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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...

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Autores principales: Xu, Zongying, Zhang, Xueli, Lu, Ruimin, Zhang, Di, Zou, Tianyuan, Chen, Meng, Zhang, Dongmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
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.
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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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