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

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) progress...

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Main Authors: Xianmei Lin, Xinyu Zhou, Xingman Liu, Lingqiong Xia, Jing Cai, Nanqu Huang, Yong Luo, Weidong Wu
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87429-2
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author Xianmei Lin
Xinyu Zhou
Xingman Liu
Lingqiong Xia
Jing Cai
Nanqu Huang
Yong Luo
Weidong Wu
author_facet Xianmei Lin
Xinyu Zhou
Xingman Liu
Lingqiong Xia
Jing Cai
Nanqu Huang
Yong Luo
Weidong Wu
author_sort Xianmei Lin
collection DOAJ
description 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.
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spelling doaj-art-6d4d7f0ee8dd4340ab3ae2fe6b5a29392025-01-26T12:30:39ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-87429-2Icaritin alleviates motor impairment and osteoporosis in Parkinson’s disease mice via the ER-PI3K/Akt pathwayXianmei Lin0Xinyu Zhou1Xingman Liu2Lingqiong Xia3Jing Cai4Nanqu Huang5Yong Luo6Weidong Wu7Guizhou University of Traditional Chinese MedicineDepartment of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi)Guizhou University of Traditional Chinese MedicineDepartment of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi)Department of Neurology, First Affiliated Hospital, Guizhou University of Traditional Chinese MedicineDepartment of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi)Department of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi)Guizhou University of Traditional Chinese MedicineAbstract 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.https://doi.org/10.1038/s41598-025-87429-2Parkinson’s diseaseIcaritinEstrogen receptorPostmenopausal womenPhosphatidylinositol 3-kinaseProtein kinase B
spellingShingle Xianmei Lin
Xinyu Zhou
Xingman Liu
Lingqiong Xia
Jing Cai
Nanqu Huang
Yong Luo
Weidong Wu
Icaritin alleviates motor impairment and osteoporosis in Parkinson’s disease mice via the ER-PI3K/Akt pathway
Scientific Reports
Parkinson’s disease
Icaritin
Estrogen receptor
Postmenopausal women
Phosphatidylinositol 3-kinase
Protein kinase B
title Icaritin alleviates motor impairment and osteoporosis in Parkinson’s disease mice via the ER-PI3K/Akt pathway
title_full Icaritin alleviates motor impairment and osteoporosis in Parkinson’s disease mice via the ER-PI3K/Akt pathway
title_fullStr Icaritin alleviates motor impairment and osteoporosis in Parkinson’s disease mice via the ER-PI3K/Akt pathway
title_full_unstemmed Icaritin alleviates motor impairment and osteoporosis in Parkinson’s disease mice via the ER-PI3K/Akt pathway
title_short Icaritin alleviates motor impairment and osteoporosis in Parkinson’s disease mice via the ER-PI3K/Akt pathway
title_sort icaritin alleviates motor impairment and osteoporosis in parkinson s disease mice via the er pi3k akt pathway
topic Parkinson’s disease
Icaritin
Estrogen receptor
Postmenopausal women
Phosphatidylinositol 3-kinase
Protein kinase B
url https://doi.org/10.1038/s41598-025-87429-2
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