关注马兜铃酸对人民健康的危害

由马兜铃酸引发的肾病,称为马兜铃酸肾病。早在1964年就有吴松寒首报服用木通所致急性肾功能衰竭病例,揭开了马兜铃属植物药材致肾毒害的面纱。此后马红梅等检索了关木通引起肾毒害者34例,其中在国内的21例中,10例死亡,9例需肾透析,仅2例病情较稳定;在国外的13例中,5例需肾透析,2例肾移植,3例肾功能障碍,仅3例停药后病情逐步改善。在用马兜铃酸静脉注射试治癌症实验中,日剂量1mg/kg,连续3天或3天以上的10例中,有几例死于肾急性中毒性肾变性,故认为马兜铃酸在人体内有积蓄性,可见马兜铃酸对人体的危害十分严重。马兜铃酸在化学上分为A、B、C、D、E等数种,存在于马兜铃属植物的根、茎和果实中。凡含有此类成分的植物,均含有马兜铃酸A,然后才有其它成分与之共存。由此,可认为这类成分在植物体内均由马兜铃酸A衍变产生。国产马兜铃属植物有39种,在相关的中药材书籍中记载供药用者已达26种之多。《中国药典》2000年版一部收载4种马兜铃属植物计5种药材,它们是:广防已（广防已的根）、马兜铃（北马兜铃或马兜铃的果实）、天仙藤（北马兜铃或马兜铃的茎）、关木通（东北马兜铃的茎）、青木香（马兜铃的根）,此5种药材均含有马兜铃酸类成分。由马兜铃属植物药材组成的成方制剂,《中国药典》2000年版收载含马     

马兜铃酸类成分检测与分析研究进展

马兜铃酸类成分是广泛存在于马兜铃科植物中的硝基菲类化合物,已被证实具有肾毒性、致癌和致基因突变等作用。我国自2003年以来采取一系列风险控制措施,其中马兜铃酸含量高的关木通、广防己和青木香等药材已被禁用。目前,一些马兜铃酸含量低的中药材与中成药仍在使用中,鉴于马兜铃酸成分对人体的严重危害性,有必要进一步加强相关药材与制剂的风险评估。在归纳马兜铃酸类成分结构等基本信息的基础上,对近年来的检测分析方法进展进行了总结,为其风险控制与安全使用提供了科学依据。     

中药的忧伤——由马兜铃属植物毒性谈起

马兜铃事件已事发多年，马兜铃酸的致毒性又有新发现，国际癌症研究中心（IARC）工作组会议最近也认为马兜铃属的某些品种对人类有一级致癌性。马兜铃酸主要存在于马兜铃属某些种的植物中，木通科木通、防已科防已等植物尚未见含有马兜铃酸的报导，但有些国家混淆了广防己、     

中药材（饮片）中马兜铃酸的含量分析及初步风险评估

目的 分析中药材（饮片）中马兜铃酸类成分的含量特征,并开展初步风险评估。方法 基于近10年的文献数据,从分布情况、相关性、样品差异等角度,分析了12个品种478批中药材（饮片）中马兜铃酸类成分的含量特征。按照危害识别、危害特征描述、暴露评估和风险描述的步骤,明确了计算公式和具体参数,采用靶标危害系数法对细辛中马兜铃酸Ⅰ的安全风险进行评估。结果 12个品种478批中药材（饮片）中共检出25种马兜铃酸类成分,整体含量马兜铃酸Ⅰ最高,马兜铃内酰胺F1最低,部分成分含量之间存在相关性。含马兜铃酸的药用植物的果实中马兜铃酸类成分远高于其他部位,各药材经炮制后马兜铃酸含量显著降低。按法定用药部位统计,各品种中马兜铃酸I和马兜铃酸П含量存在显著性差异,朱砂莲最高,鱼腥草最低。风险评估结果显示,11批细辛药材中有1批样品中马兜铃酸Ⅰ的靶标危害系数（THQ）大于1,提示其用药存在安全风险。结论 获得的中药材（饮片）中马兜铃酸类成分的含量现状和建立的风险评估方法,可为含马兜铃酸中药材（饮片）的质量控制和安全用药提供参考。     

