Objective Osteogenesis is vitally important for bone defect repair,and Zuo Gui Wan(ZGW)is a classic prescription in traditional Chinese medicine(TCM)for strengthening bones.However,the specific mechanism by which ZGW ...Objective Osteogenesis is vitally important for bone defect repair,and Zuo Gui Wan(ZGW)is a classic prescription in traditional Chinese medicine(TCM)for strengthening bones.However,the specific mechanism by which ZGW regulates osteogenesis is still unclear.The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis.Methods A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells(BMSCs).Results In total,487 no-repeat targets corresponding to the bioactive components of ZGW were screened,and 175 target genes in the intersection of ZGW and osteogenesis were obtained.And 28 core target genes were then obtained from a PPI network analysis.A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress,metal ions,and lipopolysaccharide.Additionally,KEGG pathway enrichment analysis revealed that multiple signaling pathways,including the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway,were associated with ZGW-promoted osteogensis.Further experimental validation showed that ZGW could increase alkaline phosphatase(ALP)activity as well as the mRNA and protein levels of ALP,osteocalcin(OCN),and runt related transcription factor 2(Runx 2).What’s more,Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT,and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002.Finally,the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002.Conclusion ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.展开更多
OBJECTIVE： To evaluate the effect and safety of Zuogui pill and Yougui pill, classic Y/n and Yang tonic formula （CYYTF）, in the treatment of osteoporosis and the underlying mechanism. METHODS： Participants aged 55...OBJECTIVE： To evaluate the effect and safety of Zuogui pill and Yougui pill, classic Y/n and Yang tonic formula （CYYTF）, in the treatment of osteoporosis and the underlying mechanism. METHODS： Participants aged 55 to 75 with osteoporosis and Kidney deficiency in Traditional Chi-nese Medicine （TCM） will be included and randomly allocated into two groups： treatment group and control group. Participants in the treatment group were treated with Zuogui pill or Yougui pill TCM formula granule, while the control group received pla- cebo. Primary outcomes are the lumbar spine on bone mineral density （BMD） （L1-4） and femoral BMD. Secondary outcomes include pain intensity, health-related quality of life （HRQoL）, bone turn- over markers and safety. RESULTS： Totally 200 patients were enrolled from December 2014 to April 2016 from four hospitals. There were no statistically significant differences between the two groups at baseline （P 〉 0.05） and it was good to comparability. Statistically signifi- cant differences between the two groups were ob- served for the lumbar BMD （L1-4）, pain VAS scores and HRQoL at six months and twelve months and femoral BMD at twelve months （P 〈 0.05）, but no significant differences for femoral BMD and bone turnover markers at six months （P 〉 0.05）. More- over, significant difference was observed at differ- ent time before and after treatment in terms of lum- bar spine （L1-4） BMD, femoral BMD, pain VAS scores and health-related quality of life, and there was an crossover effect between the time and groups be- fore and after treatment. In additional, in the treat- ment group, 8 patients lost to follow-up and 3 patients had adverse events （AEs） and in the control group, 10 patients lost to follow-up and 2 patients had AEs. No remarkable differences were observed between the two groups with regard to AEs, lost rate and safety （P 〉 0.05）. CONCLUSION： Zuogui pill or Yougui pill could improve BMD, ease pain, relieve Kidney deficiencysyndrome, improve the quality of life osteoporosis patients, inhibit bone conversion and regulate the coupling balance of bone formation and bone resorption, but long-term efficacy should be confirmed by a longer term follow-up and larger of samples clinical randomized controlled trials.展开更多
文摘Objective Osteogenesis is vitally important for bone defect repair,and Zuo Gui Wan(ZGW)is a classic prescription in traditional Chinese medicine(TCM)for strengthening bones.However,the specific mechanism by which ZGW regulates osteogenesis is still unclear.The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis.Methods A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells(BMSCs).Results In total,487 no-repeat targets corresponding to the bioactive components of ZGW were screened,and 175 target genes in the intersection of ZGW and osteogenesis were obtained.And 28 core target genes were then obtained from a PPI network analysis.A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress,metal ions,and lipopolysaccharide.Additionally,KEGG pathway enrichment analysis revealed that multiple signaling pathways,including the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway,were associated with ZGW-promoted osteogensis.Further experimental validation showed that ZGW could increase alkaline phosphatase(ALP)activity as well as the mRNA and protein levels of ALP,osteocalcin(OCN),and runt related transcription factor 2(Runx 2).What’s more,Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT,and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002.Finally,the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002.Conclusion ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.
基金Supported by the National Natural Science Foundation of China(No.81473711),(The epigenetic research of lnc RNA in Zuoguiwan Yougui Wan inducing chondrogenic differentiation of BMSCs)Special Fund for TCM Research in the Public Interest(No.201507006-01),(Balance chiropractic therapy for cervical spondylotic radiculopathy:study protocol for a randomized parallel-controlled trial)the Shaanxi Program of Science and Technology(No.2015SF072)(Clinical Study on Taibai Cream for Treating Osseous Arthritis Based on the Academic Thought of Old Country Chinese Medicine Doctor Yan-Min Li)
文摘OBJECTIVE： To evaluate the effect and safety of Zuogui pill and Yougui pill, classic Y/n and Yang tonic formula （CYYTF）, in the treatment of osteoporosis and the underlying mechanism. METHODS： Participants aged 55 to 75 with osteoporosis and Kidney deficiency in Traditional Chi-nese Medicine （TCM） will be included and randomly allocated into two groups： treatment group and control group. Participants in the treatment group were treated with Zuogui pill or Yougui pill TCM formula granule, while the control group received pla- cebo. Primary outcomes are the lumbar spine on bone mineral density （BMD） （L1-4） and femoral BMD. Secondary outcomes include pain intensity, health-related quality of life （HRQoL）, bone turn- over markers and safety. RESULTS： Totally 200 patients were enrolled from December 2014 to April 2016 from four hospitals. There were no statistically significant differences between the two groups at baseline （P 〉 0.05） and it was good to comparability. Statistically signifi- cant differences between the two groups were ob- served for the lumbar BMD （L1-4）, pain VAS scores and HRQoL at six months and twelve months and femoral BMD at twelve months （P 〈 0.05）, but no significant differences for femoral BMD and bone turnover markers at six months （P 〉 0.05）. More- over, significant difference was observed at differ- ent time before and after treatment in terms of lum- bar spine （L1-4） BMD, femoral BMD, pain VAS scores and health-related quality of life, and there was an crossover effect between the time and groups be- fore and after treatment. In additional, in the treat- ment group, 8 patients lost to follow-up and 3 patients had adverse events （AEs） and in the control group, 10 patients lost to follow-up and 2 patients had AEs. No remarkable differences were observed between the two groups with regard to AEs, lost rate and safety （P 〉 0.05）. CONCLUSION： Zuogui pill or Yougui pill could improve BMD, ease pain, relieve Kidney deficiencysyndrome, improve the quality of life osteoporosis patients, inhibit bone conversion and regulate the coupling balance of bone formation and bone resorption, but long-term efficacy should be confirmed by a longer term follow-up and larger of samples clinical randomized controlled trials.
