Current research situation of nephrotoxicity of Chinese herbal medicine / 中国中药杂志

To provide the basis for the future research on the nephrotoxicity of Chinese herbal medicine through systematic and comprehensive summary of all the Chinese herbal medicines which may lead to nephrotoxicity. Foreign resources included PubMed and Cochrane library， and domestic research resources was China Food and Drug Administration(CDFA) Adverse Drug Reaction Monitoring Center database. The databases were searched from establishment to January 1， 2017. There was no limitation on research type. 28 English studies were found， including 97 Chinese herbs or prescriptions with the risk of nephrotoxicity. The following six Chinese herbal medicines with the risk of nephrotoxicity had a large number of studies： aristolochic acid(5 studies)， Tripterygium wilfordii(4 studies)， Erycibe obtusifolia(2 studies)， Rheum palmatum(2 studies)， Ephedra sinica(2 studies)， and Atractylodes lances(2 studies). The remaining 91 Chinese medicines were reported with risk of nephrotoxicity in only 1 study respectively. CDFA reported 16 Chinese herbal medicines with the risk of nephrotoxicity， including Ganmaoqing Pian(capsule)， Zhenju Jiangya Pian， T. wilfordii preparation， Vc-Yinqiao Pian， Chuanhuning injection， Shuanghuanglian injection， Qingkailing injection， Lianbizhi injection， herbal decoction containing Aristolochiae Radix， Guanxin Suhe Wan， Shugan Liqi Wan， Ershiwuwei Songshi Wan， herbal decoction containing Aristolochia Fangchi， herbal granules containing root of Kaempfer Dutchmanspipe， Ganmaotong(tablets)， and Longdan Xiegan Wan. Currently， in addition to aristolochic acids， the most reported Chinese herbal medicine with the risk of nephrotoxicity is T. wilfordii preparation.

Characterization and quantitation of aristolochic acid analogs in different parts of Aristolochiae Fructus, using UHPLC-Q/TOF-MS and UHPLC-QqQ-MS / 中国天然药物

Aristolochiae Fructus, a Chinese herbal medicine derived from the fruit of Aristolochia contorta Bge., contains nephrotoxic aristolochic acid analogues (AAAs). According to ancient medical texts, various medicinal parts of the fruit of A. contorta were ever used. In order to reveal which part could be safely and effectively used, it is necessary to analyze the chemical profiles of different medicinal parts. Herein we compared the chemical compositions and determined aristolochic acid I (AA-I) and aristolochic acid II (AA-II) in the four parts viz. outer pericarp, inner pericarp, septum, and seed. Ultra-high performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was applied for chemical profiling. Ultra-high performance liquid coupled with triple quadrupole mass spectrometry (UHPLC-QqQ-MS) was employed to quantify AA-I and AA-II in different parts. It was found that the chemical compositions of the four parts varied both qualitatively and quantitatively. A total of 10 AAAs, including 5 aristolochic acids and 5 aristolactams, together with 3 alkaloids, were unambiguously or tentatively identified by UHPLC-QTOF-MS. The quantitatively analytical results obtained by UHPLC-QqQ-MS showed that AA-I and AA-II exclusively accumulate in the seeds of A. contorta. These findings provide supporting data for the rational selection of medicinal parts.

Aristolochia manshuriensis Kom ethyl acetate extract protects against high-fat diet-induced non-alcoholic steatohepatitis by regulating kinase phosphorylation in mouse

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.

Molecular identification of aucklandiae radix, vladimiriae radix, inulae radix, aristolochiae radix and kadsurae radix using ITS2 barcode / 中国中药杂志

