含马兜铃酸中药及其检测研究进展
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摘要
马兜铃酸类物质(aristolochic acids, AAs)由于具有不可逆转的肾脏毒性被列为I级致癌物,主要来自马兜铃属、细辛属等马兜铃科植物.目前,一些含AAs植物仍作为传统药物使用,甚至用于食品行业,对公众健康的利益-风险评估值得关注.本文综述了AAs的基本化学结构、含AAs中药及其基原物种鉴定、AAs含量检测方法及生物合成调控等研究进展.在此基础上,提出控制AAs的方案和建议:对潜在含AAs中药进行系统性质量评价研究;强化流行病学调查,指导公众健康生活;寻找含AAs药材的替代品;深入研究AAs生物合成途径,降低中药材和中成药AAs含量等.本文为食品药品监管部门制定政策提供依据,为科研人员进行新药和食品研发提供参考,对保障消费者的知情权具有重要意义.
Aristolochic acids(AAs), listed in class I carcinogen due to their irreversible renal toxicity, are mainly from Aristolochiaceae plants such as Aristolochia and Asarum. Up to now, some herbs containing AAs are still used as traditional Chinese medicine(TCM) or foods, so the assessment of benefit and risk for the public health deserves attention. Here, we summarize the basic chemical structure of AAs, TCM containing AAs and their species identification, the methods of AAs content detection, and biosynthetic regulation of AAs. Furthermore, we put forward the proposal of monitoring AAs: systematical quality evaluation of TCM containing AAs,strengthening epidemiological investigations, looking for alternatives to AAs-containing herbs, elucidating the biosynthetic pathways of AAs, etc. This review provides references for making regulatory policies and developing new drugs and foods, and would also be beneficial to protect consumers' right to know the truth.
Aristolochic acids(AAs), listed in class I carcinogen due to their irreversible renal toxicity, are mainly from Aristolochiaceae plants such as Aristolochia and Asarum. Up to now, some herbs containing AAs are still used as traditional Chinese medicine(TCM) or foods, so the assessment of benefit and risk for the public health deserves attention. Here, we summarize the basic chemical structure of AAs, TCM containing AAs and their species identification, the methods of AAs content detection, and biosynthetic regulation of AAs. Furthermore, we put forward the proposal of monitoring AAs: systematical quality evaluation of TCM containing AAs,strengthening epidemiological investigations, looking for alternatives to AAs-containing herbs, elucidating the biosynthetic pathways of AAs, etc. This review provides references for making regulatory policies and developing new drugs and foods, and would also be beneficial to protect consumers' right to know the truth.
引文
1 The Cancer Genome Atlas Research Network.Comprehensive and integrative genomic characterization of hepatocellular carcinoma.Cell,2017,169:1327-1341
2 Ng A W T,Poon S L,Huang M N,et al.Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia.Sci Transl Med,2017,9:eaan6446
3 Gao Y,Xiao X H,Zhu X X,et al.Study and opinion on toxicity of aristolochic acid(in Chinese).China J Chin Mater Med,2017,42:4049-4053[高月,肖小河,朱晓新,等.马兜铃酸的毒性研究及思考.中国中药杂志,2017,42:4049-4053]
4 Liang A H,Gao Y,Zhang B L.Safety issue and strategy of traditional Chinese medicines containing aristolochic acid(in Chinese).Chin Food Drug Admin Mag,2017,11:17-20[梁爱华,高月,张伯礼.含马兜铃酸中药的安全性问题及对策.中国食品药品监管,2017,11:17-20]
5 Bai Z F,Xu G,Wang J B,et al.Research progress in and countermeasures against carcinogenicity of aristolochic acids and their derivatives(in Chinese).Prog Pharm Sci,2018,42:164-169[柏兆方,徐广,王伽伯,等.马兜铃酸及其衍生物致癌性研究进展及应对措施.药学进展,2018,42:164-169]
6 Chen M L,Zhu Z L.The advance on the studies of pharmacology of Aristolochia L.plants(in Chinese).Lishizhen Med Mater Med Res,2007,18:702-704[陈孟兰,朱正兰.马兜铃属植物的生物活性和药理作用研究进展.时珍国医国药,2007,18:702-704]
7 Bhattacharjee P,Bera I,Chakraborty S,et al.Aristolochic acid and its derivatives as inhibitors of snake venom L-amino acid oxidase.Toxicon,2017,138:1-17
8 Vanherweghem J L,Tielemans C,Abramowicz D,et al.Rapidly progressive interstitial renal fibrosis in young women:association with slimming regimen including Chinese herbs.Lancet,1993,341:387-391
9 Vanhaelen M,Vanhaelen-Fastre R,But P,et al.Identification of aristolochic acid in chinese herbs.Lancet,1994,343:174