中药中马兜铃酸肾毒性研究进展

马兜铃酸(aristolochic acid,AA)是一种硝基菲类化合物,是马兜铃属植物如关木通、马兜铃中的主要成分。含有AA的中药或中成药,在临床上曾用于风湿病、毒蛇咬伤和癌症的辅助治疗等。我国也曾将以马兜铃酸I(AAI)为主的总酸称为"增噬力酸",并应用于临床。1993年Van-hei weghemJL等报道了比利时妇女因服用含有广防己的减     

马兜铃酸肾不良反应及质量控制研究进展

马兜铃酸为硝基菲类有机酸类化合物,是马兜铃、关木通、细辛等植物的主要成分。马兜铃酸药理作用广泛,有抗感染、抗肿瘤、增强细胞免疫等功能。本文总结了马兜铃酸肾毒性研究进展及其分子结构,并对近5年不同中药材和中成药中马兜铃酸质量控制的研究进行综述,对比分析不同检测方法的优缺点,为今后对马兜铃酸的进一步研究及临床合理应用提供依据。     

关木通与其复方肾毒性比较及相关毒性成分测定

马兜铃属(Aristolochia)植物关木通,使用不当可以引起肾脏损害已有临床报道和实验证实,中医用药多复方配伍应用,单味关木通与其复方应用是否具有相同的毒性?选用龙胆泻肝丸和导赤散与单味药关木通进行肾毒性比较实验,观察单味及复方配伍对实验性大鼠肾损伤作用的功能、病理改变情况，并采用高效液相色谱法检测关木通毒性成分马兜铃酸Ⅰ(AA-Ⅰ)含量.     

3种含马兜铃酸药材与替换品以及易混淆品的鉴别

中药材关木通、广防已、青木香含有马兜铃酸，马兜铃酸可引起肾脏损害及其它不良反应，国家食品药品监督管理局已取消其药用标准，在中成药生产中分别以木通、防已、土木香换。     

3种含马兜铃酸药材与替换品以及易混淆品的鉴别

中药材关木通、广防己、青木香含有马兜铃酸,马兜铃酸可引起肾脏损害及其它不良反应,国家食品药品监督管理局已取消其药用标准,在中成药生产中分别以木通、防己、土木香替换[1]。由于我国地域辽阔,中药材品种繁多,地方习用品种交叉混淆、同物异名、同名异物等现象的普遍存在,为     

部分马兜铃科药材中马兜铃酸A的含量测定研究

目的：在已有文献报道的基础上，通过比较研究进一步优化了实验条件，建立灵敏度高、重现性好的马兜铃酸A含量测定方法，并对部分马兜铃科马兜铃属、细辛属的药材中马兜铃酸A的含量进行测定。方法：采用高效液相色谱法。色谱柱：Kromasil C18柱（4．6mm×200mm，5μm）；流动相：0．3％碳酸铵（用稀盐酸调pH至7．5）-乙腈（75：25），流速：1mL·min^-1；检测波长：250nm；柱温：35℃。结果：马兜铃酸A进样量在1．02—511ng范围内线性关系良好，回归方程为：Y=5．734×10^3X＋1．239×10^3，r=0．9999（n=20）；方法的回收率（n=18）为102．3％。结论：建立的含量测定方法准确、灵敏，专属性强、重现性好，为含马兜铃酸A的药材及制剂的质量控制等研究，提供了可供借鉴的实验方法；同时，检测结果也为相关马兜铃科药材的合理使用提供了参考。     

