{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:16:42Z","timestamp":1787015802912,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770679"],"award-info":[{"award-number":["81770679"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800601"],"award-info":[{"award-number":["81800601"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970582"],"award-info":[{"award-number":["81970582"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute kidney injury (AKI) results in high morbidity and mortality among inpatients, while effective treatment and intervention are still absent. Therefore, this study aims to explore the effects of Scutellarin (Scu) in experimental models in vivo and in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vivo experiment, we employed a total of 30 Wistar rats, which further were modelled by a bilateral renal pedicle clip for 45\u2009min, then received 50\u2009mg\/kg\/day Scu. In vitro, HK\u20102 cells were administered with 20\u03bc\u039c Scu and then incubated in hypoxia\/reoxygenation (H\/R) conditions for 24\u2009h. The knockdown of Nrf2 expression was conducted by small interfering RNA (siRNA) transfection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>As a result, the AKI model was well established with an increased SCr, BUN, KIM\u20101 level, and histological injury score, while Scu treatment reduced the levels above and increased the antioxidative enzyme HO\u20101. H\/R induced an increase of ROS in HK\u20102 cells, while Scu decreased the ROS level. Bioinformatics results showed the transcription factor Nrf2 was a hub protein during the AKI, which also bound to Scu with low binding energy, indicating that the downstream effect of Scu might be mediated by Nrf2. To verify the suppose above, we employed siRNA against Nrf2, which shows a significant increase in ROS after Nrf2 was blocked. Meanwhile, the HO\u20101 showed similar expression compared with the \u2018H\/R\u2009+\u2009Nrf2 siRNA\u2019 and \u2018H\/R\u2009+\u2009Nrf2 siRNA\u2009+\u2009Scu\u2019 group, implying the protective effect of Scu was mediated by the Nrf2\/HO\u20101 pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Scu led to up\u2010regulation of HO\u20101 through activating the Nrf2 signalling pathway, protecting the kidneys from ischemia\/reperfusion (I\/R)\u2010induced oxidative damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.14069","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T05:07:15Z","timestamp":1653973635000},"page":"690-700","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Scutellarin protects the kidney from ischemia\/reperfusion injury by targeting Nrf2"],"prefix":"10.1111","volume":"27","author":[{"given":"Jie","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congjuan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2049-3976","authenticated-orcid":false,"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.751793"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.04.001"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00519-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45161"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.23876\/j.krcp.19.062"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118581"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7370"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000313957"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10010039"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.05.006"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/432623"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2013.11.026"},{"key":"e_1_2_9_14_1","first-page":"1354345","article-title":"Scutellarin exerts hypoglycemic and renal protective effects in db\/db mice via the Nrf2\/HO\u20101 signaling pathway","volume":"2019","author":"Liu Y","year":"2019","journal-title":"Oxidative Med Cell Longev"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.115"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00473"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/sms.12702"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049569"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9005.3"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i24.2605"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00066"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00469"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.05.006"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c110041"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2011.16"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002471"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00362.2016"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X18500635"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108647"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.08.127"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.584942"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25605"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15834"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153466"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.11.011"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.11.033"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.08.023"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.248"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.21037\/apm-19-516"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.907530"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2017.1422602"}],"container-title":["Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.14069","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nep.14069","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.14069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T03:58:51Z","timestamp":1692849531000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nep.14069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,15]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1111\/nep.14069"],"URL":"https:\/\/doi.org\/10.1111\/nep.14069","archive":["Portico"],"relation":{},"ISSN":["1320-5358","1440-1797"],"issn-type":[{"value":"1320-5358","type":"print"},{"value":"1440-1797","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,15]]},"assertion":[{"value":"2022-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}