10 International Agency for Research on Cancer(IARC).A Review of Human Carcinogens.A.Pharmaceuticals.Geneva:WHO Press,2012.347-361
11 Li Y M,Li J,Yu F.Current situation and research progress on the nephrotoxicity of aristolochic acid compounds(in Chinese).J Pharm Res,2017,36:534-537[李一昴,李霁,于锋.马兜铃酸类化合物使用现状及肾脏毒性研究进展.药学研究,2017,36:534-537]
12 Kuo P C,Li Y C,Wu T S.Chemical constituents and pharmacology of the Aristolochia species.Tradit Complement Med,2012,2:249-266
13 Yang Z C,Lu Y,Gu Y Q,et al.Progress in aristolochic acid carcinogenesis and its related metabolic enzymes(in Chinese).Tradit Chin Drug Res Pharmacol,2014,25:765-769[杨召聪,陆茵,顾亚琴,等.马兜铃酸I致癌作用及其与代谢酶关系的研究进展.中药新药与临床药理,2014,25:765-769]
14 Chung Y M,Chang F R,Tseng T F,et al.A novel alkaloid,aristopyridinone A and anti-inflammatory phenanthrenes isolated from Aristolochia manshuriensis.Bioorg Med Chem Lett,2011,21:1792-1794
15 Georgopoulou C,Aligiannis N,Fokialakis N,et al.Acretoside,a new sucrose ester from Aristolochia cretica.J Asian Nat Products Res,2005,7:799-803
16 Shi L S,Kuo P C,Tsai Y L,et al.The alkaloids and other constituents from the root and stem of Aristolochia elegans.Bioorg Med Chem,2004,12:439-446
17 Cai Y,Cai T G.Two new aristolochic acid derivatives from the roots of Aristolochia fangchi and their cytotoxicities.Chem Pharm Bull,2010,58:1093-1095
18 Wu T S,Damu A G,Su C R,et al.Chemical constituents and pharmacology of Aristolochia species.Stud Nat Prod Chem,2005,32:855-1018
19 Navarro-García V M,Luna-Herrera J,Rojas-Bribiesca M G,et al.Antibacterial activity of Aristolochia brevipes against multidrug-resistant Mycobacterium tuberculosis.Molecules,2011,16:7357-7364
20 Priestap H A.Seven aristololactams from Aristolochia argentina.Phytochemistry,1985,24:849-852
21 Zhang G,Shimokawa S,Mochizuki M,et al.Chemical constituents of Aristolochia constricta:antispasmodic effects of its constituents in guineapig ileum and isolation of a diterpeno-lignan hybrid.J Nat Prod,2008,71:1167-1172
22 Holzbach J C,Lopes L M X.Aristolactams and alkamides of Aristolochia gigantea.Molecules,2010,15:9462-9472
23 Nayyatip S,Thaichana P,Buayairaksa M,et al.Aristolactam-type alkaloids from Orophea enterocarpa and their cytotoxicities.Int J Mol Sci,2012,13:5010-5018
24 Wang D P,Mao X C.Research progress on traditional Chinese medicine containing aristolochic acid.J N Pharm,2014,11:97-98[王德平,毛晓春.中药马兜铃酸的研究进展.北方药学,2014,11:97-98]
25 Qiu H X,Lin Y R.Flora Reipublicae Popularis Sinicae.Beijing:Science Press,1988.159-160[丘华兴,林有润.中国植物志.北京:科学出版社,1988.159-160]
26 Pr?bstle A,Bauer R.Aristolactams and a 4,5-dioxoaporphine derivative from Houttuynia cordata.Planta Med,1992,58:568-569
27 Kim S K,Ryu S Y,No J,et al.Cytotoxic alkaloids from Houttuynia cordata.Arch Pharm Res,2001,24:518-521
28 Chen S D,Gao H,Lu C J,et al.Alkaloids and amides from Houttuynia cordata(in Chinese).J Shenyang Pharm Univ,2013,11:846-850[陈少丹,高昊,卢传坚,等.鱼腥草中生物碱和酰胺类成分的研究.沈阳药科大学学报,2013,11:846-850]
29 Bauer R,Pr?bstle A,Lotter H,et al.Cyclooxygenase inhibitory constituents from Houttuynia cordata.Phytomedicine,1996,2:305-308
30 Jong T T,Jean M Y.Alkaloids from Houttuyniae cordata.J Chin Chem Soc,1993,40:301-303
31 Chou S C,Su C R,Ku Y C,et al.The constituents and their bioactivities of Houttuynia cordata.Chem Pharm Bull,2009,57:1227-1230
32 Qu W,Wu F H,Li J,et al.Alkaloids from Houttuynia cordata and their antiplatelet aggregation activities.Chin J Nat Med,2011,9:425-428
33 Li J,Zhang L,Jiang Z,et al.Toxicities of aristolochic acid I and aristololactam I in cultured renal epithelial cells.Toxicol In Vitro,2010,24:1092-1097
34 Wei A H,Zhou D N,Ruan J L,et al.Study on the contents of aristololactams in Piper wallichii and their renal cytotoxicities.J Food Drug Anal,2011,19:349-354
35 Xin T Y,Lei M Y,Song J Y.DNA barcoding of traditional Chinese medicine(in Chinese).Mod Chin Med,2015,17:170-176[辛天怡,雷美艳,宋经元.中药材DNA条形码鉴定研究进展.中国现代中药,2015,17:170-176]
