| Objective:To study how Sini Decoction treats functional constipation in elderly people with Yang deficiency.The mechanism of Sini Decoction in treating functional constipation in the elderly was studied using prediction and analysis of network pharmacology and molecular docking approaches.In order to further the modernization of traditional Chinese medicine,it provides the framework for the therapeutic treatment of senile Yang-deficiency functional constipation.Methods:1.Clinical randomized controlled study: From the anorectal clinic of the Affiliated Hospital of Jiangxi University of Chinese Medicine,84 senior patients with functional constipation(yang deficiency type)who met the inclusion criteria were selected during December 2020 and November2022.42 people from each group were randomly assigned to the lactulose and Sini decoction groups.The Sini decoction group got one dose daily of the Sini decoction,which was administered twice while still warm.15 g of black monkshood(which is initially decocted),5g of dried ginger,and 6g of roasted licorice compensate the sini decoction.For 14 days,the lactulose group took lactulose oral liquid before going to bed,and the rest of the treatment was the same.Analyze the TCM syndrome and Quality of life scores for patients with constipation(PAC-QOL).scores of the two different groups prior to and following treatment,along with 3 months afterward.The accumulated data were statistically analyzed to assess the clinical efficacy of Sini Decoction in the treatment of Yang-deficiency senile functional constipation.2.Network pharmacological research and molecular docking verification: screen the main active ingredients of Sini Decoction(OB≥30% and DL≥0.18)from TCMSP database,and find out their corresponding targets;Mining Gene Cards,OMIM,TTD,Dis Ge NET,Drugbank,Pharm GKB and other databases to screen the relevant targets of FC.The targets of Sini decoction for FC treatment were obtained through target mapping,and the core targets of Sini decoction for FC treatment were screened by STRING database for analysis,and the protein-protein interaction(PPI)network was constructed.The Metascape database was used to analyze the gene ontology(GO)function and the signal pathway enrichment of the Kyoto Encyclopedia of Gene and Genomes(KEGG)of the core target,predict the mechanism of Sini Decoction in the treatment of functional constipation,and verify it with the "drug component-core target docking" of Sini Decoction.Results:1.Clinical randomized controlled study: the comparison between groups after treatment showed that the improvement of the total effective rate,the total score of TCM syndromes,the defecation effort,the defecation time,the chilliness of limbs,the pain of waist and knee,the clear and long urination,the pale complexion and other TCM syndromes single score,and the PAC-QOL score in the Sini Decoction group were better than those in the lactulose group,with a statistically significant difference(P<0.05);Compared with before and after treatment,the total score of TCM syndromes,the score of individual TCM syndromes and the score of PAC-QOL in Sini Decoction group were improved(P<0.05).In the intra-group control before and after treatment,the main symptoms of traditional Chinese medicine such as defecation effort,stool characteristics,defecation time,falling sensation,frequency,abdominal distension and PAC-QOL score of patients in the lactulose group were improved compared with those before treatment(P<0.05).After 3 months of follow-up,there was no statistically significant difference in the recurrence rate between the Sini Decoction group and the lactulose group(P>0.05).2.Network pharmacology and molecular docking verification:A total of221 potential compounds were extracted from the herbal ingredients of Sini Tang,and 1484 FC-related targets were obtained after disease gene mining and screening.After the target mapping,130 targets of Sini Decoction in the treatment of FC were obtained.The key targets were finally screened by network topology analysis.The biological process was mainly involved in the response to hormone,response to inorganic substance,response to lipopolysaccharide,response to peptide,response to molecule of bacterial origin,cellular response to nitrogen compound.The cell components were mainly enriched in membrane raft,membrane microdomain,caveola,plasma membrane raft,vesicle lumen,plasma membrane protein complex.The molecular functions were mainly related to the activities of DNA-binding transcription factor binding,transcription factor binding,RNA polymerase II-specific DNA-binding transcription factor binding,kinase binding,nuclear receptor activity,ligand-activated transcription factor activity.KEGG signal pathway is mainly concentrated in pathways in cancer,Proteoglycans in cancer,IL-17 signal pathway,PI3K-AKT signal pathway and TNF signal pathway,MAPK signaling pathway.The results of molecular docking showed that the main active components of Sini decoction,quercetin,kaempferol and Gancaonin G,had relatively stable binding activity with the core target AKT1,IL-6 and TNF.Conclusion:1.Compared with lactulose,Sini Decoction can significantly improve various TCM syndromes and quality of life of elderly patients with Yang-deficiency FC,with lower recurrence rate and no obvious adverse reactions,indicating that Sini Decoction has potential advantages in the treatment of elderly patients with Yang-deficiency FC,and its long-term effect is more obvious,which can provide certain drug reference for clinical practice of traditional Chinese medicine in the treatment of elderly patients with Yang-deficiency FC.2.The network pharmacology and molecular docking verification showed that the treatment of FC with the core Chinese medicine ingredients of Sini Decoction mainly achieved the effect of treating the elderly with Yang-deficiency FC through multi-component,multi-target and multi-channel,and the combination of the main active ingredients of Sini Decoction and the core target of FC was stable. |
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