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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Frontiers Media S.A.
2022-01-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.794869/full |
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author | Zhenglin Chang Zhenglin Chang Jinhu Zhang Min Lei Min Lei Zheng Jiang Zheng Jiang Xiangkun Wu Yapeng Huang Yapeng Huang Zhican He Zhican He Yuyan Zhang Shujue Li Xiaolu Duan Wenqi Wu Wenqi Wu |
author_facet | Zhenglin Chang Zhenglin Chang Jinhu Zhang Min Lei Min Lei Zheng Jiang Zheng Jiang Xiangkun Wu Yapeng Huang Yapeng Huang Zhican He Zhican He Yuyan Zhang Shujue Li Xiaolu Duan Wenqi Wu Wenqi Wu |
author_sort | Zhenglin Chang |
collection | DOAJ |
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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last_indexed | 2024-04-11T16:57:50Z |
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spelling | doaj.art-4a0e4c405b3d41d28c8a64d620e1bb2d2022-12-22T04:13:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011210.3389/fphar.2021.794869794869Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coliZhenglin Chang0Zhenglin Chang1Jinhu Zhang2Min Lei3Min Lei4Zheng Jiang5Zheng Jiang6Xiangkun Wu7Yapeng Huang8Yapeng Huang9Zhican He10Zhican He11Yuyan Zhang12Shujue Li13Xiaolu Duan14Wenqi Wu15Wenqi Wu16Guangdong Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Urology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Urology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Urology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Pathology, Nanfang Hospital and Basic Medical College, Southern Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Urology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Urology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Institute of Dermatology, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Urology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaCoptis 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.794869/fullanti-inflammatorymolecular dockingnetwork pharmacologyUTIscoptis chinensis Franch |
spellingShingle | Zhenglin Chang Zhenglin Chang Jinhu Zhang Min Lei Min Lei Zheng Jiang Zheng Jiang Xiangkun Wu Yapeng Huang Yapeng Huang Zhican He Zhican He Yuyan Zhang Shujue Li Xiaolu Duan Wenqi Wu Wenqi Wu Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli Frontiers in Pharmacology anti-inflammatory molecular docking network pharmacology UTIs coptis chinensis Franch |
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 | anti-inflammatory molecular docking network pharmacology UTIs coptis chinensis Franch |
url | https://www.frontiersin.org/articles/10.3389/fphar.2021.794869/full |
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