Icariin targets Nrf2 signaling to inhibit microglia-mediated neuroinflammation
Authors: Daidi Li
Yaxin Zheng
Guoqing Wang
Jingyi He
Feng Zhang
Guofu Zhu
Journal: International Immunopharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Icariin; Lipopolysaccharide; Microglia; Neuroinflammation; Nrf2.
Affiliations: Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China., Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China. Electronic address: .

Abstract:  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. 

Retracted: No

PubPeer comments:
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 Retraction, January 2019, found here: https: www.hindawi.com journals ecam 2019 2986594  At the request of the authors, the article titled u201cDecursin Isolated from Angelica gigas Nakai Rescues PC12 Cells from Amyloid u03b2-Protein-Induced Neurotoxicity through Nrf2-Mediated Upregulation of Heme Oxygenase-1: Potential Roles of MAPKu201d [1] has been retracted. The article was found to have serious concerns in the figures. An erratum [2] was previously published to correct Figures 2(a) andu20095(b), but an additional figure duplication issue was raised on PubPeer in which the GADPH bands in Figure 6(a) are the same as those in Figure 6(c) but rotated 180 degrees. We asked the authors to provide us with the raw blots for every figure in the original article and the erratum, but they did not have the original data because the experiments were done ten years ago. The authors said it would take a long time to repeat the results and although they do not believe this affects the conclusions, the authors asked to retract the article to avoid misleading readers. They sincerely apologize for the mistake and inconvenience. I was Peer 3 above, and I reported the concerns shown above to the journal in October 2015. ,