The role of chrysanthemum phytochemicals in neural tube development: a narrative review of underlying mechanisms

Background 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. Purpose 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. Study Design 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. Results Chrysanthemum exhibits context-dependent duality in neural tube development. Beneficial effects are mediated by chlorogenic acid, Eri-7-Glc, and flavonoids via NF-κB, Nrf2/HO-1, and Wnt/β-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. Conclusion 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.