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Gegen Qinlian standard decoction alleviated irinotecan-induced diarrhea via PI3K/AKT/NF-κB axis by network pharmacology prediction and experimental validation combination
BACKGROUND: The frequently occurred chemotherapy-induced diarrhea (CID) caused by irinotecan (CPT-11) administration has been the most representative side-effects of CPT-11, resulting in the chemotherapy suspension or failure. Our previous studies indicated that Gegen Qinlian formula exhibited a sig...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134581/ https://www.ncbi.nlm.nih.gov/pubmed/37106406 http://dx.doi.org/10.1186/s13020-023-00747-3 |
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author | Chen, Jiamei Li, Min Chen, Rong Xu, Ziyi Yang, Xiaoqin Gu, Huan Zhang, Lele Fu, Chaomei Zhang, Jinming Wu, Yihan |
author_facet | Chen, Jiamei Li, Min Chen, Rong Xu, Ziyi Yang, Xiaoqin Gu, Huan Zhang, Lele Fu, Chaomei Zhang, Jinming Wu, Yihan |
author_sort | Chen, Jiamei |
collection | PubMed |
description | BACKGROUND: The frequently occurred chemotherapy-induced diarrhea (CID) caused by irinotecan (CPT-11) administration has been the most representative side-effects of CPT-11, resulting in the chemotherapy suspension or failure. Our previous studies indicated that Gegen Qinlian formula exhibited a significant alleviation effect on CPT-11-induced diarrhea. However, referencing to Japanese Kampo medicine, the TCM standard decoction would supply the gap between ancient preparation application and modern industrial production. METHODS: The LC–MS technology combined with network pharmacology was employed to identify the active ingredients and mechanisms of GQD standard decoction for CPT-11-induced diarrhea. The anti-inflammatory activities associated with intestinal barrier function of GQD standard decoction were studied by SN-38 activated NCM460 cells in vitro and CPT-11-induced diarrhea in vivo. Proteins involved in inflammation, mRNA levels, disease severity scores, and histology involved in intestinal inflammation were analysed. RESULTS: There were 37 active compounds were identified in GQD standard decoction. Network pharmacology analyses indicated that PI3K-AKT signaling pathway were probably the main pathway of GQD standard decoction in CPT-11-induced diarrhea treatment, and PIK3R1, AKT1, NF-κB1 were the core proteins. Moreover, we found that the key proteins and pathway predicted above was verified in vivo and in vitro experiments, and the GQD standard decoction could protect the cellular proliferation in vitro and ameliorate CPT-11-induced diarrhea in mice model. CONCLUSIONS: This study demonstrated the molecular mechanism of 37 active ingredients in GQD standard decoction against CPT-11-induced diarrhea. And the core proteins and pathway were validated by experiment. This data establishes the groundwork for particular molecular mechanism of GQD standard decoction active components, and this research can provide a scientific reference for the TCM therapy of CID. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-023-00747-3. |
format | Online Article Text |
id | pubmed-10134581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101345812023-04-28 Gegen Qinlian standard decoction alleviated irinotecan-induced diarrhea via PI3K/AKT/NF-κB axis by network pharmacology prediction and experimental validation combination Chen, Jiamei Li, Min Chen, Rong Xu, Ziyi Yang, Xiaoqin Gu, Huan Zhang, Lele Fu, Chaomei Zhang, Jinming Wu, Yihan Chin Med Research BACKGROUND: The frequently occurred chemotherapy-induced diarrhea (CID) caused by irinotecan (CPT-11) administration has been the most representative side-effects of CPT-11, resulting in the chemotherapy suspension or failure. Our previous studies indicated that Gegen Qinlian formula exhibited a significant alleviation effect on CPT-11-induced diarrhea. However, referencing to Japanese Kampo medicine, the TCM standard decoction would supply the gap between ancient preparation application and modern industrial production. METHODS: The LC–MS technology combined with network pharmacology was employed to identify the active ingredients and mechanisms of GQD standard decoction for CPT-11-induced diarrhea. The anti-inflammatory activities associated with intestinal barrier function of GQD standard decoction were studied by SN-38 activated NCM460 cells in vitro and CPT-11-induced diarrhea in vivo. Proteins involved in inflammation, mRNA levels, disease severity scores, and histology involved in intestinal inflammation were analysed. RESULTS: There were 37 active compounds were identified in GQD standard decoction. Network pharmacology analyses indicated that PI3K-AKT signaling pathway were probably the main pathway of GQD standard decoction in CPT-11-induced diarrhea treatment, and PIK3R1, AKT1, NF-κB1 were the core proteins. Moreover, we found that the key proteins and pathway predicted above was verified in vivo and in vitro experiments, and the GQD standard decoction could protect the cellular proliferation in vitro and ameliorate CPT-11-induced diarrhea in mice model. CONCLUSIONS: This study demonstrated the molecular mechanism of 37 active ingredients in GQD standard decoction against CPT-11-induced diarrhea. And the core proteins and pathway were validated by experiment. This data establishes the groundwork for particular molecular mechanism of GQD standard decoction active components, and this research can provide a scientific reference for the TCM therapy of CID. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-023-00747-3. BioMed Central 2023-04-27 /pmc/articles/PMC10134581/ /pubmed/37106406 http://dx.doi.org/10.1186/s13020-023-00747-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Chen, Jiamei Li, Min Chen, Rong Xu, Ziyi Yang, Xiaoqin Gu, Huan Zhang, Lele Fu, Chaomei Zhang, Jinming Wu, Yihan Gegen Qinlian standard decoction alleviated irinotecan-induced diarrhea via PI3K/AKT/NF-κB axis by network pharmacology prediction and experimental validation combination |
title | Gegen Qinlian standard decoction alleviated irinotecan-induced diarrhea via PI3K/AKT/NF-κB axis by network pharmacology prediction and experimental validation combination |
title_full | Gegen Qinlian standard decoction alleviated irinotecan-induced diarrhea via PI3K/AKT/NF-κB axis by network pharmacology prediction and experimental validation combination |
title_fullStr | Gegen Qinlian standard decoction alleviated irinotecan-induced diarrhea via PI3K/AKT/NF-κB axis by network pharmacology prediction and experimental validation combination |
title_full_unstemmed | Gegen Qinlian standard decoction alleviated irinotecan-induced diarrhea via PI3K/AKT/NF-κB axis by network pharmacology prediction and experimental validation combination |
title_short | Gegen Qinlian standard decoction alleviated irinotecan-induced diarrhea via PI3K/AKT/NF-κB axis by network pharmacology prediction and experimental validation combination |
title_sort | gegen qinlian standard decoction alleviated irinotecan-induced diarrhea via pi3k/akt/nf-κb axis by network pharmacology prediction and experimental validation combination |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134581/ https://www.ncbi.nlm.nih.gov/pubmed/37106406 http://dx.doi.org/10.1186/s13020-023-00747-3 |
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