36 Chen S,Pang X,Song J,et al.A renaissance in herbal medicine identification:from morphology to DNA.Biotech Adv,2014,32:1237-1244
37 Wu L,Sun W,Wang B,et al.An integrated system for identifying the hidden assassins in traditional medicines containing aristolochic acids.Sci Rep,2015,5:11318
38 Ma X C,Yao H,Wu L,et al.Molecular identification of Aucklandiae Radix,Vladimiriae Radix,Inulae Radix,Aristolochiae Radix and Kadsurae Radix using ITS2 barcode(in Chinese).China J Chin Mater Med,2014,39:2169-2175[马晓冲,姚辉,邬兰,等.木香、川木香、土木香、青木香和红木香药材的ITS2条形码分子鉴定.中国中药杂志,2014,39:2169-2175]
39 Li M,Au K Y,Lam H,et al.Identification of Baiying(herba Solani lyrati)commodity and its toxic substitute Xungufeng(herba Aristolochiae mollissimae)using DNA barcoding and chemical profiling techniques.Food Chem,2012,135:1653-1658
40 Li M,Au K Y,Lam H,et al.Molecular identification and cytotoxicity study of herbal medicinal materials that are confused by Aristolochia herbs.Food Chem,2014,147:332-339
41 Coghlan M L,Haile J,Houston J,et al.Deep sequencing of plant and animal DNA contained within traditional Chinese medicines reveals legality issues and health safety concerns.PLo S Genet,2012,8:e1002657
42 Xin T Y,Xu Z C,Jia J,et al.Biomonitoring for traditional herbal medicinal products using DNA metabarcoding and single molecule,real-time sequencing.Acta Pharm Sin B,2018,8:488-497
43 Xin T Y,Su C,Lin Y L,et al.Precise species detection of traditional Chinese patent medicine by shotgun metagenomic sequencing.Phytomedicine,2018,47:40-47
44 Chinese Pharmacopoeia Commission.Pharmacopoeia of the People’s Republic of China,Vol I(in Chinese).Beijing:China Medical Science Press,2015.224-224[国家药典委员会.中华人民共和国药典(一部).北京:中国医药科技出版社,2015.224-224]
45 Bai M N.Study on the pharmacognosy of Caulis Clematidis Armandii and its substitutes(in Chinese).Dissertation for the Master’s Degree.Chengdu:Southwest Jiaotong University,2017[白梦娜.川木通及常用习用品的生药学研究.硕士学位论文.成都:西南交通大学,2017]
46 Wu W J,Wan M M,Cao Y H,et al.Study on quality standards of Clematidis Armandii(in Chinese).Chin Arch Tradit Chin Med,2015,33:313-315[武尉杰,万萌萌,曹雨虹,等.川木通的质量标准研究.中华中医药学刊,2015,33:313-315]
47 Zhao S Y.Identification of Asarum heterotropoides var.mandshuricum,Asarum forbesii and Chloranthus serratus(in Chinese).Zhejiang J Tradit Chin Med,2014,49:223-225[赵双艳.细辛与杜衡和及己的鉴别研究.浙江中医杂志,2014,49:223-225]
48 Chang S P,Li H,Jiang S Y,et al.Pharmacognostic identification of Aristolochia fordiana(in Chinese).J Chin Med Mater,2016,39:523-526[昌水平,李华,蒋三元,等.通城虎的生药鉴定.中药材,2016,39:523-526]
49 Agrawal P,Laddha K.Development of validated high-performance thin layer chromatography for quantification of aristolochic acid in different species of the Aristolochiaceae family.J Food Drug Anal,2017,25:425-429
50 Murali S,Francis M S,Rashmi T R.Determination of aristolochic acid I concentration in the four species of Aristolochia using HPLC.J Cogn Psychother,2014,6:59-68
51 Li T F,Li L K,Zhang M L,et al.Determination of aristolochic acid in Aristolochia Manshuriensis with different processing methods by RP-HPLC(in Chinese).China Med Her,2015,12:14-17[李天凤,李连坤,张美玲,等.反相高效液相色谱法测定不同方法炮制关木通中马兜铃酸的含量.中国医药导报,2015,12:14-17]
52 Wang Y,Chan W.Determination of aristolochic acids by high-performance liquid chromatography with fluorescence detection.J Agric Food Chem,2014,62:5859-5864
53 Shu X,Chen J,Lin S H,et al.Determination of limit of aristolochic acid A in Dahuang Qingwei Wan(in Chinese).Chin J Hosp Pharm,2016,36:1512-1515[舒翔,陈军,林世和,等.大黄清胃丸中马兜铃酸A的限量检测.中国医院药学杂志,2016,36:1512-1515]
54 Du X E,Fu L Q.Determination the limitation of aristolochic acid A in Jiuwei-Qianghuo pill(in Chinese).Int J Trad Chin Med,2015,37:924-927[杜仙娥,付联群.九味羌活丸中马兜铃酸A的限量检测.国际中医中药杂志,2015,37:924-927]
55 Qu X C,Ma L,Han F,et al.Limit test of aristolochic acid A in Yishenjuanbi Pill.Adv Mat Res,2013,634-638:991-995
