{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:36:41Z","timestamp":1791329801411,"version":"4.3.1"},"reference-count":33,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31501210"],"award-info":[{"award-number":["31501210"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine &amp; Pharmacotherapy"],"published-print":{"date-parts":[[2017,4]]},"DOI":"10.1016\/j.biopha.2017.01.066","type":"journal-article","created":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T16:50:17Z","timestamp":1485190217000},"page":"500-506","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":60,"special_numbering":"C","title":["Rutin attenuates H2O2-induced oxidation damage and apoptosis in Leydig cells by activating PI3K\/Akt signal pathways"],"prefix":"10.1016","volume":"88","author":[{"given":"Jianhua","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanzi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junping","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.biopha.2017.01.066_bib0005","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12958-015-0032-1","article-title":"A unique view on male infertility around the globe","volume":"13","author":"Agarwal","year":"2015","journal-title":"Reprod. Biol. Endocrinol. RB&E"},{"issue":"12","key":"10.1016\/j.biopha.2017.01.066_bib0010","doi-asserted-by":"crossref","first-page":"e1001356","DOI":"10.1371\/journal.pmed.1001356","article-title":"National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys","volume":"9","author":"Mascarenhas","year":"2012","journal-title":"PLoS Med."},{"issue":"2","key":"10.1016\/j.biopha.2017.01.066_bib0015","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.eururo.2012.04.048","article-title":"EAU guidelines on male infertility","volume":"62","author":"Jungwirth","year":"2012","journal-title":"Eur. Urol."},{"issue":"6","key":"10.1016\/j.biopha.2017.01.066_bib0020","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.fertnstert.2011.09.034","article-title":"Toward a pharmacogenetic approach to male infertility: polymorphism of follicle-stimulating hormone beta-subunit promoter","volume":"96","author":"Ferlin","year":"2011","journal-title":"Fertil. Steril."},{"issue":"6","key":"10.1016\/j.biopha.2017.01.066_bib0025","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.rbmo.2010.03.008","article-title":"A systematic review of the effect of oral antioxidants on male infertility","volume":"20","author":"Ross","year":"2010","journal-title":"Reprod. Biomed. Online"},{"issue":"22","key":"10.1016\/j.biopha.2017.01.066_bib0030","first-page":"4138","article-title":"Advances in causes and treatment of male infertility","volume":"19","author":"Ji-Mei","year":"2013","journal-title":"Med. Recapitulate"},{"issue":"3","key":"10.1016\/j.biopha.2017.01.066_bib0035","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.mrrev.2011.04.002","article-title":"Epigenetics, spermatogenesis and male infertility","volume":"727","author":"Rajender","year":"2011","journal-title":"Mutat. Res."},{"issue":"1","key":"10.1016\/j.biopha.2017.01.066_bib0040","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1365-2605.2011.01147.x","article-title":"Methylenetetrahydrofolate reductase C677T polymorphism and the risk of male infertility: a meta-analysis","volume":"35","author":"Wu","year":"2012","journal-title":"Int. J. Androl."},{"key":"10.1016\/j.biopha.2017.01.066_bib0045","first-page":"827941","article-title":"Coenzyme Q(1)(0), alpha-tocopherol, and oxidative stress could be important metabolic biomarkers of male infertility","volume":"2015","author":"Gvozdjakova","year":"2015","journal-title":"Dis. Mark."},{"issue":"1","key":"10.1016\/j.biopha.2017.01.066_bib0050","first-page":"136","article-title":"Effect of oxidative stress in male infertility","volume":"22","author":"Naher","year":"2013","journal-title":"Mymensingh Med. J. MMJ"},{"issue":"2","key":"10.1016\/j.biopha.2017.01.066_bib0055","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1439-0272.2009.01032.x","article-title":"Impact of body mass index on seminal oxidative stress","volume":"43","author":"Tunc","year":"2011","journal-title":"Andrologia"},{"issue":"1","key":"10.1016\/j.biopha.2017.01.066_bib0060","doi-asserted-by":"crossref","first-page":"60","DOI":"10.5173\/ceju.2013.01.art19","article-title":"The role of oxidative stress and antioxidants in male fertility","volume":"66","author":"Walczak-Jedrzejowska","year":"2013","journal-title":"Cent. Eur. J. Urol."},{"issue":"1","key":"10.1016\/j.biopha.2017.01.066_bib0065","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12958-016-0165-x","article-title":"Involvement of oxidative stress in tri-ortho-cresyl phosphate-induced autophagy of mouse Leydig TM3 cells in vitro","volume":"14","author":"Liu","year":"2016","journal-title":"Reprod. Biol. Endocrinol. RB&E"},{"issue":"3","key":"10.1016\/j.biopha.2017.01.066_bib0070","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/humupd\/dmv008","article-title":"Morphological and functional maturation of Leydig cells: from rodent models to primates","volume":"21","author":"Teerds","year":"2015","journal-title":"Hum. Reprod. Update"},{"issue":"3","key":"10.1016\/j.biopha.2017.01.066_bib0075","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0731-7085(93)80199-B","article-title":"Simultaneous isolation of Rutin and Esculin from plant material and drugs using solid-phase extraction","volume":"11","author":"Buszewski","year":"1993","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"3","key":"10.1016\/j.biopha.2017.01.066_bib0080","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.jep.2013.10.036","article-title":"A review on plant-based rutin extraction methods and its pharmacological activities","volume":"150","author":"Chua","year":"2013","journal-title":"J. Ethnopharmacol."},{"issue":"5","key":"10.1016\/j.biopha.2017.01.066_bib0085","first-page":"2304","article-title":"Role of oxidative stress in male reproductive dysfunctions with reference to phthalate compounds","volume":"12","author":"Sedha","year":"2015","journal-title":"Urol. J."