In order to identify Aucklandiae Radix, Vladimiriae Radix, Inulae Radix, Aristolochiae Radix and Kadsurae Radix using ITS2 barcodes, genomic DNA from sixty samples was extracted and the ITS2 (internal transcribed spacer) regions were amplified and sequenced. The genetic distances were computed using MEGA 5.0 in accordance with the kimura 2-parameter (K2P) model and the neighbor-joining (NJ) phylogenetic tree was constructed. The results indicated that for Aucklandiae Radix (Aucklandia lappa), Vladimiriae Radix (Vladimiria souliei and V. souliei var. cinerea), Inulae Radix (Inula helenium), Aristolochiae Radix (Aristolochia debilis) and Kadsurae Radix (Kadsura longipedunculata), the intra-specific variation was smaller than inter-specific one. There are 162 variable sites among 272 bp after alignment of all ITS2 sequence haplotypes. For each species, the intra-specific genetic distances were also smaller than inter-specific one. Furthermore, the NJ tree strongly supported that Aucklandiae Radix, Vladimiriae Radix, Inulae Radix, Aristolochiae Radix and Kadsurae Radix can be differentiated. At the same time, V. souliei (Dolomiaea souliei) and V. souliei var. cinerea( D. souliei var. cinerea) belonging to Vladimiriae Radix were clearly identified. In conclusion, ITS2 barcode could be used to identify Aucklandiae Radix, Vladimiriae Radix, Inulae Radix, Aristolochiae Radix and Kadsurae Radix. Our study may provide a scientific foundation for clinical safe use of the traditional Chinese medicines.

Advance in studies on toxicity of aristolochic acid and analysis on risk factors / 中国中药杂志

The renal toxicity and mutagenicity of aristolochic acid (AA) as well as its carcinogenicity on upper urinary tract transitional epithelial cells have been widely known. Since 2003, drug regulatory departments have successively cancelled the quality standards for AA-containing medicines such as Aristolochiae Radix, Aristolochiae Manshuriensis Caulis and Aristolchiae Fangchi Radix, and adopted measures for strengthening regulation and revising package insert or quality standards for other AA-containing medicines, including Aristolochia Cinnabarina Radix, Aristolochiae Fructus, Aristolochiae Mollissimae Herba, in order to control its safety risk. In recent years, domestic and foreign studies on AA have mainly involved action mechanism and clinical performance of AA toxicity, early-stage diagnosis and treatment method. In this paper, authors gave a brief summary and evaluation on risk factors for using AA-containing medicines, and offered measures and suggestions for preventing and controlling AA toxicity.

Phenolic aristolactams from leaves and stems of Aristolochia chilensis / Aristolactamas fenólicas de hojas y tallos de Aristolochia chilensis

Three phenolic aristolactams, aristolactam AII (3), velutinam (4) and piperolactam A (5), were identified from the leaves and stems of Aristolochia chilensis Bridges ex Lindl. The structures of these compounds were elucidated using a combination of HPLC-DAD, GC-MS and NMR experiments.

Tres aristolactamas fenólicas aristolactama AII(3), velutinam(4) y piperolactama A(5), se identificaron en hojas y tallos de Aristolochia chilensis Bridges ex Lindl. Las estructuras de estos compuestos se determinaron por combinación de CLAE-DAD, CG-EM y experimentos de RMN.

Development of gastric precancerous lesion animal model / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a model of gastric precancerous lesion by using Aristolochic manshuriensis which contains aristolochic acids.</p><p><b>METHOD</b>The SD rats were randomly divided into four groups: control and three different doses of ethanol extractive of A. manshuriensis (EEA) (corresponding to aristolochic acid I 2.5, 5.0, 10.0 mg x kg(-1)), respectively. EEA was intragastrically given to rats every other day. At the end of the 10th, 15th, 20th week, part of the rats in each group was sacrificed and the stomachs were weighed. The gastric tumor was assessed by the weight and the relative stomach weight to the body weight. The stomachs were fixed in 4% neutral formalin, and the paraffin imbedding tissues were sliced and HE stained. Histomorphology was observed under the light microscope to determine gastric hyperplasia, mucosa precancerosis (atypical hyperplasia) and gastric cancer formation.</p><p><b>RESULT</b>The rats treated with different doses of EEA for 10 weeks induced mucosa papillary, epithelioma hyperplasia. Histological observation showed mucosa precancerosis lesions characterized as atypical hyperplasia at the dose levels corresponding to aristolochic acid I 5.0 and 10.0 mg x kg(-1) treated for 10 weeks. The incidence rate of gastric precancerosis in those two groups was 100% at the 15th week. Malignant tumors were observed in most of the animals in 10.0 mg x kg(-1) group. The animals in 5.0 mg x kg(-1) group were well tolerant compared to 10.0 mg x kg(-1) group during the course of experiment, so the dose of aristolochic acid I 5.0 mg x kg(-1) and 10-15 weeks treatment were considered to be optimum to establish the model of gastric precancerosis.</p><p><b>CONCLUSION</b>A rat model of gastric precancerosis can be induced within a short duration by giving an oral administration of the ethanol extract of A. manshuriensis which contains aristolochic acids.</p>

