Kaempferol From Penthorum chinense Pursh Attenuates Hepatic Ischemia/Reperfusion Injury by Suppressing Oxidative Stress and Inflammation Through Activation of the Nrf2/HO-1 Signaling Pathway

• Published in: Frontiers in pharmacology Vol. 13; p. 857015
• Main Authors: Chen, Yifan, Li, Tongxi, Tan, Peng, Shi, Hao, Cheng, Yonglang, Cai, Tianying, Bai, Junjie, Du, Yichao, Fu, Wenguang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01.04.2022
• Subjects: inflammation; ischemia/reperfusion; kaempferol; Nrf2/HO-1; oxidative stress; Pharmacology; ischemia/reperfusion; kaempferol; inflammation; oxidative stress; Nrf2/HO-1
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2022.857015

The purpose of this study is to investigate the protective effect of kaempferol (KAE), the main active monomer from Pursh, on hepatic ischemia/reperfusion injury (HI/RI) and its specific mechanism. HI/RI is a common complication closely related to the prognosis of liver surgery, and effective prevention and treatment methods are still unavailable. Ischemia/reperfusion (I/R) injury is caused by tissue damage during ischemia and sustained oxidative stress and inflammation during reperfusion. Pursh is a traditional Chinese medicine widely used to treat liver disease since ancient times. Kaempferol (KAE), a highly purified flavonoid active monomer isolated and extracted from Pursh, was investigated for its protective effect on HI/RI. Our study indicates that KAE pretreatment alleviated I/R-induced transaminase elevation and pathological changes. Further analysis revealed that KAE pretreatment attenuates I/R-induced oxidative stress (as measured by the content of MDA, SOD and GSH) and reduces hypoxia/reoxygenation (H/R) -induced reactive oxygen species (ROS) generation . Meanwhile, KAE inhibits activation of NF-κB/p65 and reduces the release of pro-inflammatory factors (TNF-α and IL-6) to protect the liver from I/R-induced inflammation. Nuclear erythroid 2-related factor 2 (Nrf2) is a crucial cytoprotection regulator because it induces anti-inflammatory, antioxidant, and cytoprotective genes. Therefore, we analyzed the protein levels of Nrf2 and its downstream heme oxygenase-1 (HO-1) in the liver of mice and hepatocytes of humankind, respectively, and discovered that KAE pretreatment activates the Nrf2/HO-1 signaling pathway. In summary, this study confirmed the hepatoprotective effect of KAE on HI/RI, which inhibits oxidative stress and inflammation by activating the Nrf2/HO-1 signaling pathway.