ABSTRACT
The reduction of extracellular matrix (ECM) degradation in kidney is taken as the morphological features and pathological base in renal injury in chronic kidney disease (CKD). ECM degradation is controlled by the catabolic enzyme systems in glomerulus and renal interstitium, in which matrix metalloproteinases (MMPs) play a key role. The expression and activity of MMPs are regulated by the classical pathway, such as the genic transcription, the activation of zymogen, and the specific inhibitor. The previous studies showed that, Uremic Clearance granule, as a representation, and other prescriptions of Chinese herbal medicine, as well as some extracts from Chinese herbal medicine could intervene the pathway of ECM degradation through promoting the degradation of ECM components, affecting the expression of catabolic enzymes, regulating the genetic transcription of MMPs, and inhibiting the relative signaling transduction of MMPs.
Subject(s)
Animals , Humans , Drugs, Chinese Herbal , Pharmacology , Extracellular Matrix , Metabolism , Kidney , Cell Biology , Pathology , Matrix Metalloproteinases , Metabolism , Proteolysis , Smad Proteins , MetabolismABSTRACT
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.
Subject(s)
Animals , Humans , Drugs, Chinese Herbal , Therapeutic Uses , Kidney , Metabolism , Kidney Failure, Chronic , Drug Therapy , Genetics , Metabolism , Oxidative Stress , Transforming Growth Factor beta1 , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the potential mechanisms of huangkui capsule (HKC), an extract from Abelmoschus manihot (AM), for ameliorating renal inflammatory injury by regulating p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with adriamycin-induced nephropathy (ADRN).</p><p><b>METHOD</b>Nineteen Sprague-Dawley (SD) rats were randomly divided into three groups, the sham-operation group, the untreated model group,and the HKC-treated group. Rats in the untreated model group and the HKC-treated group were made into ADRN model by right nephrectomy and twice intravenous injections of adriamycin( ADR, 0.4 mL and 0.2 mL respectively within 4 weeks). After the model successfully established, rats in the HKC-treated group were orally given HKC (2 mg x kg(-1) per day), while rats in the untreated model group and the sham-operation group were intervened with distilled water respectively. The intervention for all rats was 4 weeks. Rats' body weight were weighted and 24 h urinary protein excretion (Upro) was detected at the end of the 1st, 2nd, 3rd, and 4th week after the intervention of HKC or distilled water. All rats were sacrificed at the end of the 8th week after nephrectomy, and then, to withdraw blood and kidney to examine the blood biochemical parameters, the glomerular morphological changes, alpha-smooth muscle actin (alpha-SMA) and collagen type I expressions,and the glomerular macrophages infiltration. Besides, the protein expression of transforming growth factor (TGF)-beta1, p38MAPK, as well as phosphorylated p38MAPK (p-p38MAPK) in renal tissues were detected by Western blotting.</p><p><b>RESULT</b>As compared with rats in the untreated model group, in the HKC-treated group,the HKC treatment significantly improved Upro, serum albumin, mesangial cell proliferation, extracellular matrix (ECM) and collagen deposition,and decreased the expression of alpha-SMA and collagen type I and the infiltration of ED1+ and ED3+ cells in glomeruli. In addition, it significantly down-regulated the protein expression of TGF-beta1 and p-p38MAPK in renal tissues.</p><p><b>CONCLUSION</b>HKC had the effects on ameliorating renal inflammatory injury in vivo. It could reduce the expression of TGF-beta1 and improve the infiltration and activation of inflammatory cells in glomeruli by way of intervening p38MAPK signaling pathway in kidney through down-regulating the protein expression of p-p38MAPK, as the key signal molecule.</p>