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

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, a...

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Main Authors: Yifan Chen, Tongxi Li, Peng Tan, Hao Shi, Yonglang Cheng, Tianying Cai, Junjie Bai, Yichao Du, Wenguang Fu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.857015/full
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author Yifan Chen
Tongxi Li
Peng Tan
Hao Shi
Yonglang Cheng
Tianying Cai
Junjie Bai
Yichao Du
Wenguang Fu
Wenguang Fu
author_facet Yifan Chen
Tongxi Li
Peng Tan
Hao Shi
Yonglang Cheng
Tianying Cai
Junjie Bai
Yichao Du
Wenguang Fu
Wenguang Fu
author_sort Yifan Chen
collection DOAJ
description 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.
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spelling doaj.art-99cadc7f38f140dca1d252a848f40a3e2022-12-21T23:55:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-04-011310.3389/fphar.2022.857015857015Kaempferol From Penthorum chinense Pursh Attenuates Hepatic Ischemia/Reperfusion Injury by Suppressing Oxidative Stress and Inflammation Through Activation of the Nrf2/HO-1 Signaling PathwayYifan Chen0Tongxi Li1Peng Tan2Hao Shi3Yonglang Cheng4Tianying Cai5Junjie Bai6Yichao Du7Wenguang Fu8Wenguang Fu9Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.857015/fullkaempferolischemia/reperfusionoxidative stressinflammationNrf2/HO-1
spellingShingle Yifan Chen
Tongxi Li
Peng Tan
Hao Shi
Yonglang Cheng
Tianying Cai
Junjie Bai
Yichao Du
Wenguang Fu
Wenguang Fu
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
Frontiers in Pharmacology
kaempferol
ischemia/reperfusion
oxidative stress
inflammation
Nrf2/HO-1
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic kaempferol
ischemia/reperfusion
oxidative stress
inflammation
Nrf2/HO-1
url https://www.frontiersin.org/articles/10.3389/fphar.2022.857015/full
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