Epimedin B exerts neuroprotective effect against MPTP-induced mousemodel of Parkinson’s disease: GPER as a potential target

Mei ZHANG, Zifan HU, Xiaoli Dong, Wenfang CHEN

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

Mitochondrial dysfunction and oxidative stress play important roles in the neuropathogenesis of Parkinson's disease (PD). Epimedin B, the second highest active ingredient in the flavonoids of Herba Epimedii, has been proven effective in treating osteoporosis and oxaliplatin-induced peripheral neuropathy. The present study aims to investigate the neuroprotective effects of Epimedin B in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced mouse model of PD, and the involvement of G protein-coupled estrogen receptor (GPER)-mediated anti-apoptosis as well as anti-endoplasmic reticulum stress. Molecular docking revealed that Epimedin B could directly bind to GPER at the same site as GPER agonist G1 and the binding energy was - 7.3 kcal/mol. Epimedin B treatment ameliorated MPTP-induced motor dysfunction and alleviated the decreased contents of DA with its metabolites in the striatum and the loss of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantial nigra pars compacta (SNpc). Epimedin B treatment markedly prevented MPTP-induced changes in apoptosis-related protein Bcl-2 and Bax as well as endoplasmic reticulum stress-related protein glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). Pharmacological blockade with GPER antagonist G15 could antagonize these neuroprotective effects of Epimedin B on the nigrostriatal system. Moreover, the anti-apoptosis and anti-endoplasmic reticulum stress effects of Epimedin B against MPTP toxicity were significantly reduced in GPER knockout (GPER-/-) mice. The present study provides the first evidence that Epimedin B can protect against MPTP-induced PD mice model. GPER may be a potential target for the neuroprotective effect of Epimedin B against PD.
Original languageEnglish
Article numberPMID: 36411637
Number of pages13
JournalBiomedicine and Pharmacotherapy
Volume156
Issue number113955
DOIs
Publication statusPublished - Dec 2022

Keywords

  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin
  • Apoptosis
  • Endoplasmic reticulum stress
  • Epimedin B
  • G protein-coupled estrogen receptor
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Pharmacology

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