2. Academic Validation
  3. Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization

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

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. yflian1117@mail.jnmc.edu.cn.
  • 5 Jining Key Laboratory of Immunology, Jining Medical University, Jining, Shandong, China. yflian1117@mail.jnmc.edu.cn.
  • 6 Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, Shandong, China. xionghuabao@mail.jnmc.edu.cn.
  • 7 Jining Key Laboratory of Immunology, Jining Medical University, Jining, Shandong, China. xionghuabao@mail.jnmc.edu.cn.
  • # 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.

Figures
Products