{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:00:19Z","timestamp":1793746819151,"version":"4.6.1"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The ovary is highly sensitive to radiation, and patients receiving radiotherapy are at significant risk of premature ovarian failure (POF). This study aimed to explore the radioprotective effect of honokiol (HKL) on ionizing radiation (IR)\u2010induced POF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female C57BL\/6 mice were administered intraperitoneally with vehicle or HKL once daily for 7 days. On day 7, the mice in the IR and HKL+IR groups were exposed to 3.2\u00a0Gy whole\u2010body radiation for one hour after the intraperitoneal injection and sacrificed 12 or 72\u00a0h after radiation exposure. The gonadosomatic index (GSI) was calculated. Blood samples were collected for enzyme\u2010linked immunosorbent assay (ELISA). Ovaries were harvested for histological examination, immunohistochemistry, immunofluorescence, TUNEL, western blot, and qPCR. The fertility assessment was evaluated by calculating live offspring number.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The optimum dose of HKL against radiation was 10\u00a0mg\/kg via intraperitoneal injection. POF was induced 72\u00a0h after irradiation with significantly downregulated proliferating cell nuclear antigen (PCNA). The numbers of primordial and preantral follicles decreased significantly after irradiation (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.001), whereas the number of atretic follicles increased (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.001). The serum levels of estradiol (E\n                      <jats:sub>2<\/jats:sub>\n                      ) and anti\u2010M\u00fcllerian hormone (AMH) decreased to 50% of the control group after irradiation (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). Moreover, the GSI after irradiation was 27% lower than in the control group (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). The number of offspring in the IR group dropped by 50% compared with the control group (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). HKL pretreatment protected the animals\u2019 fertility, GSI, PCNA, serum levels of E\n                      <jats:sub>2<\/jats:sub>\n                      and AMH, and the number of primordial and preantral follicles. Significant upregulation of apoptosis\u2010related proteins such as Pho\u2010P53, Bax, Cyto C, C\u2010caspase\u20103, C\u2010PARP, and pyroptosis\u2010related proteins such as Pho\u2010NF\u2010\u03baB p65, NLRP3, caspase\u20101, IL\u20101\u03b2, and IL\u201018 was observed after irradiation, while the expression of Bcl\u20102 decreased. HKL pretreatment prevented these changes. After irradiation, malondialdehyde (MDA), Nrf2, and HO\u20101 were upregulated. HKL treatment activated the expression of Nrf2 and HO\u20101 and promoted the nucleus translocation of Nrf2. Furthermore, HKL did not affect ovarian reserves under physiological conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HKL ameliorated IR\u2010induced POF by inhibiting apoptosis and pyroptosis by enhancing Nrf2 expression and translocation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.13769","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T05:38:15Z","timestamp":1693460295000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Honokiol alleviates radiation\u2010induced premature ovarian failure via enhancing Nrf2"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-3799","authenticated-orcid":false,"given":"Lingli","family":"Xin","sequence":"first","affiliation":[{"name":"Department 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