Study on Metabolic Trajectory of Liver Aging and the Effect of Fufang Zhenzhu Tiaozhi on Aging Mice
The aim of this study was to investigate the metabolic trajectory of liver aging, the effect of FTZ against liver aging in aging mice, and its mechanism using ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS).Methods: A total of 80 C57BL/6J Narl mice...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-08-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00926/full |
| _version_ | 1811288737882046464 |
|---|---|
| author | Duosheng Luo Duosheng Luo Jingbiao Li Jingbiao Li Kechun Chen Kechun Chen Yifan Yin Yifan Yin Zhaoyan Fang Zhaoyan Fang Huiting Pang Huiting Pang Xianglu Rong Xianglu Rong Jiao Guo Jiao Guo |
| author_facet | Duosheng Luo Duosheng Luo Jingbiao Li Jingbiao Li Kechun Chen Kechun Chen Yifan Yin Yifan Yin Zhaoyan Fang Zhaoyan Fang Huiting Pang Huiting Pang Xianglu Rong Xianglu Rong Jiao Guo Jiao Guo |
| author_sort | Duosheng Luo |
| collection | DOAJ |
| description | The aim of this study was to investigate the metabolic trajectory of liver aging, the effect of FTZ against liver aging in aging mice, and its mechanism using ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS).Methods: A total of 80 C57BL/6J Narl mice were randomly divided into five groups: 3-month-old group, 9-month-old group, 14-month-old group, 20-month-old group, and FTZ treatment group (20 months old). The mice in the treatment group received a therapeutic dose of oral FTZ extract (1.0 g/kg, on raw material weight basis) once daily during the experiment. The other groups received the corresponding volume of oral normal saline solution. Liver samples of all five groups were collected after 12 weeks, and UPLC-Q-TOF/MS was used to analyze metabolic changes. Orthogonal partial least squares–discriminant analysis (OPLS-DA) was used to analyze the resulting data. Additionally, cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), secretion levels of TNF-α, IL-6, 5-LOX, and COX-2, as well as their relative mRNA expression in the liver were determined.Results: The levels of TC, TG, AST, and ALT were increased, and liver tissue structure was damaged. The secretion levels of TNF-α, IL-6, 5-LOX, and COX-2, as well as their relative mRNA expression in the liver also increased with aging. FTZ administration reduced the symptoms of liver aging. The OPLS-DA score plot illustrated the effect of FTZ against liver aging, with N-acetyl-leukotriene E4, 20-hydroxy-leukotriene E4, leukotriene E4, and arachidonic acid among the key biomarkers. The pivotal pathways revealed by pathway analysis included arachidonic acid metabolism and biosynthesis of unsaturated fatty acids. The mechanism by which FTZ reduces the symptoms of liver aging in mice might be related to disorders of the abovementioned pathways.Conclusion: A metabolomic approach based on UPLC-Q-TOF/MS and multivariate statistical analysis was successfully applied to investigate the metabolic trajectory of liver aging. FTZ has a protective effect against liver aging, which may be mediated via interference with the metabolism of arachidonic acid, biosynthesis of unsaturated fatty acids, and downregulation of pro-inflammatory factors in the liver in mice in vivo. |
| first_indexed | 2024-04-13T03:42:29Z |
| format | Article |
| id | doaj.art-5e4a20d27a314ff4900c2836eca9a676 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T03:42:29Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-5e4a20d27a314ff4900c2836eca9a6762022-12-22T03:04:07ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-08-011010.3389/fphar.2019.00926462605Study on Metabolic Trajectory of Liver Aging and the Effect of Fufang Zhenzhu Tiaozhi on Aging MiceDuosheng Luo0Duosheng Luo1Jingbiao Li2Jingbiao Li3Kechun Chen4Kechun Chen5Yifan Yin6Yifan Yin7Zhaoyan Fang8Zhaoyan Fang9Huiting Pang10Huiting Pang11Xianglu Rong12Xianglu Rong13Jiao Guo14Jiao Guo15Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, ChinaKey Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, ChinaKey Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, ChinaKey Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, ChinaKey Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, ChinaKey Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, ChinaKey Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, ChinaKey Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, ChinaThe aim of this study was to investigate the metabolic trajectory of liver aging, the effect of FTZ against liver aging in aging mice, and its mechanism using ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS).Methods: A total of 80 C57BL/6J Narl