Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling

Considerable achievements were realized in illuminating underlying pathological mechanisms of patients with idiopathic membranous nephropathy (IMN). Although IMN patients are well diagnosed before they reach renal failure, no currently available drug intervention is effective in halting IMN progress...

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Main Authors: Shi-Xing Ma, Xiao-Jun Li, Ting-Ting Duan, Ming Pei, Liang Zou, Xiao-Yong Yu, Ying-Yong Zhao
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023072274
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author Shi-Xing Ma
Xiao-Jun Li
Ting-Ting Duan
Ming Pei
Liang Zou
Xiao-Yong Yu
Ying-Yong Zhao
author_facet Shi-Xing Ma
Xiao-Jun Li
Ting-Ting Duan
Ming Pei
Liang Zou
Xiao-Yong Yu
Ying-Yong Zhao
author_sort Shi-Xing Ma
collection DOAJ
description Considerable achievements were realized in illuminating underlying pathological mechanisms of patients with idiopathic membranous nephropathy (IMN). Although IMN patients are well diagnosed before they reach renal failure, no currently available drug intervention is effective in halting IMN progression. In this study, we assess Moshen granule (MSG) effect on IMN patients and cationic bovine serum albumin (CBSA)-induced rats. Increasing studies has indicated that activation of aryl hydrocarbon receptor (AHR) was related to oxidative stress and inflammation. We further determine MSG effect on AHR, nuclear factor ƙB (NF-ƙB) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the CBSA-induced rats. MSG markedly reduces proteinuria and improves kidney function in both IMN patients and rats induced by CBSA. MSG markedly inhibits increased mRNA expressions of intrarenal AHR and its four downstream target genes including CYP1A1, CYP1A2, CYP1B1 and COX-2 compared with untreated CBSA-induced rats. This is accompanied by markedly downregulated protein expressions of p-IƙBα and NF-ƙB p65 and its downstream gene products including MCP-1, COX-2, 12-LOX, iNOS, p47phox and p67phox, while markedly preserves protein expressions of Nrf2 and its downstream gene products including catalase, HO-1, GCLM, GCLC, MnSOD and NQO1 in the kidney tissues. These data suggests MSG blunts podocyte damage through inhibiting activation of NF-ƙB/Nrf2 pathway via AHR signaling. This finding may provide a promising therapy for treatment of IMN through oxidative stress and inflammation.
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spelling doaj.art-aec8ec286241441cbcfa051382bf7efe2023-10-01T06:02:17ZengElsevierHeliyon2405-84402023-09-0199e20019Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signallingShi-Xing Ma0Xiao-Jun Li1Ting-Ting Duan2Ming Pei3Liang Zou4Xiao-Yong Yu5Ying-Yong Zhao6Department of Nephrology, Baoji Central Hospital, Baoji, Shaanxi 721008, ChinaDepartment of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510315, ChinaGuangdong Nephrotic Drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou, Guangdong 510530, ChinaDepartment of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300073, ChinaSchool of Food and Bioengineering, Chengdu University, Chengdu, Sichuan 610106, ChinaDepartment of Nephrology, Shaanxi Traditional Chinese Medicine Hospital, Xi'an, Shaanxi 710003, China; Corresponding author. Department of Nephrology, Shaanxi Traditional Chinese Medicine Hospital, No. 4 Xihuamen, Xi'an, Shaanxi 710003, China.School of Food and Bioengineering, Chengdu University, Chengdu, Sichuan 610106, China; School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; Corresponding author. School of Pharmacy, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, Zhejiang 310053, China.Considerable achievements were realized in illuminating underlying pathological mechanisms of patients with idiopathic membranous nephropathy (IMN). Although IMN patients are well diagnosed before they reach renal failure, no currently available drug intervention is effective in halting IMN progression. In this study, we assess Moshen granule (MSG) effect on IMN patients and cationic bovine serum albumin (CBSA)-induced rats. Increasing studies has indicated that activation of aryl hydrocarbon receptor (AHR) was related to oxidative stress and inflammation. We further determine MSG effect on AHR, nuclear factor ƙB (NF-ƙB) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the CBSA-induced rats. MSG markedly reduces proteinuria and improves kidney function in both IMN patients and rats induced by CBSA. MSG markedly inhibits increased mRNA expressions of intrarenal AHR and its four downstream target genes including CYP1A1, CYP1A2, CYP1B1 and COX-2 compared with untreated CBSA-induced rats. This is accompanied by markedly downregulated protein expressions of p-IƙBα and NF-ƙB p65 and its downstream gene products including MCP-1, COX-2, 12-LOX, iNOS, p47phox and p67phox, while markedly preserves protein expressions of Nrf2 and its downstream gene products including catalase, HO-1, GCLM, GCLC, MnSOD and NQO1 in the kidney tissues. These data suggests MSG blunts podocyte damage through inhibiting activation of NF-ƙB/Nrf2 pathway via AHR signaling. This finding may provide a promising therapy for treatment of IMN through oxidative stress and inflammation.http://www.sciencedirect.com/science/article/pii/S2405844023072274Idiopathic membranous nephropathyMoshen granuleAryl hydrocarbon receptorNuclear factor kappa BNrf2
spellingShingle Shi-Xing Ma
Xiao-Jun Li
Ting-Ting Duan
Ming Pei
Liang Zou
Xiao-Yong Yu
Ying-Yong Zhao
Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling
Heliyon
Idiopathic membranous nephropathy
Moshen granule
Aryl hydrocarbon receptor
Nuclear factor kappa B
Nrf2
title Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling
title_full Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling
title_fullStr Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling
title_full_unstemmed Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling
title_short Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling
title_sort moshen granule ameliorates membranous nephropathy by regulating nf kb nrf2 pathways via aryl hydrocarbon receptor signalling
topic Idiopathic membranous nephropathy
Moshen granule
Aryl hydrocarbon receptor
Nuclear factor kappa B
Nrf2
url http://www.sciencedirect.com/science/article/pii/S2405844023072274
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