Xi-sheng Xie

Systematic review of the renal protective effect of Astragalus membranaceus (root) on diabetic nephropathy in animal models

GOALS Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease. Recent experimental studies have shown that Astragalus membranaceus (AM) (root) has an inhibitory effect on the oxidative stress that characterizes early DN. This systematic review assesses the efficacy and safety of AM (root), used as a single herb, in slowing the progression of DN in diabetic rat models. METHODS We conducted both an electronic search and a search by hand of randomized, controlled AM (root) treatment studies (including its effective components) focusing on animal models of DN. Two reviewers independently selected and assessed the studies. RESULTS Among the 41 articles identified, 13 reports that fulfilled the inclusion criteria were included. Significant beneficial effects were observed in the AM (root) treated groups compared to controls regarding fasting blood glucose levels (standardized mean difference [SMD]: -2.86, 95% confidential interval (CI): -4.26, -1.46, P < 0.001), glomerular filtration rate (SMD: -3.36, 95% CI: -4.69, -2.03, P < 0.00001), urinary albumin excretion rate (SMD: -2.46, 95% CI: -3.75, -1.16, P = 0.0002), and thickness of the glomerular basement membrane (SMD: -3.51, 95% CI: -6.68, -0.34, P = 0.03). CONCLUSIONS AM (root) and its effective components are effective in reducing fasting blood glucose and albuminuria levels, in reversing the glomerular hyperfiltration state, and in ameliorating the pathological changes of early DN in rat models.

Ginsenoside Rg1, a major active component isolated from Panax notoginseng, restrains tubular epithelial to myofibroblast transition in vitro

The medicinal herb, Panax notoginseng, has been used for thousands of years in traditional Chinese medicine and possesses anti-fibrosis properties. Epithelial-myofibroblast transition (EMT) plays an important role in renal tubulointerstitial fibrosis. The present study was designed to examine whether ginsenoside Rg1, a major active component isolated from Panax notoginseng, has an ability to block this phenotypic transition in rat renal tubular epithelial cells (NRK-52E) induced by transforming growth factor-beta1 (TGF-beta1). The morphology of tubular epithelial-myofibroblast transition was observed through light microscope and transmission electron microscopy. alpha-SMA and E-cadherin are two markers of tubular epithelial-myofibroblast transition, their protein expressions were assessed by immunohistochemistry and western blot analysis. Gene expression of alpha-SMA as well as the two major extracellular matrix components collagen I and fibronectin was measured by real-time PCR analysis. Enzyme-linked immunosorbent assay was used to quantitatively detect collagen I and fibronectin in the supernatant. Our results revealed that ginsenoside Rg1 obviously blocked morphologic transformation in NRK-52E induced by TGF-beta1. Meanwhile, ginsenoside Rg1 inhibited the expression of alpha-SMA and the loss of E-cadherin, subsequently decreased the levels of collagen I and fibronectin in a dose-dependent manner. In addition, western blot analysis indicated that ginsenoside Rg1 inhibited the expression of P-ERK1/2 in NRK-52E induced by TGF-beta1. These results suggest that ginsenoside Rg1 can restrain the process of EMT maybe via suppressing the expression of P-ERK1/2 in vitro.

Ginsenoside Rb1,a Panoxadiol Saponin against Oxidative Damage and Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction

ObjectiveTo investigate the possible protective effect and mechanism of ginsenoside Rb1 against oxidative damage and renal interstitial fibrosis on rats with unilateral ureteral obstruction (UUO).MethodsIn total, 80 male rats were randomly divided into 4 groups, 20 in each group: the sham operated group (SOR), UUO group, UUO with ginsenoside Rb1 treatment group (treated with intraperitoneal injection of 50 mg/ kg daily) and UUO with Losartan treatment group (as the positive control, treated with 20 mg/kg by gastrogavage per day). The rats were randomly sacrifificed on day 3, 7 and 14 after surgery, respectively. The histopathologic changes of renal interstitial tissues were observed with Masson staining. The mRNA of transforming growth factor β 1 (TGF-β 1), collagen I and fibronectin were reversed transcribed and quantified by Real-time PCR. Enzyme-linked immunosorbent assay was used to quantitatively detect TGF-β 1 and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. P47phox protein expression was assessed by immunohistochemistry and Western blot analysis.ResultsIn the UUO model, the obstructed kidney showed typical features of progressive renal tubulointerstitial fibrosis, and the levels of TGF-β1, collagen I and fibronectin increased (P<0.05). As compared with the UUO group, ginsennoside Rb1 significantly inhibited the interstitial fibrosis including tubular injury and collagen deposition, and decreased the levels of TGF-β1 (P<0.05). Ginsenoside Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative stress (P<0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox, a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P<0.05).ConclusionGinsenoside Rb1 can obviously inhibit renal interstitial fibrosis in rats with UUO, its mechanism possibly via against the oxidative damage and suppressing TGF-β1 expression.

