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Astragaloside (AS) is an antioxidant derivative from a traditional Chinese herbal medicine <jats:italic>Astragalus membraneaceus<\/jats:italic> Bunge. In this study, we used retinal pigment epithelial cells, which share plenty of features with neurodegenerative diseases such as AD and AMD to investigate the effect of AS. Cell cycle re\u2010entry and proapoptosis were seen in retinal pigment epithelium (RPE) cells treated with isoflurane, which was alleviated by pretreatment of AS. Further, tumor necrosis factor receptor\u2010associated factor 5 (TRAF5) and downstream nuclear factor\u2010\u03baB (NF\u2010\u03baB) were investigated to elucidate the molecular mechanism underlying protective effect of AS. RPE cells exposed to isoflurane expressed higher TRAF5 and NF\u2010\u03baB than those pretreated with AS, suggesting a critical role of TRAF5 therein. In Morris water maze (MWM) assay, Sprague\u2010Dawley rats pretreated with AS and then exposed to isoflurane spent less time in swimming to the platform, and their TRAF5 expression was significantly lower than those received anesthesia alone. Further studies on the consequence of forced downregulation or upregulation are warranted that may employ cutting\u2010edge technologies such as optogenetics to overcome the difficulties in manipulating expression of TRAF5. Although the link between TRAF5 and neurodegeneration requires more in\u2010depth investigations, our study provide a novel hint on the pathological mechanism of isoflurane and suggest a potential target for eliminating persistent side effect of anesthesia.<\/jats:p>","DOI":"10.1002\/jcb.27599","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T12:54:56Z","timestamp":1537102496000},"page":"1028-1037","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Astragaloside suppresses tumor necrosis factor receptor\u2010associated factor 5 signaling pathway and alleviates neurodegenerative changes in retinal pigment epithelial cells induced by isoflurane"],"prefix":"10.1002","volume":"120","author":[{"given":"Pei\u2010Jun","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital of Soochow University Suzhou China"},{"name":"Department of Anesthesiology The Sixth People\u2019s Hospital of Yancheng City Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u2010Quan","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Tongji Hospital of Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology The Sixth People\u2019s Hospital of Yancheng City Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0665-4924","authenticated-orcid":false,"given":"Jian\u2010Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital of Soochow University Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,14]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-015-0018-8"},{"key":"e_1_2_6_1_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200301000-00017"},{"key":"e_1_2_6_1_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/15.10.2197"},{"key":"e_1_2_6_1_5_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000103187.70627.57"},{"key":"e_1_2_6_1_6_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ane.0000167382.79889.7c"},{"key":"e_1_2_6_1_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199003000-00022"},{"key":"e_1_2_6_1_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5320-06.2007"},{"key":"e_1_2_6_1_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.anes.0000299435.59242.0e"},{"key":"e_1_2_6_1_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31817f5c47"},{"key":"e_1_2_6_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.01.009"},{"key":"e_1_2_6_1_12_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e3181605b71"},{"key":"e_1_2_6_1_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-03-00876.2003"},{"key":"e_1_2_6_1_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.anes.0000264762.48920.80"},{"key":"e_1_2_6_1_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200402000-00020"},{"key":"e_1_2_6_1_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13066772"},{"key":"e_1_2_6_1_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/pan.12786"},{"key":"e_1_2_6_1_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2012.00141"},{"key":"e_1_2_6_1_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.167635"},{"key":"e_1_2_6_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otot.2015.06.004"},{"key":"e_1_2_6_1_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039824"},{"key":"e_1_2_6_1_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.019604"},{"issue":"8","key":"e_1_2_6_1_23_1","first-page":"855","article-title":"The role of ROS and RNS in regulating life and death of blood monocytes. 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