Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory Properties

Yingying Liu,1,* Xiaohua Xu,1,* Ruisi Xu,2 Siqi Zhang1 1Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 2Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People&rsqu...

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Main Authors: Liu Y, Xu X, Xu R, Zhang S
Format: Article
Language:English
Published: Dove Medical Press 2019-10-01
Series:Drug Design, Development and Therapy
Subjects:
Online Access:https://www.dovepress.com/renoprotective-effects-of-isoliquiritin-against-cationic-bovine-serum--peer-reviewed-article-DDDT
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author Liu Y
Xu X
Xu R
Zhang S
author_facet Liu Y
Xu X
Xu R
Zhang S
author_sort Liu Y
collection DOAJ
description Yingying Liu,1,* Xiaohua Xu,1,* Ruisi Xu,2 Siqi Zhang1 1Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 2Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Siqi ZhangDepartment of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaTel +86 183 3112 5890Email zhangsiqi0914@sina.comRuisi XuEndoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaTel +86 187 3220 0909Email xrs_email@sina.comBackground: Membranous glomerulonephritis (MGN) is a nephrotic syndrome which shows the symptoms of heavy proteinuria and immune complex deposition in glomerular sub-epithelial space and finally leads to chronic kidney disease. Isoliquiritin (ILQ) is a flavonoid with a wide range of pharmacological properties, including antioxidant and anti-inflammatory activity. The present study was undertaken to investigate the possible mechanisms by which ILQ ameliorates cationic bovine serum albumin (C-BSA) induced MGN in rat model.Methods: The MGN condition was confirmed by the 24 hr proteinuria and ILQ (10 mg/kg/bw/day) or TPCA-1 (10 mg/kg/bw/day; IKKβ inhibitor) was administered to successfully induce rats for 4 weeks.Results: The present study revealed that MGN rats treated with ILQ showed significantly ameliorated kidney dysfunction and histopathological changes in kidneys. ILQ treated MGN rats alleviated the oxidative stress and were presented with increased anti-oxidative status in kidneys. Furthermore, ILQ treatment to MGN rats showed anti-oxidative effects through the prominent stimulation of Nrf2 signaling pathway and inhibition of Keap1, which consequently increases the Nrf2 nuclear translocation and thereby induces expression of NQO1 and HO-1. In addition, ILQ-treated MGN rats demonstrated anti-inflammatory effects by inhibiting NF-κB signaling pathway through decreased mRNA and protein expressions of NF-κB p65, IKKβ, COX-2, iNOS, p38-MAPK, p-p38-MAPK, TNF-α, IL-1β, IL-8, ICAM-1, E-selectin and VCAM-1 and reduced the nuclear translocation of NF-κB p65.Conclusion: The protective effect of ILQ on MGN can be explained by its anti-oxidative and anti-inflammatory activities, which in turn due to the activation of Nrf2 and downregulation of NF-κB pathway.Keywords: isoliquiritin, membranous glomerulonephritis, oxidative stress, inflammation  
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spelling doaj.art-fbf7b4e3245e4f899e95e51d4625c5802022-12-21T19:30:28ZengDove Medical PressDrug Design, Development and Therapy1177-88812019-10-01Volume 133735375149398Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory PropertiesLiu YXu XXu RZhang SYingying Liu,1,* Xiaohua Xu,1,* Ruisi Xu,2 Siqi Zhang1 1Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 2Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Siqi ZhangDepartment of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaTel +86 183 3112 5890Email zhangsiqi0914@sina.comRuisi XuEndoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaTel +86 187 3220 0909Email xrs_email@sina.comBackground: Membranous glomerulonephritis (MGN) is a nephrotic syndrome which shows the symptoms of heavy proteinuria and immune complex deposition in glomerular sub-epithelial space and finally leads to chronic kidney disease. Isoliquiritin (ILQ) is a flavonoid with a wide range of pharmacological properties, including antioxidant and anti-inflammatory activity. The present study was undertaken to investigate the possible mechanisms by which ILQ ameliorates cationic bovine serum albumin (C-BSA) induced MGN in rat model.Methods: The MGN condition was confirmed by the 24 hr proteinuria and ILQ (10 mg/kg/bw/day) or TPCA-1 (10 mg/kg/bw/day; IKKβ inhibitor) was administered to successfully induce rats for 4 weeks.Results: The present study revealed that MGN rats treated with ILQ showed significantly ameliorated kidney dysfunction and histopathological changes in kidneys. ILQ treated MGN rats alleviated the oxidative stress and were presented with increased anti-oxidative status in kidneys. Furthermore, ILQ treatment to MGN rats showed anti-oxidative effects through the prominent stimulation of Nrf2 signaling pathway and inhibition of Keap1, which consequently increases the Nrf2 nuclear translocation and thereby induces expression of NQO1 and HO-1. In addition, ILQ-treated MGN rats demonstrated anti-inflammatory effects by inhibiting NF-κB signaling pathway through decreased mRNA and protein expressions of NF-κB p65, IKKβ, COX-2, iNOS, p38-MAPK, p-p38-MAPK, TNF-α, IL-1β, IL-8, ICAM-1, E-selectin and VCAM-1 and reduced the nuclear translocation of NF-κB p65.Conclusion: The protective effect of ILQ on MGN can be explained by its anti-oxidative and anti-inflammatory activities, which in turn due to the activation of Nrf2 and downregulation of NF-κB pathway.Keywords: isoliquiritin, membranous glomerulonephritis, oxidative stress, inflammation  https://www.dovepress.com/renoprotective-effects-of-isoliquiritin-against-cationic-bovine-serum--peer-reviewed-article-DDDTisoliquiritinmembranous glomerulonephritisoxidative stressinflammation
spellingShingle Liu Y
Xu X
Xu R
Zhang S
Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory Properties
Drug Design, Development and Therapy
isoliquiritin
membranous glomerulonephritis
oxidative stress
inflammation
title Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory Properties
title_full Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory Properties
title_fullStr Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory Properties
title_full_unstemmed Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory Properties
title_short Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory Properties
title_sort renoprotective effects of isoliquiritin against cationic bovine serum albumin induced membranous glomerulonephritis in experimental rat model through its anti oxidative and anti inflammatory properties
topic isoliquiritin
membranous glomerulonephritis
oxidative stress
inflammation
url https://www.dovepress.com/renoprotective-effects-of-isoliquiritin-against-cationic-bovine-serum--peer-reviewed-article-DDDT
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