Study on mechanism of Dangshen and Baizhu in delaying intervertebral disc degeneration based on network pharmacology and experimental verification
Objective:To explore the mechanism of Dangshen and Baizhu in delaying intervertebral disc degeneration(IDD)based on network pharmacology and animal experiments.Methods:The potential active components,targets of ac-tion and IDD-related targets of Dangshen and Baizhu were obtained by using traditional Chinese medicine pharmacology da-tabase and analysis platform(TCMSP)and online mendelian inheritance in man(OMIM).The intersection targets were analyzed on the STRING platform,protein-protein interaction(PPI)network was constructed,and key target proteins were enriched and analyzed.Cytoscape software was used to construct the component-disease target-pathway network.Finally,the rat model of IDD was tested in vivo.18 IDD rats were randomly divided into control group,model group and Dangshen-Baizhu group,with 6 rats in each group.After modeling,the rats in Dangshen-Baizhu group were given traditional Chinese medicine solution,and the rats in the other two groups were given the same amount of normal saline for 4 weeks.Three in-tervertebral disc tissue samples were randomly taken from the rats in each group,and the pathological changes were de-tected by HE and Masson staining.The expressions of Aggrecan and COL2A1 protein were detected by immunohistochemis-try,and the expressions of COL2A1,It-1β,MMP9 and mRNA were detected by RT-qPCR.Results:A total of 31 poten-tial active components of Dangshen-Baizhu were obtained,which acted on 10 core targets such as Akt,IL-6,MMP-9,and participated in biological processes such as apoptosis and inflammatory response regulation,involving TNF,MAPK,PI3K-Akt and other signaling pathways.Compared with the model group,the endplate cartilage height and the immunohis-tochemical expression of Aggrecan and type Ⅱ collagen(COL2A1)in the intervertebral disc tissue of Dangshen-Baizhu group increased significantly,and the mRNA expression of IL-1βand MMP-9 in the intervertebral disc tissue was signifi-cantly down-regulated,while the mRNA expression of COL2A1 was up-regulated.The differences were statistically signifi-cant(P<0.05).Conclusion:This study reveals that Dangshen-Baizhu can effectively up-regulate the expression of extra-cellular matrix(ECM)in degenerative intervertebral disc tissue,inhibit the synthesis of inflammatory factors and matrix metalloproteinases,and thus delay IDD.
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