药学学报, 2021, 56(4): 972-982
引用本文:
郭宁, 赵雍, 孙奕, 王安琪, 徐凌川, 梁爱华. 马兜铃酸类物质的生物标记物与减毒策略研究进展[J]. 药学学报, 2021, 56(4): 972-982.
GUO Ning, ZHAO Yong, SUN Yi, WANG An-qi, XU Ling-chuan, LIANG Ai-hua. Research progress of aristolochic acids and their biomarkers[J]. Acta Pharmaceutica Sinica, 2021, 56(4): 972-982.

马兜铃酸类物质的生物标记物与减毒策略研究进展
郭宁1,2, 赵雍1, 孙奕1*, 王安琪1, 徐凌川2, 梁爱华1*
1. 中国中医科学院中药研究所, 北京 100700;
2. 山东中医药大学药学院, 山东 济南 250355
摘要:
马兜铃酸类物质(aristolochic acids,AAs)广泛存在于马兜铃科植物,是马兜铃科中药的重要毒性成分。作为致癌数据库(CPDB)中最强的致癌物之一,AAs能够产生肝毒性、肾毒性、致癌和致突变等毒副作用,在体内能够产生AA-DNA加合物等一系列代谢物,其特异的代谢物可作为生物标志物,用于相关疾病的早期诊断与治疗。因此,寻找能够快速并准确检测生物标志物的技术手段具有重要的研究价值。AAs可通过炮制、配伍和育种等方法减毒,以提高含AAs中药的临床安全性。本文对AAs来源分布、减毒方法及其生物标记物检测进行了综述,为含AAs中药的质量控制及其引发的疾病防控工作提供参考。
关键词:    马兜铃酸      毒性      生物标记物      减毒     
Research progress of aristolochic acids and their biomarkers
GUO Ning1,2, ZHAO Yong1, SUN Yi1*, WANG An-qi1, XU Ling-chuan2, LIANG Ai-hua1*
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;
2. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
Abstract:
Aristolochic acids (AAs) are widely distributed in Aristolochiaceae, and are important toxic components in medicinal plants of Aristolochiaceae. As one of the most powerful carcinogens in the Carcinogenic Potency Database (CPDB), AAs can induce hepatotoxicity, nephrotoxicity, carcinogenicity, mutagenicity, and other adverse reaction. AAs also can produce a series of metabolites such as AA-DNA adducts in the body, and their specific metabolites can be used as biomarkers for early diagnosis and treatment of related diseases. Thus, the current discovery for technical means that can quickly and accurately detect biomarkers possesses significant research value. AAs can be attenuated by processing, compatibility, molecular breeding, and other methods to improve the clinical safety of Chinese medicine containing AAs. In this review, we report the distribution of AAs, attenuation strategies and biomarker detection. We would like to provide a reference for the quality control of AAs-containing Chinese medicines, as well as for the prevention and control of diseases caused by AAs.
Key words:    aristolochic acid    toxicity    biomarker    attenuation   
收稿日期: 2020-11-05
DOI: 10.16438/j.0513-4870.2020-1719
基金项目: 国家“重大新药创制”科技重大专项(2015ZX09501004,2018ZX09101-002);中国中医科学院自主选题(ZZ12-001).
通讯作者: 孙奕,Tel:86-10-64032656,Fax:86-10-64013996,E-mail:ysun@icmm.ac.cn;梁爱华,E-mail:ahliang@icmm.ac.cn
Email: ysun@icmm.ac.cn;ahliang@icmm.ac.cn
相关功能
PDF(962KB) Free
打印本文
0
作者相关文章
郭宁  在本刊中的所有文章
赵雍  在本刊中的所有文章
孙奕  在本刊中的所有文章
王安琪  在本刊中的所有文章
徐凌川  在本刊中的所有文章
梁爱华  在本刊中的所有文章

参考文献:
[1] Michl J, Ingrouille MJ, Simmonds MS, et al. Naturally occurring aristolochic acid analogues and their toxicities[J]. Nat Prod Rep, 2014, 31:676-693.
