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Huaiyu pill (槐榆片) alleviates inflammatory bowel disease in mice via blocking toll like receptor 4/ myeloid differentiation primary response gene 88/ nuclear factor kappa B subunit 1 pathway
Received date: 2024-01-22
Accepted date: 2024-05-15
Online published: 2024-07-19
Supported by
Mechanistic Study on the Regulation of Mucin 2/interleukin 6-signal Transducer and Activator of Transcription 3 Signaling Pathway by Active Saponin Ardisiacrispin B in Improving Ulcerative Colitis Intestinal Mucosal Barrier Dysfunction(A2022479);Mechanistic Study on the Regulation of Inflammatory Microenvironment and Improvement of Ulcerative Colitis by Lingnan Traditional Medicine Ficus Quercifolia through Wilms' tumor 1-associating Protein-Mediated RNA Methyltransferase Promoting Toll Like Receptor 4 m6A Modification(2023A1515011699)
OBJECTIVE: To investigate the therapeutic effects of Huaiyu pill (槐榆片, HYP) on inflammatory bowel disease (IBD) and the underlying mechanisms have not been elucidated.
METHODS: To establish the IBD model, mice were administered with dextran sulfate sodium (DSS). Mice were intragastrically pre-treated with sulfasalazine (SASP) and HYP. Disease activity index (DAI) and colon length were monitored, and the colonic tissues were subjected to hematoxylin-eosin staining. Pro-inflammatory factors and vascular inflammation-related proteins were determined using enzyme-linked immunosorbent assay (ELISA). The potential mechanisms of HYP were examined using network pharmacology analysis.The expressions of zona occludens 1 (ZO-1), occludin, toll like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MYD88), and nuclear factor kappa B p65 subunit (NF-κB p65) in colon tissues were examined using Western blotting or immunohistochemical analyses.
RESULTS: Pre-treatment with HYP enhanced the colon length, decreased DAI scores, and mitigated histopathological alterations in DSS-treated mice. HYP alleviated intestinal inflammation by downregulating the levels of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and interleukin 17 (IL-17). Additionally, HYP suppressed the disruption of the gut barrier by upregulating the ZO-1, occludin, and mucin 2 (MUC2) levels and downregulating the endothelin 1 (ET-1) and erythropoietin (EPO) levels. Network pharmacological analysis and experimental results revealed that HYP downregulated the colonic tissue levels of TLR4, MYD88, and NF-κB p65 in DSS-treated mice.
CONCLUSION: This study investigated the in vivotherapeutic effects of HYP on IBD and the underlying molecular mechanisms. These findings provide an experimental foundation for the clinical application of HYP.
Chunyan YANG , Jia LUO , Weijie PENG , Weibo DAI . Huaiyu pill (槐榆片) alleviates inflammatory bowel disease in mice via blocking toll like receptor 4/ myeloid differentiation primary response gene 88/ nuclear factor kappa B subunit 1 pathway[J]. Journal of Traditional Chinese Medicine, 2024 , 44(5) : 916 -925 . DOI: 10.19852/j.cnki.jtcm.20240719.001
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