2. Academic Validation
  3. Lentinan enhances microbiota-derived isoursodeoxycholic acid levels to alleviate hepatic ischemia-reperfusion injury in mice

Lentinan enhances microbiota-derived isoursodeoxycholic acid levels to alleviate hepatic ischemia-reperfusion injury in mice

  • Int J Biol Macromol. 2025 Feb 6;304(Pt 2):140717. doi: 10.1016/j.ijbiomac.2025.140717.
Jiaxin Li 1,  Jingna Bao 1,  Yihong Liu 1,  Meiling Chen 2,  Yuqi Chen 2,  Lina Tuolihong 2,  Fuhui Jiang 2,  Shihao Xie 2,  Fengyuan Lyu 2,  Ye Sun 3,  Yan Cao 3,  Huarong Chen 4,  Zhongqing Chen 5,  Zhenhua Zeng 6
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
  • 2 Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
  • 3 Department of Critical Care Medicine, Yuebei People's Hospital, Shaoguan 512000, Guangdong, China.
  • 4 Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong. Electronic address: hchen2@cuhk.edu.hk.
  • 5 Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: zhongqingchen2008@163.com.
  • 6 Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: zhenhuazeng.2008@163.com.
PMID: 39920949 DOI: 10.1016/j.ijbiomac.2025.140717
Abstract

Hepatic ischemia-reperfusion injury (HIRI) is an essential clinical concern caused by liver transplantation, resection, trauma, and shock that must be addressed immediately. Although the mechanisms underlying HIRI are well-documented, effective prevention and treatment strategies are still lacking. Inflammation is a central mechanism of HIRI, with macrophages playing a crucial role in initiating and amplifying the inflammatory response. Numerous plant Polysaccharides exhibit substantial anti-inflammatory and hepatoprotective properties. However, the function of Lentinan (LNT) in HIRI has not been fully explored. Thus, this study aims to investigate the preventive potential of LNT in HIRI. Here, we reveal that oral administration of LNT considerably reduces hepatic inflammation and improves liver pathology in mice with HIRI by modulating gut microbiota. Specifically, LNT considerably increased microbiota-derived isoursodeoxycholic acid (IsoUDCA). Further experiments showed that IsoUDCA alleviates hepatic injury by suppressing macrophage inflammation. Mechanistically, IsoUDCA directly binds to and activates the neuron-derived clone 77 (Nur77) transcription factor, inhibiting the NF-κB signaling pathway in macrophages. Our findings shed light on the significant role of the LNT-microbiota-IsoUDCA-Nur77 axis in attenuating macrophage inflammation during HIRI, offering novel insights into potential therapeutic targets and avenues for preventing HIRI.

Keywords

Hepatic ischemia-reperfusion injury; Isoursodeoxycholic acid; Lentinan.

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