[2] Balachandran P, Wei F, Lin RC, et al. Structure activity relationships of aristolochic acid analogues:toxicity in cultured renal epithelial cells[J]. Kidney Int, 2005, 67:1797-1805.
[3] Priestap HA, Minor aristolochic acids from Aristolochia argentina and mass spectral analysis of aristolochic acids[J]. Phytochemistry, 1987, 26:518-529.
[4] Nagasawa H, Wu G, Inatomi H. Effects of aristoloside, a component of Guan-mu-tong (Caulis aristolochiae manshuriensis), on normal and preneoplastic mammary gland growth in mice[J]. Anticancer Res, 1997, 17:237-240.
[5] Lemos VS, Thomas G, Filho JMB. Pharmacological studies on Aristolochia papillaris Mast. (Aristolochiaceae)[J]. J Ethnopharmacol, 1993, 40:141-145.
[6] Balachandran P, Wei F, Lin RC, et al. Structure activity relationships of aristolochic acid analogues:toxicity in cultured renal epithelial cells[J]. Kidney Int, 2005, 67:1797-1805.
[7] Yu XH, Guo X, Wang M, et al. Study on biopharmaceutical classification of aristolochic acids a in 17 Chinese patent medicines[J]. Chin Trad Patent Med (中成药), 2020, 42:1596-1599.
[8] Gao Y, Xiao XH, Zhu XX, et al. Study and opinion on toxicity of aristolochic acid[J]. China J Chin Mater Med (中国中药杂志), 2017, 42:4049-4053.
[9] Vanherweghem JL, Depierreux M, Tielemans C, et al. Rapidly progressive interstitial renal fibrosis in young women:association with slimming regimen including Chinese herbs[J]. Lancet, 1993, 341:387-391.
[10] Ng AWT, Poon SL, Huang MN, et al. Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia[J]. Sci Transl Med, 2017, 9:eaan6446.
[11] Nault JC, Letouzé E. Mutational processes, hepatocellular carcinoma:the story of aristolochic acid[J]. Semin Liver Dis, 2019, 39:334-340.
[12] Chinese Academy of Sciences. Flora of the People's Republic of China (中国植物志)[M]. Vol 24. Beijing:Science Press, 1988.
[13] Yun KY, Xu ZC, Song JY. Traditional Chinese medicine containing aristolochic acids and their detection[J]. Sci Sin Vit (中国科学:生命科学), 2019, 49:238-249.
[14] Zhu XX, Wang J, Liao S, et al. Synopsis of Aristolochia L. and Isotrema Raf. (Aristolochiaceae) in China[J]. Biodiver Sci (生物多样性), 2019, 27:1143-1146.
[15] Liang AH, Gao Y, Zhang BL. Safety problems and countermeasures of traditional Chinese medicine containing aristolochic acids[J]. China Food Drug Administration Mag (中国食品药品监管), 2017, 11:17-20.
[16] Lu J. Discussion on Chinese medicinal materials related to aristolochic acids[J]. Drug Standards China (中国药品标准), 2002, 3:49-50.
[17] Tian JZ, Liang AH, Liu J, et al. Risk control of traditional Chinese medicines containing aristolochis acids (AAs) based on influencing factors of content of AAs[J]. China J Chin Mater Med (中国中药杂志), 2017, 42:4679-4686.
[18] Han JY, Xian Z, Zhang YS, et al. Systematic overview of aristolochic acids:nephrotoxicity, carcinogenicity, and underlying mechanisms[J]. Front Pharmacol, 2019, 10:648.
[19] Chen H, Cao G, Chen DQ, et al. Metabolomics insights into activated redox signaling and lipid metabolism dysfunction in chronic kidney disease progression[J]. Redox Biol, 2016, 10:168-178.