Intoxicação espontânea por larvas de Perreyia flavipes (Pergidae) em suínos no estado de Santa Catarina / Spontaneous poisoning by larvae of Perreyia flavipes (Pergidae) in pigs in the state of Santa Catarina

Descreve-se um surto de intoxicação espontânea por Perreyia flavipes em suínos. O surto ocorreu no final de maio de 2009, na cidade de Urubici, planalto serrano do Estado de Santa Catarina, Brasil. A propriedade tinha aproximadamente 50 animais criados extensivamente e desses 10 animais adoeceram. Esses suínos apresentavam anorexia, apatia, movimento constante de cabeça e bater de orelhas, dificuldade de caminhar, cambaleio, ranger de dentes e a agitação aumentava mediante ruídos e movimentos próximos. Na necropsia as alterações observadas foram a marcada evidenciação do padrão lobular hepático e a presença de larvas de P. flavipes misturadas ao conteúdo estomacal. Microscopicamente observou-se necrose de coagulação dos hepatócitos, com distribuição centrolobular a massiva que era acompanhada de congestão e hemorragia acentuada, restando uma ou duas camadas de hepatócitos com degeneração vacuolar na região portal. Os aspectos clínicos, epidemiológicos e as lesões caracterizaram hepatite tóxica por larvas de P. flavipes em suínos.

The study reports an outbreak of spontaneous poisoning by Perreyia flavipes in pigs. The outbreak occurred at the end of May 2009, in the municipality of Urubici, plateau of Santa Catarina, Brazil. The farm had about 50 pigs reared extensively and 10 animals got sick. The clinical signs were anorexia, apathy, constant movement of the head and hitting the ears, difficulty to walk and stagger, gnashing of teeth and agitation that increased with noise and movement nearby. At necropsy, pronounced hepatic lobular pattern and P. flavipes larvae mixed with the stomach content were observed. Microscopically, hepatocellular centrilobular to diffuse coagulation necrosis with severe congestion and hemorrhage was observed, with vacuolar degeneration in one or two layers of hepatocytes in the portal zones. Clinical signs, epidemiology and lesions in the pigs were characteristic of toxic hepatitis by larvae of P. flavipes.

Germinação de sementes de Aristolochia esperanzae O. Kuntze em diferentes temperaturas e condições de luminosidade / Germination of Aristolochia esperanzae O. Kuntze seeds under different temperatures and light conditions

O objetivo deste estudo foi verificar a influência da temperatura e da luz, em interação com a temperatura e de forma isolada, bem como, determinar a temperatura mais adequada para a condução do teste de germinação de sementes de Aristolochia esperanzae O. Kuntze (cipó mil-homens). Foram realizados três ensaios. No primeiro, as temperaturas utilizadas foram 15, 20, 25, 30, 35 e 40ºC. No segundo, foi avaliada a germinação das sementes nas temperaturas de 25, 30 e 35ºC, na presença e ausência de luz e no terceiro ensaio, foram testadas quatro condições de luminosidade, de forma isolada: (a) luz branca; (b) luz vermelha; (c) vermelho-distante e (d) ausência de luz, na temperatura de 25ºC. Em ambos os ensaios, foram avaliados, durante 30 dias, as porcentagens de sementes germinadas, de plântulas normais e de sementes não germinadas, e os tempos médios de sementes germinadas e de plântulas normais. Nas temperaturas de 15ºC e de 40ºC, não ocorreram germinação de sementes de A. esperanzae. O melhor resultado para sementes germinadas e para formação de plântulas normais (96 por cento) foi obtido na temperatura de 30ºC. A presença de luz e as temperaturas de 25ºC e 30ºC favoreceram a germinação de sementes e a formação de plântulas normais. As sementes de Aristolochia esperanzae tiveram sua germinação inibida na ausência de luz, caracterizando-as como fotoblásticas positivas.

