{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:50:19Z","timestamp":1791003019771,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2020.01065","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T05:05:45Z","timestamp":1594962345000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":36,"title":["Hyperoside Protected Against Oxidative Stress-Induced Liver Injury via the PHLPP2-AKT-GSK-3\u03b2 Signaling Pathway In Vivo and In Vitro"],"prefix":"10.3389","volume":"11","author":[{"given":"Haiyan","family":"Xing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoqiu","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.intimp.2014.05.014","article-title":"Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin","volume":"21","author":"Al-Harbi","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"26882","DOI":"10.1074\/jbc.M114.567685","article-title":"Nuclear heme oxygenase-1 (HO-1) modulates subcellular distribution and activation of Nrf2, impacting metabolic and anti-oxidant defenses","volume":"289","author":"Biswas","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1021\/np200001x","article-title":"Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice","volume":"74","author":"Choi","year":"2011","journal-title":"J. Nat. Prod."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e000243","DOI":"10.1136\/bmjophth-2018-000243","article-title":"Surgical management of intermittent exotropia: do we have an answer for all","volume":"4","author":"Chougule","year":"2019","journal-title":"BMJ Open Ophthalmol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.01312","article-title":"New Insights Into the Pathogenesis of Alzheimer\u2019s Disease","volume":"10","author":"Fan","year":"2019","journal-title":"Front. Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.molcel.2005.03.008","article-title":"PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth","volume":"18","author":"Gao","year":"2005","journal-title":"Mol. Cell"},{"key":"B7","doi-asserted-by":"publisher","first-page":"788","DOI":"10.3390\/molecules24040788","article-title":"Antioxidant Activity Evaluation of Dietary Flavonoid Hyperoside Using Saccharomyces Cerevisiae as a Model","volume":"24","author":"Gao","year":"2019","journal-title":"Molecules"},{"key":"B8","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1016\/j.acthis.2019.07.005","article-title":"Hyperoside protects against heart failure-induced liver fibrosis in rats","volume":"121","author":"Guo","year":"2019","journal-title":"Acta Histochem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.rvsc.2017.05.002","article-title":"Amelioration of CCl4-induced liver injury in rats by selenizing Astragalus polysaccharides: Role of proinflammatory cytokines, oxidative stress and hepatic stellate cells","volume":"114","author":"Hamid","year":"2017","journal-title":"Res. Vet. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3895","DOI":"10.18632\/oncotarget.13904","article-title":"Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis","volume":"8","author":"Ivanov","year":"2017","journal-title":"Oncotarget"},{"key":"B11","doi-asserted-by":"publisher","first-page":"7266","DOI":"10.3390\/molecules15107266","article-title":"The Nrf2 system as a potential target for the development of indirect antioxidants","volume":"15","author":"Jung","year":"2010","journal-title":"Molecules"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041663","article-title":"Protective role of morin, a flavonoid, against high glucose induced oxidative stress mediated apoptosis in primary rat hepatocytes","volume":"7","author":"Kapoor","year":"2012","journal-title":"PLoS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1096\/fj.10-171553","article-title":"Tyrosine phosphorylation controls nuclear export of Fyn, allowing Nrf2 activation of cytoprotective gene expression","volume":"25","author":"Kaspar","year":"2011","journal-title":"FASEB J."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/752506","article-title":"The effect of tert-butyl hydroperoxide-induced oxidative stress on lean and steatotic rat hepatocytes in vitro","volume":"2014","author":"Kucera","year":"2014","journal-title":"Oxid. Med. Cell Longev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2894","DOI":"10.1111\/bph.13569","article-title":"Butein provides neuroprotective and anti-neuroinflammatory effects through Nrf2\/ARE-dependent haem oxygenase 1 expression by activating the PI3K\/Akt pathway","volume":"173","author":"Lee","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1021\/jf0484780","article-title":"Antifungal activity of camptothecin, trifolin, and hyperoside isolated from Camptotheca acuminata","volume":"53","author":"Li","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1016\/j.bbamcr.2008.05.024","article-title":"Heterodimerization with small Maf proteins enhances nuclear retention of Nrf2 via masking the NESzip motif","volume":"1783","author":"Li","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"B18","doi-asserted-by":"publisher","first-page":"6192","DOI":"10.1128\/MCB.00681-09","article-title":"beta-TrCP-mediated ubiquitination and degradation of PHLPP1 are negatively regulated by Akt","volume":"29","author":"Li","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1136\/annrheumdis-2017-212658","article-title":"Tyrosine kinase Fyn promotes osteoarthritis by activating the beta-catenin pathway","volume":"77","author":"Li","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"6317","DOI":"10.1021\/acs.jafc.8b01875","article-title":"Attenuation of tert-Butyl Hydroperoxide (t-BHP)-Induced Oxidative Damage in HepG2 Cells by Tangeretin: Relevance of the Nrf2-ARE and MAPK Signaling Pathways","volume":"66","author":"Liang","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e3158","DOI":"10.1038\/cddis.2017.564","article-title":"SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity","volume":"8","author":"Liu","year":"2017","journal-title":"Cell Death Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B23","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.taap.2014.03.008","article-title":"Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt\/beta-catenin signaling","volume":"277","author":"Madankumar","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.fct.2016.01.001","article-title":"PHLPP2 down regulation influences nuclear Nrf2 stability via Akt-1\/Gsk3beta\/Fyn kinase axis in acetaminophen induced oxidative renal toxicity: Protection accorded by morin","volume":"89","author":"Mathur","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1161\/CIRCRESAHA.109.215020","article-title":"PHLPP-1 negatively regulates Akt activity and survival in the heart","volume":"107","author":"Miyamoto","year":"2010","journal-title":"Circ. Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.7150\/ijbs.5141","article-title":"Regulation of the SRC family kinases by Csk","volume":"8","author":"Okada","year":"2012","journal-title":"Int. J. Biol. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"41","DOI":"10.15430\/JCP.2016.21.1.41","article-title":"Hyperoside Induces Endogenous Antioxidant System to Alleviate Oxidative Stress","volume":"21","author":"Park","year":"2016","journal-title":"J. Cancer Prev."},{"key":"B28","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1080\/21691401.2019.1709851","article-title":"Protective effect of hyperoside against hydrogen peroxide-induced dysfunction and oxidative stress in osteoblastic MC3T3-E1 cells","volume":"48","author":"Qi","year":"2020","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jss.2017.12.030","article-title":"GYY4137 protects against myocardial ischemia\/reperfusion injury via activation of the PHLPP-1\/Akt\/Nrf2 signaling pathway in diabetic mice","volume":"225","author":"Qiu","year":"2018","journal-title":"J. Surg. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.redox.2018.05.002","article-title":"Antioxidant response elements: Discovery, classes, regulation and potential applications","volume":"17","author":"Raghunath","year":"2018","journal-title":"Redox Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/978-3-319-17121-0_55","article-title":"Photoreceptor Neuroprotection: Regulation of Akt Activation Through Serine\/Threonine Phosphatases, PHLPP and PHLPPL","volume":"854","author":"Rajala","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1007\/s10495-015-1160-y","article-title":"Morin mitigates acetaminophen-induced liver injury by potentiating Nrf2 regulated survival mechanism through molecular intervention in PHLPP2-Akt-Gsk3beta axis","volume":"20","author":"Rizvi","year":"2015","journal-title":"Apoptosis"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.1016\/j.transproceed.2019.04.066","article-title":"Hyperoside Attenuates Hepatic Ischemia-Reperfusion Injury by Suppressing Oxidative Stress and Inhibiting Apoptosis in Rats","volume":"51","author":"Shi","year":"2019","journal-title":"Transplant. Proc."},{"key":"B34","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1039\/B911410F","article-title":"SCOP\/PHLPP and its functional role in the brain","volume":"6","author":"Shimizu","year":"2010","journal-title":"Mol. Biosyst."},{"key":"B35","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.etap.2018.12.004","article-title":"Hepatoprotective benefits of vitamin C against perfluorooctane sulfonate-induced liver damage in mice through suppressing inflammatory reaction and ER stress","volume":"65","author":"Su","year":"2019","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"637","DOI":"10.14336\/AD.2018.0513","article-title":"The Anti-Inflammatory and Anti-Oxidant Mechanisms of the Keap1\/Nrf2\/ARE Signaling Pathway in Chronic Diseases","volume":"10","author":"Tu","year":"2019","journal-title":"Aging Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"3610","DOI":"10.1074\/jbc.R111.318675","article-title":"Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP): a new player in cell signaling","volume":"287","author":"Warfel","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1080\/10715762.2019.1623883","article-title":"Protective effect of hyperoside against renal ischemia-reperfusion injury via modulating mitochondrial fission, oxidative stress, and apoptosis","volume":"53","author":"Wu","year":"2019","journal-title":"Free Radic. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cbi.2016.01.004","article-title":"Protective effect of hyperoside against acetaminophen (APAP) induced liver injury through enhancement of APAP clearance","volume":"246","author":"Xie","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145183","article-title":"The Cytoprotective Effect of Hyperoside against Oxidative Stress Is Mediated by the Nrf2-ARE Signaling Pathway through GSK-3beta Inactivation","volume":"10","author":"Xing","year":"2015","journal-title":"PLoS One"},{"key":"B41","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1172\/JCI200317797","article-title":"The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice","volume":"112","author":"Xu","year":"2003","journal-title":"J. Clin. Invest."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098973","article-title":"Hyperoside, a flavonoid compound, inhibits proliferation and stimulates osteogenic differentiation of human osteosarcoma cells","volume":"9","author":"Zhang","year":"2014","journal-title":"PLoS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1002\/hep.30300","article-title":"DEAD Box Protein 5 Inhibits Liver Tumorigenesis by Stimulating Autophagy via Interaction with p62\/SQSTM1","volume":"69","author":"Zhang","year":"2019","journal-title":"Hepatology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.neuint.2012.01.003","article-title":"Involvement of activation of PI3K\/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death","volume":"60","author":"Zhu","year":"2012","journal-title":"Neurochem. Int."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.1111\/bph.13061","article-title":"MPTP-induced changes in hippocampal synaptic plasticity and memory are prevented by memantine through the BDNF-TrkB pathway","volume":"172","author":"Zhu","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.etp.2017.04.001","article-title":"The protective effect of hyperoside on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2","volume":"69","author":"Zou","year":"2017","journal-title":"Exp. Toxicol. Pathol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2020.01065\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T05:05:47Z","timestamp":1594962347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2020.01065\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,17]]},"references-count":46,"alternative-id":["10.3389\/fphar.2020.01065"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2020.01065","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,17]]},"article-number":"1065"}}