Exploring the preventive and therapeutic effects of Taxilli Herba on periodontitis based on network pharmacology and animal experiments
Objective Based on network pharmacology methods to explore the mechanism of action of Taxilli Herba in the treatment of periodontitis,and to verify through molecular docking and in vivo ex-periments,to investigate the effect of Taxilli Herba extract on the growth of P.g and its therapeutic effect on experimental periodontitis in rats.Methods The effective components of Taxilli Herba were re-trieved from traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)database and the targets were predicted from Swiss Target Prediction database.GeneCards,DisGeNET and OMIM databases were used to retrieve periodontitis-related targets.The common targets were ob-tained by Venny analysis.The PPI network was constructed by STRING database.and key genes were screened.The GO function and KEGG signal pathway enrichment analysis was performed by DAVID data-base.The"drug-component-target-pathway"network of Taxilli Herba was constructed by Cytoscape 3.10.0 software.Molecular docking was used to verify the binding of drug components and targets.The minimum inhibitory concentration(MIC)and Minimum bactericidal concentration(MBC)of ethanol ex-tract of Taxilli Herbaon P.g were determined by the ratio dilution method.42 male SD rats were ran-domly divided into 7 groups:blank group,solvent group,model group,minocycline hydrochloride group,Taxilli Herba high-dose group,Taxilli Herba medium-dose group and Taxilli Herba low-dose group.The experimental rat periodontitis model was constructed by ligating the left upper first molar with silk thread and inoculating P.g.The rats in each group were given corresponding drug intervention every day,and their weight,probing depth(PD)andsulcus bleeding index(SBI)were recorded.After 14 days,X-ray film was taken to confirm the success of modeling,and the rats in each group were sacrificed to obtain ser-um,jawbone and gingival tissue specimens.The mRNA expression levels of Interleukin 6(IL-6),tumor necrosis factor α(TNF α),tumor necrosis factor α(MMP-9),runt-related transcription factor 2(RUNX2),osteocalcin(OCN),osteoprotegerin(OPG),and receptor activator of nuclear factor-KB ligand(RANKL)were detected by RT-PCR.The expression levels of IL-6,TNF-α,and MMP-9 in serum were detected by ELISA.The inflammatory infiltration was observed by HE staining.The expression of RUNX2 and OCN protein was observed by immunohistochemical staining.Results 4 effective compo-nents of Taxilli Herba,545 drug targets and 4 151 periodontitis treatmenttargets were obtained by screening,and 186 potential targets in treating periodontitis were obtained by Venny analysis.PPI net-work analysis obtained 10 core targets such as IL-6,TNF-α and MMP9.The main pathways obtained by enrichment analysis were PI3K-Akt signal pathway and so on.The results of molecular docking showed that the effective components of Taxilli Herba had good binding ability with the screened key targets.The MIC of the ethanol extract of Taxilli Herba to P.g was 0.5 g/L,and the MBC was 2 g/L.The etha-nol extract of Taxilli Herba had a good effect on improving PD and SBI of experimental periodontitis in rats,and it can reduce the expression of IL-6,TNF-α and MMP-9 in serum,thus alleviating the inflamma-tion of periodontal tissues.At the same time,it can promote the expression of RUNX2,OCN and OPGin periodontal tissue,and inhibit the expression of RANKL to regulate bone homeostasis,thus alleviating periodontal bone tissue loss.Conclusion The ethanol extract of Taxilli Herba can inhibit and kill P.g,reduce inflammatory reaction,regulate bone homeostasis,and treat periodontitis through multi-compo-nent,multi-target and multi-pathway.
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