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1.
J Ethnopharmacol ; 319(Pt 3): 117329, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37879510

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bone defects are difficult to treat and have a high incidence of nonunion. The Epimedii folium-Rhizoma drynariae herbal pair (EDP) is a traditional Chinese medicine (TCM) used for treating bone diseases. However, the mechanisms by which EDP promotes osteogenesis or bone formation remain largely unclear. AIM OF THE STUDY: This study aimed to investigate the mechanism of EDP promoted bone formation in bone defects using network pharmacology and experiments. MATERIALS AND METHODS: The chemical components of EDP were analyzed by UHPLC-MS. The hub target and pathway enrichment analysis was conducted using molecular docking or network pharmacology. The pharmacological actions of EDP were determined by µCT and histopathology examination using a bone defect rat model. The effects of EDP on the mRNA expression of Bmp2, Smad2/5, Runx2, and Alp genes were measured by RT-PCR, while changes in the protein expressions of BMP2, COL1A1, SPP1, ALP, and RUNX2in the tibia tissues of the rats in response to EDP were analyzed by immunohistochemical staining or Western blot. We also performed cell viability assays, Alizarin Red and ALP staining assays, and RT-PCR to better understand how EDP affected osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). RESULTS: Identified 14 key compounds and 47 hub targets of EDP that may be involved in promoting osteogenesis to repair bone defects. And the BMP/Smad/Runx2 pathway was likely the key pathway through which EDP promoted bone defects repairing. The results of in vivo rat experiments indicated that EDP effectively promoted tibia repair in the model rats and activated the BMP/Smad/Runx2 pathway in the tibia tissue, with upregulating Bmp2, Bmpr1α, Smad2/5, Runx2, and Alp genes, and increased the protein expression of BMP2, COL1A1, RUNX2, and ALP. In vitro, EDP was found to increase the proliferation, differentiation, and mineralization in BMSCs- and also up-regulated the expression of key genes in the BMP/Smad/Runx2 pathway. CONCLUSION: This study highlighted the ability of EDP to promote the osteogenic differentiation to enable bone repair by activating the BMP/Smad/Runx2 pathway.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core , Osteogênese , Ratos , Animais , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Farmacologia em Rede , Simulação de Acoplamento Molecular , Células Cultivadas , Diferenciação Celular
2.
Biomed Pharmacother ; 169: 115893, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37979377

RESUMO

AIM: Diabetes osteoporosis (DOP) is a chronic bone metabolic disease induced by diabetes, whose morbidity continues to increase. Epimedium brevicornum Maxim (EB), a popular Chinese traditional medicine, has been used to treat bone diseases in China for thousands of years. But its material basis and specific mechanism of action are not clear. METHODS: Epimedium brevicornum crude polysaccharide (EPE) is the main component, in this research the characterized the structure of EBPC1 purified from EPE was detected and its effects on cell proliferation, differentiation, and cytoskeletal in osteoblasts induced by high glucose. RESULTS: The molecular weight of EBPC1 was 10.5 kDa. It was mainly comprised of glucose and galactose, and the backbone of EBPC1 was→4)-α-D-Galp-(1→4)-α-D-Galp-(1→6)-ß-D-Galp-(1→6)-ß-D-Galp-(1→4)-α-D-Glcp-(1→4)-α-D-Glcp-(1→. The results from in vitro experiments revealed that EBPC1 significantly increased alkaline phosphatase (ALP) activity and mineralized nodule formation in primary osteoblasts, also significantly up-regulated expression of Alp mRNA and Runx2 mRNA in the presence of EBPC1 pretreatment. Moreover, EBPC1 modulated apoptosis via the regulation of Bax/Bcl2. CONCLUSION: These results indicate that EBPC1 treatment can promote osteogenesis during DOP, which can ameliorate apoptosis by regulating Bax/Bcl2 and accelerating osteogenesis in osteoblasts.


Assuntos
Diabetes Mellitus , Epimedium , Osteoporose , Humanos , Epimedium/química , Osteogênese , Proteína X Associada a bcl-2/metabolismo , Osteoporose/metabolismo , Diferenciação Celular , Osteoblastos , Polissacarídeos/química , RNA Mensageiro/metabolismo , Diabetes Mellitus/metabolismo
3.
Int J Biol Macromol ; 193(Pt B): 1996-2005, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34767882

RESUMO

Osteoporosis is a systemic metabolic bone disease with an increasing incidence rate. Chinese medicinal herbs have a long history of treating bone diseases. Polysaccharides are an important category of phytochemicals in Chinese medicinal herbs, and their health benefits have increased the interest of the public. Numerous studies have indicated that polysaccharides exhibit anti-osteoporosis effects by balancing bone resorption and bone formation, but the detailed effects and mechanism have not been systematically summarized. We performed a comprehensive review of the literature to consolidate studies for the period 2000-2021 by conducting electronic searches on the PubMed, CNKI, VIP, and Wanfang databases. In total, polysaccharides from 19 kinds of Chinese medicinal herbs in 54 studies have shown bone homeostasis protective properties. In vivo and in vitro experiments have demonstrated that polysaccharides present properties in the treatment of postmenopausal osteoporosis, senile osteoporosis, and glucocorticoid-induced secondary osteoporosis, especially postmenopausal osteoporosis. Moreover, a number of signalling pathways, such as the Wnt/ß-catenin signalling pathway, BMP/SMAD/RUNX2 signalling pathway, OPG/RANKL/RANK signalling pathway, apoptosis pathway, and transcription factors, are regulated by polysaccharides and participate in improving bone homeostasis. This review will provide a better understanding of the anti-osteoporotic effects of polysaccharides and the concomitant modulations of signalling pathways.


Assuntos
Osteoporose/tratamento farmacológico , Plantas Medicinais/química , Polissacarídeos/farmacologia , Animais , Humanos , Osteoporose/metabolismo , Compostos Fitoquímicos/farmacologia , Transdução de Sinais/efeitos dos fármacos
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