<p>Acute liver injury is a highly lethal condition characterized by hepatocyte damage and dysregulation of immune homeostasis. In this study, we aimed to identify the pharmacological effects and mechanisms of action of Mogroside V (Mog V), an active triterpenoid saponin derived from <i>Siraitia grosvenorii</i> exhibits protective effects in acute liver injury. We used concanavalin A (Con A) to induce acute liver injury in C57BL/6J mice and established both preventive and therapeutic intervention models. The experimental results showed that: In the preventive model, mice were intraperitoneally injected with Mog V 3&#xa0;h prior to Con A (20&#xa0;mg/kg, tail vein injection); in the therapeutic model, Mog V was administered 1&#xa0;h after Con A challenge. In both models, Mog V treatment led to a marked reduction in serum aminotransferase (ALT/AST) levels, as well as attenuated hepatocellular necrosis and inflammatory cell infiltration. Network pharmacology analysis identified several relevant biological pathways associated with inflammation and oxidative stress. Mog V reduced oxidative damage by restoring peroxide levels and reducing liver cell apoptosis and modulated immune responses by suppressing the activation of proinflammatory M1 macrophages and reducing cytokine levels. The results of a macrophage adoptive transfer assay indicated that Mog V-treated macrophages alleviated liver injury and inflammation in mice and suppressed the activity of key inflammation-related signaling pathways. These findings suggest that Mog V has the potential to be a promising candidate for the development of therapeutic agents against Con A-induced acute liver injury, and further studies are needed to verify its clinical application potential.</p>

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Mogroside V Alleviates Concanavalin A-induced Acute Liver Injury by Inhibiting Inflammatory Responses and M1 Macrophage Polarization

  • Yuxuan Zhao,
  • Zhihong Liu,
  • Fenglian Yan,
  • Hongru Zhao,
  • Xinzhou Xie,
  • Jiaying Li,
  • Hui Zhang,
  • Lin Wang,
  • Jia Fu,
  • Chunxia Li,
  • Jun Dai,
  • Huabao Xiong,
  • Bin Yu,
  • Junfeng Zhang

摘要

Acute liver injury is a highly lethal condition characterized by hepatocyte damage and dysregulation of immune homeostasis. In this study, we aimed to identify the pharmacological effects and mechanisms of action of Mogroside V (Mog V), an active triterpenoid saponin derived from Siraitia grosvenorii exhibits protective effects in acute liver injury. We used concanavalin A (Con A) to induce acute liver injury in C57BL/6J mice and established both preventive and therapeutic intervention models. The experimental results showed that: In the preventive model, mice were intraperitoneally injected with Mog V 3 h prior to Con A (20 mg/kg, tail vein injection); in the therapeutic model, Mog V was administered 1 h after Con A challenge. In both models, Mog V treatment led to a marked reduction in serum aminotransferase (ALT/AST) levels, as well as attenuated hepatocellular necrosis and inflammatory cell infiltration. Network pharmacology analysis identified several relevant biological pathways associated with inflammation and oxidative stress. Mog V reduced oxidative damage by restoring peroxide levels and reducing liver cell apoptosis and modulated immune responses by suppressing the activation of proinflammatory M1 macrophages and reducing cytokine levels. The results of a macrophage adoptive transfer assay indicated that Mog V-treated macrophages alleviated liver injury and inflammation in mice and suppressed the activity of key inflammation-related signaling pathways. These findings suggest that Mog V has the potential to be a promising candidate for the development of therapeutic agents against Con A-induced acute liver injury, and further studies are needed to verify its clinical application potential.