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

• Published in: Pharmaceutical biology Vol. 62; no. 1; pp. 285 - 295
• Main Authors: Jia, Shiyan, Si, Ruihua, Liu, Guangzhen, Zhong, Qiming
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2024; Taylor & Francis Group
• Subjects: Animals; Antioxidants - pharmacology; Chronic kidney disease; Glomerulonephritis, Membranous - chemically induced; Glomerulonephritis, Membranous - drug therapy; Glomerulonephritis, Membranous - prevention & control; I-kappa B Kinase - metabolism; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - prevention & control; Kelch-Like ECH-Associated Protein 1 - metabolism; Male; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Nrf2/Keap1 signalling pathway; Oxidative Stress; podocyte; Rats; Rats, Sprague-Dawley; Serum Albumin, Bovine - metabolism; Serum Albumin, Bovine - pharmacology; Serum Albumin, Bovine - therapeutic use; traditional Chinese medicine; traditional Chinese medicine; Chronic kidney disease; Nrf2/Keap1 signalling pathway; podocyte
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2024.2330602

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