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Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli

Coptis chinensis Franch (CCF) is extensively used in the treatment of inflammatory-related diseases. Accumulating studies have previously demonstrated the anti-inflammatory properties of CCF, yet data on its exact targets against urinary tract infections (UTIs) remain largely unknown. Therefore, the...

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Autores principales: Chang, Zhenglin, Zhang, Jinhu, Lei, Min, Jiang, Zheng, Wu, Xiangkun, Huang, Yapeng, He, Zhican, Zhang, Yuyan, Li, Shujue, Duan, Xiaolu, Wu, Wenqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790249/
https://www.ncbi.nlm.nih.gov/pubmed/35095505
http://dx.doi.org/10.3389/fphar.2021.794869
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author Chang, Zhenglin
Zhang, Jinhu
Lei, Min
Jiang, Zheng
Wu, Xiangkun
Huang, Yapeng
He, Zhican
Zhang, Yuyan
Li, Shujue
Duan, Xiaolu
Wu, Wenqi
author_facet Chang, Zhenglin
Zhang, Jinhu
Lei, Min
Jiang, Zheng
Wu, Xiangkun
Huang, Yapeng
He, Zhican
Zhang, Yuyan
Li, Shujue
Duan, Xiaolu
Wu, Wenqi
author_sort Chang, Zhenglin
collection PubMed
description Coptis chinensis Franch (CCF) is extensively used in the treatment of inflammatory-related diseases. Accumulating studies have previously demonstrated the anti-inflammatory properties of CCF, yet data on its exact targets against urinary tract infections (UTIs) remain largely unknown. Therefore, the present study decodes the potential targets of action of CCF against UTIs by network pharmacology combined with experiment evaluations. Based on the pharmacology network analysis, the current study yielded six core ingredients: quercetin, palmatine (R)-canadine, berlambine, berberine, and berberrubine. The protein–protein interaction network (PPI) was generated by the string database, and then, four targets (IL6, FOS, MYC, and EGFR) were perceived as the major CCF targets using the CytoNCA plug-in. The results of molecular docking showed that the six core constituents of CCF had strong binding affinities toward the four key targets of UTIs after docking into the crystal structure. The enrichment analysis indicated that the possible regulatory mechanisms of CCF against UTIs were based on the modules of inflammation, immune responses, and apoptosis among others. Experimentally, the Escherichia coli (E. coli) strain CFT073 was applied to establish in vivo and in vitro models. In vivo results revealed that the key targets, IL6 and FOS, are significantly upregulated in rat bladder tissues of UTIs, whereas the expression of MYC and EGFR remained steady. Last, in vitro results further confirmed the therapeutic potential of CCF by reducing the expression of IL6 and FOS. In conclusion, IL6 and FOS were generally upregulated in the progression of E. coli–induced UTIs, whereas the CCF intervention exerted a preventive role in host cells stimulated by E. coli, partially due to inhibiting the expression of IL6 and FOS.
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spelling pubmed-87902492022-01-27 Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli Chang, Zhenglin Zhang, Jinhu Lei, Min Jiang, Zheng Wu, Xiangkun Huang, Yapeng He, Zhican Zhang, Yuyan Li, Shujue Duan, Xiaolu Wu, Wenqi Front Pharmacol Pharmacology Coptis chinensis Franch (CCF) is extensively used in the treatment of inflammatory-related diseases. Accumulating studies have previously demonstrated the anti-inflammatory properties of CCF, yet data on its exact targets against urinary tract infections (UTIs) remain largely unknown. Therefore, the present study decodes the potential targets of action of CCF against UTIs by network pharmacology combined with experiment evaluations. Based on the pharmacology network analysis, the current study yielded six core ingredients: quercetin, palmatine (R)-canadine, berlambine, berberine, and berberrubine. The protein–protein interaction network (PPI) was generated by the string database, and then, four targets (IL6, FOS, MYC, and EGFR) were perceived as the major CCF targets using the CytoNCA plug-in. The results of molecular docking showed that the six core constituents of CCF had strong binding affinities toward the four key targets of UTIs after docking into the crystal structure. The enrichment analysis indicated that the possible regulatory mechanisms of CCF against UTIs were based on the modules of inflammation, immune responses, and apoptosis among others. Experimentally, the Escherichia coli (E. coli) strain CFT073 was applied to establish in vivo and in vitro models. In vivo results revealed that the key targets, IL6 and FOS, are significantly upregulated in rat bladder tissues of UTIs, whereas the expression of MYC and EGFR remained steady. Last, in vitro results further confirmed the therapeutic potential of CCF by reducing the expression of IL6 and FOS. In conclusion, IL6 and FOS were generally upregulated in the progression of E. coli–induced UTIs, whereas the CCF intervention exerted a preventive role in host cells stimulated by E. coli, partially due to inhibiting the expression of IL6 and FOS. Frontiers Media S.A. 2022-01-12 /pmc/articles/PMC8790249/ /pubmed/35095505 http://dx.doi.org/10.3389/fphar.2021.794869 Text en Copyright © 2022 Chang, Zhang, Lei, Jiang, Wu, Huang, He, Zhang, Li, Duan and Wu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chang, Zhenglin
Zhang, Jinhu
Lei, Min
Jiang, Zheng
Wu, Xiangkun
Huang, Yapeng
He, Zhican
Zhang, Yuyan
Li, Shujue
Duan, Xiaolu
Wu, Wenqi
Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli
title Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli
title_full Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli
title_fullStr Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli
title_full_unstemmed Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli
title_short Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli
title_sort dissecting and evaluating the therapeutic targets of coptis chinensis franch in the treatment of urinary tract infections induced by escherichia coli
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790249/
https://www.ncbi.nlm.nih.gov/pubmed/35095505
http://dx.doi.org/10.3389/fphar.2021.794869
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