Clinical Effect Observation And Network Pharmacological Study Of Compound Kidney-invigorating Granule In The Treatment Of Senile Osteoporosis

Objective:(1)To observe the clinical efficacy of Compound Kidney-Invigorating Granule(CKG)in treating senile osteoporosis(SOP).(2)The possible molecular pharmacological mechanism of CKG in the treatment of SOP was further investigated by network pharmacology.Methods:(1)A total of 80 patients(Kidney deficiency and blood stasis type SOP)were enrolled in the study.All the patients were selected from the first area of orthopedics department of the First Affiliated Hospital of Anhui University of Chinese Medicine(outpatient).Subjects were randomly divided into one of two groups.Participants in the control group were given baseline treatment.CKG was administered to the experimental group based on the control treatment regimen.Treatment duration was 3 months.Traditional Chinese Medicine(TCM)syndrome integral,quality of life rating,visual analog scale(VAS)and bone turnover markers(BTM)were evaluated and recorded.SPSS 27.0 and R studio were used for statistical analysis.(2)The active constituents and their targets of compound Bushen Huoxue granules were retrieved and screened from the database of traditional Chinese medicine.The "Drug-Compounds-Targets(D-C-T)" network was constructed on the basis of their relationship.Disease targets of SOP were retrieved from the disease database.By taking the overlapped part of the targets of the drug and the disease as the therapeutic targets.Construct a Protein-protein interaction(PPI)network of therapeutic targets.The core targets were screened out in the PPI network.Further enrichment analysis of the biological functions of the core therapeutic targets was carried out.Finally,the molecular docking between the core therapeutic targets and the active ingredients were realized.Results:(1)This study results showed that both groups could significantly reduced the TCM syndrome integral of patients with SOP(P< 0.05).The TCM syndrome integral of the experimental group declined more obviously and the effective rate was greater than that of the control groups’(P < 0.05).Pain symptom relief was more evident in the experimental arm(P<0.05).Post-treatment,all dimensions of SF-36 scale in both groups were obviously improved.The experimental group was superior to the control group in most part of SF-36 scale data except the physical role,social function and emotional role aspests(P >.05).In both groups,P1 NP and N-MID levels were increased effectively,and β-CTX level was decreased effectively(P< 0.05).Moreover,the effect of the experimental group on improving BTM was more obvious(P< 0.05).(2)A total of 65 active ingredients,250 drug targets,1260 SOP disease targets,and 126 drug and disease intersection targets were obtained from this network pharmacology.Gene Ontology(GO)enrichment analysis yielded 1661 items.In GO analysis results,SOP is closely related to the presence of reactive oxygen species,the cellular response to oxidative stress,the regulation of mi RNA.A total of 179 items were obtained by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.In KEGG analysis results,several signaling pathways were closely linked to SOP.These include primarily the MAPK signaling pathway,the TNF signaling pathway,and so forth.The procedures involved include osteoclast differentiation,cell apoptosis,cell senescence and so on.Kaempferol,quercetin,β-sitosterol and so on were the main active components of CKG.The core targets of CKG in the treatment of SOP were JUN,TNF and IL-6.Based on molecular docking results,the core active ingredients were able to dock well with the core therapeutic targets.Conclusions:(1)CKG has good efficacy in improving TCM syndrome integrals,improving patients’ life quality for SOP(Kidney deficiency and blood stasis type),and also significantly improving patients’ BTM,so it can be further promoted in clinical practice.(2)This study adopted the method of network pharmacology to preliminarily conclude that CKG may regulate multiple pathways and influence multiple procedures through multi-component targeting multi-target to play the role of anti-SOP,providing sufficient theoretical basis for further mechanism research.