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淫羊藿素通过内质网-磷脂酰肌醇-3-激酶/蛋白激酶B通路减轻帕金森病小鼠的运动功能障碍和骨质疏松。

Icaritin alleviates motor impairment and osteoporosis in Parkinson's disease mice via the ER-PI3K/Akt pathway.

作者信息

Lin Xianmei, Zhou Xinyu, Liu Xingman, Xia Lingqiong, Cai Jing, Huang Nanqu, Luo Yong, Wu Weidong

机构信息

Guizhou University of Traditional Chinese Medicine, Guiyang, 550000, Guizhou, China.

Department of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, 56300, Guizhou, China.

出版信息

Sci Rep. 2025 Jan 25;15(1):3190. doi: 10.1038/s41598-025-87429-2.

Abstract

This study investigates the role of flavonoid Icaritin (ICT) in estrogen-deficient ovariectomized (OVX) female mice by activating the Estrogen receptor (ER)/ Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, potentially delaying Parkinson's disease (PD) progression post-castration. Seventy-five 8-week-old C57BL/6J female mice underwent ovariectomy, followed by MPTP (20 mg/kg) injection for 7 days. ICT (20 mg/kg) was administered for 14 days, and motor function was assessed using various behavioral tests. Serum estradiol, FSH, LH levels were measured by ELISA, and the expression of PI3K/Akt signaling and apoptosis proteins was analyzed by Western blot. Bone mineral density was assessed via dual-energy X-ray absorption, and histology of the uterus and femur was performed. Results showed that ICT alleviated MPTP-induced motor deficits, increased serum estradiol, and improved uterine atrophy. At the molecular level, ICT activated the PI3K/Akt pathway, reduced apoptosis, and mitigated PD symptoms and osteoporosis induced by OVX. These findings suggest ICT may offer therapeutic potential in managing OVX-induced motor dysfunction and PD.

摘要

本研究通过激活雌激素受体(ER)/磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路,探讨黄酮类化合物淫羊藿素(ICT)在雌激素缺乏的去卵巢(OVX)雌性小鼠中的作用,这可能会延缓去势后帕金森病(PD)的进展。75只8周龄的C57BL/6J雌性小鼠接受去卵巢手术,随后注射MPTP(20mg/kg),持续7天。给予ICT(20mg/kg)14天,并用各种行为测试评估运动功能。通过酶联免疫吸附测定法(ELISA)检测血清雌二醇、卵泡刺激素(FSH)、黄体生成素(LH)水平,并用蛋白质免疫印迹法分析PI3K/Akt信号通路和凋亡蛋白的表达。通过双能X线吸收法评估骨密度,并对子宫和股骨进行组织学检查。结果表明,ICT减轻了MPTP诱导的运动缺陷,增加了血清雌二醇,并改善了子宫萎缩。在分子水平上,ICT激活了PI3K/Akt通路,减少了细胞凋亡,并减轻了OVX诱导的PD症状和骨质疏松症。这些发现表明,ICT在治疗OVX诱导的运动功能障碍和PD方面可能具有治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6a6/11762315/e10e78856989/41598_2025_87429_Fig1_HTML.jpg

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