Risk control of traditional Chinese medicines containing aristolochis acids (AAs) based on influencing factors of content of AAs

TIAN Jing-zhuo1 LIANG Ai-hua1 LIU Jing1 ZHANG Bo-li2

(1.Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China 100700)
(2.China Academy of Chinese Medical Sciences, Beijing, China 100700)

【Abstract】Aristolochic acids (AAs) widely exist in such plants as Aristolochia and Asarum. The renal toxicity of AAs as well as its carcinogenicity to urinary system have been widely known. In 2003 and 2004, China prohibited the use of Caulis Aristolochia Manshuriensis, Radix Aristolochiae Fangchi and Radix Aristolochiae Debilis, and required administering other AAs-containing medicines in accordance with the regulations for prescription drugs. In this paper, we retrieved literatures on the content determination of AAs in recent 10 years in China. It suggested that the AAs content is lower in Asarum herb, especially in its roots and rhizomes. There were no AA-I detected in most of Asarum-containing medicines and fairly small amount of AA-I detected in a few of them. Some of traditional Chinese medicines show fairly small amount of detectable AA-I. The AAs content in Aristolochia herb (including Fructus Aristolochiae, Kaempfer dutchmanspipe root , and Aristolochiae Mollissimae) is relatively high; however, there are less literature for studying the content determination of AAs in Chinese patent medicines. There were many factors affecting AAs content, including the parts used, origins, processing methods, extraction process. It suggested that we should pay attention to the toxicity of Chinese medicines containing AAs and use these decoction pieces and traditional Chinese medicines cautiously. In addition, basic studies for the origins, processing methods and extraction process of Chinese patent medicines containing AAs, as well as supervision and detection of AAs content in traditional Chinese medicinal materials, decoction pieces and Chinese patent medicines shall be strengthened for reducing medication risk and guaranteeing clinical medication safety.

【Keywords】 aristolochic acids; content; influencing factor;

【DOI】

【Funds】 National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2015ZX09501004) Special Scientific Research Fund of Public Welfare Profession of China (201507004) Beijing Science and Technology Program (Z151100000115012, Z161100004916025) Science and Technology Project of China Academy of Chinese Medical Science (ZZ10025, Project of Chinese Materia Medica containing aristolochic acids)

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(Translated by XIONG Y)

    References

    [1] Jiang GZ, Chen L. New research progress of toxicity of aristolochic acid in Traditional Chinese Medicine [J]. Chinese Agricultural Science Bulletin, 2008, 24 (9): 84 (in Chinese).

    [2] Cosyns J P. Aristolochic acid and “Chinese herbs nephropathy”: a review of the evidence to date [J]. Drug Saf, 2003, 26 (1): 33.

    [3] Liang SK. 马兜铃酸致癌性研究进展 [J]. Urology and Nephrology Foreign Medical Sciences, 2005, 25 (2): 256 (in Chinese).

    [4] China Food and Drug Administration.可能含有马兜铃酸的马兜铃科药材名单 [EB/OL]. (2017-10-30) [2017-11-23]. http://www.sda.gov.cn/WS01/CL1991/215894.html.

    [5] Zhang P. Determination of aristolochic acid A in different organs of Valeriana jatamansi by UV spectrophotometric [J]. Value Engineering, 2012, 31 (1): 293 (in Chinese).

    [6] Liu J, Bi XY, Chu LJ, et al. Limit test of aristolochic acid in the compound preparations by thin-layer chromatography [J]. Progress in Modern Biomedicine, 2010, 10 (24): 4755 (in Chinese).

    [7] Ni L, Yang X. Determination of hydroxysafflor yellow A, gallic acid and aristolochic acid A in Wuwei Zhaxun Pill by HPLC [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2012, 18 (18): 109 (in Chinese).

    [8] Han N, Lu JC, Bi KS, et al. Assaying of aristolochic acid A in 14 traditional Chinese medicines by RP-HPLC [J]. Journal of Shenyang Pharmaceutical University, 2008, 25 (2): 115 (in Chinese).

    [9] Xue Y, Tong XH, Wang F, et al. Analysis of aristolochic acid A from the aerial and underground parts of Asarum by UPLC-UV [J]. Acta Pharmaceutica Sinica, 2008, 43 (2): 221 (in Chinese).

    [10] Li GH, Chen S, Wu L, et al. Determination of aristolochic acid in Traditional Chinese Medicine by UPLC-QQQ-MS [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2017, 23 (13): 61 (in Chinese).

