{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:41:34Z","timestamp":1787719294640,"version":"build-2784847793"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"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. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Recently, central precocious puberty (CPP) is becoming a major public health concern worldwide due to its enhanced prevalence. Traditional Chinese medicine (TCM) compounds offer unique therapeutic advantages for treating this condition, and luteolin, a bioactive monomer compound commonly found in these herbs, has drawn increasing attention. However, the therapeutic effects of luteolin on CPP development remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A danazol-induced CPP model was established in Sprague-Dawley rats to explore the potential therapeutic effects of luteolin. Sexual development indicators, organ coefficients, gonadal histopathology, and sex hormone levels were evaluated to assess treatment outcomes. Additionally, a comprehensive approach involving network pharmacology, molecular docking, and transcriptomic analyses was used to identify luteolin-related signaling pathways and target proteins involved in CPP treatment. Finally, we carried out enzyme-linked immunosorbent assay (ELISA) and reverse transcription- quantitative polymerase chain reaction (RT-qPCR) for finding validation and exploring the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the danazol-induced CPP model, luteolin treatment significantly decreased the abundances of Estradiol (E2), luteinizing hormone serum, and follicle-stimulating hormone in sera; reduced organ coefficients and ovarian and uterine wet weights; and delayed vaginal opening. Network pharmacology and transcriptomic analyses revealed that luteolin exerted its therapeutic effects mainly by modulating immune and inflammatory pathways, including the tumor necrosis factor-\u03b1, Toll-like receptor, and IL-17 signaling pathways. Molecular docking demonstrated stable binding of luteolin to key targets such as Cxcl10, Cxcl11, Stat1, Tlr3, and Irf7. ELISA results confirmed that luteolin inhibited pro-inflammatory cytokines while promoting anti-inflammatory factors in the CPP model. Furthermore, RT-qPCR analysis revealed that luteolin enhanced Irf7 and Stat1 expression within the Toll-like receptor pathway, mainly by upregulating Tlr3, thereby enhancing the abundances of downstream effector molecules Cxcl10 and Cxcl11.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study is the first to determine that luteolin ameliorates CPP via\u00a0the Toll-like receptor signaling pathway. These findings enhance our understanding of luteolin\u2019s pharmacological actions and support its potential role in CPP treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1666932","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T05:38:29Z","timestamp":1757655509000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Therapeutic potential of luteolin in central precocious puberty: insights from a danazol-induced rat 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