Dissecting the mechanisms of velvet antler extract against diabetic osteoporosis via network pharmacology and proteomics

Ethnopharmacological relevance: Velvet antler (VAE) is a famous traditional Chinese medicine (TCM), which has been used for thousands of years to treat bone-related diseases. Nonetheless, whether VAE has anti-diabetic osteoporosis (DOP) properties remains to be elucidated. Aim of the study: The therapeutic mechanism of VAE on DOP is based on integrated proteomics of network pharmacology strategies to study related targets and pathways. Materials and methods: Liquid chromatography-mass spectrometry (LC/MS) was used to analyze the main molecular components present in the VAE. The DOP mouse model was created by combining a high-fat diet with streptozotocin (STZ). High glucose (HG) induced MC3T3-E1 cells were used as a cell model to evaluate the therapeutic effect of VAE. The mechanisms of VAE in treating DOP were predicted through proteomics. Molecular docking, molecular dynamics simulations, DARTS and functional experiments were employed to further verify its mechanisms. Results: Altogether 30 components were identified by LC-MS. In vitro and in vivo results were confirmed that VAE had a protective effect on DOP. Combined with network pharmacology, proteomics and functional experiments revealed that TNF/PI3K-AKT signaling pathway may be the potential biochemical pathway for VAE in treating DOP. Conclusions: The innovation of this study was investigating the effectiveness of VAE in treating DOP in vivo and in vitro and suggested that VAE might exert anti-DOP effects through the TNF/PI3K-AKT signaling pathway by network pharmacology and proteomics and found that ATK1 was the core target of VAE, which provided valuable insights for the clinical application of VAE in DOP.