Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization
Abstract Acute liver failure (ALF) is a life-threatening clinical syndrome with a substantial risk of mortality. A murine model of lipopolysaccharide (LPS)- and D-galactosamine (D-GalN)-induced ALF is widely used to investigate the underlying mechanisms and potential therapeutic drugs for human live...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-86977-x |
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| author | Hui Zhang Min Gao Haiyan Wang Junfeng Zhang Lin Wang Guanjun Dong Qun Ma Chunxia Li Jun Dai Zhihua Li Fenglian Yan Huabao Xiong |
| author_facet | Hui Zhang Min Gao Haiyan Wang Junfeng Zhang Lin Wang Guanjun Dong Qun Ma Chunxia Li Jun Dai Zhihua Li Fenglian Yan Huabao Xiong |
| author_sort | Hui Zhang |
| collection | DOAJ |
| description | Abstract Acute liver failure (ALF) is a life-threatening clinical syndrome with a substantial risk of mortality. A murine model of lipopolysaccharide (LPS)- and D-galactosamine (D-GalN)-induced ALF is widely used to investigate the underlying mechanisms and potential therapeutic drugs for human liver failure. Atractylenolide I (ATR-I) is an active component of the Atractylodes macrocephala rhizome and possesses various pharmacological activities, including anti-tumor, anti-inflammatory, and anti-oxidant properties. Given the key role of oxidative stress and inflammation in ALF pathogenesis, this study investigates the protective effects of ATR-I on LPS/D-GalN-induced ALF in mice. The results suggest that ATR-I pretreatment significantly ameliorates ALF, as evidenced by decreased serum aminotransferase levels and prolonged mice survival. Additionally, ATR-I pretreatment inhibits oxidative stress. Furthermore, the ATR-I pretreatment markedly suppresses M1 macrophage activation in hepatic mononuclear cells. In vitro experiments with bone marrow-derived macrophages indicate that ATR-I regulates macrophage polarization through the mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) signaling pathways. Collectively, ATR-I pretreatment protects mice from LPS/D-GalN-induced ALF partially by regulating M1 macrophage polarization. |
| format | Article |
| id | doaj-art-1c0ac6523b9e41d99e8ab1080c410029 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-1c0ac6523b9e41d99e8ab1080c4100292025-02-02T12:22:13ZengNature PortfolioScientific Reports2045-23222025-02-0115111510.1038/s41598-025-86977-xAtractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarizationHui Zhang0Min Gao1Haiyan Wang2Junfeng Zhang3Lin Wang4Guanjun Dong5Qun Ma6Chunxia Li7Jun Dai8Zhihua Li9Fenglian Yan10Huabao Xiong11Institute of Immunology and Molecular Medicine, Jining Medical UniversityClinical Laboratory, Jining First People’s HospitalInstitute of Immunology and Molecular Medicine, Jining Medical UniversityInstitute of Immunology and Molecular Medicine, Jining Medical UniversityInstitute of Immunology and Molecular Medicine, Jining Medical UniversityInstitute of Immunology and Molecular Medicine, Jining Medical UniversityInstitute of Immunology and Molecular Medicine, Jining Medical UniversityInstitute of Immunology and Molecular Medicine, Jining Medical UniversityInstitute of Immunology and Molecular Medicine, Jining Medical UniversityInstitute of Immunology and Molecular Medicine, Jining Medical UniversityInstitute of Immunology and Molecular Medicine, Jining Medical UniversityInstitute of Immunology and Molecular Medicine, Jining Medical UniversityAbstract Acute liver failure (ALF) is a life-threatening clinical syndrome with a substantial risk of mortality. A murine model of lipopolysaccharide (LPS)- and D-galactosamine (D-GalN)-induced ALF is widely used to investigate the underlying mechanisms and potential therapeutic drugs for human liver failure. Atractylenolide I (ATR-I) is an active component of the Atractylodes macrocephala rhizome and possesses various pharmacological activities, including anti-tumor, anti-inflammatory, and anti-oxidant properties. Given the key role of oxidative stress and inflammation in ALF pathogenesis, this study investigates the protective effects of ATR-I on LPS/D-GalN-induced ALF in mice. The results suggest that ATR-I pretreatment significantly ameliorates ALF, as evidenced by decreased serum aminotransferase levels and prolonged mice survival. Additionally, ATR-I pretreatment inhibits oxidative stress. Furthermore, the ATR-I pretreatment markedly suppresses M1 macrophage activation in hepatic mononuclear cells. In vitro experiments with bone marrow-derived macrophages indicate that ATR-I regulates macrophage polarization through the mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) signaling pathways. Collectively, ATR-I pretreatment protects mice from LPS/D-GalN-induced ALF partially by regulating M1 macrophage polarization.https://doi.org/10.1038/s41598-025-86977-xAcute liver failureAtractylenolide IM1 macrophage polarizationInflammationOxidative stress |
| spellingShingle | Hui Zhang Min Gao Haiyan Wang Junfeng Zhang Lin Wang Guanjun Dong Qun Ma Chunxia Li Jun Dai Zhihua Li Fenglian Yan Huabao Xiong Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization Scientific Reports Acute liver failure Atractylenolide I M1 macrophage polarization Inflammation Oxidative stress |
| title | Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization |
| title_full | Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization |
| title_fullStr | Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization |
| title_full_unstemmed | Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization |
| title_short | Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization |
| title_sort | atractylenolide i prevents acute liver failure in mouse by regulating m1 macrophage polarization |
| topic | Acute liver failure Atractylenolide I M1 macrophage polarization Inflammation Oxidative stress |
| url | https://doi.org/10.1038/s41598-025-86977-x |
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