2. Academic Validation
  3. Icaritin attenuates ischemia-reperfusion injury by anti-inflammation, anti-oxidative stress, and anti-autophagy in mouse liver

Icaritin attenuates ischemia-reperfusion injury by anti-inflammation, anti-oxidative stress, and anti-autophagy in mouse liver

  • Int Immunopharmacol. 2024 Sep 10:138:112533. doi: 10.1016/j.intimp.2024.112533.
Qian Sun 1,  Ruining Yang 2,  Tao Chen 3,  Shipeng Li 4,  Hao Wang 5,  Dejun Kong 6,  Weiye Zhang 7,  Jinliang Duan 8,  Hong Zheng 9,  Zhongyang Shen 10,  Jianjun Zhang 11
Affiliations

Affiliations

  • 1 The First Central Clinical School, Tianjin Medical University, Tianjin, China. Electronic address: sunxiaoqian0218@163.com.
  • 2 The First Central Clinical School, Tianjin Medical University, Tianjin, China. Electronic address: Yruining0628@163.com.
  • 3 The First Central Clinical School, Tianjin Medical University, Tianjin, China. Electronic address: ct3353831@163.com.
  • 4 Department of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China. Electronic address: shipengli2010@163.com.
  • 5 Department of Kidney Transplantation, Shenzhen Third People's Hospital, China. Electronic address: wanghao1717@tmu.edu.cn.
  • 6 School of Medicine, Nankai University, Tianjin, China. Electronic address: dejunk@tmu.edu.cn.
  • 7 Research Institute of Transplant Medicine, Nankai University, Tianjin, China; Organ Transplant Department, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China. Electronic address: zwy7795@vip.sina.com.
  • 8 School of Medicine, Nankai University, Tianjin, China. Electronic address: stduan@126.com.
  • 9 Research Institute of Transplant Medicine, Nankai University, Tianjin, China; Organ Transplant Department, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China. Electronic address: zhenghongyx@139.com.
  • 10 Research Institute of Transplant Medicine, Nankai University, Tianjin, China; Organ Transplant Department, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China. Electronic address: zhongyangshen@vip.sina.com.
  • 11 Research Institute of Transplant Medicine, Nankai University, Tianjin, China; Organ Transplant Department, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China. Electronic address: yzxzhangjianjun@163.com.
PMID: 38924868 DOI: 10.1016/j.intimp.2024.112533
Abstract

Background: Hepatic ischemia-reperfusion (IR) injury is a major complication of liver transplantation and gravely affects patient prognosis. Icaritin (ICT), the primary plasma metabolite of icariin (ICA), plays a critical role in anti-inflammatory and immunomodulatory processes. However, the role of ICT in hepatic IR injury remains largely undefined. In this study, we aimed to elucidate the role of ICT in hepatic IR injury.

Methods: We established hepatic IR injury models in Animals, as well as an oxygen-glucose deprivation/reperfusion (OGD/R) cell model. Liver injury in vivo was assessed by measuring serum alanine aminotransferase (ALT) levels, necrotic areas by liver histology and local hepatic inflammatory responses. For in vitro analyses, we implemented flow-cytometric and western blot analyses, transmission electron microscopy, and an mRFP-GFP-LC3 adenovirus reporter assay to assess the effects of ICT on OGD/R injury in AML12 and THLE-2 cell lines. Signaling pathways were explored in vitro and in vivo to identify possible mechanisms underlying ICT action in hepatic IR injury.

Results: Compared to the mouse model group, ICT preconditioning considerably protected the liver against IR stress, and diminished the levels of necrosis/Apoptosis and inflammation-related cytokines. In additional studies, ICT treatment dramatically boosted the expression ratios of p-PI3K/PI3K, p-AKT/Akt, and p-mTOR/mTOR proteins in hepatic cells following OGD/R damage. We also applied LY294002 (a PI3K Inhibitor) and RAPA (rapamycin, an mTOR Inhibitor), which blocked the protective effects of ICT in hepatocytes subjected to OGD/R.

Conclusion: This study indicates that ICT attenuates ischemia-reperfusion injury by exerting anti-inflammation, anti-oxidative stress, and anti-autophagy effects, as demonstrated in mouse livers. We thus posit that ICT could have therapeutic potential for the treatment of hepatic IR injury.

Keywords

Autophagy; Hepatic ischemia–reperfusion injury; Icaritin; Inflammation; PI3K/AKT/mTOR.

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