Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro

Abstract

Membranous nephropathy is a major cause of nephrotic syndrome in adults where podocyte injuries were found to mediate the development of proteinuria. Triptolide, a major active component of Tripterygium wilfordii Hook F, has potent immunosuppressive, anti-inflammatory and antiproteinuric effects. To study its antiproteinuric properties, we established an experimental rat model of passive Heymann nephritis and a C5b-9 injury model of podocytes in vitro. Treatment or pretreatment with triptolide markedly reduced established proteinuria as well as the titer of circulating rat anti-rabbit IgG antibodies in these nephritic rats, accompanied by a reduction in glomerular C5b-9 deposits. Expression of desmin, a marker of podocyte injury, diminished after triptolide treatment, whereas quantitative analysis of mean foot process width showed that effacement of foot processes was substantially reversed. In in vitro studies we found that triptolide deactivated NADPH oxidase, suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase, and restored RhoA signaling activity. Triptolide did not interfere with the formation of C5b-9 on the membrane of podocytes. Thus, triptolide reduces established heavy proteinuria and podocyte injuries in rats with passive Heymann nephritis, and protects podocytes from C5b-9-mediated injury.

The Water-Soluble Triptolide Derivative PG490-88 Protects against Cisplatin-Induced Acute Kidney Injury

“…Triptolide attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction (Yuan et al, 2011). Triptolide can dramatically attenuate albuminuria and renal lesion accompanied with dyslipidemia and obesity in db/db diabetic mice (Gao et al, 2010), and in experimental membranous nephropathy, triptolide decreases reactive oxygen species and p38 MAPK (Chen et al, 2010). Triptolide protects podocytes from puromycin aminonucleoside-induced injury in vivo and in vitro (Zheng Fig.…”

“…For example, PG490-88 prolongs renal allograft survival in monkeys (Chen et al, 2006). Triptolide reduces cyst growth in autosomal dominant polycystic kidney disease (ADPKD) (Leuenroth et al, 2007), decreases experimental membranous nephropathy (Chen et al, 2010) and podocyte injury (Zheng et al, 2008), and attenuates diabetic nephropathy in rodents (Gao et al, 2010). Triptolide decreases interstitial fibrosis in a model of unilateral kidney obstruction (Yuan et al, 2011).…”

The Clinical Efficacy of Low-Dose Tacrolimus Combined with Tripterygium to Treat the Steroid-Resistant Nephrotic Syndrome

“…In recent years, in vitro experiments have indicated that triptolide can stabilize the skeleton mycin aminonucleoside (PAN) to podocyte, and when podocyte is damaged, triptolide can reverse the damage of podocytes and recover the skeleton structure of podocytes and the expression of relevant molecules [8]. Currently, the influence of triptolide on podocytes is considered to be an important factor for the decrease of urine protein of patients with glomeru-lonephritis [8,9].…”

“…In recent years, in vitro experiments have indicated that triptolide can stabilize the skeleton mycin aminonucleoside (PAN) to podocyte, and when podocyte is damaged, triptolide can reverse the damage of podocytes and recover the skeleton structure of podocytes and the expression of relevant molecules [8]. Currently, the influence of triptolide on podocytes is considered to be an important factor for the decrease of urine protein of patients with glomeru-lonephritis [8,9]. With the research on the influence of glomerular podocytes on proteinuria production, people have recognized that for some diseases of the renal glomeruli which are characterized in a great quantity of proteinuria and accompanied by the damage to podocyte such as minute lesion, focal segmental glomerulo-sclerosis and membranous nephropathy, TW works well on reducing proteinruia to all the above diseases [9,12].…”

“…In the 1980s, Leishi Li first used common threewingnut root, a traditional medicine on the treat-ment of renal glomerulus diseases and in the later sever aldecades, through clinical application, it has been found that tripterygium (TW) presents its unique curative effects in the treatment of many renal glomerulus diseases such as minimal change disease, IgM nephropathy and IgA nephropathy. Researches showed that common threewingnut root has obvious functions of anti-inflammation and immunosuppression; In addition, a series of basic researches in recent years have proved that common threewingnut root has unique functions of podocyte protection and it can reduce the urine protein amount of glomerulonephritis patients [8,9].…”