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

  • Sci Rep. 2025 Jan 25;15(1):3190. doi: 10.1038/s41598-025-87429-2.
Xianmei Lin  #  1 Xinyu Zhou  #  2 Xingman Liu  1 Lingqiong Xia  2 Jing Cai  3 Nanqu Huang  4  5  6 Yong Luo  7  8  9 Weidong Wu  10
Affiliations
  • 1. Guizhou University of Traditional Chinese Medicine, Guiyang, 550000, Guizhou, China.
  • 2. Department of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, 56300, Guizhou, China.
  • 3. Department of Neurology, First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550000, Guizhou, China.
  • 4. Department of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, 56300, Guizhou, China. [email protected].
  • 5. Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi, Guizhou, China. [email protected].
  • 6. Department of Geriatrics, Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou, China. [email protected].
  • 7. Department of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, 56300, Guizhou, China. [email protected].
  • 8. Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi, Guizhou, China. [email protected].
  • 9. Department of Geriatrics, Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou, China. [email protected].
  • 10. Guizhou University of Traditional Chinese Medicine, Guiyang, 550000, Guizhou, China. [email protected].
  • # Contributed equally.
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.

Keywords
Estrogen receptor; Icaritin; Parkinson’s disease; Phosphatidylinositol 3-kinase; Postmenopausal women; Protein kinase B.
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