{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:32:39Z","timestamp":1792801959792,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018916","name":"Suzhou Municipal Health Commission","doi-asserted-by":"publisher","award":["SZWJ2023a082"],"award-info":[{"award-number":["SZWJ2023a082"]}],"id":[{"id":"10.13039\/100018916","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Adverse pregnancy outcomes represented by recurrent spontaneous abortion remain a global clinical problem, with excessive oxidative stress-induced trophoblast dysfunction as its well-recognized core pathological mechanism. Quercetin is a natural flavonoid with strong antioxidant and cytoprotective effects, but its protective effect and molecular mechanism on human trophoblasts under oxidative stress remain unclear. This study investigated whether quercetin alleviates H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced oxidative damage in HTR-8\/SVneo trophoblasts via regulating the EGFR\/PI3K\/AKT-NRF2\/HO-1 axis. We performed CCK-8 assay, flow cytometry, migration assays, RT-qPCR, Western blot, molecular docking and network pharmacology. The results showed that quercetin pretreatment significantly improved the viability of injured trophoblasts, inhibited apoptosis, alleviated G0\/G1 phase arrest, restored migration, maintained redox homeostasis, and upregulated NRF2 and HO-1. Mechanistically, computational predictions suggest that quercetin may interact with EGFR and enhance EGFR\/PI3K\/AKT phosphorylation; inhibition of EGFR or NRF2 significantly reversed the protective effects of quercetin. In conclusion, quercetin protects trophoblasts against oxidative stress injury via activating the EGFR\/PI3K\/AKT-NRF2\/HO-1 axis, providing a novel mechanism and potential intervention for adverse pregnancy outcomes.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1887502","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T05:33:59Z","timestamp":1785994439000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Quercetin protects HTR-8\/SVneo human trophoblast cells against oxidative stress injury via activating EGFR\/PI3K\/AKT-NRF2\/HO-1 signaling axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Lujia","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Reproductive Medicine and Embryo, Wanbei Coal Electric Group General Hospital","place":["Suzhou, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixian","family":"Ding","sequence":"additional","affiliation":[{"name":"Central Laboratory, Wanbei Coal Electric Group General Hospital","place":["Suzhou, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yina","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Reproductive Medicine and Embryo, Wanbei Coal Electric Group General Hospital","place":["Suzhou, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Wanbei Coal Electric Group General Hospital","place":["Suzhou, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Tao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Reproductive Medicine and Embryo, Wanbei Coal Electric Group General Hospital","place":["Suzhou, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Reproductive Medicine and Embryo, Wanbei Coal Electric Group General Hospital","place":["Suzhou, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Tang","sequence":"additional","affiliation":[{"name":"Central Laboratory, Wanbei Coal Electric Group General Hospital","place":["Suzhou, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"102726","DOI":"10.1016\/j.redox.2023.102726","article-title":"The keap1-nrf2 pathway: targets for therapy and role in cancer","volume":"63","author":"Adinolfi","year":"2023","journal-title":"Redox Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.3390\/biom15010151","article-title":"The role of quercetin, a flavonoid in the management of pathogenesis through regulation of oxidative stress, inflammation, and biological activities","volume":"15","author":"Alharbi","year":"2025","journal-title":"Biomolecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.placenta.2021.06.008","article-title":"Aopps induce htr-8\/svneo cell apoptosis by downregulating the nrf-2\/are\/ho-1 anti-oxidative pathway: potential implications for preeclampsia","volume":"112","author":"Chen","year":"2021","journal-title":"Placenta"},{"key":"B4","doi-asserted-by":"publisher","first-page":"4532","DOI":"10.3390\/ijms25084532","article-title":"The pathophysiological, genetic, and hormonal changes in preeclampsia: a systematic review of the molecular mechanisms","volume":"25","author":"Chiang","year":"2024","journal-title":"Int. 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