RP-HPLC法测定14种中药材中马兜铃酸A的含量

目的对14种中药材中的马兜铃酸A进行含量测定。方法采用RP-HPLC法。色谱柱为Kromasil ODS柱(200 mm×4.6 mm,5μm),流动相为甲醇-体积分数为1%的冰醋酸溶液(体积比70∶30),检测波长为319 nm,流速为1.0 mL.min-1,柱温为25℃。结果14种中药材中马兜铃酸A的含量分别为:苕叶细辛0.22 mg.g-1,万源山慈菇0.18 mg.g-1,宜宾防己0.72 mg.g-1,川细辛0.58 mg.g-1,寻骨风0.52 mg.g-1,广西山慈菇0.13 mg.g-1,短尾细辛0.15 mg.g-1,淮通0.94 mg.g-1,关木通0.49 mg.g-1,广元防己3.00 mg.g-1;平昌防己、冕宁防己、穆平马兜铃、北细辛地上及地下部分中均未检出马兜铃酸A。结论应用本实验中所建立的方法对多种中药材中的马兜铃酸A进行检测,为相关药材及中成药应用提供了科学依据。     

Determination of aristolochic acid I and II in North American species of Asarum and Aristolochia

Wild ginger, Asarum canadense, which has folk uses as a medicinal and food plant, has been reported to contain aristolochic acid I. Rhizomes of North American species of Aristolochiaceae were surveyed for the presence of aristolochic acids by HPLC. Aristolochic acid I (1) and aristolochic acid II (2) were present in Aristolochia species and Hexastylis; 1 alone was detected in multiple accessions of A. canadense and Asarum caudatum, though not in Asarum wagneri. Concentrations in A. canadense were highly variable, reaching as much as 0.037 percent of dry weight.     

Detection of aristolochic acid in Chinese phytomedicines and dietary supplements used as slimming regimens.

Over the last 10 years, numerous cases of intoxications, leading for the most part to end-stage renal failure, have been reported after consumption of slimming regimens made of Chinese herbal preparations. These intoxications were associated with species of the Aristolochia genus, such as Aristolochia fangchi (Aristolochiaceae), known to contain very nephrotoxic and carcinogenic metabolites named aristolochic acids. Several commercial dietary supplements, teas and phytomedicines used as slimming regimens were analysed for their aristolochic acid I content. A preliminary detection of this toxic compound was made by thin-layer chromatography. The presence of aristolochic acid I in these preparations was confirmed by a HPLC/UV-DAD/MS analysis. A quantitative determination of aristolochic acid I was also achieved in the incriminated preparations using both UV and MS detection. Out of 42 analysed preparations, four were found to contain aristolochic acid I and two were suspected to contain aristolochic acid derivatives. Immediate removal of these products from the Swiss market was called for.     

Interaction of phospholipase A2 from Vipera russelli venom with aristolochic acid: a circular dichroism study

The interaction of aristolochic acid, an alkaloid from Aristolochia species, with phospholipase A2 (PLA2) from Vipera russelli venom was followed by circular dichroism measurements. Aristolochic acid is a non-competitive inhibitor of PLA2. The binding of aristolochic acid to PLA2 induces an extrinsic CD band at 320 nm. The association constant was determined by following the intensity of the extrinsic CD band. Aristolochic acid forms a 1:1 complex with PLA2, with an association constant K, of 5.4 X 10(3) M-1 and a Gibb's free energy change (delta G0) for the reaction of -5.1 kcal/mole. The values of association constant and delta G0 suggest that the interaction is weak. Binding of aristolochic acid causes a change in the secondary structure of the protein which is characterized by an increase in the apparent content of alpha-helix, without any detectable change in the tertiary structure of PLA2.     

