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Mechanism of Fructus Mume Pills Underlying Their Protective Effects in Rats with Acetic Acid-Inducedulcerative Colitis via the Regulation of Inflammatory Cytokines and the VEGF-PI3K/Akt-eNOS Signaling Pathway
BACKGROUND: Fructus mume pills (FMPs) have been clinically proven to be effective for treating ulcerative colitis (UC). However, the therapeutic and protective mechanisms have not been fully studied. AIM: We aimed to explore the mechanism of FMPs in an acetic acid (AA)-induced ulcerative colitis rat...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9129976/ https://www.ncbi.nlm.nih.gov/pubmed/35620404 http://dx.doi.org/10.1155/2022/4621131 |
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author | Xu, Zongying Zhang, Xueli Lu, Ruimin Zhang, Di Zou, Tianyuan Chen, Meng Zhang, Dongmei |
author_facet | Xu, Zongying Zhang, Xueli Lu, Ruimin Zhang, Di Zou, Tianyuan Chen, Meng Zhang, Dongmei |
author_sort | Xu, Zongying |
collection | PubMed |
description | BACKGROUND: Fructus mume pills (FMPs) have been clinically proven to be effective for treating ulcerative colitis (UC). However, the therapeutic and protective mechanisms have not been fully studied. AIM: We aimed to explore the mechanism of FMPs in an acetic acid (AA)-induced ulcerative colitis rat model. METHODS: The targets, GO terms, and KEGG pathways for the FMPs and UC were screened and constructed using network pharmacology. A possible mechanism was verified in a 4% AA-induced colitis rat model. Colitis activity and state were evaluated using the disease activity index, and colon ulceration and intestinal mucosal damage were determined by histopathological observation through HE, AB-PAS, and Masson pathological staining. The concentrations of TNF-α, IL-6, IL-8, IL-10, MPO, MMP9, CXCR1, eNOS, and VEGF were measured to evaluate vascular permeability effects. RESULTS: The network pharmacology results showed 108 active compounds, and 139 FMP-related targets were identified. Twenty-nine targets were identified for FMPs against UC, which included MMP9, MMP3, ESR1, PTGS1, PPARA, MPO, and NOS2. A total of 1,536 GO terms and 41 pathways were associated with FMP treatment of UC. The pharmacological evaluation showed that FMPs attenuated inflammation in AA-induced colitis by reducing the serum concentrations of TNF-α, IL-6, IL-8, and IL-10 and the colonic concentrations of MPO, MMP9, and CXCR1. FMPs ameliorated hyperpermeability by reducing the colonic VEGF and eNOS concentrations. FMPs also significantly decreased the VEGFA, VEGFR2, Src, and eNOS protein expressions in colon tissue through the VEGF-PI3K/Akt-eNOS signaling pathway. CONCLUSION: These results suggest that FMPs control UC inflammation by regulating inflammatory cytokine concentrations. FMPs alleviate AA-induced UC by regulating microvascular permeability through the VEGF-PI3K/Akt-eNOS signaling pathway. |
format | Online Article Text |
id | pubmed-9129976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-91299762022-05-25 Mechanism of Fructus Mume Pills Underlying Their Protective Effects in Rats with Acetic Acid-Inducedulcerative Colitis via the Regulation of Inflammatory Cytokines and the VEGF-PI3K/Akt-eNOS Signaling Pathway Xu, Zongying Zhang, Xueli Lu, Ruimin Zhang, Di Zou, Tianyuan Chen, Meng Zhang, Dongmei Evid Based Complement Alternat Med Research Article BACKGROUND: Fructus mume pills (FMPs) have been clinically proven to be effective for treating ulcerative colitis (UC). However, the therapeutic and protective mechanisms have not been fully studied. AIM: We aimed to explore the mechanism of FMPs in an acetic acid (AA)-induced ulcerative colitis rat model. METHODS: The targets, GO terms, and KEGG pathways for the FMPs and UC were screened and constructed using network pharmacology. A possible mechanism was verified in a 4% AA-induced colitis rat model. Colitis activity and state were evaluated using the disease activity index, and colon ulceration and intestinal mucosal damage were determined by histopathological observation through HE, AB-PAS, and Masson pathological staining. The concentrations of TNF-α, IL-6, IL-8, IL-10, MPO, MMP9, CXCR1, eNOS, and VEGF were measured to evaluate vascular permeability effects. RESULTS: The network pharmacology results showed 108 active compounds, and 139 FMP-related targets were identified. Twenty-nine targets were identified for FMPs against UC, which included MMP9, MMP3, ESR1, PTGS1, PPARA, MPO, and NOS2. A total of 1,536 GO terms and 41 pathways were associated with FMP treatment of UC. The pharmacological evaluation showed that FMPs attenuated inflammation in AA-induced colitis by reducing the serum concentrations of TNF-α, IL-6, IL-8, and IL-10 and the colonic concentrations of MPO, MMP9, and CXCR1. FMPs ameliorated hyperpermeability by reducing the colonic VEGF and eNOS concentrations. FMPs also significantly decreased the VEGFA, VEGFR2, Src, and eNOS protein expressions in colon tissue through the VEGF-PI3K/Akt-eNOS signaling pathway. CONCLUSION: These results suggest that FMPs control UC inflammation by regulating inflammatory cytokine concentrations. FMPs alleviate AA-induced UC by regulating microvascular permeability through the VEGF-PI3K/Akt-eNOS signaling pathway. Hindawi 2022-05-02 /pmc/articles/PMC9129976/ /pubmed/35620404 http://dx.doi.org/10.1155/2022/4621131 Text en Copyright © 2022 Zongying Xu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Xu, Zongying Zhang, Xueli Lu, Ruimin Zhang, Di Zou, Tianyuan Chen, Meng Zhang, Dongmei Mechanism of Fructus Mume Pills Underlying Their Protective Effects in Rats with Acetic Acid-Inducedulcerative Colitis via the Regulation of Inflammatory Cytokines and the VEGF-PI3K/Akt-eNOS Signaling Pathway |
title | Mechanism of Fructus Mume Pills Underlying Their Protective Effects in Rats with Acetic Acid-Inducedulcerative Colitis via the Regulation of Inflammatory Cytokines and the VEGF-PI3K/Akt-eNOS Signaling Pathway |
title_full | Mechanism of Fructus Mume Pills Underlying Their Protective Effects in Rats with Acetic Acid-Inducedulcerative Colitis via the Regulation of Inflammatory Cytokines and the VEGF-PI3K/Akt-eNOS Signaling Pathway |
title_fullStr | Mechanism of Fructus Mume Pills Underlying Their Protective Effects in Rats with Acetic Acid-Inducedulcerative Colitis via the Regulation of Inflammatory Cytokines and the VEGF-PI3K/Akt-eNOS Signaling Pathway |
title_full_unstemmed | Mechanism of Fructus Mume Pills Underlying Their Protective Effects in Rats with Acetic Acid-Inducedulcerative Colitis via the Regulation of Inflammatory Cytokines and the VEGF-PI3K/Akt-eNOS Signaling Pathway |
title_short | Mechanism of Fructus Mume Pills Underlying Their Protective Effects in Rats with Acetic Acid-Inducedulcerative Colitis via the Regulation of Inflammatory Cytokines and the VEGF-PI3K/Akt-eNOS Signaling Pathway |
title_sort | mechanism of fructus mume pills underlying their protective effects in rats with acetic acid-inducedulcerative colitis via the regulation of inflammatory cytokines and the vegf-pi3k/akt-enos signaling pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9129976/ https://www.ncbi.nlm.nih.gov/pubmed/35620404 http://dx.doi.org/10.1155/2022/4621131 |
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