Pectolinarigenin attenuates hepatic ischemia/reperfusion injury via activation of the PI3K/AKT/Nrf2 signaling pathway

  • Chem Biol Interact. 2023 Oct 11:110763. doi: 10.1016/j.cbi.2023.110763.
Hao Li  1 ,  Yabin Chen  2 ,  Mingjie Ding  3 ,  Zhiping Yan  4 ,  Wenzhi Guo  5 ,  Ran Guo  6
Affiliations
  • 1. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. Electronic address: [email protected].
  • 2. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Henan Key Laboratory for Hepatopathy and Transplantation Medicine, Zhengzhou, China. Electronic address: [email protected].
  • 3. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Henan Engineering & Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, Zhengzhou, China. Electronic address: [email protected].
  • 4. Henan Key Laboratory for Hepatopathy and Transplantation Medicine, Zhengzhou, China; National Organ Transplantation Physician Training Center, Zhengzhou, China. Electronic address: [email protected].
  • 5. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Henan Key Laboratory for Hepatopathy and Transplantation Medicine, Zhengzhou, China; Department of Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: [email protected].
  • 6. Henan Key Laboratory for Hepatopathy and Transplantation Medicine, Zhengzhou, China; Henan Engineering & Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, Zhengzhou, China. Electronic address: [email protected].
PMID: 37832626 DOI: 10.1016/j.cbi.2023.110763
Abstract

Hepatic ischemia/reperfusion (I/R) injury is an unavoidable complication of liver hepatectomy, transplantation, and systemic shock. Pectolinarigenin (Pec) is a flavonoid with many biological activities, which include anti-inflammatory, anti-apoptotic, and antioxidant stress. This study explored whether Pec pretreatment could reduce hepatic I/R injury and the potential mechanisms at play. After pretreatment of mice and AML12 cells with Pec, I/R and hypoxia/reoxygenation (H/R) models were established. By examining markers related to liver injury, cell viability, oxidative stress, inflammatory response, and Apoptosis, the effect of Pec on important processes involved in hepatic I/R injury was assessed. Protein levels associated with the PI3K/Akt/Nrf2 pathway were analyzed by relative quantification to investigate possible pathways through which Pec plays a role in the I/R process. Pec treatment corrected abnormal transaminase levels resulting from I/R injury, improved liver injury, and increased AML12 cell viability. Moreover, Pec treatment inhibited oxidative stress, inflammation and Apoptosis and could activate the PI3K/Akt/Nrf2 pathway during I/R and H/R. Further studies found that LY294002 (PI3K Inhibitor) suppressed the protective effect of Pec on hepatic I/R injury. In summary, our results show that Pec inhibits oxidative stress, inflammatory responses, and Apoptosis, thereby attenuating I/R-induced liver injury and H/R-induced cell damage via activation of the PI3K/Akt/Nrf2 pathway.

Keywords
Apoptosis; Hepatic ischemia/reperfusion injury; Inflammatory response; Oxidative stress; PI3K/Akt/Nrf2 pathway; Pectolinarigenin.
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