{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:13:11Z","timestamp":1779343991300,"version":"3.51.4"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004480","name":"Natural Science Foundation of Shanxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004480","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neural tube defects (NTDs) have long been attributed to genetic and hereditary factors, but emerging evidence highlights the significant role of pharmacological and environmental agents. The global integration of traditional medicine systems, including Traditional Chinese Medicine, has introduced diverse bioactive compounds with potential to influence neurodevelopmental processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This narrative review aims to comprehensively summarize and critically evaluate the current evidence on the bioactivity of chrysanthemum (Chrysanthemum morifolium and related species) extracts and their constituents in the context of neural tube development, with a focus on elucidating underlying molecular mechanisms to inform potential therapeutic applications and toxicological risks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>We performed a narrative review of chrysanthemum compounds in neural development, focusing on neural tube formation. PubMed, Web of Science, and ScienceDirect were searched from January 1985 to March 2026 using terms related to chrysanthemum (e.g., Chrysanthemum, extract, phytochemicals), neurodevelopmental outcomes (neural tube defects, neurulation), and mechanisms (inflammation, oxidative stress, apoptosis). Reference lists were manually screened. No formal bias assessment or quantitative synthesis was performed; instead, findings were qualitatively synthesized to present the dual role of chrysanthemum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Chrysanthemum exhibits context-dependent duality in neural tube development. Beneficial effects are mediated by chlorogenic acid, Eri-7-Glc, and flavonoids via NF-\u03baB, Nrf2\/HO-1, and Wnt\/\u03b2-catenin pathways, reducing oxidative stress and supporting neurulation. Conversely, natural pyrethrins induce oxidative stress and DNA damage; high-dose flavonoids act as pro-oxidants and endocrine disruptors, and readily cross the placenta, raising fetal concerns. The convergence on caspase-8 suggests a double-edged sword effect. However, direct evidence in mammalian embryos, pregnancy pharmacokinetics, and dose-response data are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Chrysanthemum shows context-dependent dual effects on neurodevelopment, underscoring the need for rigorous mechanistic and toxicological studies to guide its safe use, particularly in pregnancy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1804458","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:45:37Z","timestamp":1779342337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of chrysanthemum phytochemicals in neural tube development: a narrative review of underlying mechanisms"],"prefix":"10.3389","volume":"14","author":[{"given":"Jiaojiao","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Biological and Food Engineering, Lyuliang University","place":["Lvliang, Shanxi, China"]},{"name":"Department of Neurology, The First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yage","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajing","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery and Liver Transplant Center, The First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanxi Second People\u2019s Hospital","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinglian","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit, Lvliang People\u2019s Hospital","place":["Lvliang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Department of Hepatobiliary Surgery and Liver Transplant Center, The First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Department of Intensive Care Unit, Lvliang People\u2019s Hospital","place":["Lvliang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1002\/bdra.20195","article-title":"Maternal influenza during pregnancy and risk of congenital abnormalities in offspring","volume":"73","author":"Acs","year":"2005","journal-title":"Birth Defects Res. 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