The aim of this study was to verify the influence of temperature and light, interacting or separately, as well as to establish the most suitable temperature to conduct the germination test of Aristolochia esperanzae O. Kuntze ("cipó mil-homens") seeds. Three assays were performed. In the first one, temperatures were 15, 20, 25, 30, 35 and 40ºC. In the second assay, seed germination was evaluated at 25, 30 and 35ºC, in the presence and absence of light. In the third assay, four light conditions were tested separately: (a) white light; (b) red light; (c) far-red light; and (d) no light, at 25ºC. In all assays, the percentages of germinated seeds, normal seedlings and non-germinated seeds, besides the mean times of germinated seeds and normal seedlings, were evaluated during 30 days. At 15ºC and 40ºC, there was no A. esperanzae seed germination. The best result for germinated seeds and normal seedlings (96 percent) was obtained at 30ºC. The presence of light and the temperatures 25ºC and 30ºC favored seed germination and normal seedling formation. Aristolochia esperanzae seeds had their germination inhibited in the absence of light, which characterizes them as positive photoblastic.

Antimycobacterial neolignans isolated from Aristolochia taliscana

Tuberculosis (TB - Mycobacterium tuberculosis) is an ancient infectious disease that has appeared once again as a serious worldwide health problem and now comprises the second leading cause of death resulting from a single infection. The prevalence of multidrug resistance (MDR) TB is increasing and therapeutic options for treatment are not always accessible; in fact, some patients do not respond to the available drugs. Therefore, there is an urgent need to develop novel anti-TB agents. The aim of the present study was to screen extracts of Aristolochia taliscana, a plant used in traditional Mexican medicine to treat cough and snake bites, for antimycobacterial activity. The hexanic extract of A. taliscana was tested by microdilution alamar blue assay against Mycobacterium strains and bioguided fractionation led to the isolation of the neolignans licarin A, licarin B and eupomatenoid-7, all of which had antimycobacterial activity. Licarin A was the most active compound, with minimum inhibitory concentrations of 3.12-12.5 ìg/mL against the following M. tuberculosis strains: H37Rv, four mono-resistant H37Rv variants and 12 clinical MDR isolates, as well as against five non-tuberculous mycobacteria (NTM) strains. In conclusion, licarin A represents a potentially active anti-TB agent to treat MDR M. tuberculosis and NTM strains.

Comparative study on metabonomics and on liver and kidney toxicity of Aristolochia fangchi and Stephania tetrandra / 中国中药杂志

<p><b>OBJECTIVE</b>Combined the blood biochemical markers, the renal histopathological changes and the metabonomics profile were investigated to study the toxicity differences between Aristolochia fangchi and Stephania tetrandra.</p><p><b>METHOD</b>Ten rats were randomly selected from 70 male Wistar rats as blank control group. The remaining 60 rats were divided into three groups. The two treated groups were orally administrated by 8.1 g x kg(-1) of A. fangchi and S. tetrandra respectively and the control group by equal volume of distilled water for 4weeks. Before the administrated and every 2 weeks, urine and plasma were collected and their 1H-NMR spectra were acquired, and then subjected to data process and PCA. Blood biochemical analysis and histopathological examination were carried out.</p><p><b>RESULT</b>On the 2nd weekend, the BUN of the two treated groups, the AST of A. fangchi group were all markedly higher than that of the control group (P < 0.05). Compared with the A. fangchi group, the SCr higher in the S. tetrandra group (P < 0.05). The kidney pathological changes were apparently in the two treated groups and the pathological changes in the liver apparently in the S. tetrandra group. Along with the lasting of administration to the 4th week, the BUN, ALT and AST of the two treated groups, the SCr of A. fangchi group were all significantly higher than that of the control group (P < 0.01). The renal and liver injuries in the two treated groups were all become more seriously. Comparing the A. fangchi group, the BUN, SCr and AST were all higher in the S. tetrandra group (P < 0.05). Compared with control group, the urinary concentrations of citrate, 2-oxo-glutarate, taurine, hippurate, TMAO, creatine and the plasma concentrations of 3-D-hydroxybutyrate, acetone, NAC, OAC, creatinine were all changed.</p><p><b>CONCLUSION</b>The A. fangchi and S. tetrandra all can induce the renal and liver lesion and its seriousness is correspondent to the lasting of administration. The liver and kidney toxicity of S. tetrandra are all more serious than the A. fangchi.</p>

