Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment
Si-Wu-Tang (SWT), a traditional Chinese medicine formula firstly recorded from the Tang dynasty, has been reported to alleviate gynecological and liver diseases. We preliminarily demonstrated that SWT could improve liver fibrosis via modulating intestinal microbiota, but little was known about the m...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222012239 |
| _version_ | 1811237711203270656 |
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| author | Zhi Ma Xiaoyong Xue Jinzhao Bai Yajie Cai Xuejing Jin Kexin Jia Mingning Ding Xiangjun Lyu Xiaojiaoyang Li |
| author_facet | Zhi Ma Xiaoyong Xue Jinzhao Bai Yajie Cai Xuejing Jin Kexin Jia Mingning Ding Xiangjun Lyu Xiaojiaoyang Li |
| author_sort | Zhi Ma |
| collection | DOAJ |
| description | Si-Wu-Tang (SWT), a traditional Chinese medicine formula firstly recorded from the Tang dynasty, has been reported to alleviate gynecological and liver diseases. We preliminarily demonstrated that SWT could improve liver fibrosis via modulating intestinal microbiota, but little was known about the mechanisms linking its therapeutic effects to the reshaped immune microenvironment within fibrotic livers. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis murine model to evaluate the hepatoprotective effects and potential mechanisms of SWT. The high-performance liquid chromatography, RNA sequencing and other molecular biological techniques were also performed in our study. Our data demonstrated that SWT significantly improved BDL-induced liver fibrosis and inflammatory responses by inhibiting the expression of genes associated with extracellular matrix synthesis and degradation. Combined with the analysis of immune cell infiltration and gene set enrichment analysis (GSEA), we found that SWT remarkably repaired the unbalanced immune microenvironment by modulating the biological functions of different immune cells, especially for macrophages, neutrophils and CD8+ T cells. In addition, SWT significantly inhibited the activation of M2-like macrophages to reduce the release of profibrotic-cytokines and prevented the activation of neutrophils to suppress neutrophil extracellular trap formation. SWT also efficiently promoted the apoptosis of activated hepatic stellate cells via Fas/FasL signaling pathway, which might be mediated by CD8+ tissue-resident memory T cells. In conclusion, our research not only unraveled the intricate mechanisms underlying the hepatoprotective activities of SWT against liver fibrosis but also provided a novel therapeutic strategy for the treatment of liver fibrosis and its relative complications. |
| first_indexed | 2024-04-12T12:29:05Z |
| format | Article |
| id | doaj.art-ca0923eebc7d4fc7b8e821a4a252f07a |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-12T12:29:05Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-ca0923eebc7d4fc7b8e821a4a252f07a2022-12-22T03:33:05ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-11-01155113834Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environmentZhi Ma0Xiaoyong Xue1Jinzhao Bai2Yajie Cai3Xuejing Jin4Kexin Jia5Mingning Ding6Xiangjun Lyu7Xiaojiaoyang Li8School of Life Sciences, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, ChinaCentre for Evidence-Based Medicine, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, China; Corresponding author at: School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.Si-Wu-Tang (SWT), a traditional Chinese medicine formula firstly recorded from the Tang dynasty, has been reported to alleviate gynecological and liver diseases. We preliminarily demonstrated that SWT could improve liver fibrosis via modulating intestinal microbiota, but little was known about the mechanisms linking its therapeutic effects to the reshaped immune microenvironment within fibrotic livers. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis murine model to evaluate the hepatoprotective effects and potential mechanisms of SWT. The high-performance liquid chromatography, RNA sequencing and other molecular biological techniques were also performed in our study. Our data demonstrated that SWT significantly improved BDL-induced liver fibrosis and inflammatory responses by inhibiting the expression of genes associated with extracellular matrix synthesis and degradation. Combined with the analysis of immune cell infiltration and gene set enrichment analysis (GSEA), we found that SWT remarkably repaired the unbalanced immune microenvironment by modulating the biological functions of different immune cells, especially for macrophages, neutrophils and CD8+ T cells. In addition, SWT significantly inhibited the activation of M2-like macrophages to reduce the release of profibrotic-cytokines and prevented the activation of neutrophils to suppress neutrophil extracellular trap formation. SWT also efficiently promoted the apoptosis of activated hepatic stellate cells via Fas/FasL signaling pathway, which might be mediated by CD8+ tissue-resident memory T cells. In conclusion, our research not only unraveled the intricate mechanisms underlying the hepatoprotective activities of SWT against liver fibrosis but also provided a novel therapeutic strategy for the treatment of liver fibrosis and its relative complications.http://www.sciencedirect.com/science/article/pii/S0753332222012239Si-Wu-TangLiver fibrosisBile duct ligationImmune cellsHepatic stellate cell |
| spellingShingle | Zhi Ma Xiaoyong Xue Jinzhao Bai Yajie Cai Xuejing Jin Kexin Jia Mingning Ding Xiangjun Lyu Xiaojiaoyang Li Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment Biomedicine & Pharmacotherapy Si-Wu-Tang Liver fibrosis Bile duct ligation Immune cells Hepatic stellate cell |
| title | Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment |
| title_full | Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment |
| title_fullStr | Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment |
| title_full_unstemmed | Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment |
| title_short | Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment |
| title_sort | si wu tang ameliorates bile duct ligation induced liver fibrosis via modulating immune environment |
| topic | Si-Wu-Tang Liver fibrosis Bile duct ligation Immune cells Hepatic stellate cell |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222012239 |
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