56 Zhou X H,Li Z H,Chen Y H,et al.Determination the limitation of aristolochic acid A in Mahuang Zhisou Wan by SPE-HPLC(in Chinese).Guid J Tradit Chin Med Pharm,2015,21:44-46[周雪红,李志浩,陈银华,等.SPE-HPLC法测定麻黄止嗽丸中马兜铃酸A的含量.中医药导报,2015,21:44-46]
57 Tian J Z,Liang A H,Liu J,et al.Risk control of traditional Chinese medicines containing aristolochis acids(AAs)based on influencing factors of content of AAs(in Chinese).China J Chin Mater Med,2017,42:4679-4686[田婧卓,梁爱华,刘靖,等.从马兜铃酸含量影响因素探讨含马兜铃酸中药的风险控制.中国中药杂志,2017,42:4679-4686]
58 Tagami T,Takeda A,Asada A,et al.A simple and selective detection method for aristolochic acid in crude drugs using solid-phase extraction.JNat Med,2013,67:838-843
59 Zhou H,Fu J,Cai Z W.Research of aristolochic acid I,aristolochic acid II and their metabolites in rat liver microsomes using HPLC-MS/MS(in Chinese).J Chin Mass Spectrom Soc,2017,38:30-36[周慧,付佳,蔡宗苇.基于HPLC-MS/MS法研究马兜铃酸I和马兜铃酸II的大鼠肝微粒体酶S9体外代谢.质谱学报,2017,38:30-36]
60 Kong D Q,Gao H Y,Li X,et al.Rapid determination of eight aristolochic acid analogues in five Aristolochiaceae plants by ultra-high performance liquid chromatography quadrupole/time-of-flight mass spectrometry.J Chin Phar Sci,2015,24:364-375
61 Li G H,Chen S,Wu L,et al.Determination of aristolochic acid I in traditional Chinese medicine by UPLC-QQQ-MS(in Chinese).Chin J Exp Tradit Med Formul,2017,23:61-65[李功辉,陈莎,邬兰,等.UPLC-QQQ-MS测定中药材中马兜铃酸I的含量.中国实验方剂学杂志,2017,23:61-65]
62 Mao W W,Gao W,Liang Z T,et al.Characterization and quantitation of aristolochic acid analogs in different parts of Aristolochiae Fructus,using UHPLC-Q/TOF-MS and UHPLC-Qq Q-MS.Chin J Nat Med,2017,15:392-400
63 Gan S,Han T,Liu H G,et al.Determination of aristolochic acid A in Qingxueneixiao pills by LC-MS-MS(in Chinese).Chin J Exp Tradit Med Formul,2013,16:163-167[甘盛,韩婷,刘华钢,等.液相色谱-质谱串联法测定清血内消丸中马兜铃酸A含量.中国实验方剂学杂志,2013,16:163-167]
64 Zhang L,Wang Y.LC-MS detection of aristolochic acid A in Xiaofeng Zhiyang granula(in Chinese).Chin J Pharm Anal,2012,32:78-81[张俐,王玉.LC-MS法检测消风止痒颗粒中马兜铃酸A.药物分析杂志,2012,32:78-81]
65 Luo J W,Wu Y Y,Li Y H,et al.Determination of aristolochic acid A in health food by UHPLC-MS/MS(in Chinese).Chin J Mod Appl Pharm,2013,30:186-189[罗金文,吴鸳鸯,李樱红,等.超高效液相色谱-串联质谱测定保健食品中马兜铃酸A.中国现代应用药学,2013,30:186-189]
66 Gu J,Zhang P,Zhang F,et al.Determination of aristolochic acids in rat serum by high performance liquid chromatography-Q-TOF tandem mass spectrometry.Anal Methods,2013,5:718-721
67 Zhang P.Determination of aristolochic acid A in different organs of Valeriana jatamansi by UV spectrophotometric(in Chinese).Value Eng,2012,31:293-294[张萍.紫外分光光度法测定马蹄香植物不同器官中马兜铃酸A的含量.价值工程,2012,31:293-294]
68 Yu Y,Xiu L L,Wei X Z,et al.Determination of total aristolochic acid in different extracts of Asarum heterotropoides(in Chinese).Chin J Exp Tradit Med Formul,2012,18:141-143[于艳,修丽丽,魏新智,等.北细辛不同提取物中总马兜铃酸的含量测定.中国实验方剂学杂志,2012,18:141-143]
69 Yu Y,Wang X R,Wei X Z,et al.Determination of total aristolochic acid content in three kinds of Asarum(in Chinese).J Liaoning Univ Tradit Chin Med,2013,15:44-45[于艳,王晓荣,魏新智,等.北细辛汉城细辛及华细辛中总马兜铃酸含量测定.辽宁中医药大学学报,2013,15:44-45]
70 Liu X X,Wang L,Xiao H B.Content of total aristolochic acid in Aristolochia debilis from different localities(in Chinese).Lishizhen Med Mater Med Res,2017,28:74-76[刘欣欣,王莉,肖红斌.不同产地马兜铃药材中马兜铃总酸的含量.时珍国医国药,2017,28:74-76]
71 Fu X,Liu Y,Li W,et al.Analysis of aristolochic acids by CE-MS with carboxymethyl chitosan-coated capillary.Electrophoresis,2009,30:1783-1789
72 Nan T G,He S P,Tan G Y,et al.Development of sensitive monoclonal antibody-based enzyme-linked immunosorbent assay for renal toxicity ingredient aristolochic acid A in Chinese herb medicine(in Chinese).Chin J Anal Chem,2010,38:1206-1210[南铁贵,何素平,谭桂玉,等.中药致肾毒性成分马兜铃酸A单抗制备及酶联免疫分析方法的建立.分析化学,2010,38:1206-1210]
73 Ioset J R,Raoelison G E,Hostettmann K.Detection of aristolochic acid in Chinese phytomedicines and dietary supplements used as slimming regimens.Food Chem Toxicol,2003,41:29-36