[20] Arlt VM, Marie S, Schmeiser HH. Aristolochic acid as a probable human cancer hazard in herbal remedies:a review[J]. Mutagenesis, 2002, 17:265-277.
[21] Arlt VM, Stiborová M, Vom BJ, et al. Aristolochic acid mutagenesis:molecular clues to the aetiology of Balkan endemic nephropathy-associated urothelial cancer[J]. Carcinogenesis, 2007, 28:2253-2261.
[22] Yue H, Chan W, Yu KJ, et al. Recent progress in quantitative analysis of DNA adducts of nephrotoxin aristolochic acid[J]. Sci China Ser B Chem, 2009, 52:1576-1582.
[23] Stiborová M, Arlt VM, Schmeiser HH. DNA adducts formed by aristolochic acid are unique biomarkers of exposure and explain the initiation phase of upper urothelial cancer[J]. Int J Mol Sci, 2017, 18:2144.
[24] Yang HY, Yang CC, Wu CY, et al. Aristolochic acid and immunotherapy for urothelial carcinoma:directions for unmet needs[J]. Int J Mol Sci, 2019, 20:3162.
[25] Schmeiser HH, Kucab JE, Arlt VM, et al. Evidence of exposure to aristolochic acid in patients with urothelial cancer from a Balkan endemic nephropathy region of Romania[J]. Environ Mol Mutagen, 2012, 53:636-641.
[26] Stiborová M, Martínek V, Frei E, et al. Enzymes metabolizing aristolochic acid and their contribution to the development of aristolochic acid nephropathy and urothelial cancer[J]. Curr Drug Metab, 2013, 14:695-705.
[27] Couture A, Deniau E, Grandelaudon P, et al. Synthesis and biological evaluation of aristolctams[J]. Bioorg Med Chem Lett, 2002, 12:3557-3559.
[28] Liu MC, Maruyama S, Mizuno M, et al. The nephrotoxicity of aristolochia manshuriensis in rats is attributable to its aristolochic acids[J]. Clin Exp Nephro, 2003, 7:186-194.
[29] Jelakovi B, Dika I, Arlt VM, et al. Balkan endemic nephropathy and the causative role of aristolochic acid[J]. Semin Nephrol, 2019, 39:284-296.
[30] Chen CH, Dickman KG, Moriya M, et al. Aristolochic acid-associated urothelial cancer in Taiwan[J]. Proc Natl Acad Sci U S A, 2012, 109:8241-8246.
[31] Wu F, Wang T. Risk assessment of upper tract urothelial carcinoma related to aristolochic acid[J]. Cancer Epidemiol Biomarkers Prev, 2013, 22:812-820.
[32] Chan W, Poon WT, Chan YW, et al. A new approach for the sensitive determination of DNA adduct of aristolochic acid Ⅱ by using high-performance liquid chromatography with fluorescence detection[J]. J Chromatogr B Analyt Technol Biomed Life, 2009, 877:848-852.
[33] Pfau W, Schmeiser HH, Wiessler M. Aristolochic acid binds covalently to the exocyclic amino group of purine nucleotides in DNA[J]. Carcinogenesis, 1990, 11:313-319.
[34] Ivana B, Tobias K, Jian J, et al. Software tools and approaches for compound identification of LC-MS/MS data in metabolomics[J]. Metabolites, 2018, 8:31.
[35] Cui L, Lu H, Lee YH. Challenges and emergent solutions for LC-MS/MS based untargeted metabolomics in diseases[J]. Mass Spectrom Rev, 2018, 37:772-792.
[36] Guo J, Yun BH, Upadhyaya P, et al. Multiclass carcinogenic DNA adduct quantification in formalin-fixed paraffin-embedded tissues by ultraperformance liquid chromatography-tandem mass spectrometry[J]. Anal Chem, 2016, 88:4780-4787.
