Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization

  • Sci Rep. 2025 Feb 1;15(1):4015. doi: 10.1038/s41598-025-86977-x.
Hui Zhang  #  1  2 ,  Min Gao  #  3 ,  Haiyan Wang  #  1  2 ,  Junfeng Zhang  1  2 ,  Lin Wang  1  2 ,  Guanjun Dong  1  2 ,  Qun Ma  1  2 ,  Chunxia Li  1  2 ,  Jun Dai  1  2 ,  Zhihua Li  1  2 ,  Fenglian Yan  4  5 ,  Huabao Xiong  6  7
Affiliations
  • 1. Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, Shandong, China.
  • 2. Jining Key Laboratory of Immunology, Jining Medical University, Jining, Shandong, China.
  • 3. Clinical Laboratory, Jining First People's Hospital, Jining, Shandong, China.
  • 4. Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, Shandong, China. [email protected].
  • 5. Jining Key Laboratory of Immunology, Jining Medical University, Jining, Shandong, China. [email protected].
  • 6. Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, Shandong, China. [email protected].
  • 7. Jining Key Laboratory of Immunology, Jining Medical University, Jining, Shandong, China. [email protected].
  • # Contributed equally.
PMID: 39893238 DOI: 10.1038/s41598-025-86977-x
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.

Keywords
Acute liver failure; Atractylenolide I; Inflammation; M1 macrophage polarization; Oxidative stress.
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