LSKL, a peptide antagonist of thrombospondin-1, attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction

The effects of LSKL, the peptide antagonist of thrombospondin-1 (TSP-1), on renal interstitial fibrosis in rats subjected to unilateral ureteral obstruction (UUO) were investigated. Rats were divided randomly into three groups (n = 20 each): UUO group, sham-operation group and UUO plus LSKL treatment group. Collagen deposition was studied using histopathology and reverse transcription polymerase chain reaction analysis (RT-PCR). TSP-1, transforming growth factor beta 1 (TGF-β1), phosphorylated Smad2 (pSsmad2) and α-smooth muscle actin (α-SMA) in the kidney were measured using immunocytochemistry, western blotting analysis, RT-PCR and enzyme-linked immunosorbent assay. Biochemical analyses in the serum and urine were made. Histopathology showed severe tubular dilatation and atrophy, interstitial inflammation and collagen accumulation after surgery and LSKL significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. The protein and mRNA levels of TSP-1 increased notably at different time point and significantly decreased in the presence of LSKL. The expression of TGF-β1 and pSmad2 were upregulated in the obstructed kidney and substantially suppressed by LSKL treatment. Myofibroblast accumulation could be alleviated after administration of LSKL. Biochemical parameters did not show differences among the three groups. As TSP-1 is the major activator of TGF-β1, we demonstrate that LSKL can attenuate renal interstitial fibrosis in vivo by preventing TSP-1-mediated TGF-β1 activation.

Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-β in rats with unilateral ureteral obstruction

Astragalus mongholicus (AM) derived from the dry root of Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction (UUO). We divided 48 Sprague-Dawley rats randomly into 4 groups: sham-operated group (Sham), untreated UUO group, AM-treated (10 g/(kg·d)) UUO group, and losartan-treated (20 mg/(kg·d)) UUO group as positive control. Haematoxylin & eosin (HE) and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin (FN), type I collagen (colI), hepatocyte growth factor (HGF), transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA) were analyzed by real-time polymerase chain reaction (PCR), immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and colI from UUO by reducing the expressions of TGF-β1 and α-SMA (P<0.05), whereas HGF increased greatly with AM treatment (P<0.05). Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition of myofibroblast activation, inducing of HGF and reducing of TGF-β1 expression.

Ginsenoside Rg1 Modulation on Thrombospondin-1 and Vascular Endothelial Growth Factor Expression in Early Renal Fibrogenesis in Unilateral Obstruction

Renal interstitial fibrosis is the major histopathological change seen in a variety of renal disorders and is closely related to renal dysfunction. Progressive interstitial fibrosis accompanied by the loss of renal tubules and interstitial capillaries typifies all progressive renal disease. Thrombospondin‐1 (TSP‐1) is a major angiogenic inhibitor. It is demonstrated that TSP‐1 levels were correlated with the loss of glomerular and peritubular capillaries and TSP‐1 could promote renal scarring by effects on the endothelium. It has been reported that ginsenoside Rg1 inhibited renal interstitial fibrosis in rats via suppressing the expression of TSP‐1. The present study was designed to examine whether ginsenoside Rg1 could modulate the integrity of the microvasculature and hence affect the progression of renal fibrosis in a rat unilateral ureteral obstruction (UUO) model. In UUO control kidneys, associated with interstitial fibrosis, lower peritubular capillary densities were prominent. These changes were all improved by ginsenoside Rg1 treatment. Interestingly, ginsenoside Rg1 decreased the expression of TSP‐1 and enhanced vascular endothelial growth factor (VEGF) expression. The results show for the first time that ginsenoside Rg1 can evidently inhibit renal interstitial fibrosis in rats with UUO. The mechanism might be related to suppression of the expression of TSP‐1 and to repair of the peritubular capillary. Copyright

Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction *

Total saponins of Panax notoginseng (PNS) have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rg1 on renal fibrosis in rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into 3 groups: sham-operation (n=15), UUO (n=15) and UUO with ginsenoside Rg1 treatment (n=15, 50 mg per kg body weight, intraperitoneally (i.p.) injected). The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rg1 significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. α-smooth muscle actin (α-SMA) and E-cadherin are two markers of tubular epithelial-myofibroblast transition (TEMT). Interestingly, ginsenoside Rg1 notably decreased α-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA (mRNA) of transforming growth factor-β1 (TGF-β1), a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-β1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-β1 mRNA and the activation of latent TGF-β1. These results suggest that ginsenoside Rg1 inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.

A case report of an effective treatment for diabetic foot ulcers with integration of traditional Chinese medicine and Western medicine

Diabetes contributes 75-85% of the factors predisposing to foot amputations, usually in association with infection and gangrene. The treatment of foot ulcers is expensive, and the effectiveness of treatment varies. We report herein a case of a diabetic foot ulcer that was treated with integrated traditional Chinese and Western medicine, with desirable cost-effective results. Traditional Chinese medicine (TCM) therapeutic principles include improving the spleen, nourishing yin, regulating qi, and resolving dampness, as well as activating stagnant blood. Western medicine includes wound debridement, skin grafting, and use of insulin, antibiotics, and vasodilators. The patient was treated with a holistic multidisciplinary approach (i.e., a combination of TCM and Western medicine, surgical management, education for diabetic foot care, and psychological counseling). Without this approach, the patient might have ended up with foot amputation and/or sepsis.

Hydraulic pressure inducing renal tubular epithelial-myofibroblast transdifferentiation in vitro

ObjectiveThe effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) were investigated.MethodsWe applied hydraulic pressure (50 cmH2O) to normal rat kidney tubular epithelial cells (NRK52E) for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression of myofibroblastic marker protein and transforming growth factor-β1 (TGF-β1) of NRK52E cells were examined. Results: Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression of α-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-β1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-β1.ConclusionWe illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-β1 secretion.