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Decoding the key compounds and mechanism of Shashen Maidong decoction in the treatment of lung cancer
BACKGROUND: Lung cancer is a malignant tumour with the fastest increase in morbidity and mortality around the world. The clinical treatments available have significant side effects, thus it is desirable to identify alternative modalities to treat lung cancer. Shashen Maidong decoction (SMD) is a com...
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/PMC10184424/ https://www.ncbi.nlm.nih.gov/pubmed/37189139 http://dx.doi.org/10.1186/s12906-023-03985-y |
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author | Cai, Jieqi Chen, Yupeng Wang, Kexin Li, Yi Wu, Jie Yu, Hailang Li, Qingping Wu, Qi Meng, Wei Wang, Handuo Lu, Aiping Huang, Mianbo Wei, Genxia Guan, Daogang |
author_facet | Cai, Jieqi Chen, Yupeng Wang, Kexin Li, Yi Wu, Jie Yu, Hailang Li, Qingping Wu, Qi Meng, Wei Wang, Handuo Lu, Aiping Huang, Mianbo Wei, Genxia Guan, Daogang |
author_sort | Cai, Jieqi |
collection | PubMed |
description | BACKGROUND: Lung cancer is a malignant tumour with the fastest increase in morbidity and mortality around the world. The clinical treatments available have significant side effects, thus it is desirable to identify alternative modalities to treat lung cancer. Shashen Maidong decoction (SMD) is a commonly used traditional Chinese medicine (TCM) formula for treating lung cancer in the clinic. While the key functional components (KFC) and the underlying mechanisms of SMD treating lung cancer are still unclear. METHODS: We propose a new integrated pharmacology model, which combines a novel node-importance calculation method and the contribution decision rate (CDR) model, to identify the KFC of SMD and to deduce their mechanisms in the treatment of lung cancer. RESULTS: The enriched effective Gene Ontology (GO) terms selected from our proposed node importance detection method could cover 97.66% of enriched GO terms of reference targets. After calculating CDR of active components in key functional network, the first 82 components covered 90.25% of the network information, which were defined as KFC. 82 KFC were subjected to functional analysis and experimental validation. 5–40 μM protocatechuic acid, 100–400 μM paeonol or caffeic acid exerted significant inhibitory activity on the proliferation of A549 cells. The results show that KFC play an important therapeutic role in the treatment of lung cancer by targeting Ras, AKT, IKK, Raf1, MEK, and NF-κB in the PI3K-Akt, MAPK, SCLC, and NSCLC signaling pathways active in lung cancer. CONCLUSIONS: This study provides a methodological reference for the optimization and secondary development of TCM formulas. The strategy proposed in this study can be used to identify key compounds in the complex network and provides an operable test range for subsequent experimental verification, which greatly reduces the experimental workload. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-023-03985-y. |
format | Online Article Text |
id | pubmed-10184424 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101844242023-05-16 Decoding the key compounds and mechanism of Shashen Maidong decoction in the treatment of lung cancer Cai, Jieqi Chen, Yupeng Wang, Kexin Li, Yi Wu, Jie Yu, Hailang Li, Qingping Wu, Qi Meng, Wei Wang, Handuo Lu, Aiping Huang, Mianbo Wei, Genxia Guan, Daogang BMC Complement Med Ther Research BACKGROUND: Lung cancer is a malignant tumour with the fastest increase in morbidity and mortality around the world. The clinical treatments available have significant side effects, thus it is desirable to identify alternative modalities to treat lung cancer. Shashen Maidong decoction (SMD) is a commonly used traditional Chinese medicine (TCM) formula for treating lung cancer in the clinic. While the key functional components (KFC) and the underlying mechanisms of SMD treating lung cancer are still unclear. METHODS: We propose a new integrated pharmacology model, which combines a novel node-importance calculation method and the contribution decision rate (CDR) model, to identify the KFC of SMD and to deduce their mechanisms in the treatment of lung cancer. RESULTS: The enriched effective Gene Ontology (GO) terms selected from our proposed node importance detection method could cover 97.66% of enriched GO terms of reference targets. After calculating CDR of active components in key functional network, the first 82 components covered 90.25% of the network information, which were defined as KFC. 82 KFC were subjected to functional analysis and experimental validation. 5–40 μM protocatechuic acid, 100–400 μM paeonol or caffeic acid exerted significant inhibitory activity on the proliferation of A549 cells. The results show that KFC play an important therapeutic role in the treatment of lung cancer by targeting Ras, AKT, IKK, Raf1, MEK, and NF-κB in the PI3K-Akt, MAPK, SCLC, and NSCLC signaling pathways active in lung cancer. CONCLUSIONS: This study provides a methodological reference for the optimization and secondary development of TCM formulas. The strategy proposed in this study can be used to identify key compounds in the complex network and provides an operable test range for subsequent experimental verification, which greatly reduces the experimental workload. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-023-03985-y. BioMed Central 2023-05-15 /pmc/articles/PMC10184424/ /pubmed/37189139 http://dx.doi.org/10.1186/s12906-023-03985-y 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 Cai, Jieqi Chen, Yupeng Wang, Kexin Li, Yi Wu, Jie Yu, Hailang Li, Qingping Wu, Qi Meng, Wei Wang, Handuo Lu, Aiping Huang, Mianbo Wei, Genxia Guan, Daogang Decoding the key compounds and mechanism of Shashen Maidong decoction in the treatment of lung cancer |
title | Decoding the key compounds and mechanism of Shashen Maidong decoction in the treatment of lung cancer |
title_full | Decoding the key compounds and mechanism of Shashen Maidong decoction in the treatment of lung cancer |
title_fullStr | Decoding the key compounds and mechanism of Shashen Maidong decoction in the treatment of lung cancer |
title_full_unstemmed | Decoding the key compounds and mechanism of Shashen Maidong decoction in the treatment of lung cancer |
title_short | Decoding the key compounds and mechanism of Shashen Maidong decoction in the treatment of lung cancer |
title_sort | decoding the key compounds and mechanism of shashen maidong decoction in the treatment of lung cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10184424/ https://www.ncbi.nlm.nih.gov/pubmed/37189139 http://dx.doi.org/10.1186/s12906-023-03985-y |
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