Pien-Tze-Huang alleviates lithocholic acid-induced cholestasis in mice by shaping bile acid-submetabolome
Abstract Background Cholestasis is one of the most common and devastating manifestations of liver diseases. Although bile acid (BA) metabolism disturbances have been disclosed to be related to the etiopathogenesis of cholestasis, further research is desired to obtain an in-depth understanding of cho...
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BMC
2025-07-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-025-01161-7 |
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| author | Yan Cao Yanhong Zhai Qihong Deng Shufen Song Wei Li Youran Li Yifan Lu Jun Li Zheng Cao Yuelin Song |
| author_facet | Yan Cao Yanhong Zhai Qihong Deng Shufen Song Wei Li Youran Li Yifan Lu Jun Li Zheng Cao Yuelin Song |
| author_sort | Yan Cao |
| collection | DOAJ |
| description | Abstract Background Cholestasis is one of the most common and devastating manifestations of liver diseases. Although bile acid (BA) metabolism disturbances have been disclosed to be related to the etiopathogenesis of cholestasis, further research is desired to obtain an in-depth understanding of cholestasis. Additionally, only a limited number of treatment approaches are available for this disorder. Pien-Tze-Huang (PTH), a traditional Chinese medicine prescription, has been extensively utilized to treat various liver diseases. However, the effects of PTH on BA-submetabolome and the underlying mechanisms haven’t been revealed. Methods A strategy integrating widely targeted metabolomics, untargeted proteomics, and 16S rDNA sequencing, was employed to explore the regulatory effect and the mechanisms of PTH on BA-submetabolome of lithocholic acid (LCA)-induced cholestasis mice. Furthermore, LCA-induced injury HepG2 cells were deployed for efficacy justification and the mechanism exploration. Results Both in vivo and in vitro assays demonstrated that PTH could protect liver against LCA-induced injury. Based on the quantitative BA-submetabolome migration and cell viability assays, 3-dehydroCA, CDCA, CA-7-S, HDCA, 3-ketocholanic acid, 7-ketoLCA, and 7,12-diketoLCA were identified as the key BA species correlating with hepatoprotective effects of PTH. Moreover, PTH restored the dramatically deflected BA-submetabolome in cholestasis mice through two different ways. On the one hand, the significantly decreased BA species can be directly supplemented during PTH administration or repaired via upregulating BA-related enzymes. On the other hand, the significantly increased BAs, such as T-β-MCA, TCDCA, TCA, TLCA, TMDCA, TUDCA, and TDCA, should be eliminated by the increased abundance of Lactobacillaceae and Lactobacillus. Conclusions PTH alleviates cholestasis by synergistically regulating certain BA species, enzymes and gut microbiota, leading to holistic BA-submetabolome shaping. |
| format | Article |
| id | doaj-art-b0dd0becee4342b8b0915c3047215ebd |
| institution | Kabale University |
| issn | 1749-8546 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Chinese Medicine |
| spelling | doaj-art-b0dd0becee4342b8b0915c3047215ebd2025-08-20T03:42:00ZengBMCChinese Medicine1749-85462025-07-0120111210.1186/s13020-025-01161-7Pien-Tze-Huang alleviates lithocholic acid-induced cholestasis in mice by shaping bile acid-submetabolomeYan Cao0Yanhong Zhai1Qihong Deng2Shufen Song3Wei Li4Youran Li5Yifan Lu6Jun Li7Zheng Cao8Yuelin Song9Department of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care HospitalDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care HospitalFujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development, Zhangzhou Pien Tze Huang Pharmaceutical Co., LtdFujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development, Zhangzhou Pien Tze Huang Pharmaceutical Co., LtdModern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese MedicineDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care HospitalDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care HospitalModern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese MedicineDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care HospitalModern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese MedicineAbstract Background Cholestasis is one of the most common and devastating manifestations of liver diseases. Although bile acid (BA) metabolism disturbances have been disclosed to be related to the etiopathogenesis of cholestasis, further research is desired to obtain an in-depth understanding of cholestasis. Additionally, only a limited number of treatment approaches are available for this disorder. Pien-Tze-Huang (PTH), a traditional Chinese medicine prescription, has been extensively utilized to treat various liver diseases. However, the effects of PTH on BA-submetabolome and the underlying mechanisms haven’t been revealed. Methods A strategy integrating widely targeted metabolomics, untargeted proteomics, and 16S rDNA sequencing, was employed to explore the regulatory effect and the mechanisms of PTH on BA-submetabolome of lithocholic acid (LCA)-induced cholestasis mice. Furthermore, LCA-induced injury HepG2 cells were deployed for efficacy justification and the mechanism exploration. Results Both in vivo and in vitro assays demonstrated that PTH could protect liver against LCA-induced injury. Based on the quantitative BA-submetabolome migration and cell viability assays, 3-dehydroCA, CDCA, CA-7-S, HDCA, 3-ketocholanic acid, 7-ketoLCA, and 7,12-diketoLCA were identified as the key BA species correlating with hepatoprotective effects of PTH. Moreover, PTH restored the dramatically deflected BA-submetabolome in cholestasis mice through two different ways. On the one hand, the significantly decreased BA species can be directly supplemented during PTH administration or repaired via upregulating BA-related enzymes. On the other hand, the significantly increased BAs, such as T-β-MCA, TCDCA, TCA, TLCA, TMDCA, TUDCA, and TDCA, should be eliminated by the increased abundance of Lactobacillaceae and Lactobacillus. Conclusions PTH alleviates cholestasis by synergistically regulating certain BA species, enzymes and gut microbiota, leading to holistic BA-submetabolome shaping.https://doi.org/10.1186/s13020-025-01161-7Pien-Tze-HuangLCA-induced cholestasisBile acid-submetabolomeWidely targeted metabolomicsTherapeutic mechanisms |
| spellingShingle | Yan Cao Yanhong Zhai Qihong Deng Shufen Song Wei Li Youran Li Yifan Lu Jun Li Zheng Cao Yuelin Song Pien-Tze-Huang alleviates lithocholic acid-induced cholestasis in mice by shaping bile acid-submetabolome Chinese Medicine Pien-Tze-Huang LCA-induced cholestasis Bile acid-submetabolome Widely targeted metabolomics Therapeutic mechanisms |
| title | Pien-Tze-Huang alleviates lithocholic acid-induced cholestasis in mice by shaping bile acid-submetabolome |
| title_full | Pien-Tze-Huang alleviates lithocholic acid-induced cholestasis in mice by shaping bile acid-submetabolome |
| title_fullStr | Pien-Tze-Huang alleviates lithocholic acid-induced cholestasis in mice by shaping bile acid-submetabolome |
| title_full_unstemmed | Pien-Tze-Huang alleviates lithocholic acid-induced cholestasis in mice by shaping bile acid-submetabolome |
| title_short | Pien-Tze-Huang alleviates lithocholic acid-induced cholestasis in mice by shaping bile acid-submetabolome |
| title_sort | pien tze huang alleviates lithocholic acid induced cholestasis in mice by shaping bile acid submetabolome |
| topic | Pien-Tze-Huang LCA-induced cholestasis Bile acid-submetabolome Widely targeted metabolomics Therapeutic mechanisms |
| url | https://doi.org/10.1186/s13020-025-01161-7 |
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