Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in Mice
Intrahepatic cholestasis is a serious symptom of liver disorders with limited therapies. In this study, we investigated the efficacy of Huangqi decoction (HQD), a two-herb classic traditional Chinese medicine (TCM), in the treatment of alpha-naphthylisothiocyanate (ANIT)-induced intrahepatic cholest...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00938/full |
| _version_ | 1811317470418436096 |
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| author | Jia-Sheng Wu Yi-Fei Li Yuan-Yuan Li Yan Dai Wen-Kai Li Min Zheng Zheng-Chun Shi Rong Shi Tian-Ming Wang Bing-Liang Ma Ping Liu Yue-Ming Ma Yue-Ming Ma |
| author_facet | Jia-Sheng Wu Yi-Fei Li Yuan-Yuan Li Yan Dai Wen-Kai Li Min Zheng Zheng-Chun Shi Rong Shi Tian-Ming Wang Bing-Liang Ma Ping Liu Yue-Ming Ma Yue-Ming Ma |
| author_sort | Jia-Sheng Wu |
| collection | DOAJ |
| description | Intrahepatic cholestasis is a serious symptom of liver disorders with limited therapies. In this study, we investigated the efficacy of Huangqi decoction (HQD), a two-herb classic traditional Chinese medicine (TCM), in the treatment of alpha-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. HQD treatment ameliorated impaired hepatic function and tissue damage. A metabolomics study revealed that the endogenous metabolites significantly affected by HQD were related to bile acid (BA) biosynthesis and glutathione metabolism pathways. HQD treatment decreased the intrahepatic accumulation of cytotoxic BAs, normalized serum BA levels, and increased biliary and urinary BA excretion. Additionally, HQD restored the hepatic glutathione content and suppressed reactive oxygen species (ROS) in cholestatic mice. Protein and gene analysis revealed that HQD increased the expression of the hepatic metabolizing enzymes cytochrome P450 (CYP) 2B10 and UDP glucuronosyltransferase family 1 member A1 (UGT1A1), as well as multidrug resistance-associated protein 2 (Mrp2), Mrp3, and Mrp4, which play crucial roles in BA homeostasis. Further, HQD increased the protein expression of glutamate-cysteine ligase, which is involved in the synthesis of glutathione. Importantly, HQD increased the nuclear expression of nuclear factor-E2-related factor-2 (Nrf2). In conclusion, HQD protects against intrahepatic cholestasis by reversing the disordered homeostasis of BAs and glutathione. |
| first_indexed | 2024-04-13T12:08:34Z |
| format | Article |
| id | doaj.art-bfcab09aca754afebbb38bd96ea4b641 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T12:08:34Z |
| publishDate | 2017-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-bfcab09aca754afebbb38bd96ea4b6412022-12-22T02:47:34ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-12-01810.3389/fphar.2017.00938305152Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in MiceJia-Sheng Wu0Yi-Fei Li1Yuan-Yuan Li2Yan Dai3Wen-Kai Li4Min Zheng5Zheng-Chun Shi6Rong Shi7Tian-Ming Wang8Bing-Liang Ma9Ping Liu10Yue-Ming Ma11Yue-Ming Ma12Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Compound Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaIntrahepatic cholestasis is a serious symptom of liver disorders with limited therapies. In this study, we investigated the efficacy of Huangqi decoction (HQD), a two-herb classic traditional Chinese medicine (TCM), in the treatment of alpha-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. HQD treatment ameliorated impaired hepatic function and tissue damage. A metabolomics study revealed that the endogenous metabolites significantly affected by HQD were related to bile acid (BA) biosynthesis and glutathione metabolism pathways. HQD treatment decreased the intrahepatic accumulation of cytotoxic BAs, normalized serum BA levels, and increased biliary and urinary BA excretion. Additionally, HQD restored the hepatic glutathione content and suppressed reactive oxygen species (ROS) in cholestatic mice. Protein and gene analysis revealed that HQD increased the expression of the hepatic metabolizing enzymes cytochrome P450 (CYP) 2B10 and UDP glucuronosyltransferase family 1 member A1 (UGT1A1), as well as multidrug resistance-associated protein 2 (Mrp2), Mrp3, and Mrp4, which play crucial roles in BA homeostasis. Further, HQD increased the protein expression of glutamate-cysteine ligase, which is involved in the synthesis of glutathione. Importantly, HQD increased the nuclear expression of nuclear factor-E2-related factor-2 (Nrf2). In conclusion, HQD protects against intrahepatic cholestasis by reversing the disordered homeostasis of BAs and glutathione.http://journal.frontiersin.org/article/10.3389/fphar.2017.00938/fullintrahepatic cholestasisHuangqi decoctiontraditional Chinese medicineNrf2metabolomics |
| spellingShingle | Jia-Sheng Wu Yi-Fei Li Yuan-Yuan Li Yan Dai Wen-Kai Li Min Zheng Zheng-Chun Shi Rong Shi Tian-Ming Wang Bing-Liang Ma Ping Liu Yue-Ming Ma Yue-Ming Ma Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in Mice Frontiers in Pharmacology intrahepatic cholestasis Huangqi decoction traditional Chinese medicine Nrf2 metabolomics |
| title | Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in Mice |
| title_full | Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in Mice |
| title_fullStr | Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in Mice |
| title_full_unstemmed | Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in Mice |
| title_short | Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in Mice |
| title_sort | huangqi decoction alleviates alpha naphthylisothiocyanate induced intrahepatic cholestasis by reversing disordered bile acid and glutathione homeostasis in mice |
| topic | intrahepatic cholestasis Huangqi decoction traditional Chinese medicine Nrf2 metabolomics |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00938/full |
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