    [11] Zhang YZ, Tang Q, Chen B, et al. Determination of moisture and aristolochic acid content a in Yao medicine Tianzuan [J]. China Pharmaceuticals, 2014, 23 (9): 4 (in Chinese).

    [12] Chinese Pharmacopoeia. Vol. 1 [S]. 2015: 230 (in Chinese).

    [13] Song SJ, Shai LG, Chen B, et al. Determination of aristolochic acid Ⅰ and asarinin in four species of Asari Radix et Rhizoma by HPLC [J]. Chinese Traditional Patent Medicine, 2014, 36 (8): 1711 (in Chinese).

    [14] Chen J, Sun BH, Huang J, et al. Determination of aristolochic acid IVA in the different parts of Asarum eterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag. by HPLC [J]. Journal of Shenyang Pharmaceutical University, 2011, 28 (10): 797 (in Chinese).

    [15] Zhao H, Jiang H. Determination of aristolochic acid A in Saruma henryi by HPLC [J]. Guihaia, 2009, 29 (4): 548 (in Chinese).

    [16] Zhang P. Determination of aristolochic acid A in different organs of Valeriana Jatamansi by UV spectrophotometric [J]. Value Engineering, 2012, 31 (1): 293 (in Chinese).

    [17] Jiang Y, Hu LY, Hao F. RP-HPLC测定两种冠心苏合丸中桂皮酸和马兜铃酸A的含量 [J]. Chinese Traditional Patent Medicine, 2007, 29 (4): 599 (in Chinese).

    [18] Shen MQ, Xu G, Zhang Q. 高效液相色谱法测定龙胆泻肝丸马兜铃酸A含量 [J]. Herald of Medicine, 2008, 27 (2): 221 (in Chinese).

    [19] Liu Y, Han S, Feng Q, et al. Determination of aristolochic acids A and B in Chinese herbals and traditional Chinese patent medicines using ultra high performance liquid chromatography-triple quadrupole mass spectrometry [J]. Chinese Journal of Chromatography, 2011, 29 (11): 1076 (in Chinese).

    [20] Li M, Wang Z, Jin ZW, et al. The analysis of renal toxicity adverse reactions caused by Bolus of Gentian for Purging Liver-fire and its influencing factors [J]. China Licensed Pharmacist, 2012, 9 (5): 47 (in Chinese).

    [21] Hao JD. 从关木通被禁用, 看本草考证的重要性 [J]. Journal of Chinese Medicinal Materials, 2003, 26 (S1): 16 (in Chinese).

    [22] Zhang P, Ran HL, Xiao XY, et al. Qualitative and quantitative analysis of aristolochic acid in Herba Asari [J]. Chinese Journal of Pharmaceutical Analysis, 2006, 26 (6): 811 (in Chinese).

    [23] Chen JM. Enlightening Primer of Materia Medica [M]. Checked by Wang SM. Beijing: People’s Medical Publishing House Co., Ltd., 1998: 89 (in Chinese).

    [24] Tang SW. Classified Materia Medica [M]. Checked by Shang ZJ, Beijing: Huaxia Publishing House, 1993: 83 (in Chinese).

    [25] Li SZ. Compendium of Materia Medica. Vol. 18. Tome 2 [M]. The revised version. Beijing: People’s Medical Publishing House Co., Ltd., 1977:1251 (in Chinese).

    [26] Zhang JL, Gong QF, Yao DQ. HPLC法测定不同产地马兜铃不同部位马兜铃酸A的含量 [C]. Wuhan: 2012第五届全国临床中药学学术研讨会, 2012 (in Chinese).

    [27] Liu XX, Wang L, Xiao HB. Content of total aristolochic acid in Aristolochia debilis from different localities [J]. Lishizhen Medicine and Materia Medica Research, 2017, 28 (1): 74 (in Chinese).

    [28] Ni MH, Di LQ, Zhu RR, et al. HPLC determination of content of aristolochic acid A in different parts of Herba cum Radice Asari and in Xuetie Dingchuan Plaster [J]. Journal of Nanjing University of Traditional Chinese Medicine, 2006, 22 (2): 96 (in Chinese).

    [29] Xie ZM, Li SX, Liu J. Aristolochic acid A content in different parts of Herba Asari [J]. Chinese Traditional Patent Medicine, 2007, 29 (12): 1808 (in Chinese).

    [30] Wu YB, Wang Q. Determination of aristolochic acid A in the different parts of asarum and preparations by HPLC [J]. Northwest Pharmaceutical Journal, 2006, 22 (3): 108 (in Chinese).