74 Spenser I D,Tiwari H P.Biosynthesis of aristolochic acid.Chem Commun(London),1966,0:55
75 Schütte H R,Orban U,Mothes K.Biosynthesis of aristolochic acid.Eur J Biochem,1967,1:70-72
76 Comer F,Tiwari H P,Spenser I D.Biosynthesis of aristolochic acid.Can J Chem,1969,47:481-487
77 Sharma V,Jain S,Bhakuni D S,et al.Biosynthesis of aristolochic acid.JCS Perkin I,1982,40:1153-1155
78 Attaluri S,Iden C R,Bonala R R,et al.Total synthesis of the aristolochic acids,their major metabolites,and related compounds.Chem Res Toxicol,2014,27:1236-1242
79 Wang X H.Biosynthetic related enzymes of aristolochic acid in Asarum(in Chinese).Dissertation for the Master’s Degree.Changchun:Jilin Agricultural University,2014[王潇晗.细辛马兜铃酸生物合成相关酶的初步探讨.硕士学位论文.长春:吉林农业大学,2014]
80 Yang R Y,Zeng Q P.Cloning,sequencing and homologous analysis of tyrosine decarboxylase gene from Aristolochia contorta Bge(in Chinese).JGuangzhou Univ Tradit Chin Med,2005,22:152-156[杨瑞仪,曾庆平.马兜铃酪氨酸脱羧酶基因克隆、测序及同源性分析.广州中医药大学学报,2005,22:152-156]
81 Chen Z,Chen S J.Poisoning the devil.Cell,2017,168:556-560
82 Guo W,Shen Z Y,Liu C S,et al.Resource investigation of wild Stephania tetrandra in Anhui and Jiangxi Province(in Chinese).China J Tradit Chin Med Pharm,2010,25:909-911[呙未,沈湛云,刘春生,等.皖赣两省野生粉防己资源调查报告.中华中医药杂志,2010,25:909-911]
2 Ng A W T,Poon S L,Huang M N,et al.Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia.Sci Transl Med,2017,9:eaan6446
3 Gao Y,Xiao X H,Zhu X X,et al.Study and opinion on toxicity of aristolochic acid(in Chinese).China J Chin Mater Med,2017,42:4049-4053[高月,肖小河,朱晓新,等.马兜铃酸的毒性研究及思考.中国中药杂志,2017,42:4049-4053]
4 Liang A H,Gao Y,Zhang B L.Safety issue and strategy of traditional Chinese medicines containing aristolochic acid(in Chinese).Chin Food Drug Admin Mag,2017,11:17-20[梁爱华,高月,张伯礼.含马兜铃酸中药的安全性问题及对策.中国食品药品监管,2017,11:17-20]
5 Bai Z F,Xu G,Wang J B,et al.Research progress in and countermeasures against carcinogenicity of aristolochic acids and their derivatives(in Chinese).Prog Pharm Sci,2018,42:164-169[柏兆方,徐广,王伽伯,等.马兜铃酸及其衍生物致癌性研究进展及应对措施.药学进展,2018,42:164-169]
6 Chen M L,Zhu Z L.The advance on the studies of pharmacology of Aristolochia L.plants(in Chinese).Lishizhen Med Mater Med Res,2007,18:702-704[陈孟兰,朱正兰.马兜铃属植物的生物活性和药理作用研究进展.时珍国医国药,2007,18:702-704]
7 Bhattacharjee P,Bera I,Chakraborty S,et al.Aristolochic acid and its derivatives as inhibitors of snake venom L-amino acid oxidase.Toxicon,2017,138:1-17
8 Vanherweghem J L,Tielemans C,Abramowicz D,et al.Rapidly progressive interstitial renal fibrosis in young women:association with slimming regimen including Chinese herbs.Lancet,1993,341:387-391
9 Vanhaelen M,Vanhaelen-Fastre R,But P,et al.Identification of aristolochic acid in chinese herbs.Lancet,1994,343:174
10 International Agency for Research on Cancer(IARC).A Review of Human Carcinogens.A.Pharmaceuticals.Geneva:WHO Press,2012.347-361
11 Li Y M,Li J,Yu F.Current situation and research progress on the nephrotoxicity of aristolochic acid compounds(in Chinese).J Pharm Res,2017,36:534-537[李一昴,李霁,于锋.马兜铃酸类化合物使用现状及肾脏毒性研究进展.药学研究,2017,36:534-537]
12 Kuo P C,Li Y C,Wu T S.Chemical constituents and pharmacology of the Aristolochia species.Tradit Complement Med,2012,2:249-266
13 Yang Z C,Lu Y,Gu Y Q,et al.Progress in aristolochic acid carcinogenesis and its related metabolic enzymes(in Chinese).Tradit Chin Drug Res Pharmacol,2014,25:765-769[杨召聪,陆茵,顾亚琴,等.马兜铃酸I致癌作用及其与代谢酶关系的研究进展.中药新药与临床药理,2014,25:765-769]
14 Chung Y M,Chang F R,Tseng T F,et al.A novel alkaloid,aristopyridinone A and anti-inflammatory phenanthrenes isolated from Aristolochia manshuriensis.Bioorg Med Chem Lett,2011,21:1792-1794
15 Georgopoulou C,Aligiannis N,Fokialakis N,et al.Acretoside,a new sucrose ester from Aristolochia cretica.J Asian Nat Products Res,2005,7:799-803
16 Shi L S,Kuo P C,Tsai Y L,et al.The alkaloids and other constituents from the root and stem of Aristolochia elegans.Bioorg Med Chem,2004,12:439-446
