Multi-Glycoside of <i>Tripterygium wilfordii </i>Hook f. Ameliorates Prolonged Mesangial Lesions in Experimental Progressive Glomerulonephritis

Abstract

Background/Aims: Multi-glycoside from Tripterygium wilfordii Hook f. (GTW) is used for treatment of progressive glomerulonephritis (GN) in China. We have previously reported the beneficial effects of GTW on acute GN induced by an anti-Thy-1.1 monoclonal antibody (mAb). In the present study, the effect and potential mechanisms of GTW on the chronic irreversible model of GN were investigated. Methods: Progressive GN was induced in rats by two intravenous injections of anti-Thy-1.1 mAb 1-22-3. Daily oral administration of GTW was started before the second injection of mAb until the day of sacrifice. Ten rats were randomly divided into a control (vehicle-treated) and a GTW-treated group, and sacrificed on day 45 after the first injection of mAb 1-22-3. Proteinuria was determined on days 0, 1, 3, 5, 7, 10, 14, 20, 25, 30, 35, 40, and 45. Blood biochemical parameters, morphological changes of mesangium, glomerular infiltration of macrophage and T lymphocyte, and glomerular mRNA expression of cytokines (TGF-β, IL-2, and IFN-γ) were examined from the samples taken at terminal sacrifice. Results: GTW treatment significantly ameliorated proteinuria, renal function, prolonged mesangial lesions and inflammatory cell accumulation in glomerulus. In addition, it significantly reduced the glomerular mRNA expression for TGF-β, IL-2, and IFN-γ. Conclusion: GTW ameliorates prolonged glomerular lesions presumably through suppression of cytokine production (TGF-β, IL-2, and IFN-γ). GTW could be an effective therapeutic agent for treatment of chronic renal diseases.

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

“…Therefore, we contrasted mesangial morphological change, α-SMA and collagen type I staining score, serum level of creatinine and BUN, and proteinuria after GTW treatment with different doses between the acute and chronic anti-Thy1.1 GN models. The same as our results in the past studies (9,35), using two types of anti-Thy1.1 GN model, we corroborated again that both high and low doses of GTW could promote the restoration of glomerular injury. Furthermore, it is likely that the suppression of the activated inflammatory cells, such as ED3 + macrophages and CD4 + T helper lymphocytes, might contribute to the amelioration of glomerular lesion through the inhibition of inflammatory cytokine expression in glomeruli.…”

“…Further detailed analysis of the relationship between the doseeffect of GTW and the activation of infiltrated inflammatory cells in glomeruli in the chronic anti-Thy1.1 GN are needed to address this hypothesis. To our knowledge, there is a strong causality between the glomerular inflammatory response and mesangial injurious change in the development of anti-Thy1.1 GN induced by mAb 1-22-3 (35). Therefore, we contrasted mesangial morphological change, α-SMA and collagen type I staining score, serum level of creatinine and BUN, and proteinuria after GTW treatment with different doses between the acute and chronic anti-Thy1.1 GN models.…”

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

“…35,36) Due to the merits of resource abundance and cheap price, TWHF has been widely used in glomerulonephritis and kidney transplantation. 11,[37][38][39] Triptolide is a major active ingredient of TWHF and has been shown to possess multiple biological activities. 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.…”

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.…”