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

Abstract

The purpose of this study is to investigate the protective effect of kaempferol (KAE), the main active monomer from Penthorum chinense 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. Penthorum chinense 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 Penthorum chinense 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) in vivo and reduces hypoxia/reoxygenation (H/R) -induced reactive oxygen species (ROS) generation in vitro. 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.

Network pharmacology-based analysis on the key mechanisms of Yiguanjian acting on chronic hepatitis

“…Recent research showed that quercetin reduced liver inflammation and fibrosis by modulating M1 macrophage polarization [ 39 ]. Kaempferol was found to mitigate oxidative stress and inflammation by suppressing the NF-κB/p65 and Nrf2/HO-1 pathways [ 40 ]. It treats CH by attenuating HBsAg and HBeAg, activating caspase-3, and down-regulating the PI3K-Akt signaling pathway [ 41 ].…”

Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway

“…Nrf2 is a key transcription factor for cell regulation of OS, which can activate the transcription and expression of downstream anti-OS-related enzymes, such as HO-1 and SOD to eliminate the abnormal accumulation of ROS in cells, thereby alleviating OS injury [ 77 , 78 ]. ROS is crucial in the stimulation of NLRP3 inflammasome, and suppression of ROS levels in cells can inhibit the stimulation of NLRP3 inflammasome [ 21 , 23 ].…”

Probing the Potential Mechanism of Quercetin and Kaempferol against Heat Stress-Induced Sertoli Cell Injury: Through Integrating Network Pharmacology and Experimental Validation

“…In the present study, quercetin and kaempferol protected testicular SCs from oxidative stress injury and improved their resistance to heat stress, which was consistent with previous studies [ 61 , 62 ]. Quercetin and kaempferol have a weak ability to improve SOD activity of heat-damaged supporting cells, but for flavonoid monomers, their antioxidant ability lies not only in improving the level of antioxidants, such as SOD but also in their unique active structure to prevent and eliminate oxygen free radicals [ 63 , 64 ]. Quercetin has one more ortho phenolic hydroxyl than kaempferol.…”