Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Genistein alleviates skin inflammation in atopic dermatitis by inhibiting mast cell degranulation through toll-like receptor.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Du Hongfen, Wang Na, Wang Chao, Luo Shiqiong, Ji Xiaolan, Li Rui, Wang Yuejin, Lai Xiurong, Li Henan, Ding Yuanyuan, An Hongli
Аннотация
BACKGROUND: Atopic dermatitis (AD) is a mast cell-driven inflammatory disorder with limited treatment options. This study aimed to explore the therapeutic potential and mechanism of the natural compound genistein against AD.
OBJECTIVE: We investigated the efficacy of genistein treatment on atopic dermatitis and the underlying immune mechanism of cytokine release by mast cell.
METHODS: We employed an MC903-induced murine AD model and LAD2 human mast cells. Evaluations included behavioral assessment, serological, histopathology, mast cell degranulation assays, RNA-seq, molecular docking, SPR, pathway analysis, and functional validation via TRAM mutagenesis and rescue experiments.
RESULTS: Genistein alleviated ear thickening and scratching behavior, reduced the spleen-to-body weight ratio, decreased serum levels of IgE and IL-4 in the AD model, and significantly suppressed mast cell degranulation. Transcriptomic analysis provided evidence that genistein alleviated AD symptoms through the mast cell and TLR signaling pathways. Genistein markedly inhibited the occurrence of systemic allergic reactions and local inflammation; suppressed the release of β-hexosaminidase, histamine, MCP-1, tryptase, TNF-α, and calcium in LAD2 cells. Mechanistically, genistein directly binding to the D127 and R226 sites of TRAM with high affinity (Kᴅ = 0.491 µM), played as the inhibitor of TRAM, a key molecule in the TLR signaling pathway in mast cells, thereby suppressing activation of the NF-κB signaling pathway.
CONCLUSION: Our findings demonstrate that genistein alleviates AD by specifically targeting the D127 and R226 sites of TRAM to inhibit mast cell activation via the PLCγ1-IKKβ-NF-κB pathway. This work elucidates a novel pharmacological mechanism of a natural compound and identifies TRAM as a promising new therapeutic target for allergic inflammatory diseases, highlighting the value of natural products in developing targeted immunomodulatory therapies.
OBJECTIVE: We investigated the efficacy of genistein treatment on atopic dermatitis and the underlying immune mechanism of cytokine release by mast cell.
METHODS: We employed an MC903-induced murine AD model and LAD2 human mast cells. Evaluations included behavioral assessment, serological, histopathology, mast cell degranulation assays, RNA-seq, molecular docking, SPR, pathway analysis, and functional validation via TRAM mutagenesis and rescue experiments.
RESULTS: Genistein alleviated ear thickening and scratching behavior, reduced the spleen-to-body weight ratio, decreased serum levels of IgE and IL-4 in the AD model, and significantly suppressed mast cell degranulation. Transcriptomic analysis provided evidence that genistein alleviated AD symptoms through the mast cell and TLR signaling pathways. Genistein markedly inhibited the occurrence of systemic allergic reactions and local inflammation; suppressed the release of β-hexosaminidase, histamine, MCP-1, tryptase, TNF-α, and calcium in LAD2 cells. Mechanistically, genistein directly binding to the D127 and R226 sites of TRAM with high affinity (Kᴅ = 0.491 µM), played as the inhibitor of TRAM, a key molecule in the TLR signaling pathway in mast cells, thereby suppressing activation of the NF-κB signaling pathway.
CONCLUSION: Our findings demonstrate that genistein alleviates AD by specifically targeting the D127 and R226 sites of TRAM to inhibit mast cell activation via the PLCγ1-IKKβ-NF-κB pathway. This work elucidates a novel pharmacological mechanism of a natural compound and identifies TRAM as a promising new therapeutic target for allergic inflammatory diseases, highlighting the value of natural products in developing targeted immunomodulatory therapies.