Regulative mechanisms of oxidative stress in kidney in diabetic nephropathy and interventional effects of Chinese herbal medicine / 中国中药杂志

In the development of diabetic nephropathy (DN), reactive oxygen specie (ROS) over much in vivo leads to oxidative stress(OS)-related renal injuries, which are characterized by the structural and functional changes in glomerular and renal tubular cells in morphology. The regulative approaches of OS involve the several signaling pathways, in which, both p38 mitogen-activated protein kinase (MAPK) signaling pathway and adenosine monophosphate-activated protein kinase (AMPK) signaling pathway play the important roles as the target of anti-oxidants. The interventional actions of Chinese herbal compound prescriptions and the extracts of single Chinese herbal medicine (CHM) on OS in the kidney in DN include regulating the balance between ROS and antioxidants, reducing the production of AGEs, inhibiting the expression of growth factors and intervening the activity of signaling pathways.

Recognition of experimental animal model with kidney disease / 中国中药杂志

Animal models with kidney disease are generally divided into two types. One belongs to the models which imitate human kidney disease by the artificial operations, such as anti-glomerular basement membrane antibody nephritis, Heymann nephritis, anti-Thyl. 1 antibody nephritis, BSA nephritis and puromycin nephropathy. The other one pertains to the models which make themselves kidney disease, and appear the pathological characteristics naturally as like as human, such as HIGA mice with IgA nephropathy and NZB/WF1 and MRL/1pr mice with lupus nephritis. In addition,the transgenic animal models with kidney disease can also be established by the modern molecular biologic techniques including gene knockout and siRNA transfection. As for the studies related with kidney disease in pharmacodynamics and pharmacology of Chinese herbal medicine (CHM), it is important to understand deeply the features of each animal model with kidney disease, and select accurately the proper models according to the different experimental objectives, and then, build the special models provided with the combination of disease with syndrome in traditional Chinese medicine (TCM). Therefore,it is the developmental direction for the further study to establish animal models with kidney disease, which should possess the characteristics of syndrome in TCM.

Effects and mechanisms of multi-glycoside of Tripterygium wilfordii improving glomerular inflammatory injury by regulating p38MAPK signaling activation in diabetic nephropathy rats / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the effects and mechanisms of multi-glycoside of Tripterygium wilfordii (GTW) on improving glomerular inflammatory lesion in rats with diabetic nephropathy (DN).</p><p><b>METHOD</b>DN model was induced by unilateral nephrectomy and intraperitoneal injection of STZ (35 mg x kg(-1)) twice. The rats were randomly divided into 3 groups, the sham-operated group (Sham group, n = 5), the vehicle-given group (Vehicle group, n = 5 ) and GTW-treated group (GTW group, n = 5). After the model was successfully established, the rats in GTW group were daily oral administrated with GTW suspension (50 mg x kg(-1) x d(-1)), meanwhile, the rats in Vehicle group were daily oral administrated with distilled water (2 mL) for 8 weeks. From the beginning of the administration, all rats were killed 8 weeks later. Blood and renal tissues were collected,and then UAlb, renal function, glomerular morphology characteristics and glomerular macrophages (ED1 + cells) infiltration, as well as the protein expressions of inflammatory cytokines including tumor necrosis factor(TNF)-α and interleukin(IL)-lβ, and the key molecules in p38MAPK signaling pathway including p38 mitogenactivated protein kinase (MAPK), phosphorylated p38 (p-p38MAPK) and transforming growth factor(TGF)-β1 were investigated respectively.</p><p><b>RESULT</b>GTW not only ameliorated the general state of health and body weight,but also attenuated UAlb, glomerulosclerosis, the infiltration of glomerular ED1 + cells and the protein expressions of TNF-α, IL-1β, p-p38MAPK and TGF-β1 in the kidney in DN model rats.</p><p><b>CONCLUSION</b>By means of DN model rats, we demonstrated that GTW has the protective effect on renal inflammatory damage in vivo via inhibiting inflammatory cells infiltration and inflammatory cytokines expression. Furthermore, GTW could improve renal inflammatory lesion through down-regulating the expressions of the key signaling molecules in p38MAPK pathway such as p-p38MAPK and TGF-β1 ,and inhibiting the activation of p38MAPK signaling in the kidney.</p>

Effects and mechanisms of huangkui capsule ameliorating renal fibrosis in diabetic nephropathy rats via inhibiting oxidative stress and p38MAPK signaling pathway activity in kidney / 中国中药杂志

<p><b>OBJECTIVE</b>To demonstrate the effects and mechanisms of Huangkui capsule (HKC) on renal fibrosis in rats with diabetic nephropathy (DN).</p><p><b>METHOD</b>Rats were randomly divided into 5 groups, the sham-operated group (Sham group, n = 5), the vehicle-given group (Vehicle group, n = 7), the low dose of HKC-treated group (L-HKC group, n = 7), the high dose of HKC-treated group (H-HKC group, n = 7) and the lipoic acid (LA)-treated group (LA group, n = 7). DN models were induced by intraperitoneal injection of streptozotocin (STZ,35 mg x kg(-1)) twice and unilateral nephrectomy. After models were successfully established, the rats in HKC and LA groups were daily administrated with HKC suspensions (0.75, 2 g x kg(-1)) or LA suspensions (60 mg x kg(-1)) respectively, and at the same time, the rats in Vehicle group were daily administrated with distilled water (2 mL) for 8 weeks. All rats were sacrificed at the end of week 8 to collect blood and renal tissues. UAlb, renal function, renal fibrotic morphologic characteristics, as well as oxidative stress (OS)-related markers, the protein expressions of the key signaling molecules in p38 mitogen-activated protein kinase (p38MAPK) signaling pathway, fibrogenic cytokines and inflammatory factors were examined respectively.</p><p><b>RESULT</b>HKC, similar to LA, improved the general state of health, body weight, UAlb, BUN, UA and Alb in DN model rats. Of note, renal fibrosis was ameliorated in HKC groups,especially in H-HKC group which was better than that in LA group. In addition, HKC not only improved the main indexes of OS in the kidney like LA, but also down-regulated the protein expressions of phosphorylated-p38MAPK (p-p38MAPK), transforming growth factor (TGF)-β1 and tumor necrosis factor(TNF)-α in the kidney, whereas, LA only decreased the protein expression of TNF-α in the kidney in DN model rats.</p><p><b>CONCLUSION</b>HKC, similar to LA, has the actions of anti-OS in vivo. Moreover, HKC could attenuate renal fibrosis by suppressing the activation of p38MAPK signaling pathway and the protein expressions of fibrogenic cytokines and inflammatory factors in the kidney in DN model rats, which is different from LA.</p>

