首页|Rheum palmatum L.and Salvia miltiorrhiza Bge.Alleviates Acute Pancreatitis by Regulating Th17 Cell Differentiation:An Integrated Network Pharmacology Analysis,Molecular Dynamics Simulation and Experimental Validation
Rheum palmatum L.and Salvia miltiorrhiza Bge.Alleviates Acute Pancreatitis by Regulating Th17 Cell Differentiation:An Integrated Network Pharmacology Analysis,Molecular Dynamics Simulation and Experimental Validation
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Objective:To identify the core targets of Rheum palmatum L.and Salvia miltiorrhiza Bge.,(Dahuang-Danshen,DH-DS)and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmacology approach and validate the findings in animal experiments.Methods:Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP.The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation.Finally,the results of network pharmacology enrichment analysis were verified by immunohistochemistry,Western blot analysis and real-time quantitative PCR,respectively.Results:Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3(MAPK3),Janus kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3),protein c-Fos(FOS)were identified as core targets in the protein interaction(PPI)network analysis.Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP,and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation.Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3,STAT3 and FOS.Molecular dynamics simulation revealed that FOS-isotanshinone Ⅱ and STAT3-dan-shexinkum d had good binding capacity.Animal experiments indicated that compared with the AP model group,DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1 β,interleukin-6 and tumor necrosis factor-a,and blocking the activation of Th17 cell differentiation(P＜0.01).Conclusion:DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues,which would be functioned by regulating Th17 cell differentiation-related mRNA and protein expressions.
NETL
NSTL
万方数据
