Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling
Backgroud and aims: Ductular reaction (DR) is a common pathological change and thought to have a key role in the pathogenesis and progression of liver fibrosis. Our previous study reported Gypenosides (GPs) ameliorated liver fibrosis, however, the anti-fibrotic mechanisms of GPs are still unclear.Me...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1033103/full |
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| author | Yonghong Hu Yonghong Hu Xiaoli He Xiaoli He Xiaoxi Zhou Xiaoxi Zhou Yue Liang Yue Liang Yadong Fu Linzhang Zhang Jing Fang Jing Fang Wei Liu Wei Liu Gaofeng Chen Gaofeng Chen Yongping Mu Yongping Mu Hua Zhang Hua Zhang Hong Cai Chenghai Liu Chenghai Liu Ping Liu Ping Liu Ping Liu Jiamei Chen Jiamei Chen |
| author_facet | Yonghong Hu Yonghong Hu Xiaoli He Xiaoli He Xiaoxi Zhou Xiaoxi Zhou Yue Liang Yue Liang Yadong Fu Linzhang Zhang Jing Fang Jing Fang Wei Liu Wei Liu Gaofeng Chen Gaofeng Chen Yongping Mu Yongping Mu Hua Zhang Hua Zhang Hong Cai Chenghai Liu Chenghai Liu Ping Liu Ping Liu Ping Liu Jiamei Chen Jiamei Chen |
| author_sort | Yonghong Hu |
| collection | DOAJ |
| description | Backgroud and aims: Ductular reaction (DR) is a common pathological change and thought to have a key role in the pathogenesis and progression of liver fibrosis. Our previous study reported Gypenosides (GPs) ameliorated liver fibrosis, however, the anti-fibrotic mechanisms of GPs are still unclear.Methods: Liver fibrosis was induced in rats by carbon tetrachloride combining with 2-acerylaminofluorene (CCl4/2-AAF), and Mdr2 knockout (Mdr2−/−) mice to evaluate the anti-fibrotic role of GPs. In vitro, WB-F344 cells, a hepatic progenitor cells (HPCs) line, with or without Gli1 overexpressing lentiviral vectors, were induced by sodium butyrate (SB) to validate the mechanism of GPs and NPLC0393, the main ingredient of GPs.Results: Both in CCl4/2-AAF-treated rats and Mdr2−/− mice, GPs obviously reduced the deposition of collagen and hydroxyproline content, inhibited the activation of hepatic stellate cells and inflammatory cell infiltration. Notably, GPs reduced the expressions of Epcam, CK19, CK7, Dhh, Smo, Ptch2, Gli1 and Gli2. Furthermore, CK19+ cells co-expressed Gli1, while the number of CK19+/Gli1+ cells was decreased by GPs. In vitro, GPs and NPLC0393 inhibited the differentiation of WB-F344 cells toward a biliary phenotype. Mechanistically, GPs and NPLC0393 protected against DR by inhibiting hedgehog signaling, which was supported by the results that DR, triggered directly by Gli1 overexpressing lentiviral vector was blocked by administration with GPs or NPLC0393.Conclusion: GPs attenuated DR and liver fibrosis by inhibiting hedgehog signaling, which provided more evidences and a novel mechanism of anti-fibrotic effect of GPs. |
| first_indexed | 2024-04-13T12:36:39Z |
| format | Article |
| id | doaj.art-bd568c79ebd44c3ca821701fcd4b88d8 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T12:36:39Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-bd568c79ebd44c3ca821701fcd4b88d82022-12-22T02:46:38ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.10331031033103Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signalingYonghong Hu0Yonghong Hu1Xiaoli He2Xiaoli He3Xiaoxi Zhou4Xiaoxi Zhou5Yue Liang6Yue Liang7Yadong Fu8Linzhang Zhang9Jing Fang10Jing Fang11Wei Liu12Wei Liu13Gaofeng Chen14Gaofeng Chen15Yongping Mu16Yongping Mu17Hua Zhang18Hua Zhang19Hong Cai20Chenghai Liu21Chenghai Liu22Ping Liu23Ping Liu24Ping Liu25Jiamei Chen26Jiamei Chen27Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaInstitute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaXiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaInstitute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, ChinaBackgroud and aims: Ductular reaction (DR) is a common pathological change and thought to have a key role in the pathogenesis and progression of liver fibrosis. Our previous study reported Gypenosides (GPs) ameliorated liver fibrosis, however, the anti-fibrotic mechanisms of GPs are still unclear.Methods: Liver fibrosis was induced in rats by carbon tetrachloride combining with 2-acerylaminofluorene (CCl4/2-AAF), and Mdr2 knockout (Mdr2−/−) mice to evaluate the anti-fibrotic role of GPs. In vitro, WB-F344 cells, a hepatic progenitor cells (HPCs) line, with or without Gli1 overexpressing lentiviral vectors, were induced by sodium butyrate (SB) to validate the mechanism of GPs and NPLC0393, the main ingredient of GPs.Results: Both in CCl4/2-AAF-treated rats and Mdr2−/− mice, GPs obviously reduced the deposition of collagen and hydroxyproline content, inhibited the activation of hepatic stellate cells and inflammatory cell infiltration. Notably, GPs reduced the expressions of Epcam, CK19, CK7, Dhh, Smo, Ptch2, Gli1 and Gli2. Furthermore, CK19+ cells co-expressed Gli1, while the number of CK19+/Gli1+ cells was decreased by GPs. In vitro, GPs and NPLC0393 inhibited the differentiation of WB-F344 cells toward a biliary phenotype. Mechanistically, GPs and NPLC0393 protected against DR by inhibiting hedgehog signaling, which was supported by the results that DR, triggered directly by Gli1 overexpressing lentiviral vector was blocked by administration with GPs or NPLC0393.Conclusion: GPs attenuated DR and liver fibrosis by inhibiting hedgehog signaling, which provided more evidences and a novel mechanism of anti-fibrotic effect of GPs.https://www.frontiersin.org/articles/10.3389/fphar.2022.1033103/fullgypenosidesliver fibrosisductular reactionhedgehog signalingNPLC0393 |
| spellingShingle | Yonghong Hu Yonghong Hu Xiaoli He Xiaoli He Xiaoxi Zhou Xiaoxi Zhou Yue Liang Yue Liang Yadong Fu Linzhang Zhang Jing Fang Jing Fang Wei Liu Wei Liu Gaofeng Chen Gaofeng Chen Yongping Mu Yongping Mu Hua Zhang Hua Zhang Hong Cai Chenghai Liu Chenghai Liu Ping Liu Ping Liu Ping Liu Jiamei Chen Jiamei Chen Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling Frontiers in Pharmacology gypenosides liver fibrosis ductular reaction hedgehog signaling NPLC0393 |
| title | Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling |
| title_full | Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling |
| title_fullStr | Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling |
| title_full_unstemmed | Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling |
| title_short | Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling |
| title_sort | gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling |
| topic | gypenosides liver fibrosis ductular reaction hedgehog signaling NPLC0393 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1033103/full |
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