[37] Yun BH, Xiao S, Yao LH, et al. A rapid throughput method to extract DNA from formalin-fixed paraffin-embedded tissues for biomonitoring carcinogenic DNA adducts[J]. Chem Res Toxicol, 2017, 30:2130-2139.
[38] Guo L, Wu H, Yue H, et al. A novel and specific method for the determination of aristolochic acid-derived DNA adducts in exfoliated urothelial cells by using ultra performance liquid chromatography-triple quadrupole mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2011, 879:153-158.
[39] Chan W, Zheng YF, Cai ZW. Liquid chromatography-tandem mass spectrometry analysis of the DNA adducts of aristolochic acids[J]. J Am Soc Mass Spectrom, 2007, 18:642-650.
[40] Chan W, Yue H, Poon WT, et al. Quantification of aristolochic acid-derived DNA adducts in rat kidney and liver by using liquid chromatography-electrospray ionization mass spectrometry[J]. Mutat Res, 2008, 646:17-24.
[41] Yun BH, Bellamri M, Rosenquist TA, et al. Method for biomonitoring DNA adducts in exfoliated urinary cells by mass spectrometry[J]. Anal Chem, 2018, 90:9943-9950.
[42] Romanov V, Sidorenko V, Rosenquist TA, et al. A fluorescence-based analysis of aristolochic acid-derived DNA adducts[J]. Anal Biochem, 2012, 427:49-51.
[43] Li WW, Hu Q, Chan W. Mass spectrometric and spectrofluorometric studies of the interaction of aristolochic acids with proteins[J]. Sci Rep, 2015, 5:15192.
[44] Schmeiser HH, Nortier JL, Singh R, et al. Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients with aristolochic acid nephropathy[J]. Int J Cancer, 2014, 135:502-507.
[45] Grollman AP, Shibutani S, Moriya M, et al. Aristolochic acid and the etiology of endemic (Balkan) nephropathy[J]. Proc Natl Acad Sci U S A, 2007, 104:12129-12134.
[46] Trnacevic S, Nislic E, Trnacevic E, et al. Early screening of Balkan endemic nephropathy[J]. Mater Sociomed, 2017, 29:207-210.
[47] Lin CE, Chang WS, Lee JA, et al. Proteomics analysis of altered proteins in kidney of mice with aristolochic acid nephropathy using the fluorogenic derivatization-liquid chromatography-tandem mass spectrometry method[J]. Biomed Chromatogr, 2017, 32:e4127.
[48] Leung EM, Chan W. Comparison of DNA and RNA adduct formation:significantly higher levels of RNA than DNA modifications in the internal organs of aristolochic acid-dosed rats[J]. Chem Res Toxicol, 2015, 28:248-255.
[49] Zhao Y, Chan CK, Chan KKJ, et al. Quantitation of N6-formyl-lysine adduct following aristolochic acid exposure in cells and rat tissues by liquid chromatography-tandem mass spectrometry coupled with stable isotope-dilution method[J]. Chem Res Toxicol, 2019, 32:2086-2094.
[50] Mantle P, Modalca M, Nicholls A, et al. Comparative 1H NMR metabolomic urinalysis of people diagnosed with Balkan endemic nephropathy, and healthy subjects, in Romania and Bulgaria:a pilot study[J]. Toxins, 2011, 3:815-833.
[51] Huang F, Clifton J, Yang XL, et al. SELDI-TOF as a method for biomarker discovery in the urine of aristolochic-acid-treated mice[J]. Electrophoresis, 2009, 30:1168-1174.
[52] Ni Y, Su M, Qiu Y, et al. Metabolic profiling using combined GC-MS and LC-MS provides a systems understanding of aristolochic acid-induced nephrotoxicity in rat[J]. Febs Lett, 2007, 581:707-711.
[53] Yang M, Zhong LY, Xue X, et al. Inheritance and innovation of traditional processing technology of Chinese medicine[J]. China J Chin Mater Med (中国中药杂志), 2016, 41:357-361.