},{"issue":"4","key":"10.1016\/j.biopha.2017.01.066_bib0090","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1210\/jcem-59-4-756","article-title":"Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men","volume":"59","author":"Neaves","year":"1984","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"7","key":"10.1016\/j.biopha.2017.01.066_bib0095","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3109\/02713683.2015.1082186","article-title":"Protective effect of rutin against H2O2-induced oxidative stress and apoptosis in human lens epithelial cells","volume":"41","author":"Zhou","year":"2016","journal-title":"Curr. Eye Res."},{"issue":"1","key":"10.1016\/j.biopha.2017.01.066_bib0100","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cbi.2006.03.004","article-title":"Membrane cholesterol contents influence the protective effects of quercetin and rutin in erythrocytes damaged by oxidative stress","volume":"161","author":"Lopez-Revuelta","year":"2006","journal-title":"Chem. Biol. Interact."},{"issue":"1\u20132","key":"10.1016\/j.biopha.2017.01.066_bib0105","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.tox.2007.02.006","article-title":"Investigations of protective effects of the flavonoids quercetin and rutin on stress resistance in the model organism Caenorhabditis elegans","volume":"234","author":"Kampkotter","year":"2007","journal-title":"Toxicology"},{"issue":"6","key":"10.1016\/j.biopha.2017.01.066_bib0110","first-page":"749","article-title":"Lipid peroxidation and the thiobarbituric acid assay: standardization of the assay when using saturated and unsaturated fatty acids","volume":"37","author":"Rael","year":"2004","journal-title":"J. Biochem. Mol. Biol."},{"issue":"4","key":"10.1016\/j.biopha.2017.01.066_bib0115","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/15368370601054787","article-title":"In vivo effects of ELF MFs on collagen synthesis, free radical processes, natural antioxidant system, respiratory burst system, immune system activities, and electrolytes in the skin, plasma, spleen, lung, kidney, and brain tissues","volume":"25","author":"Seyhan","year":"2006","journal-title":"Electromagn. Biol. Med."},{"issue":"10","key":"10.1016\/j.biopha.2017.01.066_bib0120","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/S0891-5849(00)00408-1","article-title":"Role of glutathione S-transferases in oxidative stress-induced male germ cell apoptosis","volume":"29","author":"Rao","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.biopha.2017.01.066_bib0125","first-page":"3180","article-title":"Lutein and zeaxanthin supplementation reduces H2O2-induced oxidative damage in human lens epithelial cells","volume":"17","author":"Gao","year":"2011","journal-title":"Mol. Vis."},{"issue":"1\u20133","key":"10.1016\/j.biopha.2017.01.066_bib0130","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ejphar.2009.11.028","article-title":"Rutin inhibits hydrogen peroxide-induced apoptosis through regulating reactive oxygen species mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells","volume":"628","author":"Gong","year":"2010","journal-title":"Eur. J. Pharmacol."},{"issue":"Pt B","key":"10.1016\/j.biopha.2017.01.066_bib0135","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jsbmb.2014.09.016","article-title":"Basic fibroblast growth factor promotes stem Leydig cell development and inhibits LH-stimulated androgen production by regulating microRNA expression","volume":"144","author":"Liu","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"issue":"4","key":"10.1016\/j.biopha.2017.01.066_bib0140","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/j.1745-7262.2008.00414.x","article-title":"Cytoprotective effects of Morinda officinalis against hydrogen peroxide-induced oxidative stress in Leydig TM3 cells","volume":"10","author":"Chang","year":"2008","journal-title":"Asian J. Androl."},{"issue":"2","key":"10.1016\/j.biopha.2017.01.066_bib0145","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1210\/en.2002-220710","article-title":"Sertoli and germ cell development in hypogonadal (hpg) mice expressing transgenic follicle-stimulating hormone alone or in combination with testosterone","volume":"144","author":"Haywood","year":"2003","journal-title":"Endocrinology"},{"issue":"1","key":"10.1016\/j.biopha.2017.01.066_bib0150","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10495-005-3087-1","article-title":"H2O2 at physiological concentrations modulates Leydig cell function inducing oxidative stress and apoptosis","volume":"11","author":"Gautam","year":"2006","journal-title":"Apoptosis"},{"issue":"7","key":"10.1016\/j.biopha.2017.01.066_bib0155","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/j.fct.2009.03.044","article-title":"Rutin from Lonicera japonica inhibits myocardial ischemia\/reperfusion-induced apoptosis in vivo and protects H9c2 cells against hydrogen peroxide-mediated injury via ERK1\/2 and PI3K\/Akt signals in vitro","volume":"47","author":"Jeong","year":"2009","journal-title":"Food Chem. Toxicol."},{"issue":"4","key":"10.1016\/j.biopha.2017.01.066_bib0160","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.cell.2014.02.055","article-title":"The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C. elegans","volume":"157","author":"Yee","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.biopha.2017.01.066_bib0165","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.biocel.2015.11.018","article-title":"Dehydroepiandrosterone ameliorates H2O2-induced Leydig cells oxidation damage and apoptosis through inhibition of ROS production and activation of PI3K\/Akt pathways","volume":"70","author":"Ding","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."}],"container-title":["Biomedicine &amp; Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332216327779?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332216327779?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T12:14:30Z","timestamp":1778242470000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0753332216327779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4]]},"references-count":33,"alternative-id":["S0753332216327779"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2017.01.066","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2017,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Rutin attenuates H2O2-induced oxidation damage and apoptosis in Leydig cells by activating PI3K\/Akt signal pathways","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2017.01.066","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}]}}