Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway

AbstractContext Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects.Objective To investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat mode...

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Main Authors: Shiyan Jia, Ruihua Si, Guangzhen Liu, Qiming Zhong
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Pharmaceutical Biology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/13880209.2024.2330602
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author Shiyan Jia
Ruihua Si
Guangzhen Liu
Qiming Zhong
author_facet Shiyan Jia
Ruihua Si
Guangzhen Liu
Qiming Zhong
author_sort Shiyan Jia
collection DOAJ
description AbstractContext Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects.Objective To investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat model of MGN.Materials and methods Fourty male Sprague-Dawley rats were randomized into four groups. The MGN model was established and treated with a DG dose (10 mg/kg) and a positive control (TPCA1, 10 mg/kg), while normal control and MGN groups received distilled water by gavage for four consecutive weeks. At the end of the experiment, 24 h urinary protein, biochemical indices, oxidation and antioxidant levels, inflammatory parameters, histopathological examination, immunohistochemistry and immunoblotting were evaluated.Results DG significantly ameliorated kidney dysfunction by decreasing urinary protein (0.56-fold), serum creatinine (SCr) (0.78-fold), BUN (0.71-fold), TC (0.66-fold) and TG (0.73-fold) levels, and increasing ALB (1.44-fold). DG also reduced MDA (0.82-fold) and NO (0.83-fold) levels while increasing the activity of SOD (1.56-fold), CAT (1.25-fold), glutathione peroxidase (GPx) (1.55-fold) and GSH (1.81-fold). Furthermore, DG reduced Keap1 (0.76-fold) expression, Nrf2 nuclear translocation (0.79-fold), and induced NQO1 (1.25-fold) and HO-1 (1.46-fold) expression. Additionally, DG decreased IL-2 (0.55-fold), TNF-α (0.80-fold) and IL-6 (0.75-fold) levels, and reduced protein expression of NF-κB p65 (0.80-fold), IKKβ (0.93-fold), p-IKKβ (0.89-fold), ICAM-1 (0.88-fold), VCAM-1 (0.91-fold), MCP-1 (0.88-fold) and E-selectin (0.87-fold), and also inhibited the nuclear translocation of NF-κB p65 (0.64-fold).Discussion and conclusions The results suggest a potential therapeutic benefit of DG against MGN due to the inhibition of the NF-κB pathway, supporting the need for further clinical trials.
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spelling doaj.art-e4aa6ca4be49495585f6b100ed142c6d2024-03-22T09:53:13ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162024-12-0162128529510.1080/13880209.2024.2330602Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathwayShiyan Jia0Ruihua Si1Guangzhen Liu2Qiming Zhong3Department of Anesthesiology, Anesthesia and Trauma Research Unit, Hebei Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Cangzhou, ChinaCollege of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, ChinaDepartment of Nephrology, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, ChinaDepartment of Nephrology, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, ChinaAbstractContext Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects.Objective To investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat model of MGN.Materials and methods Fourty male Sprague-Dawley rats were randomized into four groups. The MGN model was established and treated with a DG dose (10 mg/kg) and a positive control (TPCA1, 10 mg/kg), while normal control and MGN groups received distilled water by gavage for four consecutive weeks. At the end of the experiment, 24 h urinary protein, biochemical indices, oxidation and antioxidant levels, inflammatory parameters, histopathological examination, immunohistochemistry and immunoblotting were evaluated.Results DG significantly ameliorated kidney dysfunction by decreasing urinary protein (0.56-fold), serum creatinine (SCr) (0.78-fold), BUN (0.71-fold), TC (0.66-fold) and TG (0.73-fold) levels, and increasing ALB (1.44-fold). DG also reduced MDA (0.82-fold) and NO (0.83-fold) levels while increasing the activity of SOD (1.56-fold), CAT (1.25-fold), glutathione peroxidase (GPx) (1.55-fold) and GSH (1.81-fold). Furthermore, DG reduced Keap1 (0.76-fold) expression, Nrf2 nuclear translocation (0.79-fold), and induced NQO1 (1.25-fold) and HO-1 (1.46-fold) expression. Additionally, DG decreased IL-2 (0.55-fold), TNF-α (0.80-fold) and IL-6 (0.75-fold) levels, and reduced protein expression of NF-κB p65 (0.80-fold), IKKβ (0.93-fold), p-IKKβ (0.89-fold), ICAM-1 (0.88-fold), VCAM-1 (0.91-fold), MCP-1 (0.88-fold) and E-selectin (0.87-fold), and also inhibited the nuclear translocation of NF-κB p65 (0.64-fold).Discussion and conclusions The results suggest a potential therapeutic benefit of DG against MGN due to the inhibition of the NF-κB pathway, supporting the need for further clinical trials.https://www.tandfonline.com/doi/10.1080/13880209.2024.2330602Chronic kidney diseasepodocytetraditional Chinese medicineNrf2/Keap1 signalling pathway
spellingShingle Shiyan Jia
Ruihua Si
Guangzhen Liu
Qiming Zhong
Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway
Pharmaceutical Biology
Chronic kidney disease
podocyte
traditional Chinese medicine
Nrf2/Keap1 signalling pathway
title Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway
title_full Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway
title_fullStr Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway
title_full_unstemmed Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway
title_short Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway
title_sort diosgenin protects against cationic bovine serum albumin induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the nf κb pathway
topic Chronic kidney disease
podocyte
traditional Chinese medicine
Nrf2/Keap1 signalling pathway
url https://www.tandfonline.com/doi/10.1080/13880209.2024.2330602
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AT guangzhenliu diosgeninprotectsagainstcationicbovineserumalbumininducedmembranousglomerulonephritisbyattenuatingoxidativestressandrenalinflammationviathenfkbpathway
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