淫羊藿苷改善卵巢切除模型中的促性腺激素失调：治疗效果和机制
Icariin ameliorates gonadotropin dysregulation in an ovariectomy model: Therapeutic effect and mechanism.
摘要(中文译文)
微小RNA-7（miR-7）可抑制垂体促性腺激素，而淫羊藿苷（icariin）是淫羊藿（Epimedium brevicornu Maxim.）中的一种活性化合物，具有雌激素样特性。然而，淫羊藿苷是否通过miR-7调控促性腺激素尚不清楚。本研究探讨了淫羊藿苷是否通过miR-7调控促性腺激素，并阐明其潜在的分子机制。研究采用去卵巢小鼠模型、原代垂体细胞培养及分子技术相结合的综合方法。在体内实验中，去卵巢C57BL/6小鼠接受淫羊藿苷灌胃（20、40、80 mg·kg·d）、17β-雌二醇（20 μg·kg·d）或溶剂对照，持续28天。收集血清和垂体组织。在体外实验中，原代垂体细胞用淫羊藿苷（0.1至1000 nM）处理12小时。评估其对miR-7和促性腺激素的影响。机制研究采用模拟物/抑制剂、拮抗剂、小干扰RNA、生物信息学、荧光素酶报告基因实验、实时定量聚合酶链反应和蛋白质印迹法进行检测。中、高剂量淫羊藿苷可增加miR-7表达并逆转去卵巢引起的促性腺激素升高，其效果与17β-雌二醇相当。在原代垂体细胞中，淫羊藿苷（100 nM）同样上调miR-7并抑制促性腺激素。在机制上，我们的数据提示G蛋白偶联雌激素受体参与了淫羊藿苷的作用。丝裂原活化蛋白激酶激酶4（Map2k4）被鉴定为miR-7的靶点。Map2k4敲低减弱了淫羊藿苷对促黄体生成素β亚基的抑制作用，并阻断了淫羊藿苷诱导的c-Jun氨基末端激酶磷酸化抑制。淫羊藿苷通过膜雌激素受体介导的通路上调miR-7，进而直接靶向Map2k4，从而调控垂体促性腺激素，该机制参与促性腺激素亚基的调控，其下游通路的差异性参与揭示了其雌激素活性。
Abstract
MicroRNA-7 (miR-7) suppresses pituitary gonadotropins, while icariin, an active compound from Epimedium brevicornu Maxim., exhibits estrogen-like properties. However, whether icariin regulates gonadotropins via miR-7 remains unclear. This study investigated whether icariin regulates gonadotropins through miR-7 and elucidated the underlying molecular mechanisms. An integrated approach combining ovariectomized mouse model, primary pituitary cell cultures, and molecular techniques was employed. In vivo, ovariectomized C57BL/6 mice received intragastric icariin (20, 40, 80 mg·kg·d), 17β-estradiol (20 μg·kg·d), or vehicle for 28 days. Serum and pituitary tissues were collected. In vitro, primary pituitary cells were treated with icariin (0.1 to 1000 nM) for 12 h. Effects on miR-7 and gonadotropins were assessed. Mechanistic studies were examined using mimic/inhibitor, antagonists, small interfering RNAs, bioinformatics, luciferase reporter assay, quantitative real-time polymerase chain reaction and western blot. Icariin at medium and high doses increased miR-7 expression and reversed ovariectomy-induced gonadotropin elevation, with effects comparable to 17β-estradiol. In primary pituitary cells, icariin (100 nM) similarly up-regulated miR-7 and suppressed gonadotropins. Mechanistically, our data suggest the involvement of G protein-coupled estrogen receptor in icariin action. Mitogen-activated protein kinase kinase 4 (Map2k4) was identified as a miR-7 target. Map2k4 knockdown attenuated icariin's inhibition of luteinizing hormone beta subunit and blocked icariin-induced suppression of c-Jun N-terminal kinase phosphorylation. Icariin regulates pituitary gonadotropins via a membrane estrogen receptor-mediated pathway that upregulates miR-7 to directly target Map2k4, a mechanism contributing to gonadotropin subunit regulation, with differential involvement of downstream pathways revealing its estrogenic activity.
如何引用
AMA
Jing He, Aiming Chen, Bingyan Cai, Kai Huang, Zengjun Ji. Icariin ameliorates gonadotropin dysregulation in an ovariectomy model: Therapeutic effect and mechanism.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158255.
APA
Jing He, Aiming Chen, Bingyan Cai, Kai Huang, Zengjun Ji (2026). Icariin ameliorates gonadotropin dysregulation in an ovariectomy model: Therapeutic effect and mechanism.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158255
GB/T 7714
Jing He, Aiming Chen, Bingyan Cai, Kai Huang, Zengjun Ji. Icariin ameliorates gonadotropin dysregulation in an ovariectomy model: Therapeutic effect and mechanism.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158255.
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