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β-Patchoulene Ameliorates Water Transport and the Mucus Barrier in 5-Fluorouracil-Induced Intestinal Mucositis Rats via the cAMP/PKA/CREB Signaling Pathway
Intestinal mucositis (IM) is the main side effect observed in patients who receive cancer chemotherapy. The characteristics of ulceration, vomiting, and severe diarrhea cause patients to delay or abandon further treatment, thereby aggravating their progress. Hence, IM cannot be overlooked. β-patchou...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424048/ https://www.ncbi.nlm.nih.gov/pubmed/34512326 http://dx.doi.org/10.3389/fphar.2021.689491 |
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author | Wu, Jiazhen Gan, Yuxuan Luo, Huijuan Xu, Nan Chen, Liping Li, Mengyao Guan, Fengkun Su, Ziren Lin, Zhixiu Xie, Jianhui Liu, Yuhong |
author_facet | Wu, Jiazhen Gan, Yuxuan Luo, Huijuan Xu, Nan Chen, Liping Li, Mengyao Guan, Fengkun Su, Ziren Lin, Zhixiu Xie, Jianhui Liu, Yuhong |
author_sort | Wu, Jiazhen |
collection | PubMed |
description | Intestinal mucositis (IM) is the main side effect observed in patients who receive cancer chemotherapy. The characteristics of ulceration, vomiting, and severe diarrhea cause patients to delay or abandon further treatment, thereby aggravating their progress. Hence, IM cannot be overlooked. β-patchoulene (β-PAE) is an active ingredient isolated from Pogostemon cablin (Blanco) Benth (Labiatae) and has shown a marked protective effect against gastrointestinal diseases in previous studies. However, whether β-PAE plays a positive role in IM is still unknown. Herein, we explore the effects and the underlying mechanism of β-PAE against 5-fluorouracil (5-FU)-induced IM in IEC-6 cells and rats. β-PAE significantly recovered cell viability, upregulated the IM-induced rat body weight and food intake and improved the pathological diarrhea symptoms. Aquaporin is critical for regulating water fluid homeostasis, and its abnormal expression was associated with pathological diarrhea in IM. β-PAE displayed an outstanding effect in inhibiting aquaporin 3 (AQP3) via the cAMP/protein kinase A (PKA)/cAMP-response element-binding protein (CREB) signaling pathway. Besides, inflammation-induced mucus barrier injury deteriorated water transport and aggravated diarrhea in IM-induced rats. β-PAE’s effect on suppressing inflammation and recovering the mucus barrier strengthened its regulation of water transport and thus alleviated diarrhea in IM-induced rats. In sum, β-PAE improved IM in rats mainly by improving water transport and the mucus barrier, and these effects were correlated with its function on inhibiting the cAMP/PKA/CREB signaling pathway. |
format | Online Article Text |
id | pubmed-8424048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84240482021-09-09 β-Patchoulene Ameliorates Water Transport and the Mucus Barrier in 5-Fluorouracil-Induced Intestinal Mucositis Rats via the cAMP/PKA/CREB Signaling Pathway Wu, Jiazhen Gan, Yuxuan Luo, Huijuan Xu, Nan Chen, Liping Li, Mengyao Guan, Fengkun Su, Ziren Lin, Zhixiu Xie, Jianhui Liu, Yuhong Front Pharmacol Pharmacology Intestinal mucositis (IM) is the main side effect observed in patients who receive cancer chemotherapy. The characteristics of ulceration, vomiting, and severe diarrhea cause patients to delay or abandon further treatment, thereby aggravating their progress. Hence, IM cannot be overlooked. β-patchoulene (β-PAE) is an active ingredient isolated from Pogostemon cablin (Blanco) Benth (Labiatae) and has shown a marked protective effect against gastrointestinal diseases in previous studies. However, whether β-PAE plays a positive role in IM is still unknown. Herein, we explore the effects and the underlying mechanism of β-PAE against 5-fluorouracil (5-FU)-induced IM in IEC-6 cells and rats. β-PAE significantly recovered cell viability, upregulated the IM-induced rat body weight and food intake and improved the pathological diarrhea symptoms. Aquaporin is critical for regulating water fluid homeostasis, and its abnormal expression was associated with pathological diarrhea in IM. β-PAE displayed an outstanding effect in inhibiting aquaporin 3 (AQP3) via the cAMP/protein kinase A (PKA)/cAMP-response element-binding protein (CREB) signaling pathway. Besides, inflammation-induced mucus barrier injury deteriorated water transport and aggravated diarrhea in IM-induced rats. β-PAE’s effect on suppressing inflammation and recovering the mucus barrier strengthened its regulation of water transport and thus alleviated diarrhea in IM-induced rats. In sum, β-PAE improved IM in rats mainly by improving water transport and the mucus barrier, and these effects were correlated with its function on inhibiting the cAMP/PKA/CREB signaling pathway. Frontiers Media S.A. 2021-08-25 /pmc/articles/PMC8424048/ /pubmed/34512326 http://dx.doi.org/10.3389/fphar.2021.689491 Text en Copyright © 2021 Wu, Gan, Luo, Xu, Chen, Li, Guan, Su, Lin, Xie and Liu. 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 Wu, Jiazhen Gan, Yuxuan Luo, Huijuan Xu, Nan Chen, Liping Li, Mengyao Guan, Fengkun Su, Ziren Lin, Zhixiu Xie, Jianhui Liu, Yuhong β-Patchoulene Ameliorates Water Transport and the Mucus Barrier in 5-Fluorouracil-Induced Intestinal Mucositis Rats via the cAMP/PKA/CREB Signaling Pathway |
title | β-Patchoulene Ameliorates Water Transport and the Mucus Barrier in 5-Fluorouracil-Induced Intestinal Mucositis Rats via the cAMP/PKA/CREB Signaling Pathway |
title_full | β-Patchoulene Ameliorates Water Transport and the Mucus Barrier in 5-Fluorouracil-Induced Intestinal Mucositis Rats via the cAMP/PKA/CREB Signaling Pathway |
title_fullStr | β-Patchoulene Ameliorates Water Transport and the Mucus Barrier in 5-Fluorouracil-Induced Intestinal Mucositis Rats via the cAMP/PKA/CREB Signaling Pathway |
title_full_unstemmed | β-Patchoulene Ameliorates Water Transport and the Mucus Barrier in 5-Fluorouracil-Induced Intestinal Mucositis Rats via the cAMP/PKA/CREB Signaling Pathway |
title_short | β-Patchoulene Ameliorates Water Transport and the Mucus Barrier in 5-Fluorouracil-Induced Intestinal Mucositis Rats via the cAMP/PKA/CREB Signaling Pathway |
title_sort | β-patchoulene ameliorates water transport and the mucus barrier in 5-fluorouracil-induced intestinal mucositis rats via the camp/pka/creb signaling pathway |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424048/ https://www.ncbi.nlm.nih.gov/pubmed/34512326 http://dx.doi.org/10.3389/fphar.2021.689491 |
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