), S. 304
Veröffentlichung:	Amsterdam ; New York : Elsevier Science, c2001-, 2019
Medientyp:	academicJournal
ISSN:	1878-1705 (electronic)
DOI:	10.1016/j.intimp.2019.05.033
Schlagwort:	Animals Cells, Cultured Heme Oxygenase-1 genetics Heme Oxygenase-1 metabolism Inflammation genetics Lipopolysaccharides Membrane Proteins genetics Membrane Proteins metabolism Mice Microglia metabolism NAD(P)H Dehydrogenase (Quinone) genetics NAD(P)H Dehydrogenase (Quinone) metabolism NF-E2-Related Factor 2 genetics Rats Signal Transduction drug effects Flavonoids pharmacology Inflammation metabolism Microglia drug effects NF-E2-Related Factor 2 metabolism Neuroprotective Agents pharmacology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Int Immunopharmacol] 2019 Aug; Vol. 73, pp. 304-311. <i>Date of Electronic Publication: </i>2019 May 22. MeSH Terms: Flavonoids / pharmacology ; Inflammation / metabolism ; Microglia / drug effects ; NF-E2-Related Factor 2 / metabolism ; Neuroprotective Agents / *pharmacology ; Animals ; Cells, Cultured ; Heme Oxygenase-1 / genetics ; Heme Oxygenase-1 / metabolism ; Inflammation / genetics ; Lipopolysaccharides ; Membrane Proteins / genetics ; Membrane Proteins / metabolism ; Mice ; Microglia / metabolism ; NAD(P)H Dehydrogenase (Quinone) / genetics ; NAD(P)H Dehydrogenase (Quinone) / metabolism ; NF-E2-Related Factor 2 / genetics ; Rats ; Signal Transduction / drug effects Comments: Erratum in: Int Immunopharmacol. 2020 Nov;88:107004. (PMID: 32950402) Contributed Indexing: Keywords: Icariin; Lipopolysaccharide; Microglia; Neuroinflammation; Nrf2 Substance Nomenclature: 0 (Flavonoids) ; 0 (Lipopolysaccharides) ; 0 (Membrane Proteins) ; 0 (NF-E2-Related Factor 2) ; 0 (Neuroprotective Agents) ; 0 (Nfe2l2 protein, mouse) ; EC 1.14.14.18 (Heme Oxygenase-1) ; EC 1.14.14.18 (Hmox1 protein, mouse) ; EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone)) ; EC 1.6.5.2 (Nqo1 protein, mouse) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20190526 Date Completed: 20200128 Latest Revision: 20200128 Update Code: 20240513

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Icariin targets Nrf2 signaling to inhibit microglia-mediated neuroinflammation.