    [31] Liu YJ, Li CY, Zhao YL, et al. 不同产地细辛中有效成分与马兜铃酸Ⅰ含量差异比较 [J]. China Licensed Pharmacist, 2010, 7 (12): 29 (in Chinese).

    [32] Yang C, Tian DJ, Li J. Determination of aristolochic acid A in different parts of Asarum Heterotropoides by HPLC [J]. China Pharmaceuticals, 2010, 19 (13): 24 (in Chinese).

    [33] Guan WQ, Li XM, Xiao JS. 可逆高效液相色谱法测定细辛药材及其制剂中马兜铃酸的含量 [J]. Chinese Remedies & Clinics, 2005, 5 (4): 283 (in Chinese).

    [34] Zeng C, Liu XM, Meng WX, et al. Determination of aristolochic acid in Herba asar from different habitats by HPLC [J]. Internal Medicine of China, 2013, 8 (1): 56 (in Chinese).

    [35] Li L, Gao HM, Wang ZM, et al. Determination of aristolochic acid A in Guanxinsuhe preparations by RP-HPLC [J]. China Journal of Chinese Materia Medica, 2006, 31 (2): 122 (in Chinese).

    [36] Yu Y, Xiu LL, Wei XZ, et al. Determination of total aristolochic acid in different extracts of Asarum heterotropoides [J]. 中国实验方剂学杂志, 2012, 18 (24): 141 (in Chinese).

    [37] Zhu HL, Mao XB, Li LY, et al. Analysis of aristolochie acid A content in Asarum volatile oil [J]. Journal of Southwest China Normal University (Natural Science Edition), 2015, 40 (10): 177 (in Chinese).

    [38] Hu ZX, Wang YH, Peng CS, et al. Advances in studies on aristolochic acid in Radix et Rhizoma Asari and its preparation in recent five years [J]. Chinese Traditional and Herbal Drugs, 2010, 41 (2): 318 (in Chinese).

    [39] Tian HG, Wang HM. Determination of aristolochic acid A in Wantong Jingu Pian by RP-HPLC [J]. Pharmaceutical Journal of Chinese People’s Liberation Army, 2007, 23 (6): 456 (in Chinese).

    [40] Tang XL, He SH, Xie TF. Determination of aristolochic acid A in Xiaozhongzhitong tincture by SPE-HPLC [J]. Chinese Journal of Pharmaceutical Analysis, 2012, 32 (9): 1690 (in Chinese).

    [41] Li D, Wu HJ. 炮制对关木通中马兜铃酸A含量的影响 [J]. Acta Chinese Medicine and Pharmacology, 2013, 41 (3): 57 (in Chinese).

    [42] Li ZH, Yang B, Yang WL, et al. Effect of honey-toasting on the constituents and contents of aristolochic acid analogues in Aristolochiae Fructus [J]. Journal of Chinese Medicinal Materials, 2013, 36 (4): 538 (in Chinese).

    [43] Yang B, Li ZH, Yang WL, et al. The effect of various drug processing technologies on the contents of aristolochic acid analogues in Axistolchiae Fructus [J]. Lishizhen Medicine and Materia Medica Research, 2012, 23 (10): 2553 (in Chinese).

    [44] Tao L, Lu Y, Wang AY, et al. Compatibility of drug property in effective components of Chinese materia medica [J]. Chinese Traditional and Herbal Drugs, 2012, 43 (11): 2107 (in Chinese).

    [45] Li CX, Ding LY, Li GC, et al. The concentration of aristolochic acid A in Manchurian Dutchman was reduced by compatibility methed [J]. Journal of Hebei Medical University, 2006, 27 (5): 354 (in Chinese).

    [46] Yin SM, Wang M, Lin XY, et al. UPLC Determination of content of aristolochine A in Compound Nanxing Analgesic Plaster [J]. Journal of Nanjing University of Traditional Chinese Medicine, 2009, 25 (5): 396 (in Chinese).

    [47] Ren W, Li SH, Long Y G, et al. Limit detection of aristolochic acid A in Xinsheng Granula by HPLC [J]. Traditional Chinese Drug Research and Clinical Pharmacology, 2010, 21 (1): 67 (in Chinese).

This Article

ISSN:1001-5302

CN: 11-2272/R

Vol 42, No. 24, Pages 4679-4686

December 2017

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Article Outline

Abstract

  • 1 Existing HCAAs and AAs-containing medicines
  • 2 Content of AAs in CMMs
  • 3 Content of AAs in CPMs
  • 4 Discussion
  • References