Therapeutic Mechanism of Saikosaponin-d in Anti-Thy1 mAb 1-22-3-Induced Rat Model of Glomerulonephritis

Abstract

Aims: Mesangioproliferative glomerulonephritis is a common kidney disease and at present, there is no effective treatment. Our previous studies have demonstrated that Sairei-to can significantly prevent progression of experimental glomerulonephritis in rats. Although we have reported that the active component of Sairei-to in treatment of glomerulonephritis was Saikosaponin-d (Ssd), mechanism of Ssd in prevention of mesangioproliferative glomerulonephritis progression is still unknown. Therefore, current study examines the effects of Ssd on progression of mesangioproliferative glomerulonephritis induced by anti-Thy1 monoclonal antibody 1-22-3 (mAb 1-22-3) in uninephrectomized rats. Methods: Eighteen female Wistar rats first received uninephrectomy and mAb 1-22-3 injection and were then divided into 3 groups: treated daily with phosphate-buffered saline (PBS), 0.6 or 1.8 mg/kg of Ssd. Urinary protein concentration and systolic blood pressure were evaluated and the kidneys were collected and subjected to histological and immunohistological evaluation. The mRNA and protein of the kidneys were extracted and subjected to reverse transcriptase polymerase chain reaction and Western blot analysis, respectively. Results: Ssd reduced the amount of urinary protein and systolic blood pressure. Ssd administration also decreased extracellular matrix expansion, crescentic formation as well as infiltration of macrophages and CD8+ T lymphocytes. Moreover, Ssd significantly reduced expression of transforming growth factor beta 1 (TGF-β1) and type I collagen in the kidneys. Conclusion: Ssd inhibits the progression of mesangioproliferative glomerulonephritis through reduction of the expression of TGF-β1 and the infiltration of macrophages and CD8+ T lymphocytes.

Saikosaponin-D reduces cisplatin-induced nephrotoxicity by repressing ROS-mediated activation of MAPK and NF-κB signalling pathways

“…HK-2 cells were treated with SSD (0,20,40,60,80,100 or 150 μM) for 24 h (A) and were then uniformly treated with the maximum dose of SSD (100 μM) for different periods (0, 6, 12, 24 or 48 h; B). The cells were treated with DDP (0, 2.5, 5, 10, 20 or 30 μM) for 24 h (C) and were pretreated with SSD (100 μM) for different periods (0, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 16 h or 32 h) and were pretreated with SSD (20,40,60,80,100 or 150 μM) for 2 h and then were treated with 10 μM DDP (E) for 24 h. Cell viability was determined using the CCK-8 assay according to the absorbance value (A). The data are presented as the mean values ± SD from five independent experiments.…”

Saireito and Saikosaponin D Prevent Urinary Protein Excretion via Glucocorticoid Receptor in Adrenalectomized WKY Rats with Heterologous-Phase Anti-GBM Nephritis

“…Previous reports have demonstrated that saikosaponin D was effective in anti-Thy1 mAb-induced nephritis [26] and anti-GBM nephritis [27] in rats. Anti-GBM nephritis during the heterologous phase and anti-Thy1 nephritis were mainly developed by binding of heterogeneous antibodies to the GBM or mesangial cells.…”

Saikosaponins: a potential treatment option for systemic lupus erythematosus

“…This may herald a novel approach for further studies of Ssd as a candidate for use in the treatment of inflammatory and autoimmune diseases. Li et al [20] reported that Ssd can inhibits the progression of mesangioproliferative glomerulonephritis through reduction of the expression of Transforming growth factor beta 1 (TGF-b1) and the infiltration of macrophages and CD8? T lymphocytes.…”