Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis.

ABSTRACT: Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein-protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.

A Composite Deferoxamine/Black Phosphorus Nanosheet/Gelatin Hydrogel Scaffold for Ischemic Tibial Bone Repair.

Introduction: Bone delay union is mostly caused by lack of blood supply. Although autografts, allografts and artificial bone have been widely used to treat bone delay union, the bone regeneration fails in the ischemic site accompanied by the bone donor site complications and disease transmission. Recently, there is a growing recognition of the importance of hydrogel scaffolds which are regarded as an eligible engineer tissue for bone repair. However, hydrogel is still limited in improving neovascularization. Methods: In this work, black phosphorus nanosheet and deferoxamine (BPN-DFO) were loaded in the gelatin hydrogel to overcome the high risk of bone delay union and systemically investigated the regeneration capability of BPN-DFO hydrogel in vitro and vivo. Results: The resulting BPN-DFO hydrogel scaffold showed superior swollen, degradation and release rate, as well as satisfied biocompatibility. BPN-DFO hydrogel shown the significant up-expression of mRNA related to bone regeneration and cell proliferation. In vivo, the proposed BPN-DFO hydrogel significantly improved osteogenesis and neovascularization in the ischemic tibial bone site of SD rats with acute femoral artery occlusion. Both macroscopic and histological evaluation of new regenerated bone showed newly formed blood vessel and collagen using BPN-DFO hydrogel. The immunohistochemistry and RT-PCR revealed that the bone regeneration could be improved via BMP/Runx2 pathway. Conclusion: The BPN-DFO hydrogel possesses potential tissue engineer material for ischemic bone defect treatment. However, furthermore studies are needed to testify the safety and efficacy of BPN-DFO hydrogel.