epimedin-b and Disease-Models--Animal

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

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Disease Models, Animal; Estrogens; Flavonoids; Mice; Molecular Docking Simulation; Neuroprotective Agents; Parkinson Disease; Receptors, G-Protein-Coupled

With the ageing of populations, the management of osteoporosis is a priority of society in general. Epimedin B, a major ingredient of Herba Epimedii, which has the advantages of high content and hypotoxicity has been proved to be effective in preventing osteoporosis in vitro. However, the efficacy and mechanism of Epimedin B on osteoporosis in vivo have not been well elucidated yet. This study aimed to investigate the effects and the potential mechanisms of 8-week repeated oral administration of Epimedin B (10 and 20 mg/kg/day) on a mouse osteoporosis model. Effects of Epimedin B were evaluated by examinations of serum bone turnover markers, bone mineral density, bone microstructure parameters and histopathological section. Epimedin B significantly rose N-terminal propeptide of type I procollagen (P1NP) and dropped C-telopeptide of type I collagen (CTX1). Connectivity density (Conn.D) increased significantly while structure model index (DA) decreased significantly after treated by Epimedin B. Meanwhile, Epimedin B administration significantly increased the number of trabecular bones while significantly decreased the gap between them. Overall, Epimedin B showed beneficial effects on osteoporosis. Furthermore, RNA sequencing-based analysis revealed 5 significantly down-regulated transcripts and 107 significantly up-regulated transcripts between the Epimedin B administration group and the model group. These transcripts were mapped to 15 pathways by KEGG enrichment analysis, of which PI3K-Akt signalling pathway, MAPK signalling pathway and PPAR signalling pathway were most connected to osteoporosis. To conclude, Epimedin B is effective in treating osteoporosis in mice via regulating PI3K-Akt, MAPK and PPAR signalling pathway.

Topics: Administration, Oral; Animals; Bone Density; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Flavonoids; Male; MAP Kinase Signaling System; Mice; Mice, Inbred ICR; Osteoporosis; Peroxisome Proliferator-Activated Receptors; Phosphatidylinositol 3-Kinase; Sequence Analysis, RNA; Signal Transduction; Up-Regulation