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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.999935/full |
| _version_ | 1818494055305183232 |
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| author | Shuai Wang Shuai Wang Shuai Wang Xin-Xin Yang Xin-Xin Yang Xin-Xin Yang Tian-Jiao Li Tian-Jiao Li Tian-Jiao Li Lin Zhao Lin Zhao Lin Zhao Yong-Rui Bao Yong-Rui Bao Yong-Rui Bao Xian-Sheng Meng Xian-Sheng Meng Xian-Sheng Meng |
| author_facet | Shuai Wang Shuai Wang Shuai Wang Xin-Xin Yang Xin-Xin Yang Xin-Xin Yang Tian-Jiao Li Tian-Jiao Li Tian-Jiao Li Lin Zhao Lin Zhao Lin Zhao Yong-Rui Bao Yong-Rui Bao Yong-Rui Bao Xian-Sheng Meng Xian-Sheng Meng Xian-Sheng Meng |
| author_sort | Shuai Wang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T18:01:44Z |
| format | Article |
| id | doaj.art-d7d5675604eb48fd9017a30ae32cbae9 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T18:01:44Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d7d5675604eb48fd9017a30ae32cbae92022-12-22T01:38:45ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.999935999935Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinomaShuai Wang0Shuai Wang1Shuai Wang2Xin-Xin Yang3Xin-Xin Yang4Xin-Xin Yang5Tian-Jiao Li6Tian-Jiao Li7Tian-Jiao Li8Lin Zhao9Lin Zhao10Lin Zhao11Yong-Rui Bao12Yong-Rui Bao13Yong-Rui Bao14Xian-Sheng Meng15Xian-Sheng Meng16Xian-Sheng Meng17College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaLiaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, ChinaLiaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, ChinaCollege of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaLiaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, ChinaLiaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, ChinaCollege of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaLiaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, ChinaLiaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, ChinaCollege of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaLiaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, ChinaLiaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, ChinaCollege of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaLiaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, ChinaLiaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, ChinaCollege of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaLiaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, ChinaLiaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.999935/fullliquidambaris fructushepatocellular carcinomaabsorbed constituentspharmacology and efficacymechanism of action |
| spellingShingle | Shuai Wang Shuai Wang Shuai Wang Xin-Xin Yang Xin-Xin Yang Xin-Xin Yang Tian-Jiao Li Tian-Jiao Li Tian-Jiao Li Lin Zhao Lin Zhao Lin Zhao Yong-Rui Bao Yong-Rui Bao Yong-Rui Bao Xian-Sheng Meng Xian-Sheng Meng Xian-Sheng Meng Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma Frontiers in Pharmacology liquidambaris fructus hepatocellular carcinoma absorbed constituents pharmacology and efficacy mechanism of action |
| 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 | liquidambaris fructus hepatocellular carcinoma absorbed constituents pharmacology and efficacy mechanism of action |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.999935/full |
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