| Abstrakt: |
Ilex Cornutastems (ICSs) have been known for anti-inflammatory agents in East Asia, including Korea, and gut microbiota (GM) might have combinational effects with ICSs via its orchestrated mode. Extensively, ICSs, GM, mechanism(s), target(s), and bioactive(s) for the treatment of Crohn's disease (CD) as severe inflammatory symptoms have yet to be studied with holistic viewpoint. Thus, this study is to focus on elucidating the therapeutic components between ICSs and GM with the devised platform. The biomolecules from ICSs were identified by gas chromatography mass spectrometry (GC-MS) and its corresponding targets were retrieved by cheminformatics. In parallel, CD-responded targets were selected by human disease databases. The protein-protein interaction (PPI) network, mechanisms, GM's metabolites, and ICSs; GM-mechanism-targets-biomolecules (IG-M-T-B) network were constructed by R program. Finally, molecular docking test (MDT) and density functional theory (DFT) were employed to identify key bioactive(s) against CD. The 44 biomolecules from ICSs, its 311 corresponding targets, 1437 targets responded to CD, and final 82 targets were identified by data-driven analysis. IL6+Equol was the most notable component in PPI networks (82 nodes, and 618 edges), indicating that Equol enables to produce from Lactobacillus paracasei JS1. Then, a key mechanism (PI3K-Akt signaling pathway), key targets (IL6, MAPK1, PIK3CG, MDM2, MCL1, PRKCA, and FGF2), and six biomolecules were revealed by MDT, and DFT. Overall, this study suggests that the incorporated strategy between ICSs and GM holds therapeutic potentiality with inactivating PI3K-Akt signaling pathway against CD. |
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