{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:26:01Z","timestamp":1790706361083,"version":"4.1.0"},"reference-count":27,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The study aimed to investigate the role of luteolin in alleviating POF and its underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>POF model was established in rats by intraperitoneal injection of 100\u00a0mg\/kg cyclophosphamide. Then, rats in the treatment group received intragastric administration of with luteolin at doses of 25\u00a0mg\/kg, 50\u00a0mg\/kg and 100\u00a0mg\/kg, respectively. Rats in POF model group were administered the same volume of saline intragastrically. The concentrations of E2, FSH, AMH, P, LH, SOD and MDA in serum were quantified using ELISA kits. H&amp;E and TUNEL staining were employed to assess pathological alterations and apoptosis. The cellular localizations of 4-HNE, 8-OHdG and NTY were detected by immunohistochemistry staining. The PharmMapper database and UbiBrowser prediction were used for the prediction of luteolin interaction with RNF8\/HDAC2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Luteolin treatment significantly increased serum levels of estradiol (E2) (P &lt; 0.01) and anti-M\u00fcllerian hormone (AMH) (P &lt; 0.01) while reducing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels (P &lt; 0.05), restoring ovarian function. Additionally, luteolin could significantly improve ovarian tissue morphology and reduce apoptosis. ELISA kit results indicated luteolin significantly reduced the levels of SOD and MDA. Immunohistochemical staining results revealed a significant decrease in the expressions of 4-HNE, 8-OHdG and NTY in luteolin treatment group. Combining The PharmMapper database and UbiBrowser prediction, we found luteolin could bind RNF8 and inhibit HDAC2 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Luteolin could mitigate cyclophosphamide-induced ovarian senescence, with its molecular mechanisms involving the regulation of RNF8\/HDAC2 signaling axis and the inhibition of oxidative stress.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09603271251350802","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T18:02:58Z","timestamp":1750788178000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Luteolin alleviates cyclophosphamide-induced premature ovarian failure in rats by regulating RNF8\/HDAC2"],"prefix":"10.1177","volume":"44","author":[{"given":"Ye","family":"Pan","sequence":"first","affiliation":[{"name":"Guizhou Provincial People\u2019s Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zeng","sequence":"additional","affiliation":[{"name":"Guizhou Provincial People\u2019s Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Rong","sequence":"additional","affiliation":[{"name":"Guizhou Provincial People\u2019s Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2210-2165","authenticated-orcid":false,"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"Guizhou University of Traditional Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"issue":"3","key":"e_1_3_7_2_2","first-page":"492","article-title":"Apoptotic mechanism of premature ovarian failure and rescue effect of Traditional Chinese Medicine: a review","volume":"41","author":"Cai L","year":"2021","unstructured":"Cai L, Zong DK, Tong GQ, et al. Apoptotic mechanism of premature ovarian failure and rescue effect of Traditional Chinese Medicine: a review. J Tradit Chin Med 2021; 41(3): 492\u2013498.","journal-title":"J Tradit Chin Med"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03779-7"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-018-0203-7"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12124042"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2016.09.046"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-018-00569-x"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112542"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.112842"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/156800908786241050"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153437"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2018.1539607"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2022.12.018"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03253-8"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-018-0409-9"},{"issue":"5","key":"e_1_3_7_16_2","first-page":"1016","article-title":"Effect of dexpanthenol on cyclophosphamide-induced ovarian toxicity: a histological and molecular study in rats","volume":"48","author":"Mehmet E","year":"2024","unstructured":"Mehmet E, Ate\u015f MB, Ba\u015f-Ekici H, et al. Effect of dexpanthenol on cyclophosphamide-induced ovarian toxicity: a histological and molecular study in rats. Reprod Biomed Online 2024; 48(5): 1016\u20131025.","journal-title":"Reprod Biomed Online"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01747-5"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03733-5"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1289"},{"issue":"6","key":"e_1_3_7_20_2","first-page":"2686","article-title":"Ubiquitin specific peptidase 38 promotes the progression of gastric cancer through upregulation of fatty acid synthase","volume":"12","author":"Zheng Z","year":"2022","unstructured":"Zheng Z, Shang Y, Xu R, et al. Ubiquitin specific peptidase 38 promotes the progression of gastric cancer through upregulation of fatty acid synthase. Am J Cancer Res 2022; 12(6): 2686\u20132696.","journal-title":"Am J Cancer Res"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab962"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.854215"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17264"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100380050088"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI120401"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.08.009"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02880-w"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.112208"}],"container-title":["Human &amp; Experimental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09603271251350802","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/09603271251350802","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09603271251350802","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:49:25Z","timestamp":1777448965000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/09603271251350802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":27,"alternative-id":["10.1177\/09603271251350802"],"URL":"https:\/\/doi.org\/10.1177\/09603271251350802","relation":{},"ISSN":["0960-3271","1477-0903"],"issn-type":[{"value":"0960-3271","type":"print"},{"value":"1477-0903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,24]]},"article-number":"09603271251350802"}}