穆坪马兜铃化学成分的研究

自穆坪马兜铃(Aristolochia moupinensis Franch)根、茎中分得十三个化合物,其中化合物Ⅰ～Ⅻ经鉴定分別为马兜铃酸Ⅰ(aristolochic acid Ⅰ)(Ⅰ),尿囊素(allantoin)(Ⅱ),紫丁香酸(syringic acid)(Ⅲ),香豆酸(P-coumaric acid)(Ⅳ),马兜铃酸Ⅳ(aristolochic acid Ⅳ)(Ⅴ),β-谷甾醇(Ⅵ),木兰碱(magnoflorine)(Ⅶ),马兜铃酸Ⅳ甲醚aristolochic acid Ⅳmethyl ether(Ⅵ),棕榈酸(Ⅸ),马兜铃酸Ⅱ(aristolochic acid Ⅱ)(Ⅹ),N(Phydroxyphenethy1)P-coumaramide(Ⅺ),马兜铃酸Ⅳ甲醚甲酯(aristolochic acid Ⅳmethyl ether methyl ester)(Ⅻ),化合物ⅩⅢ为新化合物,经光谱分析和化学合成等方法证明其结构为N(P-hydroxyphenethyl)-ferulamide,命名为穆坪马兜铃酰胺(moupinamide)。初步药理试验表明穆坪马兜铃酰胺体外有抑制血小板聚集和影响血小板内前列腺素合成的作用。     

Interaction of aristolochic acid with Vipera russelli phospholipase A2: its effect on enzymatic and pathological activities

Aristolochic acid, an alkaloid from the plant Aristolochia species, interacts with the major basic phospholipase A2 from Vipera russelli venom. It is an uncompetitive inhibitor with a Ki of 9.9 X 10(-4)M when phosphatidylcholine is used as substrate. The inhibition of direct and indirect hemolysis is higher compared to the inhibition of phosphatidylcholine hydrolysis. Edema-inducing activity of Vipera russelli phospholipase A2 is inhibited by aristolochic acid when injected either as a mixture or separately. Both i.m. and i.p. administration of aristolochic acid following phospholipase injection are equally effective in inhibiting edema. The alkaloid inhibits the edema-inducing activity as soon as it reaches the site, but does not aid in recovery. Aristolochic acid failed to inhibit other pathological activities of the enzyme.     

6-O-beta-D-glucoside of aristolochic acid IIIa and other components from the roots of Aristolochia baetica

From the root extract of the European Aristolochia baetica L. we isolated aristolochic acid IIIa-6-O-beta-D-glucoside (1) besides magnoflorine chloride, the free aristolochic acids I and II, and five aristolactams. Saccharose and fructose were found as major constituents.     

北马兜铃的化学成分研究——Ⅱ、马兜铃酸E的化学结构

From the root of Aristolochia contorta Bunge six chemical constituents were isolated; one of them is a new phenanthrene compound containing nitro group for which the name aristolochic acid E is suggested. By means of spectral methods combined with chemical analysis the chemical structure of aristolochic acid E was determined to be 7-methoxy-8-hydroxy-aristolochic acid. The other components were identified as allantoin, aristolochic acid A, magnoflorine, β-sitosterol and daucosterol respectively.     

Comparative study of the contents of analogues of aristolochic acid in two kinds of Aristolochiae Fructus by high-performance liquid chromatography

Aristolochiae Fructus (??Madouling??) is derived from the fruits of Aristolochia contorta and A. debilis (Aristolochiaceae). These two species contain potentially nephrotoxic constituents, but are officially used in China. Distinction of constituents and toxicity between these two species remains unclear. A high-performance liquid chromatography method was developed and validated for the simultaneous determination of seven analogues of aristolochic acid (aristolochic acids I, II, IIIa, IVa and VIIa), as well as aristololactams I and II in Aristolochiae Fructus. Chromatographic separation was achieved on a Zorbax SB-C₁₈ column with a gradient mobile phase comprising acetonitrile and 1?% acetic acid?C30?mM triethylamine (20:1, v/v) buffer. Analytes were detected with a diode array detector at 250 and 260?nm. The contents of seven constituents in samples (11 batches of A. contorta fruits, 15 batches of A. debilis fruits and 33 commercial samples of Madouling) were determined. The content of aristolochic acid IVa was higher than that of aristolochic acid VIIa in A. contorta fruits, whereas the opposite was true in A. debilis fruits. This feature can be used to distinguish the two species from each other and identify the resource plant of Madouling. Through a morphological method and a newly found principle based on the ratio AA-IVa/AA-VIIa, we found that the 33 commercial samples collected from 12 provinces in China were all derived from the fruits of A. contorta.