17 Cai Y,Cai T G.Two new aristolochic acid derivatives from the roots of Aristolochia fangchi and their cytotoxicities.Chem Pharm Bull,2010,58:1093-1095
18 Wu T S,Damu A G,Su C R,et al.Chemical constituents and pharmacology of Aristolochia species.Stud Nat Prod Chem,2005,32:855-1018
19 Navarro-García V M,Luna-Herrera J,Rojas-Bribiesca M G,et al.Antibacterial activity of Aristolochia brevipes against multidrug-resistant Mycobacterium tuberculosis.Molecules,2011,16:7357-7364
20 Priestap H A.Seven aristololactams from Aristolochia argentina.Phytochemistry,1985,24:849-852
21 Zhang G,Shimokawa S,Mochizuki M,et al.Chemical constituents of Aristolochia constricta:antispasmodic effects of its constituents in guineapig ileum and isolation of a diterpeno-lignan hybrid.J Nat Prod,2008,71:1167-1172
22 Holzbach J C,Lopes L M X.Aristolactams and alkamides of Aristolochia gigantea.Molecules,2010,15:9462-9472
23 Nayyatip S,Thaichana P,Buayairaksa M,et al.Aristolactam-type alkaloids from Orophea enterocarpa and their cytotoxicities.Int J Mol Sci,2012,13:5010-5018
24 Wang D P,Mao X C.Research progress on traditional Chinese medicine containing aristolochic acid.J N Pharm,2014,11:97-98[王德平,毛晓春.中药马兜铃酸的研究进展.北方药学,2014,11:97-98]
25 Qiu H X,Lin Y R.Flora Reipublicae Popularis Sinicae.Beijing:Science Press,1988.159-160[丘华兴,林有润.中国植物志.北京:科学出版社,1988.159-160]
26 Pr?bstle A,Bauer R.Aristolactams and a 4,5-dioxoaporphine derivative from Houttuynia cordata.Planta Med,1992,58:568-569
27 Kim S K,Ryu S Y,No J,et al.Cytotoxic alkaloids from Houttuynia cordata.Arch Pharm Res,2001,24:518-521
28 Chen S D,Gao H,Lu C J,et al.Alkaloids and amides from Houttuynia cordata(in Chinese).J Shenyang Pharm Univ,2013,11:846-850[陈少丹,高昊,卢传坚,等.鱼腥草中生物碱和酰胺类成分的研究.沈阳药科大学学报,2013,11:846-850]
29 Bauer R,Pr?bstle A,Lotter H,et al.Cyclooxygenase inhibitory constituents from Houttuynia cordata.Phytomedicine,1996,2:305-308
30 Jong T T,Jean M Y.Alkaloids from Houttuyniae cordata.J Chin Chem Soc,1993,40:301-303
31 Chou S C,Su C R,Ku Y C,et al.The constituents and their bioactivities of Houttuynia cordata.Chem Pharm Bull,2009,57:1227-1230
32 Qu W,Wu F H,Li J,et al.Alkaloids from Houttuynia cordata and their antiplatelet aggregation activities.Chin J Nat Med,2011,9:425-428
33 Li J,Zhang L,Jiang Z,et al.Toxicities of aristolochic acid I and aristololactam I in cultured renal epithelial cells.Toxicol In Vitro,2010,24:1092-1097
34 Wei A H,Zhou D N,Ruan J L,et al.Study on the contents of aristololactams in Piper wallichii and their renal cytotoxicities.J Food Drug Anal,2011,19:349-354
35 Xin T Y,Lei M Y,Song J Y.DNA barcoding of traditional Chinese medicine(in Chinese).Mod Chin Med,2015,17:170-176[辛天怡,雷美艳,宋经元.中药材DNA条形码鉴定研究进展.中国现代中药,2015,17:170-176]
36 Chen S,Pang X,Song J,et al.A renaissance in herbal medicine identification:from morphology to DNA.Biotech Adv,2014,32:1237-1244
37 Wu L,Sun W,Wang B,et al.An integrated system for identifying the hidden assassins in traditional medicines containing aristolochic acids.Sci Rep,2015,5:11318
38 Ma X C,Yao H,Wu L,et al.Molecular identification of Aucklandiae Radix,Vladimiriae Radix,Inulae Radix,Aristolochiae Radix and Kadsurae Radix using ITS2 barcode(in Chinese).China J Chin Mater Med,2014,39:2169-2175[马晓冲,姚辉,邬兰,等.木香、川木香、土木香、青木香和红木香药材的ITS2条形码分子鉴定.中国中药杂志,2014,39:2169-2175]
39 Li M,Au K Y,Lam H,et al.Identification of Baiying(herba Solani lyrati)commodity and its toxic substitute Xungufeng(herba Aristolochiae mollissimae)using DNA barcoding and chemical profiling techniques.Food Chem,2012,135:1653-1658
40 Li M,Au K Y,Lam H,et al.Molecular identification and cytotoxicity study of herbal medicinal materials that are confused by Aristolochia herbs.Food Chem,2014,147:332-339
41 Coghlan M L,Haile J,Houston J,et al.Deep sequencing of plant and animal DNA contained within traditional Chinese medicines reveals legality issues and health safety concerns.PLo S Genet,2012,8:e1002657
