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Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma
Background: Hepatocellular carcinoma (HCC) refers to one of the top 10 cancers in terms of morbidity and mortality globally, seriously influencing people’s lives. First recorded in Compendium of Materia Medica, liquidambaris fructus (LF) generates definite anti-liver tumor effect. However, its effec...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468745/ https://www.ncbi.nlm.nih.gov/pubmed/36110518 http://dx.doi.org/10.3389/fphar.2022.999935 |
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author | Wang, Shuai Yang, Xin-Xin Li, Tian-Jiao Zhao, Lin Bao, Yong-Rui Meng, Xian-Sheng |
author_facet | Wang, Shuai Yang, Xin-Xin Li, Tian-Jiao Zhao, Lin Bao, Yong-Rui Meng, Xian-Sheng |
author_sort | Wang, Shuai |
collection | PubMed |
description | Background: Hepatocellular carcinoma (HCC) refers to one of the top 10 cancers in terms of morbidity and mortality globally, seriously influencing people’s lives. First recorded in Compendium of Materia Medica, liquidambaris fructus (LF) generates definite anti-liver tumor effect. However, its effective substances and mechanism remain to be elucidated. Methods: Serum pharmacochemistry and UPLC-QTOF-MS technologies were employed to explore the plasma of rats after intragastric administration of liquidambaris fructus extract (LFE) in order to find the active ingredients. Subsequently, DEN-induced rat liver cancer model was established with the purpose of investigating the anti-tumor activity of LFE from physiological, pathological and biochemical aspects. Finally, non-target metabonomics combined with q-PCR and Western blot methods were adopted for revealing the mechanism. Results: Totally 11 prototype blood transfused ingredients, including imperatorin and phellopterin were detected. LFE presents excellent impact on enhancing the quality of life, prolonging the life cycle, reducing inflammatory reaction, protecting hepatocytes, improving body immunity and killing liver tumor cells. Altogether 82 endogenous differential metabolites were found in metabonomics, suggesting that LFE can treat HCC by acting on key targets of PTEN/PI3K/Akt pathway and fatty acid metabolism. Further research also verified that LFE can upregulate the relative expression levels of PTEN, PDCD4, Caspase 9, Caspase 3, Bax and Bad as well as lower the relative expression levels of PI3K, AKT, VEGFA and Bcl-2. Conclusion: This study revealed the pharmacodynamic material basis of LFE in the treatment of HCC, and from the perspective of metabolomics proved that the effects of inhibiting the growth of tumor cells, promoting tumor cell apoptosis, reducing inflammatory reaction, protecting hepatocytes, improving the survival state of tumor rats, and prolonging the life cycle are related to its impact on PTEN/PI3K/Akt, fatty acid metabolism and other key signal pathways. |
format | Online Article Text |
id | pubmed-9468745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94687452022-09-14 Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma Wang, Shuai Yang, Xin-Xin Li, Tian-Jiao Zhao, Lin Bao, Yong-Rui Meng, Xian-Sheng Front Pharmacol Pharmacology Background: Hepatocellular carcinoma (HCC) refers to one of the top 10 cancers in terms of morbidity and mortality globally, seriously influencing people’s lives. First recorded in Compendium of Materia Medica, liquidambaris fructus (LF) generates definite anti-liver tumor effect. However, its effective substances and mechanism remain to be elucidated. Methods: Serum pharmacochemistry and UPLC-QTOF-MS technologies were employed to explore the plasma of rats after intragastric administration of liquidambaris fructus extract (LFE) in order to find the active ingredients. Subsequently, DEN-induced rat liver cancer model was established with the purpose of investigating the anti-tumor activity of LFE from physiological, pathological and biochemical aspects. Finally, non-target metabonomics combined with q-PCR and Western blot methods were adopted for revealing the mechanism. Results: Totally 11 prototype blood transfused ingredients, including imperatorin and phellopterin were detected. LFE presents excellent impact on enhancing the quality of life, prolonging the life cycle, reducing inflammatory reaction, protecting hepatocytes, improving body immunity and killing liver tumor cells. Altogether 82 endogenous differential metabolites were found in metabonomics, suggesting that LFE can treat HCC by acting on key targets of PTEN/PI3K/Akt pathway and fatty acid metabolism. Further research also verified that LFE can upregulate the relative expression levels of PTEN, PDCD4, Caspase 9, Caspase 3, Bax and Bad as well as lower the relative expression levels of PI3K, AKT, VEGFA and Bcl-2. Conclusion: This study revealed the pharmacodynamic material basis of LFE in the treatment of HCC, and from the perspective of metabolomics proved that the effects of inhibiting the growth of tumor cells, promoting tumor cell apoptosis, reducing inflammatory reaction, protecting hepatocytes, improving the survival state of tumor rats, and prolonging the life cycle are related to its impact on PTEN/PI3K/Akt, fatty acid metabolism and other key signal pathways. Frontiers Media S.A. 2022-08-30 /pmc/articles/PMC9468745/ /pubmed/36110518 http://dx.doi.org/10.3389/fphar.2022.999935 Text en Copyright © 2022 Wang, Yang, Li, Zhao, Bao and Meng. 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 Wang, Shuai Yang, Xin-Xin Li, Tian-Jiao Zhao, Lin Bao, Yong-Rui Meng, Xian-Sheng Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma |
title | Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma |
title_full | Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma |
title_fullStr | Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma |
title_full_unstemmed | Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma |
title_short | Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma |
title_sort | analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468745/ https://www.ncbi.nlm.nih.gov/pubmed/36110518 http://dx.doi.org/10.3389/fphar.2022.999935 |
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