[54] Tang TY. A preliminary study on the history of processing theory of Chinese materia medica (the first part of Qing Dynasty)[J]. Mod Chin Med (中国现代中药), 2018, 20:230-238.
[55] Wang ZM, You LS, Jiang X, et al. Methodological study on the removal of toxic components from Aristolochia manshuriensis by processing technology[J]. China J Chin Mater Med (中国中药杂志), 2005, 30:1243-1246.
[56] Dong LS, Shang M, Cai SQ. A study on the varieties, origin and processing history of Aristolochiae Fructus[J]. China J Chin Materia Med (中国中药杂志), 2003, 28:33-37.
[57] Mao WW, Gao W, Liang ZT, et al. Characterization and quantitation of aristolochic acid analogs in different parts of Aristolochiae Fructus, using UHPLC-Q/TOF-MS and UHPLC-QqQ-MS[J]. Chin J Nat Med, 2017, 15:392-400.
[58] 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]. J Chin Med Mater (中药材), 2013, 36:538-541.
[59] Yuan JB, Huang Q, Ren G, et al. Acute and subacute toxicity of the extract of Aristolochiae Fructus and honey-fried Aristolochiae Fructus in rodents[J]. Biol Pharm Bull, 2014, 37:387-393.
[60] Yang B, Li ZH, Yang WL, et al. The effect of various drug processing technologies on the contents of aristolochic acid analogues in Aristolchiae Fructus[J]. Lishizhen Med Mater Med Res (时珍国医国药), 2012, 23:2553-2555.
[61] 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 Pharm Sin (药学学报), 2008, 43:221-223.
[62] Chen YJ, Wang W, Xiao HB. Monitoring and quantitative analysis of trace aristolochic acid Ⅰ in a Qing-Fei-Pai-Du decoction using liquid chromatographymass spectrometry[J]. Acta Pharm Sin (药学学报), 2020, 55:1903-1907.
[63] Qiang XJ, Yin D, Zhu ZH. History and research progress of Asari Radix et Rhizoma processing[J]. Chin J Inf Tradit Chin Med (中国中医药信息杂志), 2017, 24:130-132.
[64] Yan JY, Wang YQ, Wang Y, et al. Research on reducing safrole and aristolochic acid A in Asari Radix et Rhizoma based on different processing techniques[J]. Chin Tradit Herb Drugs (中草药), 2015, 46:216-220.
[65] Jiang X, Li L, Wang WH, et al. Toxicologically studies of raw radix aristolochiae and it's processed product[J]. Chin Remed Clinic (中国药物与临床), 2006, 6:485-487.
[66] Pan JH, Yan GJ, Song J. The determination of aristolochic acid A in different processed Aristolochia Manshuriensis and the test of influence about renal function in rats[J]. J Chin Med Mater (中药材), 2010, 33:1228-1233.
[67] Li TF, Li LK, Zhang ML, et al. Determination of aristolochic acid in Aristolochia Manshuriensis with different processing methods by RP-HPLC[J]. Chin Med Her (中国医药导报), 2015, 12:14-17.
[68] He M, Zhang J, Yang L. Application of RBF and RSM in optimizing the processing conditions of Manchurian Dutchmanspipe stem with alkali[J]. Her Med (医药导报), 2014, 33:914-916.
[69] Ren HZ. Determination of the content of aristolochic acid-ain processed Aristolochia cinnabarine by HPLC[J]. Asia-Pacific Tradit Med (亚太传统医药), 2015, 11:23-25.
[70] Ren HZ, Lin HX, Xiao LX. Comparatively study on the analgesic effect of the raw and processed Aristolochia Cinnabarine root tuber[J]. Asia-Pacific Tradit Med (亚太传统医药), 2016, 12:18-20.
[71] Quan SJ, Ding J, Wang HD. Effect of Chinese traditional medicine of nourishing Yin and nourishing blood on aristolochic acid A content of Caulis Aristolochiae Manshuriensis[J]. Liaoning J Tradit Chin Med (辽宁中医杂志), 2009, 36:1766-1767.