42 Xin T Y,Xu Z C,Jia J,et al.Biomonitoring for traditional herbal medicinal products using DNA metabarcoding and single molecule,real-time sequencing.Acta Pharm Sin B,2018,8:488-497
43 Xin T Y,Su C,Lin Y L,et al.Precise species detection of traditional Chinese patent medicine by shotgun metagenomic sequencing.Phytomedicine,2018,47:40-47
44 Chinese Pharmacopoeia Commission.Pharmacopoeia of the People’s Republic of China,Vol I(in Chinese).Beijing:China Medical Science Press,2015.224-224[国家药典委员会.中华人民共和国药典(一部).北京:中国医药科技出版社,2015.224-224]
45 Bai M N.Study on the pharmacognosy of Caulis Clematidis Armandii and its substitutes(in Chinese).Dissertation for the Master’s Degree.Chengdu:Southwest Jiaotong University,2017[白梦娜.川木通及常用习用品的生药学研究.硕士学位论文.成都:西南交通大学,2017]
46 Wu W J,Wan M M,Cao Y H,et al.Study on quality standards of Clematidis Armandii(in Chinese).Chin Arch Tradit Chin Med,2015,33:313-315[武尉杰,万萌萌,曹雨虹,等.川木通的质量标准研究.中华中医药学刊,2015,33:313-315]
47 Zhao S Y.Identification of Asarum heterotropoides var.mandshuricum,Asarum forbesii and Chloranthus serratus(in Chinese).Zhejiang J Tradit Chin Med,2014,49:223-225[赵双艳.细辛与杜衡和及己的鉴别研究.浙江中医杂志,2014,49:223-225]
48 Chang S P,Li H,Jiang S Y,et al.Pharmacognostic identification of Aristolochia fordiana(in Chinese).J Chin Med Mater,2016,39:523-526[昌水平,李华,蒋三元,等.通城虎的生药鉴定.中药材,2016,39:523-526]
49 Agrawal P,Laddha K.Development of validated high-performance thin layer chromatography for quantification of aristolochic acid in different species of the Aristolochiaceae family.J Food Drug Anal,2017,25:425-429
50 Murali S,Francis M S,Rashmi T R.Determination of aristolochic acid I concentration in the four species of Aristolochia using HPLC.J Cogn Psychother,2014,6:59-68
51 Li T F,Li L K,Zhang M L,et al.Determination of aristolochic acid in Aristolochia Manshuriensis with different processing methods by RP-HPLC(in Chinese).China Med Her,2015,12:14-17[李天凤,李连坤,张美玲,等.反相高效液相色谱法测定不同方法炮制关木通中马兜铃酸的含量.中国医药导报,2015,12:14-17]
52 Wang Y,Chan W.Determination of aristolochic acids by high-performance liquid chromatography with fluorescence detection.J Agric Food Chem,2014,62:5859-5864
53 Shu X,Chen J,Lin S H,et al.Determination of limit of aristolochic acid A in Dahuang Qingwei Wan(in Chinese).Chin J Hosp Pharm,2016,36:1512-1515[舒翔,陈军,林世和,等.大黄清胃丸中马兜铃酸A的限量检测.中国医院药学杂志,2016,36:1512-1515]
54 Du X E,Fu L Q.Determination the limitation of aristolochic acid A in Jiuwei-Qianghuo pill(in Chinese).Int J Trad Chin Med,2015,37:924-927[杜仙娥,付联群.九味羌活丸中马兜铃酸A的限量检测.国际中医中药杂志,2015,37:924-927]
55 Qu X C,Ma L,Han F,et al.Limit test of aristolochic acid A in Yishenjuanbi Pill.Adv Mat Res,2013,634-638:991-995
56 Zhou X H,Li Z H,Chen Y H,et al.Determination the limitation of aristolochic acid A in Mahuang Zhisou Wan by SPE-HPLC(in Chinese).Guid J Tradit Chin Med Pharm,2015,21:44-46[周雪红,李志浩,陈银华,等.SPE-HPLC法测定麻黄止嗽丸中马兜铃酸A的含量.中医药导报,2015,21:44-46]
57 Tian J Z,Liang A H,Liu J,et al.Risk control of traditional Chinese medicines containing aristolochis acids(AAs)based on influencing factors of content of AAs(in Chinese).China J Chin Mater Med,2017,42:4679-4686[田婧卓,梁爱华,刘靖,等.从马兜铃酸含量影响因素探讨含马兜铃酸中药的风险控制.中国中药杂志,2017,42:4679-4686]
58 Tagami T,Takeda A,Asada A,et al.A simple and selective detection method for aristolochic acid in crude drugs using solid-phase extraction.JNat Med,2013,67:838-843
59 Zhou H,Fu J,Cai Z W.Research of aristolochic acid I,aristolochic acid II and their metabolites in rat liver microsomes using HPLC-MS/MS(in Chinese).J Chin Mass Spectrom Soc,2017,38:30-36[周慧,付佳,蔡宗苇.基于HPLC-MS/MS法研究马兜铃酸I和马兜铃酸II的大鼠肝微粒体酶S9体外代谢.质谱学报,2017,38:30-36]
60 Kong D Q,Gao H Y,Li X,et al.Rapid determination of eight aristolochic acid analogues in five Aristolochiaceae plants by ultra-high performance liquid chromatography quadrupole/time-of-flight mass spectrometry.J Chin Phar Sci,2015,24:364-375
61 Li G H,Chen S,Wu L,et al.Determination of aristolochic acid I in traditional Chinese medicine by UPLC-QQQ-MS(in Chinese).Chin J Exp Tradit Med Formul,2017,23:61-65[李功辉,陈莎,邬兰,等.UPLC-QQQ-MS测定中药材中马兜铃酸I的含量.中国实验方剂学杂志,2017,23:61-65]
