| Objective: To analyse the relevant studies on the treatment of PMO in several databases through systematic evaluation and data mining,and to investigate the effect of Gujin Dan on PMO and its mechanism through in vivo and in vitro experiments.Methods:1.RCTs of PMO treated with Chinese herbal compound retrieved from multiple databases and Meta-statistical analysis was performed using the Revman 5.4.3 software provided by the Cochrane Collaboration.A systematic evaluation of the efficiency,lumbar spine BMD,femoral neck BMD,Ward’s triangle BMD,blood calcium,serum BGP,ALP and E2 after treatment was performed.2.The research literatures on the treatment of PMO in Chinese medicine were searched from several databases.The TCMISS V2.5 software was used to statistically analyse all the literature,screen out the clinical observation literature that met the criteria,statistically summarise and analyse their four qi,five tastes and returning to the meridians,core formulae and formulae patterns,and analyse their formulae patterns in conjunction with Gujin Dan.3.High performance liquid chromatography was used to analyse the composition of GJD;the proliferation of MC3T3-E1 cells was investigated by different concentrations of GJD,and its differentiation and mineralization were further studied;the effect of GJD on the gene expression of MC3T3-E1 cells was investigated by RNA-seq technology,bioinformatics analysis and q RT-PCR,and the molecular mechanism of its regulation of osteoblasts was clarified.4.Eight-week-old C57BL/6 female mice were used to establish the OVX model and were divided into sham-operated and OVX groups,low,medium and high dose groups of Gujin Dan.After 7 weeks of continuous gavage,the mice were analysed for serum-related parameters,bone tissue of the distal femur,expression of genes related to bone metabolism and their possible involvement in the relevant signalling pathways.Results:1.Through statistical screening,a total of 1158 patients were included in the final total of 11 publications,579 in the treatment group and 579 in the control group.The treatment group showed significant advantages in improving the overall efficiency of patients after medication,improving the BMD of the lumbar spine,BMD of the femoral neck,BMD of the Ward’s triangle,and raising the blood calcium and E2 levels,but there was no significant difference between the treatment group and the control group in improving the serum BGP and ALP levels of patients after medication.2.A total of 117 clinical observation papers meeting the criteria were selected through statistical screening,and 119 prescriptions were obtained,with a total of 156 Chinese medicines.It was found that the top 5 Chinese medicines with frequency ≥ 20 were Radix Rehmanniae Praeparata,Epimedium,Rhizoma Drynariae,Angelica and Astragalus;among the 156 Chinese medicines,the frequencies of warm,neutral,cold,hot and cool medicines were 807,372,196,36 and 33,respectively;the frequencies of sweet,bitter,pungent,sour,salty and astringent medicines were 967,538,471,129,83 and 69,respectively.The frequency of sweet,bitter,pungent,sour,salty and astringent drugs was 967,538,471,129,83 and 69 in that order;the top 5 drugs ranked according to their meridians were liver,kidney,spleen,heart and lung in that order;the association rule analysis by complex system entropy clustering analysis revealed that "Cornus officinalis,Epimedium → Radix Rehmanniae Praeparata " was the most confident combination pattern.The 19 herbs in the Gujin Dan formula were analysed and found to be mainly warming in nature;the most sweet tasting drugs accounted for 10 flavours;through the attribution of meridians,it was found that the Gujin Dan formula is mainly attributed to the liver and kidney meridians.The whole formula is effective in tonifying the liver and kidney,soothing the tendons and strengthening the bones,dispelling wind and relieving pain.Widely used clinically for bone metabolism related disorders such as bone atrophy due to liver and kidney deficiency.3.By analysing the composition of GJD,we found that it contained paeoniflorin,pinoresinol diglucoside,strychnoside,glycyrrhizin,mullein,tetrahydropalmatine and catalpol.Follow-up activity experiments showed that GJD could promote the proliferation,differentiation and mineralization of MC3T3-E1 cells.In addition,an RNA-seq study showed that GJD could synergistically enhance osteoblast proliferation and differentiation,reduce osteoclast production and differentiation,and decrease the expression level of its related proapoptotic genes.The multiple actions work together in synergy to act against osteoporosis and other effects.4.Serum E2,P1 NP,CTX and BGP were improved by the establishment of OVX model mice and the treatment of GJD with different doses of intervention.HE staining showed varying degrees of improvement in each of the GJD dose groups compared to the OVX group.Micro-CT imaging also showed results consistent with the previous HE staining,and the associated bone metabolism genes were also improved to varying degrees.GJD intervention was found to increase the expression of Wnt3 a,β-catenin,Runx2,ALP and ColX related proteins to varying degrees.Conclusion:1.Meta-analysis revealed that the clinical effects of Chinese herbal compounding in the treatment of PMO are inextricably linked to the synergistic effects of Chinese herbal medicine and the combination of Chinese herbal medicine with each other,which also demonstrates the clinical advantages of Chinese herbal compounding in the treatment of PMO.2.Through data mining,we analysed the patterns of medication used in the treatment of PMO in Chinese medicine and discovered the commonly used drugs and their properties and ascriptions.The results laterally validate the scientific connotations of Gujin Dan in the treatment of PMO and provide a reliable theoretical basis for clinical treatment.3.GJD promotes the cellular activity and proliferation of MC3T3-E1 cells and their osteogenic differentiation.Analysis of the RNA-seq results showed that GJD can synergistically act against osteoporosis by enhancing the expression of genes related to osteoblast proliferation and differentiation,as well as decreasing osteoclast production and differentiation and decreasing the expression of genes related to pro-apoptosis.4.GJD has anti-osteoporosis therapeutic effects in OVX mice,which can be achieved by improving E2 levels,stimulating bone formation and inhibiting bone resorption,thereby improving the skeletal microenvironment,increasing BMD,restoring bone trabecular thickness and restoring bone remodelling balance.Studies have found that GJD may act against osteoporosis by mediating the Wnt3a/β-catenin signalling pathway and differentially upregulating the expression levels of Runx2,Alp and ColX proteins. |
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