Chemical constituent from fruit of Aristolochia contorta / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of the fruit of Aristolochia contorta.</p><p><b>METHOD</b>The compounds were isolated by chromatographic techniques and crystalization, the structures were elucidated by spectrum analysis.</p><p><b>RESULT</b>Fifteen compounds were isolated from the dry fruit of A. contorta, which were six aristolochic acids: aristolochic acid I, aristolochic acid III a, aristolochic acid IVa, aristolochic acid II, aristolochic acid III and aristolochic acid VIIa. Three aristolactams: aristololactam I, aristololactam II and aristololactam IIIa. Three phenolic acids syringic acid, vanillic acid and p-coumaric acid. Three other type compounds: pentacosane acid, beta-sitosterol and daucossterol.</p><p><b>CONCLUSION</b>Aristolochic acid III, aristolochic acid VIIa, aristololactam IIIa, and penfacosane acid were isolated from A. contorta for the first time, and compounds 4-13 were isolated from the furit of A. contorta for the first time.</p>

Study on LC-MS fingerprint for quality assessment of Aristolochia manshuriensis with chemical pattern recognition / 中国中药杂志

<p><b>OBJECTIVE</b>To analyze LC-MS fingerprints of Aristolochia manshuriensis for quality assessment with two different chemical pattern recognition models.</p><p><b>METHOD</b>LC-MS fingerprints of A. manshuriensis were established from 24 batches of samples from different habitats. SIMCA and Clustering analysis were used to compare the parameters of the 29 common peaks.</p><p><b>RESULT</b>Two methods had good consistency, while they reflected the inherent sample information from different perspectives, respectively.</p><p><b>CONCLUSION</b>Modern equipment analysis technology and multivariable chemical pattern recognition would be an efficient way for quality control and variety identification of A. manshuriensis.</p>

Hepatic and renal injury induced by Radix Aristolochiae or Guanxin Suhe Wan for a long-term in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the toxicity of Radix Aristolochiae supplied experimental evidence of rational use of drug in clinic.</p><p><b>METHOD</b>After treatment with small dose Radix Aristolochiae, Guanxin Suhe Wan (with Radix Aristolochiae) and Guanxin Suhe Wan (without Radix Aristolochiae) in different group for a long- term, respectively, the biochemical indicator of PT, ALT, AST, ALB, ALP, Crea and BUN were detected, and the kidney, liver, stomach and urinary bladder were examined by pathologic assaying.</p><p><b>RESULT</b>In Radix Aristolochiae group and Guanxin Suhe Wan (with Radix Aristolochiae) group, all of biochemical indicator were changed significantly, and hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered.</p><p><b>CONCLUSION</b>Radix Aristolochiae and Guanxin Suhe Wan (with Radix Aristolochiae) can damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity.</p>

Efectos tóxicos de cuatro plantas amazónicas sobre Chironomus calligraphus Goeldi 1905 (Diptera: Chironomidae) y Artemia franciscana Kellog 1906 (Anostraca: Artemiidae) / Toxic effects of four amazonian plants on Chironomus calligraphus Goeldi 1905 (Diptera: Chironomidae) and Artemia franciscana Kellog 1906 (anostraca: artemiidae)

The aim of current research was to evaluate the ecotoxic effect of four Amazonian plants of ethnobotanical importance in Pucallpa, Peru: Dutchman’s Pipe Aristolochia pilosa Kunth (Aristolochiaceae) in stem and leaves, Soapberry Paullinia clavigera Simpson (Sapindaceae) in cortex, Wandering Jew Tradescantia zebrina Hort ex Bosse (Commelinaceae) in all plant and Curare Chondrodendron tomentosum Ruiz & Pavon corr. Miers (Menispermaceae) in cortex and leaves on first instars’ insect larvae of Chironomus calligraphus Goeldi 1905 and second instars’ nauplii of brine shrimp Artemia franciscana Kellog, 1906. Standard procedures were employed to detect semiqualitative phytochemistry of hexane, chloroform and hydroalcohol extracts, for each plant evaluated. The LC50 mean values of hexane and chloroform extracts of all plants on A. franciscana and hydroalcoholic extract on C. calligraphus were lower than values of chloroform extracts on C. calligraphus. Leaves hexane extract and stem chloroform extract of A. pilosa, and hydroalcohol extract of P. clavigera had higher activity on C. calligraphus. However, hexane and chloroform extracts of T. zebrina, and stem hydroalcoholic extract of A. pilosa had higher activity on A. franciscana.