mice were randomly divided into five groups: 3-month-old group, 9-month-old group, 14-month-old group, 20-month-old group, and FTZ treatment group (20 months old). The mice in the treatment group received a therapeutic dose of oral FTZ extract (1.0 g/kg, on raw material weight basis) once daily during the experiment. The other groups received the corresponding volume of oral normal saline solution. Liver samples of all five groups were collected after 12 weeks, and UPLC-Q-TOF/MS was used to analyze metabolic changes. Orthogonal partial least squares–discriminant analysis (OPLS-DA) was used to analyze the resulting data. Additionally, cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), secretion levels of TNF-α, IL-6, 5-LOX, and COX-2, as well as their relative mRNA expression in the liver were determined.Results: The levels of TC, TG, AST, and ALT were increased, and liver tissue structure was damaged. The secretion levels of TNF-α, IL-6, 5-LOX, and COX-2, as well as their relative mRNA expression in the liver also increased with aging. FTZ administration reduced the symptoms of liver aging. The OPLS-DA score plot illustrated the effect of FTZ against liver aging, with N-acetyl-leukotriene E4, 20-hydroxy-leukotriene E4, leukotriene E4, and arachidonic acid among the key biomarkers. The pivotal pathways revealed by pathway analysis included arachidonic acid metabolism and biosynthesis of unsaturated fatty acids. The mechanism by which FTZ reduces the symptoms of liver aging in mice might be related to disorders of the abovementioned pathways.Conclusion: A metabolomic approach based on UPLC-Q-TOF/MS and multivariate statistical analysis was successfully applied to investigate the metabolic trajectory of liver aging. FTZ has a protective effect against liver aging, which may be mediated via interference with the metabolism of arachidonic acid, biosynthesis of unsaturated fatty acids, and downregulation of pro-inflammatory factors in the liver in mice in vivo.https://www.frontiersin.org/article/10.3389/fphar.2019.00926/fullFufang Zhenzhu Tiaozhimetabolomicsliver agingultra-performance liquid chromatographymass spectrometry |
| spellingShingle | Duosheng Luo Duosheng Luo Jingbiao Li Jingbiao Li Kechun Chen Kechun Chen Yifan Yin Yifan Yin Zhaoyan Fang Zhaoyan Fang Huiting Pang Huiting Pang Xianglu Rong Xianglu Rong Jiao Guo Jiao Guo Study on Metabolic Trajectory of Liver Aging and the Effect of Fufang Zhenzhu Tiaozhi on Aging Mice Frontiers in Pharmacology Fufang Zhenzhu Tiaozhi metabolomics liver aging ultra-performance liquid chromatography mass spectrometry |
| title | Study on Metabolic Trajectory of Liver Aging and the Effect of Fufang Zhenzhu Tiaozhi on Aging Mice |
| title_full | Study on Metabolic Trajectory of Liver Aging and the Effect of Fufang Zhenzhu Tiaozhi on Aging Mice |
| title_fullStr | Study on Metabolic Trajectory of Liver Aging and the Effect of Fufang Zhenzhu Tiaozhi on Aging Mice |
| title_full_unstemmed | Study on Metabolic Trajectory of Liver Aging and the Effect of Fufang Zhenzhu Tiaozhi on Aging Mice |
| title_short | Study on Metabolic Trajectory of Liver Aging and the Effect of Fufang Zhenzhu Tiaozhi on Aging Mice |
| title_sort | study on metabolic trajectory of liver aging and the effect of fufang zhenzhu tiaozhi on aging mice |
| topic | Fufang Zhenzhu Tiaozhi metabolomics liver aging ultra-performance liquid chromatography mass spectrometry |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00926/full |
| work_keys_str_mv | AT duoshengluo studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT duoshengluo studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT jingbiaoli studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT jingbiaoli studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT kechunchen studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT kechunchen studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT yifanyin studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT yifanyin studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT zhaoyanfang studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT zhaoyanfang studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT huitingpang studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT huitingpang studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT xianglurong studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT xianglurong studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT jiaoguo studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice AT jiaoguo studyonmetabolictrajectoryofliveragingandtheeffectoffufangzhenzhutiaozhionagingmice |