Elucidating the therapeutic mechanism of Atractylodes lancea for ulcerative colitis based upon network pharmacology and animal experiments
OBJECTIVE To elucidate the therapeutic mechanism of Atractylodes lancea for ulcerative colitis(UC)based upon network pharmacology and in vivo experiments.METHODS The active ingredients and potential targets of Atractylodes lancea were selected through the databases of TCMSP and BATMAN-TCM.And the relevant targets of UC were retrieved through the databases of OMIM and GeneCards.Then the above targets were entered into Venny 2.1 for intersecting with impor-tant disease targets of UC.For obtaining a common target of Atractylodes lancea against UC,a"Atractylodes lancea-active ingredient-common target"network of Atractylodes lancea against UC was constructed with Cytoscape 3.7.1 and its key active ingredients were examined.Common targets were imported into the database of STRING for constructing a protein-protein inter-action(PPI)network diagram and screening out core targets.Common targets were imported into the database of Matescape for Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Then Maestro 11.1 software was utilized for molecular docking between the active components of Atractylodes lancea and the core targets.After an induction of dextran sodium sulfate(DSS),BALB/c mice were randomized into four groups of control group,model,Atracty-lodes lancea extract(1 110 mg·kg-1·d-1)and sulfasalazine(SASP,250 mg·kg-1·d-1)(n=6 each).After a once daily gavage(10 mL·kg-1)for 7 consecutive days,the animals were sacrificed at Hour 1 after the last dosing with relevant indicators tested.RESULTS There were 26 potential active ingredients of Atractylodes lancea against UC and 273 drug disease common targets.KEGG enrichment analysis revealed that the major signaling pathways of cancer,MAPK and PI3K/Akt.The result of molecular docking indicated a strong affinity between its key components and core targets.Animal experiments showed that Atractylodes lancea could significantly enhance colonic length,lower DAI scores and lessen the degree of colonic tissue lesions,boost the num-ber of goblet cells,suppress the high expressions of IL-1β,MMP-2 and MMP-9 in colonic tissue and modulate the activation of PI3K/Akt signaling pathway.CONCLUSION This study has preliminarily confirmed that Atractylodes lancea could improve colonic injury in UC through participating in the regulation of PI3K/Akt signaling pathway and inflammatory targets(e.g.IL-1β).It provided scientific and theoretical rationales for in-depth researches on the mechanism of Atractylodes lancea and its active ingredients against UC.
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