ABSTRACT
Aristolochia manshuriensis Kom (AMK) is an herb used as a traditional medicine; however, it causes side effects such as nephrotoxicity and carcinogenicity. Nevertheless, AMK can be applied in specific ways medicinally, including via ingestion of low doses for short periods of time. Non-alcoholic steatohepatitis (NASH) induced the hepatocyte injury and inflammation. The protective effects of AMK against NASH are unclear; therefore, in this study, the protective effects of AMK ethyl acetate extract were investigated in a high-fat diet (HFD)-induced NASH model. We found decreased hepatic steatosis and inflammation, as well as increased levels of lipoproteins during AMK extract treatment. We also observed decreased hepatic lipid peroxidation and triglycerides, as well as suppressed hepatic expression of lipogenic genes in extract-treated livers. Treatment with extract decreased the activation of c-jun N-terminal kinase 1/2 (JNK1/2) and increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). These results demonstrate that the protective effect of the extract against HFD-induced NASH occurred via reductions in reactive oxygen species production, inflammation suppression, and apoptosis related to the suppression of JNK1/2 activation and increased ERK1/2 phosphorylation. Taken together, these results indicate that that ethyl acetate extract of AMK has potential therapeutic effects in the HFD-induced NASH mouse model.
Subject(s)
Animals , Mice , Apoptosis , Aristolochia , Diet, High-Fat , Eating , Fatty Liver , Hepatocytes , Inflammation , JNK Mitogen-Activated Protein Kinases , Lipid Peroxidation , Lipoproteins , Liver , Medicine, Traditional , Non-alcoholic Fatty Liver Disease , Phosphorylation , Phosphotransferases , Reactive Oxygen Species , Therapeutic Uses , TriglyceridesABSTRACT
Objective To optimize the processing conditions of Manchuiran Dutchmanspipe Stem with alkali. Methods The combination of radial basis function ( RBF) and response surface methodology ( RSM) was used to investigate the influence of NaHCO3 , concentration, duration and cycles of processing on the content of aristolochic acid. Results The optimal process was achieved when Manchuiran Dutchmanspipe Stem was soaked for 3 cycles in 0. 05 mol·L-1 NaHCO3 solution, for 24 hours in each cycle. The removal rate of total aristolochic acid approached to 83. 74%. Conclusion The combination of RBF and RSM provided a new method and good guidance for further toxicity attenuation for Manchuiran Dutchmanspipe Stem.
ABSTRACT
Objective To observe the renal lesion caused by aristolochia manshuriensis kom(AMK) through 2 infants who had used AMK before hospitalization.Method Retrospecting the 2 cases of infants caused by AMK from 2002 to 2003,and evaluating their pathogenesis,treatment,and prognosis.Result Two infants both presented with symptoms of acute renal failure(ARF),and poor outcome.Conclusions Renal lesion in infant caused by AMK is serious.Some medcines,such as glucocorticosteroid,may be useful for its treatment and prognosis.
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Objective To establish the experimental animal model of acute tubular necrosis (ATN) in rats induced by caulis aristolochiae manshuriensis (CAM) containting aristolochic acid (AA) and compare the interventional effects among ligustrazine, prednisone and benazepril. Methods Male SD rats were divided randomly into six groups, 12 rats in each group. Control group, model group, prednisone group, benazepril group, ligustrazineⅠgroup and ligustrazineⅡgroup were given respectively by gavage with 3 ml/d distilled water,5 g?kg-1?d-1 CAM decoction (CAM 2 g/ml, AA 0.54 mg/ml, AA-Ⅰ0.46 mg/ml) for 60 days, then 3 ml/d distilled water, 10 g?g-1?d-1 CAM decoction for 30 days. Two hours after CAM gavage, control group and model group were given with normal saline. Prednisone group, benazepril group, ligustrazine group and ligustrazineⅡgroup were given with prednisone 5 mg?kg-1?d-1, benazepril 1.7 mg?kg-1?d-1, ligustrazine 50 mg?kg-1?d-1, ligustrazine 150 mg?kg-1?d-1 respectively by gavage for 90 days. Histopathology of kidney tissue was examined after 90 days. Results The renal tissue of control group was normal. Light microscopy of model group revealed patchy vacuolar changes of cells from proximal convoluted tubular epithelium, disorder and loss of brush border, exfoliated epithelial cells in the lumina, exposure of areas of denuded and rupture and thickness and atrophy of tubular basement membrane (TBM), edema and infiltration of inflammatory cells in the interstitium, focal segmental proliferation of glomerular mesangial cells and increase of mesangial matrix, part thickness of interlobular arterial walls. The above abnormalities of other four groups were significantly attenuated compared to model group. Electron microscopy of model group revealed patchy vacuolar changes and fatty degeneration of cells from proximal convoluted tubular epithelium, swelling of mitonchondria, reduce of organelle, karyorrhexis, apoptosis, infiltration of inflammatory cells (phagocytes and lymphocytes) in the interstitium and infiltration of lymphocytes in the epithelium, thickness of interlobular arterial walls, stenosis of lumina. The above abnormalities of electron microscopy in other four groups were remarkably improved compared to model group as well, especially in ligustrazine II group and prednisone group. Conclusions Pathological change of ATN is confirmed in kidney tissue and the rat ATN model induced of AA is successfully established. Benazepril, prednisone and ligustrazine can attenuate the toxic effects by AA. Prednisone and ligustrazine have a better efficacy.