El objetivo del presente trabajo fue evaluar el efecto ecotoxico de cuatro plantas amazónicas de importancia etnobotánica en Pucallpa, Perú: “Huancahuisacha” Aristolochia pilosa Kunth (Aristolochiaceae) en talloy hoja, “Sacha Yoco” Paullinia clavigera Simpson (Sapindaceae) en corteza, “Oreja de Tigre” Tradescantia zebrina Hort ex Bosse (Commelinaceae) toda la planta y “Curare” Chondrodendron tomentosum Ruiz & Pavon corr. Miers (Menispermaceae) en corteza y hoja sobre las larvas de primer estadio de Chironomus calligraphus Goeldi 1905 y sobre los nauplios de segundo estadio del camarón salino Artemia franciscana Kellog, 1906. Se emplearon procedimientos estándares para la detección fitoquímica semicualitativa de los extractos hexánicos, clorofórmicos e hidroalcohólicos de las plantas evaluadas...

Plant extracts for topic therapy of Bothrops alternatus envenomation

Two plants were investigated for their properties against the local effects of Bothrops alternatus venom in rabbits, namely Curcuma longa L. (Zingiberaceae) and Aristolochia cymbifera L. (Aristolochiaceae). The experiments showed that, Curcuma longa extract topic application was the most effective treatment against local symptoms (edema, hemorrhages and necrosis) caused by Bothrops venom, whereas the results with Aristolochia cymbifera L. were doubtful, because they led to a larger damaged area during the early phase of the inflammation process, besides skin mummification.

Extratos de duas plantas, Curcuma longa L. (Zingiberaceae) e Aristolochia cymbifera L. (Aristolochiaceae), foram utilizados no tratamento local do envenenamento por Bothrops alternatus em coelhos. Este estudo demonstrou que o extrato tópico de Curcuma longa foi o mais efetivo tratamento contra os efeitos locais (edema, hemorragia e necrose) causados pelo veneno botrópico. O tratamento com o extrato de Aristolochia cymbifera apresentou resultados duvidosos, pois causou uma grande área de lesão no início do processo inflamatório, além de mumificação da pele.

Studies on solid phase extraction method of aristolochic acids and aristololactams in rat urine / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a urine pretreatment method of Solid Phase Extraction (SPE) for the quantitative determination of a number of aristolochic acids (AAs) and aristololactams (ALs) in rat urine.</p><p><b>METHOD</b>The HPLC peak area of AA-I , AA-II, AL-I and AL-II, and other sixteen AAs and ALs was chosen as evaluating index to study the extract results of five Solid Phase Extraction columns (Agilent C18/100 mg, Alltech HG18/100 mg, Alltech C18/100 mg, Alltech C18/300 mg and Agilent Phenyl/200 mg) comparatively. The influences of two washing solvents (water and 1% acetic acid-0.02% triethylamine solution) and seven eluting solvents (ether, acetone, chloroform, ethyl acetate, dichloromethane, methanol and acetonitrile) on extract results of AAs and ALs are comparatively studied with the extracting recoveries of AA-I , AA-II, AL-I and AL-II as indicators. The HPLC peak area of AA-I , AA-II, AL-I and AL-II, and other seven AAs and ALs with good separation being targets, several factors which affect extracting efficiency of analytes, including activating volume, cleansing volume, washing volume and eluting volume, are optimized by orthogonal design experiments with four factors at three levels.</p><p><b>RESULT</b>The established method of SPE is as follows: Agilent Phenyl SPE column of 200 mg, activating with 1.0 mL methanol, cleansing with 1 mL water, adding 1.0 mL rat urine sample, washing with 0.8 mL 1% acetic acid 0.02% triethylamine solution, and eluting with 3.0 mL methanol.</p><p><b>CONCLUSION</b>The established method of SPE is efficient, selective, simple and fast, and can be used as urine pretreatment method to analyze a variety of aristolochic acids and aristololactams in rat urine.</p>

