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Recently, in search for a promising therapeutic target that could stop neurodegenerative diseases progression, the antioxidant signaling pathway regulated by transcription factor nuclear factor erythroid 2\u2010related factor 2 (Nrf2) has attracted new hopes. Icariin (ICA) exhibited a battery of pharmacological properties, including antioxidation, anti\u2010aging, and anti\u2010inflammation activities. Recent studies indicate ICA conferred neuroprotection against brain ischemic injury and neurodegenerative diseases. However, the mechanisms underlying ICA\u2010mediated neuroprotection remain unelucidated. This study aimed at analyzing whether ICA evoked neuroprotection against 6\u2010hydroxydopamine (6\u2010OHDA)\u2010induced neurotoxicity in PC12 cells and the mechanisms of action. ICA protected against 6\u2010OHDA\u2010induced neuronal damage, accompanied by the inhibition of cell apoptosis through the marked decreases in the Bax\/Bcl\u20102 ratio, cytochrome <jats:italic>c<\/jats:italic> release, and caspase\u20103 cleavage. In addition, the activation of Nrf2 signaling pathway was responsible for ICA\u2010mediated neuroprotection. First, ICA relieved reactive oxygen species accumulation and increased superoxide dismutase generation via the activation of Nrf2 signaling. Second, Nrf2 knockdown by siRNA reversed ICA\u2010mediated neuroprotection. Together, these results suggested ICA\u2010mediated neuroprotection might be attributable to the activation of Nrf2 pathway via antioxidative signaling pathways.<\/jats:p>","DOI":"10.1002\/bab.1743","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T11:33:45Z","timestamp":1553081625000},"page":"465-471","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Activation of Nrf2 signaling by Icariin protects against 6\u2010OHDA\u2010induced neurotoxicity"],"prefix":"10.1002","volume":"66","author":[{"given":"Li","family":"Zhu","sequence":"first","affiliation":[{"name":"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 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DaiDi","family":"Li","sequence":"additional","affiliation":[{"name":"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 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce","family":"Chen","sequence":"additional","affiliation":[{"name":"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 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GuoQing","family":"Wang","sequence":"additional","affiliation":[{"name":"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 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JingShan","family":"Shi","sequence":"additional","affiliation":[{"name":"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 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0956-9351","authenticated-orcid":false,"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"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 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12020"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.114.007500"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2247"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/382685a0"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2004.07.028"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/130.4.1007S"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1179\/016164105X49463a","volume":"27","author":"Streit W. 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