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The mechanism of action of the active components of Aconitum Carmichaelii Debx Rhizoma in the treatment of vasospasm based on network pharmacology and in vitro experiments

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Author:
No author available
Journal Title:
Global Traditional Chinese Medicine
Issue:
8
DOI:
10.3969/j.issn.1674-1749.2024.08.010
Key Word:
附子;网络药理学;分子对接;血管痉挛;细胞增殖;血管平滑肌细胞;血管紧张素Ⅱ;Aconitum Carmichaelii Debx Rhizoma;network pharmacology;molecular docking;vasospasm;cell proliferation;vascular smooth muscle cells;angiotensin Ⅱ

Abstract: Objective To explore the potential mechanism of the active components of Aconitum Carmichaelii Debx Rhizoma in thetreatment of vasospasm by integrating network pharmacology and in vitro cell experiments.Methods The TCMSP,SwissTargetPrediction,Uniprot,Genecards,OMIM,TTD,Disgenet,String database,and other related literature were searched to obtain active components in Aconitum Carmichaelii Debx Rhizoma,action targets Rhizoma,and corresponding disease targets.The intersection of action and disease targets was taken as the potential targets.A protein-protein interaction network(PPI)for potential targets was constructed based on String platform.The R language software package was used to analyze the function of gene ontology(GO)and the enrichment of Kyoto Encyclopedia of genes and genomes(KEGG),and then Cytoscape software was used to analyze its network topology and further screen core targets.Molecular docking was carried out to verify the predicted results.Subsequently,the effect of active components in Aconitum Carmichaelii Debx Rhizoma on the proliferation of vascular smooth muscle cells(vSMCs)induced by angiotensinⅡ(AngⅡ)was detected by MTT method.Results There are 15 main potential active components of Aconitum Carmichaelii Debx Rhizoma in the treatment of vasospasm and 27 drug-disease targets.The signaling pathways involved mainly include lipid and atherosclerosis,calcium signaling pathway,neuroactive ligand-receptor interaction,sphingolipid signaling pathway,fluid shear stress and atherosclerosis,relaxin signaling pathway,vascular smooth muscle contraction,etc.The stable conformations were formed between the core target and theactive component,hypaconitine and sitosterol.The results in vitro showed that hypaconitine may inhibit AngⅡ-induced proliferation and phenotype trans-formation of vSMCs through inactivating mitogen-activated protein kinase(MAPK)signaling pathways.Conclusion Various active components of Aconitum Ccarmichaelii Debx Rhizoma may play a role in the treatment of vasospasm by acting on targets,such as MAPK1,nuclear receptor subfamily 3 group C member 1(NR3C1),angiotensin I converting enzyme(ACE),nitric oxide synthase 3(NOS3),etc.The study provides a scientific basis for revealing the mechanism of active components of Aconitum Carmichaelii Debx Rhizoma in the treatment of vasospasm.

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