Contrasting Dose–Effects of Multi-glycoside of Tripterygium wilfordii HOOK. f. on Glomerular Inflammation and Hepatic Damage in Two Types of Anti-Thy1.1 Glomerulonephritis

Abstract

Abstract. Multi-glycoside, one of the extracted compounds from Tripterygium wilfordii HOOK. f. (GTW), has been shown to be clinically effective in suppressing glomerular inflammation in chronic kidney disease. However, its clinical application is often limited by its cytotoxic actions on the liver. This study was performed to contrast the dose-effects of GTW on glomerular inflammation and hepatic damage in two types of anti-Thy1.1 glomerulonephritis (GN). Rats with acute or chronic anti-Thy1.1 GN were either left untreated (the Vehicle group) or treated with a high or low dose of GTW and sacrificed on day 7 or day 45. GTW was administrated 3 days before or at the same time as the antibody injection and lasted until sacrifice. GTW at high dose ameliorated glomerular macrophage accumulation, mesangial proliferation, proteinuria, and interleukin-2 expression in the acute anti-Thy1.1 GN model, but caused structural and functional lesions in the liver. In contrast, GTW at low dose improved activated macrophage and T lymphocyte infiltration, mesangial injury, proteinuria, and interleukin-2 and interferon-γ expressions without hepatic toxicity in the chronic model of GN induced by anti-Thy1.1 antibody. In conclusion, GTW at low dose not only effectively inhibits glomerular inflammation but also avoids severe injuries to the liver. It is known that the progressive state of CKD both in animal models and humans is characterized by the infiltration of inflammatory cells and the proliferation of mesangial cells (14,15). The density of macrophages and T lymphocytes, especially the activated macrophages and T lymphocytes in glomeruli, predicts the disease progression in . Therefore, these cells could be targeted for therapeutic purposes and for exploring the mechanism of anti-inflammatory agents against MsPGN. Anti-Thy1.1 GN, induced by the injection of anti-Thy1.1 monoclonal antibody (mAb) 1-22-3, is commonly used as the model of human . It is reported that, the accumulation of macrophages and T lymphocytes into glomeruli is one of the hallmarks of anti-Thy1.1 GN and plays an important pathogenetic role (22). Indeed, the involvement of ED3 + macrophages and CD4 + T helper lymphocytes in the development of the anti-Thy1.1 GN model induced by the injection of mAb 1-22-3 has been reported. In addition, the critical roles of the activated ED3 + cell and CD4 + cell, as well as the related inflammatory mediators, such as IL-2 and IFN-γ, in the chronic anti-Thy1.1 GN model induced by two consecutive injections of mAb 1-22-3 in an interval of 2 weeks (23, 24) has also been documented. Thus we believe that comparing glomerular ED3 + cell and CD4 + cell activation between two types of anti-Thy1.1 GN model would be a successful way to identify the anti-inflammatory effectiveness and mechanism of GTW at the different doses in vivo. KeywordsIn this report, using the acute and chronic types of anti-Thy1.1 GN model induced by mAb 1-22-3, we contrasted the effects of different doses of GTW on glomerular inflammation and hepatic damage in th...

Triptriolide Alleviates Lipopolysaccharide-Induced Liver Injury by Nrf2 and NF-κB Signaling Pathways

“…Currently, more than 200 compounds have been identified from the extracts of TwHF (Wan et al, 2012). Most of them show extensive pharmacological effects on anti-inflammation, immunosuppress, anti-tumor and anti-oxidant (Tao and Lipsky, 2000; Marks, 2011; Lu et al, 2014).…”

Effects of <i>Tripterygium wilfordii</i> Induction Therapy to IgA Nephropathy Patients with Heavy Proteinuria

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“…Triptolide was proved to be a potent inhibitor of vascular endothelial growth factor (VEGF) expression and production in endothelial cells, which could contribute to its anti-proteinuria effect in Thy1.1 glomerulonephritis and puromycin-induced nephrosis. 11,40,41) In cultured mouse podocytes, triptolide pretreatment suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase activation while restoring RhoA signaling activity. 42) Our previous studies have confirmed that increased oxidative stress led to prominent tubule cell injury and podocyte damage.…”

“…9,10) Recent researches indicated that triptolide, one of the major active components of TWHF, was proved to suppress reactive oxygen species generation and ameliorate podocyte injury. 11,12) However, the application of purified triptolide was hampered by the more often and severe side effects. 13) Up to now, TWHF is still widely used in clinical practice.…”

Effects and mechanism of Tripterygium wilfordii on chronic glomerulo nephritis

“…Many clinical reports show that treatment combining traditional Chinese medicine (TCM) and western medicine leads to significant curative effects which are better than that of TCM or western medicine alone. T. wilfordii is a Chinese herbal extract which has anti-inflammation and immunologic suppression properties and is extensively applied to treat rheumatic disease, systemic lupus erythematosus, inflammatory bowel disease, nephritis, and many immune diseases (Wan et al, 2010;Wan et al, 2012;Chen et al, 2013). In this research, conventional treatment combined with orally-taken T. wilfordii tablets resulted in a distinct decrease of uTP and peripheral SCr, BUN, and TC with a significant increase in the ALB level, and the improvement was greater than that of conventional treatment.…”