Nephrotoxicity of Radix Aristolochice and it's substitution material Radix Inulae in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the toxicity of Radix Aristolochiae and Radix Inulae, and to supply the toxicity experimental data that Radix Inulae supersedes Radix Aristolochiae in clinic.</p><p><b>METHOD</b>A long dose of Radix Aristolochice and Radix Inulae was given intragastrically to rats for six months, then drug withdrawal for a month. The hematology and biochemical indicators were measured, and the pathologic changes of kidney, liver, stomach and urinary bladder were examined.</p><p><b>RESULT</b>The rats of Radix Aristolochice showed serious toxic responses of renal tubule atrophy and necrosis, meanwhile, the levels of BUN, Cr and NAG were increased obviously. Hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered with pathologic assaying. But the rats of Radix Inulae did not.</p><p><b>CONCLUSION</b>Radix Aristolochiae could damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity. Radix Inulae could take the place of Radix Aristolochiae to use in clinic.</p>

Pharmacodynamic and toxicologic comparative study of crude and processed radix aristolochice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the accumulated toxic action to bandicoot of aqueous extract of crude and processed Radix Aristolochice and the pharmacodynamic action of aqueous and alcoholic extract of crude and processed Radix Aristolochice.</p><p><b>METHOD</b>The LD50 of acute toxicity to mice and chronic accumulated toxicity to bandicoots of crude and processed Radix Aristolochice were observated. Intestinal and myokinetic influence of normal and revulsive hyperactive gastrointestinal motility of mice induced by neostigmine were observated by giving aqueous extract and alcoholic extract of crude and processed Radix Aristolochice. Relieving pain and eliminating inflammation to mice also were observated.</p><p><b>RESULT</b>The LD50 of aqueous extract of crude and processed Radix Aristolochice were 146. 45, 846.06 g X kg(-1) (equivalently to crude drug) respectively by intragastric administration. Bandicoot' general condition, peripheral blood, serum, organic coefficient, histopathologic examination weren't obvious changes after 1 month administrating aqueous extract of crude and processed drug in three dose. Serum indicators-urea nitrogen, cholesterol total, alkaline phosphatase manifestly were heightened and some animals'hepatic cells, nephric tubules and mucosa emerged differently damage at histomorphology by giving crude high dose after 2 months. Above organs emerged different damage in crude middle and high dose and processed high dose after 3 months and serum indicators- creatinine, urea nitrogen manifestly were increased, the coefficients of liver, kidney and gaster manifestly were heightened. However, the toxicity of identical dose processed product was lower than that of crude one. Aqueous extract and alcoholic extract of crude and processed Radix Aristolochice could obviously inhibite normal and revulsive hyperactive gastrointestinal motility by neostigmine of mice, relieve pain in mouse, stretching and heat stimulation models and inhibite dimethyl benzene-induc mouse, auricle inflammation. Pharmacodynamic action wasnt obvious difference in same dose of crude product and processed one.</p><p><b>CONCLUSION</b>Acute toxicity and chronic accumulated toxicity are stepped down after giving processed Radix Aristolochice, but pharmacodynamic effect wasn t lower. In pharmacodynamic effect, aqueous extract can't compare with alcoholic extract in same dose.</p>

Nephrotoxicity of Aristolochia manshriensis and Longdan Xiegan decoction / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the renal function, histology and the levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) in rats administered with Aristolochi manshriensis (AM) and Longdan Xiegan decoction (LDXG) containing AM.</p><p><b>METHOD</b>Divided SD rats into control, AM and LDXG groups (n = 10 per group) at random and administrated orally for 8 weeks with distilled water, AM (6 g x kg(-1) x d(-1)) and LDXG (17. 5 g x kg(-1) x d(-1), containing AM 6 g x kg(-1) x d(-1)), respectively. Measured renal functional parameters in serum, urine and IL-1beta, IL-6 in renal homogenate, and observe renal histologic lesions at the end of 8 weeks.</p><p><b>RESULT</b>Two kinds of water abstract induced significantly renal injury in rats, IL-1beta, IL-6 levels in renal homogenate were significantly increased compared with controls, histological section showed inflammatory cell infiltration play important role in renal tubulointerstitium damage. LDXG caused less seriously damage than AM.</p><p><b>CONCLUSION</b>AM and LDXG in experimental dosage can induce renal injury, inflammatory cell infiltration in renal tubulointerstitium and high levels of IL-1beta, IL-6 presumpt that the nephrotoxicity of AM and LDXG refered to the immune mechanism. LDXG has light nephrotoxicity due to its restraining the inflammatory reaction caused by AM.</p>