Clinical implication of urinary protein markers in diabetic nephropathy and interventional effects of Chinese herbal medicine / 中国中药杂志

In clinic, some urinary protein makers can dynamically and noninvasively reflect the degree of renal tubular injury in patients with diabetic nephropathy (DN). These urinary biomarkers of tubular damage are broadly divided into two categories. One is newfound, including kidney injury molecule-1 (Kim-1), neutrophil getatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP) and cystatin C (CysC); the other one is classical, including beta2 microglobulin (beta2-MG), retinal binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG). It is reported that, the increases in urinary protein markers are not only closely related to the damage of tubular epithelial cells in DN patients, but also can be ameliorated by the treatment with Chinese herbal compound preparations or Chinese herbal medicine. Recently, although urinary proteomics are used in the protein separation and identification, the traditional associated detection of urinary protein markers is more practical in clinic. At present, it is possible that the associated detection of urinary biomarkers of glomerular and tubular damages may be a feasible measure to reveal the clinical significance of urinary protein markers in DN patients and the interventional effects of Chinese herbal medicine.

Regulative mechanism of renal inflammatory-related p38MAPK signaling pathway in diabetic nephropathy and interventional effects of Chinese herbal medicine / 中国中药杂志

It is reported, in the process of diabetic nephropathy (DN), inflammatory-related p38 mitogen-activated protein kinase (MAPK) signaling pathway has a close relationship with renal injury. On the one hand,many factors in the upstream including hyperglycemia, abnormal hemodynamics, oxidative stress, and pro-inflammatory cytokines could activate p38MAPK signaling pathway. On the other hand,the activated p38MAPK signaling pathway could lead to renal damage via activating inflammatory cells, inducing the expression of inflammatory mediators, and intervening cytokines production. CHM could intervene p38MAPK signaling pathway through multi-ways, including inhibiting inflammatory cytokines expression, regulating phosphorylated p38MAPK (p-p38MAPK) expression, and reducing fibrogenic factors expression.

Overview research of uremic ulearance granule treating chronic renal failure / 中国中药杂志

The effective bioactivity compositions of uremic clearance granul (UCG) include isoflavonoids, emodin, astragaloside, paeoniflorin, salvianolic acid A, and so on. The effects of UCG treating chronic renal failure (CRF) in clinical pharmacodynamics mainly refer to improve renal function and the complications of CRF. The mechanisms involved in vivo basically include depressing transforming growth factor (TGF)-beta1 over-expression, lessening podocyte injury,inhibiting tubular epithelial myofibroblast transdifferentiation, ameliorating microinflammation status, retarding oxidative stress, and alleviating insulin resistance.

Characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy and its regression analysis with traditional Chinese medicine symptom / 中国中药杂志

To analyze the characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy (DN) and its compliance with traditional Chinese medicine (TCM)symptom, for the sake of providing a basis for clarifying the rules of TCM syndrome differentiation in DN. Adopting the traditional epidemiological retrospective method, thirty-eight TCM syndromes and urinary protein with medium or low molecular weight, as well as urinary enzyme, including 24 h urinary protein (Upro), urinary albumin( UAlb), urinary retinal binding protein( URBP), urinary cystatin C (UCysC), urinary N-acetyl-beta-D-glucosaminidase (UNAG), were collected from 108 patients with stage III DN, and a multiple factor regression analysis between them was conducted. As the results, the levels of Upro, UAlb, URBP, UCysC, and UNAG were increased in 108 patients with stage III DN. Qi-Yin deficiency type was the major type. The level of UAlb in patients with Qi-Yin deficiency type was significantly higher than those without Qi-Yin deficiency type (P < 0.05). The elevation of Upro with the factors as swift digestion with rapid hungering, lassitude and lack of strength, weakness of waist and knees was complied, the elevation of UA1b with the factors as dry mouth with desire to drink, the elevation of URBP with the factors as numbness of extremities, shortness of breath, the elevation of UCysC with the factors as clear urine in large amounts, and the elevation of UNAG with the factors as frequent micturition, were complied respectively. In conclusion, for 108 stage III DN patients. The increase in urinary protein spectrum including UAlb, URBP, UCysC, and UNAG is the major characteristic. Shen and Pi are the major organs related to the appearance of urinary protein; Pi-Shen deficiency is the basic pathogenesis. The level of UAlb is taken as one of the objective syndrome factors for Qi-Yin deficiency type. The levels of UNAG and UCysC are possibly the objective syndrome factors for Shen-Qi deficiency type.