[Effect of multi-glycoside of Tripterygium wilfordii Hook. f. in intervening TGF-beta1/Smad signaling pathway of adriamycin-induced nephropathy model rat].

OBJECTIVE: To explore the potential molecular mechanisms of multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) for ameliorating glomerulosclerosis (GS) by observing its intervention effect on transforming growth factor (TGF)-beta1/Smad signaling pathway in adriamycin-induced nephropathy (ADRN) model rat. METHODS: Fifteen female Sprague-Dawley (SD) rats were randomly divided into three groups, the sham-operation group (A), the untreated model group (B), and the GTW treated model group (C). Rats in Group B and C were made into ADRN model by right nephrectomy and intravenous injection of adriamycin (ADR, 0. 4 mL and 0. 2 mL respectively in 4 weeks). After the model was successfully established, rats in Group C were orally given GTW (50 mg/kg per day), while rats in Group B were intervened with distilled water. The intervention for two groups was 6 weeks. Rats' body weight were weighed and 24 h urinary protein excretion (Upro) detected by the end of the 2nd, 4th, 8th and 10th week. All rats were sacrificed at the end of 10th week after operation to withdraw blood and kidney tissue to examine serum biochemical parameters, glomerular morphological changes, alpha-smooth muscle actin (alpha-SMA), and collagen type I expression. Besides, the mRNA expressions of TGF-beta1, Smad3 and Smad7, as well as protein expressions of TGF-beta1, and phosphorylated Smad2/3 (p-Smad2/3) in glomeruli were detected by RT-PCR or Western blotting. RESULTS: As compared with Group B, in Group C, Upro and serum albumin were improved significantly, but no difference between groups was found in levels of blood urea nitrogen(BUN), serum creatinine(SCr), or hepatic cell injury. Mesangial cell proliferation, extracellular matrix (ECM) and collagen deposition were suppressed by GTW. Expressions of alpha-SMA and collagen type I decreased, and the characteristic changes of GS were attenuated. The mRNA expressions of TGF-P,31, Smad3 and protein expression of TGF-beta1, p-Smad2/3 in renal tissues were down-regulated, while the protein expression of Smad7 mRNA was up-regulated. CONCLUSION: GTW showed effect in ameliorating GS in vivo. It could reduce the ECM deposition and improve GS by way of intervening TGF-beta1/Smad signaling pathway in the kidney through regulating the mRNA or protein expressions of key signal molecules, such as Smad3 and p-Smad2/3.

[Regulative mechanism of Chinese herbal medicine on cell signaling pathway in kidney].

In kidney, the role of cell proliferation, differentiation, apoptosis, inflammatory mediators and cytokines expression is closely related with cell signaling pathways, including tyrosine kinase pathway, transforming growth factor-beta/Smad pathway, Rho/Rho-associated coiled-coil forming protein kinase pathway, phosphoinositol pathway, cyclic nucleotide pathway, nuclear factor kappaB pathway and so on. Some Chinese herbs and their extracts, such as rhubarb and triptolide, as well as some Chinese herbal prescriptions, such as astragalus-angelica mixture and Chailing decoction, not only could ameliorate proliferation, differentiation and apoptosis of renal cell by regulating cell signaling pathways, but also could control target gene transcription, expression and its biological effects through inhibiting the phosphorylation of key signaling molecules.

[Preventive effects of multi-glycoside of Tripterygium wilfordii on glomerular lesions in experimental diabetic nephropathy].

OBJECTIVE: To observe the preventive effects of multi-glycoside of Tripterygium wilfordii (GTW) on glomerular lesions in experimental diabetic nephropathy (DN). METHOD: The DN model of rats was established with streptozotocin (STZ) and intervened with GTW. In the same time, normal, benazepril, and vehicle control groups were set up. After 8 weeks of oral treatment with GTW (50 mg x kg(-1) BW), benazepril (6 mg x kg(-1) BW), and vehicle (physiological saline), the changes of body weight, urine albumin (UA1b), blood glucose (BG), serum creatinine (Scr), blood urea nitrogen (BUN) and glomerular morphology were examined. In addition, the level of protein expression of alpha-smooth muscle actin (alpha-SMA) and collagen type I in glomeruli was determined by immunofluorescence. RESULT: Both GTW and benazepril reduced UA1b. GTW ameliorated glomerular injury, such as mesangial cell proliferation, alpha-SMA and collagen type I over-expression, in DN model. Compared with benazepril, beneficial effects of GTW on glomerulusclerosis were more significant (total cell number: GTW group 54.44 +/- 2.41, benazepril group microg/67.83 +/- 4.41, P < 0.05; alpha-SMA score: GTW group 1.98 +/- 0.52, benazepril group 2.27 +/- 0.46, P < 0.05; collagen type I score: GTW group 2.11 +/- 0.37, benazepril group 2.88 +/- 0.58, P < 0.05). CONCLUSION: Preventive effects of GTW on glomerular lesion in DN model are related to decreasing UA1b and ameliorating glomerulusclerosis.

Multi-glycoside of Tripterygium wilfordii Hook f. ameliorates prolonged mesangial lesions in experimental progressive glomerulonephritis.

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-beta, IL-2, and IFN-gamma) 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-beta, IL-2, and IFN-gamma. CONCLUSION: GTW ameliorates prolonged glomerular lesions presumably through suppression of cytokine production (TGF-beta, IL-2, and IFN-gamma). GTW could be an effective therapeutic agent for treatment of chronic renal diseases.

[Mechanism of Chinese herbal medicine delaying progression of chronic kidney disease].

The pathomechanisms of the progression of chronic kidney disease (CKD) include glomerulosclerosis, renal interstitial fibrosis and renal arteriosclerosis. Chinese herbal medicine can delay the progression of CKD by ameliorating the harmful factors of these pathological changes, such as podocyte and slit diaphragm injury, nephrotoxicity of proteinuria, hyperactivity of renin-angiotensin-aldosterone system, cytokines over-expression, tubular epithelial myofibroblast transdifferentiation, hyperlipidemia and hypertension.