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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Taylor & Francis Group
2024-12-01
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Series: | Pharmaceutical Biology |
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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. |
first_indexed | 2024-04-24T20:20:02Z |
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institution | Directory Open Access Journal |
issn | 1388-0209 1744-5116 |
language | English |
last_indexed | 2024-04-24T20:20:02Z |
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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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