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Objective To observe the oncogenetic process and pathological features of tumor induced by Aristolochia manshuriensis Kom. in rats. Methods Male Sprague-Dawley rats were divided into two groups. The rats in experimental group( n = 30) received by gastric tube about 20 mg ? kg-1 ? d-1 aristolochic acid contained in the extract of Aristolochia manshuriensis Kom. for 5 days in the 1 st week, and then 15 mg ? kg-1 ? d-1 for 7 days in each group were killed at the end of 1st, 4th, 8th, 12th and 16th week, respectively. Each rat was autopsied. Ttrachea, thyroid, heart, lungs, liver, spleen, pancreas, stomach, small and large intestine, kidneys, ureters, bladder and testes were excised and fixed in 10% formalin for histological examination. Results Of the examined organs in the rats of experimental group only forestomach and bladder developed carcinomas. Forestomach: hyperplasia and atypical hyperplasia of squamous cells were found at the end of the 4th week. Squamous cell carcinoma was detected in some rats from the end of 8th week and in all rats of the 16th week. Bladder: Hyperplasia, atypical hyperplasia and carcinoma of transitional cells were found from the end of the 8th week, and this carcinoma was present in all rats at 16th week. No tumor was found in all examined organs in the rats of control group. Conclusions Aristolochia manshuriensis Kom. is a potent oncogen which can induce the squamous cell carcinoma in forestomach and the transitional cell carcinoma in bladder. Its oncogenicity is time-dependent and may be organ-specific.
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Objective To study the metabolic profiles in the urine samples of rats dosed with decoction of the caulis of Aristolochia manshuriensis and the relationship between the results of blood biochemical analysis and histopathological analysis,and to explore the feasibility of the application of NMR-based metabonomics to toxicology of Chinese medicine.Methods Male Wistar rats were administrated by ig 36,32,28,and 24 g/kg of A.manshuriensis or the equal volume of distilled water for 6 d,respectively.Urine were collected and their()~1H-NMR spectra were acquired,and then subjected to data process and principal component ana-(lysis)(PCA).Blood biochemical analysis and histopathological examination were carried out.Results(Compared) to control groups,the urinary concentrations of TMAO,taurine,creatinine,DMG,citrate,and DMA in dosed groups decreased,while those of acetate,alanine,and some other amino acids increased to a great extent.The dosed groups can be readily discriminated from the controls based on PCA,with acetate and TMAO as main discriminators.A good agreement was achieved within clinical chemistry,microscopically examination and PCA data.Conclusion The caulis of A.manshuriensis can induce renal lesion as revealed by the metabonomic analysis of rat urine samples as well as blood biochemical analysis and histopathological examinations.The results show that the metabonomic approach is a promising new technology in toxicology.
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Objective To establish the analytical method for fingerprint of Aristolochia manshuriensis by HPLC-DAD-ESI/MS,which can be used as the basis for quality control of the drug and for the further studies on kidney toxicity metabolite.Methods Samples A.manshuriensis from different habitats were extracted by 75% methanol and analyzed by HPLC-DAD-ESI/MS,whose chromatographic fingerprints were established.Two ways to calculate the similarity were selected to compare the results by determining the common peaks.Results There were 30 main characteristic components in A.manshuriensis.The HPLC-DAD-ESI/MS fingerprint of the 30 common peaks was established preliminarily.The samples of A.manshuriensis from different habitats was found having a good similarity,and the range of similarities for 24 balches of A.manshuriensis were 0.871—0.998.Conclusion The method is reliable,accurate,and of good stability,and can be used for the quality control and variety identification of A.manshuriensis.
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Object To understand if abnormal prostaglandin production is involved in the pathogenesis of chronic renal failure induced by the cane of Aristolochia manshuriensis Kom. Methods Rats in experimental group were given 10 g/kg of the cane of A. manshuriensis everyday for eight weeks. The control group was given the same amount of tap water. At the 8th week, kidney pathology, renal function, serum creatinine (SCr), blood urea nitrogen (BUN) and urinary protein excretion were recorded. The content of 6 keto PGF 1? and TXB 2 in the urine, plasma and renal cortex tissues were determined. Results The urinary protein excretion, SCr and BUN had been significantly increased in rat experimental group. Microscopic examination of the kidney revealed focal degeneration and necrosis of tubular epithelial cells and slight intersititial fibrosis. The ratio of 6 keto PGF 1? /TXB 2 was markedly decreased in the urine, plasma as well as renal cortex tissues. Conclusion Abnormal prostaglandin production is an important pathogenic factor in the pathogenesis of chronic renal failure induced by the cane of A. manshuriensis