Background:Compound cortex phellodendri liquid(CPL)is a kind of classical compound preparation,which has potential curative effect in treating inflammatory diseases.Increasing evidences support that inflammation plays...Background:Compound cortex phellodendri liquid(CPL)is a kind of classical compound preparation,which has potential curative effect in treating inflammatory diseases.Increasing evidences support that inflammation plays important roles in the pathogenesis of myeloproliferative neoplasms(MPN).This study aims to preliminarily clarify the therapeutic potential and molecular mechanisms of CPL for MPN based on network pharmacology and molecular docking techniques.Methods:The active components and corresponding action targets of CPL were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),while MPN-related targets were searched through GeneCards,DisGeNET,OMIM,DrugBank and TTD databases respectively.Protein-Protein Interaction(PPI)Networks of potential targets were constructed using STRING 11.5 and analyzed visually with Cytoscape 3.9.1.In addition,Metascape platform was used for GO and KEGG analysis that were subsequently visualized with Cytoscape 3.9.1 built-in plug-ins CluoGO or SangerBox platform.Finally,Autodock Vina was used for molecular docking of potential targets and main active ingredients,which were visualized with Pymol software.Experimentally,we used in vitro mouse primary cells culture system to evaluate the effect of CPL on the erythroid and megakaryocytes differentiation that are excessively driven in MPN respectively.Results:The active components of CPL in the treatment of MPN are mainly flavonoids.The core proteins of CPL for MPN intervention are correlated to TP53,AKT1,JUN,CASP3,EGFR,TNF,MYC,IL6.Multiple signaling pathways were closely related to the treatment of MPN intervened by CPL,including PI3K-Akt signaling,TNF-αsignaling,JAK-STAT signaling and NF-κB signaling pathways.These potential targets had good conformation with the core active ingredients of CPL.In line with above findings,we demonstrated that CPL significantly inhibits the proliferation of differentiation of erythrocytes and megakaryocytes in vitro,further supporting the therapeutic potential of CPL for MPN.Conclusion:This study revealed the active ingredients and potential molecular mechanism of CPL in the treatment of MPN,providing a reference for subsequent basic research.展开更多
基金This work was supported by grants from the Taishan Scholars Program(TSQN201812015)Rongxiang Regenerative Medicine Foundation(2019SDRX-04)the program for Multidisciplinary Research and Innovation Team of Young Scholars of Shandong University(2020QNQT007).
文摘Background:Compound cortex phellodendri liquid(CPL)is a kind of classical compound preparation,which has potential curative effect in treating inflammatory diseases.Increasing evidences support that inflammation plays important roles in the pathogenesis of myeloproliferative neoplasms(MPN).This study aims to preliminarily clarify the therapeutic potential and molecular mechanisms of CPL for MPN based on network pharmacology and molecular docking techniques.Methods:The active components and corresponding action targets of CPL were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),while MPN-related targets were searched through GeneCards,DisGeNET,OMIM,DrugBank and TTD databases respectively.Protein-Protein Interaction(PPI)Networks of potential targets were constructed using STRING 11.5 and analyzed visually with Cytoscape 3.9.1.In addition,Metascape platform was used for GO and KEGG analysis that were subsequently visualized with Cytoscape 3.9.1 built-in plug-ins CluoGO or SangerBox platform.Finally,Autodock Vina was used for molecular docking of potential targets and main active ingredients,which were visualized with Pymol software.Experimentally,we used in vitro mouse primary cells culture system to evaluate the effect of CPL on the erythroid and megakaryocytes differentiation that are excessively driven in MPN respectively.Results:The active components of CPL in the treatment of MPN are mainly flavonoids.The core proteins of CPL for MPN intervention are correlated to TP53,AKT1,JUN,CASP3,EGFR,TNF,MYC,IL6.Multiple signaling pathways were closely related to the treatment of MPN intervened by CPL,including PI3K-Akt signaling,TNF-αsignaling,JAK-STAT signaling and NF-κB signaling pathways.These potential targets had good conformation with the core active ingredients of CPL.In line with above findings,we demonstrated that CPL significantly inhibits the proliferation of differentiation of erythrocytes and megakaryocytes in vitro,further supporting the therapeutic potential of CPL for MPN.Conclusion:This study revealed the active ingredients and potential molecular mechanism of CPL in the treatment of MPN,providing a reference for subsequent basic research.