62 Mao W W,Gao W,Liang Z T,et al.Characterization and quantitation of aristolochic acid analogs in different parts of Aristolochiae Fructus,using UHPLC-Q/TOF-MS and UHPLC-Qq Q-MS.Chin J Nat Med,2017,15:392-400
63 Gan S,Han T,Liu H G,et al.Determination of aristolochic acid A in Qingxueneixiao pills by LC-MS-MS(in Chinese).Chin J Exp Tradit Med Formul,2013,16:163-167[甘盛,韩婷,刘华钢,等.液相色谱-质谱串联法测定清血内消丸中马兜铃酸A含量.中国实验方剂学杂志,2013,16:163-167]
64 Zhang L,Wang Y.LC-MS detection of aristolochic acid A in Xiaofeng Zhiyang granula(in Chinese).Chin J Pharm Anal,2012,32:78-81[张俐,王玉.LC-MS法检测消风止痒颗粒中马兜铃酸A.药物分析杂志,2012,32:78-81]
65 Luo J W,Wu Y Y,Li Y H,et al.Determination of aristolochic acid A in health food by UHPLC-MS/MS(in Chinese).Chin J Mod Appl Pharm,2013,30:186-189[罗金文,吴鸳鸯,李樱红,等.超高效液相色谱-串联质谱测定保健食品中马兜铃酸A.中国现代应用药学,2013,30:186-189]
66 Gu J,Zhang P,Zhang F,et al.Determination of aristolochic acids in rat serum by high performance liquid chromatography-Q-TOF tandem mass spectrometry.Anal Methods,2013,5:718-721
67 Zhang P.Determination of aristolochic acid A in different organs of Valeriana jatamansi by UV spectrophotometric(in Chinese).Value Eng,2012,31:293-294[张萍.紫外分光光度法测定马蹄香植物不同器官中马兜铃酸A的含量.价值工程,2012,31:293-294]
68 Yu Y,Xiu L L,Wei X Z,et al.Determination of total aristolochic acid in different extracts of Asarum heterotropoides(in Chinese).Chin J Exp Tradit Med Formul,2012,18:141-143[于艳,修丽丽,魏新智,等.北细辛不同提取物中总马兜铃酸的含量测定.中国实验方剂学杂志,2012,18:141-143]
69 Yu Y,Wang X R,Wei X Z,et al.Determination of total aristolochic acid content in three kinds of Asarum(in Chinese).J Liaoning Univ Tradit Chin Med,2013,15:44-45[于艳,王晓荣,魏新智,等.北细辛汉城细辛及华细辛中总马兜铃酸含量测定.辽宁中医药大学学报,2013,15:44-45]
70 Liu X X,Wang L,Xiao H B.Content of total aristolochic acid in Aristolochia debilis from different localities(in Chinese).Lishizhen Med Mater Med Res,2017,28:74-76[刘欣欣,王莉,肖红斌.不同产地马兜铃药材中马兜铃总酸的含量.时珍国医国药,2017,28:74-76]
71 Fu X,Liu Y,Li W,et al.Analysis of aristolochic acids by CE-MS with carboxymethyl chitosan-coated capillary.Electrophoresis,2009,30:1783-1789
72 Nan T G,He S P,Tan G Y,et al.Development of sensitive monoclonal antibody-based enzyme-linked immunosorbent assay for renal toxicity ingredient aristolochic acid A in Chinese herb medicine(in Chinese).Chin J Anal Chem,2010,38:1206-1210[南铁贵,何素平,谭桂玉,等.中药致肾毒性成分马兜铃酸A单抗制备及酶联免疫分析方法的建立.分析化学,2010,38:1206-1210]
73 Ioset J R,Raoelison G E,Hostettmann K.Detection of aristolochic acid in Chinese phytomedicines and dietary supplements used as slimming regimens.Food Chem Toxicol,2003,41:29-36
74 Spenser I D,Tiwari H P.Biosynthesis of aristolochic acid.Chem Commun(London),1966,0:55
75 Schütte H R,Orban U,Mothes K.Biosynthesis of aristolochic acid.Eur J Biochem,1967,1:70-72
76 Comer F,Tiwari H P,Spenser I D.Biosynthesis of aristolochic acid.Can J Chem,1969,47:481-487
77 Sharma V,Jain S,Bhakuni D S,et al.Biosynthesis of aristolochic acid.JCS Perkin I,1982,40:1153-1155
78 Attaluri S,Iden C R,Bonala R R,et al.Total synthesis of the aristolochic acids,their major metabolites,and related compounds.Chem Res Toxicol,2014,27:1236-1242
79 Wang X H.Biosynthetic related enzymes of aristolochic acid in Asarum(in Chinese).Dissertation for the Master’s Degree.Changchun:Jilin Agricultural University,2014[王潇晗.细辛马兜铃酸生物合成相关酶的初步探讨.硕士学位论文.长春:吉林农业大学,2014]
80 Yang R Y,Zeng Q P.Cloning,sequencing and homologous analysis of tyrosine decarboxylase gene from Aristolochia contorta Bge(in Chinese).JGuangzhou Univ Tradit Chin Med,2005,22:152-156[杨瑞仪,曾庆平.马兜铃酪氨酸脱羧酶基因克隆、测序及同源性分析.广州中医药大学学报,2005,22:152-156]
81 Chen Z,Chen S J.Poisoning the devil.Cell,2017,168:556-560
82 Guo W,Shen Z Y,Liu C S,et al.Resource investigation of wild Stephania tetrandra in Anhui and Jiangxi Province(in Chinese).China J Tradit Chin Med Pharm,2010,25:909-911[呙未,沈湛云,刘春生,等.皖赣两省野生粉防己资源调查报告.中华中医药杂志,2010,25:909-911]