Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver Injury
Green tea extract (GTE) is popular in weight loss, and epigallocatechin gallate (EGCG) is considered as the main active component. However, GTE is the primary cause of herbal and dietary supplement-induced liver injury in the United States. Whether there is a greater risk of liver injury when EGCG i...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.609378/full |
| _version_ | 1818913976043438080 |
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| author | Zhuo Shi Zhuo Shi Jing-xiao Zhu Jing-xiao Zhu Yu-ming Guo Ming Niu Le Zhang Can Tu Ying Huang Ying Huang Peng-yan Li Xu Zhao Zi-teng Zhang Zhao-fang Bai Guang-qin Zhang Yang Lu Xiao-he Xiao Jia-bo Wang Jia-bo Wang |
| author_facet | Zhuo Shi Zhuo Shi Jing-xiao Zhu Jing-xiao Zhu Yu-ming Guo Ming Niu Le Zhang Can Tu Ying Huang Ying Huang Peng-yan Li Xu Zhao Zi-teng Zhang Zhao-fang Bai Guang-qin Zhang Yang Lu Xiao-he Xiao Jia-bo Wang Jia-bo Wang |
| author_sort | Zhuo Shi |
| collection | DOAJ |
| description | Green tea extract (GTE) is popular in weight loss, and epigallocatechin gallate (EGCG) is considered as the main active component. However, GTE is the primary cause of herbal and dietary supplement-induced liver injury in the United States. Whether there is a greater risk of liver injury when EGCG is consumed during dieting for weight loss has not been previously reported. This study found for the first time that EGCG could induce enhanced lipid metabolism pathways, suggesting that EGCG had the so-called “fat burning” effect, although EGCG did not cause liver injury at doses of 400 or 800 mg/kg in normal mice. Intriguingly, we found that EGCG caused dose-dependent hepatotoxicity on mice under dietary restriction, suggesting the potential combination effects of dietary restriction and EGCG. The combination effect between EGCG and dietary restriction led to overactivation of linoleic acid and arachidonic acid oxidation pathways, significantly increasing the accumulation of pro-inflammatory lipid metabolites and thus mediating liver injury. We also found that the disruption of Lands’ cycle and sphingomyelin-ceramides cycle and the high expression of taurine-conjugated bile acids were important metabolomic characteristics in EGCG-induced liver injury under dietary restriction. This original discovery suggests that people should not go on a diet while consuming EGCG for weight loss; otherwise the risk of liver injury will be significantly increased. This discovery provides new evidence for understanding the “drug-host” interaction hypothesis of drug hepatotoxicity and provides experimental reference for clinical safe use of green tea-related dietary supplements. |
| first_indexed | 2024-12-19T23:39:02Z |
| format | Article |
| id | doaj.art-01d041b037a04df28afe4b8922a10e50 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T23:39:02Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-01d041b037a04df28afe4b8922a10e502022-12-21T20:01:29ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-01-011110.3389/fphar.2020.609378609378Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver InjuryZhuo Shi0Zhuo Shi1Jing-xiao Zhu2Jing-xiao Zhu3Yu-ming Guo4Ming Niu5Le Zhang6Can Tu7Ying Huang8Ying Huang9Peng-yan Li10Xu Zhao11Zi-teng Zhang12Zhao-fang Bai13Guang-qin Zhang14Yang Lu15Xiao-he Xiao16Jia-bo Wang17Jia-bo Wang18School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaHunan University of Chinese Medicine, Changsha, ChinaChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaCollege of Pharmacy, Southwest Minzu University, Chengdu, ChinaBeijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaHunan University of Chinese Medicine, Changsha, ChinaChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaIntegrative Medical Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaGreen tea extract (GTE) is popular in weight loss, and epigallocatechin gallate (EGCG) is considered as the main active component. However, GTE is the primary cause of herbal and dietary supplement-induced liver injury in the United States. Whether there is a greater risk of liver injury when EGCG is consumed during dieting for weight loss has not been previously reported. This study found for the first time that EGCG could induce enhanced lipid metabolism pathways, suggesting that EGCG had the so-called “fat burning” effect, although EGCG did not cause liver injury at doses of 400 or 800 mg/kg in normal mice. Intriguingly, we found that EGCG caused dose-dependent hepatotoxicity on mice under dietary restriction, suggesting the potential combination effects of dietary restriction and EGCG. The combination effect between EGCG and dietary restriction led to overactivation of linoleic acid and arachidonic acid oxidation pathways, significantly increasing the accumulation of pro-inflammatory lipid metabolites and thus mediating liver injury. We also found that the disruption of Lands’ cycle and sphingomyelin-ceramides cycle and the high expression of taurine-conjugated bile acids were important metabolomic characteristics in EGCG-induced liver injury under dietary restriction. This original discovery suggests that people should not go on a diet while consuming EGCG for weight loss; otherwise the risk of liver injury will be significantly increased. This discovery provides new evidence for understanding the “drug-host” interaction hypothesis of drug hepatotoxicity and provides experimental reference for clinical safe use of green tea-related dietary supplements.https://www.frontiersin.org/articles/10.3389/fphar.2020.609378/fullgreen tea extractepigallocatechin gallatehepatotoxicitycombination effectlipid metabolismmetabolomics |
| spellingShingle | Zhuo Shi Zhuo Shi Jing-xiao Zhu Jing-xiao Zhu Yu-ming Guo Ming Niu Le Zhang Can Tu Ying Huang Ying Huang Peng-yan Li Xu Zhao Zi-teng Zhang Zhao-fang Bai Guang-qin Zhang Yang Lu Xiao-he Xiao Jia-bo Wang Jia-bo Wang Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver Injury Frontiers in Pharmacology green tea extract epigallocatechin gallate hepatotoxicity combination effect lipid metabolism metabolomics |
| title | Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver Injury |
| title_full | Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver Injury |
| title_fullStr | Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver Injury |
| title_full_unstemmed | Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver Injury |
| title_short | Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver Injury |
| title_sort | epigallocatechin gallate during dietary restriction potential mechanisms of enhanced liver injury |
| topic | green tea extract epigallocatechin gallate hepatotoxicity combination effect lipid metabolism metabolomics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.609378/full |
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