{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:09:12Z","timestamp":1790086152199,"version":"4.0.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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. Physiol."],"abstract":"\n Introduction<\/jats:title>\n To investigate the protective effects of kaempferol (KPF) against gestational diabetes mellitus (GDM) and elucidate its underlying molecular mechanisms.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A GDM rat model was established to assess metabolic abnormalities, inflammation, oxidative stress, and placental injury following KPF treatment.\n In vitro<\/jats:italic>\n , high glucose (HG)-stimulated HTR-8\/SVneo trophoblast cells were used to investigate the protective mechanisms of KPF. Mitochondrial dysfunction, lipid peroxidation, ferroptosis-related alterations, and AIM2 inflammasome activation were evaluated. STAT3 knockdown and AIM2 overexpression were further performed to determine their roles in HG-induced trophoblast injury.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n KPF significantly improved glucose and lipid metabolism, reduced inflammatory cytokine levels, alleviated placental injury, and decreased oxidative stress in GDM rats. In HG-stimulated trophoblasts, KPF attenuated mitochondrial dysfunction, lipid peroxidation, and ferroptosis-related alterations by restoring GPX4 and SLC7A11 expression and inhibiting AIM2 inflammasome activation. Mechanistically, KPF suppressed STAT3 activation, while STAT3 knockdown reduced STAT1\/IRF1 activation and AIM2 expression under hyperglycemic conditions. AIM2 overexpression aggravated ferroptosis-related changes and inflammatory responses.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n KPF alleviates GDM-associated placental dysfunction by modulating STAT3-associated signaling and AIM2 inflammasome activation, thereby reducing ferroptosis-related injury and inflammatory activation in trophoblasts. These findings provide new insights into the mechanisms of GDM and support KPF as a potential therapeutic candidate.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphys.2026.1857741","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:55:30Z","timestamp":1790085330000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Kaempferol ameliorates gestational diabetes mellitus by regulating STAT3-associated AIM2 inflammasome activation and ferroptotic injury in trophoblasts"],"prefix":"10.3389","volume":"17","author":[{"given":"Ronghui","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Yantaishan Hospital","place":["Yantai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanjie","family":"Yi","sequence":"additional","affiliation":[{"name":"Institute of Literature in Chinese Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1530\/joe-15-0424","article-title":"Gestational diabetic transcriptomic profiling of microdissected human trophoblast","volume":"229","author":"Bari","year":"2016","journal-title":"J. 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