[72] Wang WW, Zhang JY, Cheng J. Effect of Salvia Miltiorrhiza on renal pathological change and expression of ACE and ACE2 in rats with aristolochic acid induced nephropathy[J]. Chin J Integrat Tradit West Nephrol (中国中西医结合肾病杂志), 2009, 10:109-112.
[73] Wu JH, Zhang ZH, Lv YJ, et al. Study on Rhizoma Coptidis decreasing the content of aristolochic acid A by HPLC[J]. J Hubei Univ Chin Med (湖北中医药大学学报), 2012, 14:39-42.
[74] Liu YQ, Zhao HH, Hou N, et al. Determination of aristolochic acid A in decoction of Caulis Aristolochiae Manshuriensis and its combination with other Chinese herbal by reversed phase high perfarmance liquid chromatography[J]. Chin J Anal Chem (分析化学), 2006, 34:161-164.
[75] Zhang YC, Wang JC, Pan JH, et al. Discussion on mechanism of attenuating toxicity and saving effect of Aristolochia Manshuriensis compatibility with processed Aconiti Lateralis Radix Praeparata and Zingiberis Rhizoma based on'Fuyang Buxu'theory[J]. Chin J Exp Tradit Med Form (中国实验方剂学杂志), 2017, 23:7-12.
[76] Zhang MZ, Zhang DN. Kidney-nourishing and blood-activating therapy for aristolochic acid nephropathy in 65 cases[J]. Shanghai J Tradit Chin Med (上海中医药杂志), 2003, 37:30-32.
[77] Fang J, Chen YP, Yang YF, et al. Antagonistic effect of Yishen Ruanjian San contained serum against aristolochic acid in antagonizing human renal interstitial fibroblasts[J]. Chin J Integrat Tradit West Med (中国中西医结合杂志), 2004, 24:811-815.
[78] Chen JL, Wu YH, Deng YY, et al. Protective effect of Radix Salviae Miltiorrhizae on the aristolochic acid induced renal tubular epithelial cell injury[J]. Chin J Integrat Tradit West Nephrol (中国中西医结合肾病杂志), 2005, 6:445-448.
[79] Ruan YP, Hu XM, Zhao YM. Effect of Chinese herbal medicine compatibility on aristolochic acid content in Danggui Sini Decoction[J]. Chin Arch Tradit Chin Med (中华中医药学刊), 2012, 30:549-551.
[80] Sun XY, Sun QS, Jia LY. Determination of the contents of aristolochic acid A in growthing Asarum heterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag. planted after the pretreatment of the seeds by HPLC[J]. J Shenyang Pharm Univ (沈阳药科大学学报), 2009, 26:299-302.
[81] Cheng Z, Hu YS. Effect of shade on the content of aristolochic acid A in Asarum heterotropoides[J]. Guizhou Agri Sci (贵州农业科学), 2014, 42:69-71.
[82] Schutte HR, Orban U, Mothes K. Biosynthesis of aristolochic acid[J]. Eur J Biochem, 1967, 1:70-72.
[83] Yang RY, Zeng QP. Cloning, sequencing and homology analysis of tyrDC in Aristolochia debilis[J]. J Guangzhou Univ of Chin Med (广州中医药大学学报), 2005, 2:152-159.
[84] Yu M, Man YL, Chen MH, et al. Hirsutella sinensis inhibits NLRP3 inflammasome activation to block aristolochic acid-induced renal tubular epithelial cell transdifferentiation[J]. Hum Cell, 2020, 33:79-87.
[85] Chen M, Gong LK, Qi XM, et al. Inhibition of renal NQO1 activity by dicoumarol suppresses nitroreduction of aristolochic acid I and attenuates its nephrotoxicity[J]. Toxicol Sci, 2011, 122:288-296.
[86] Ding YJ, Sun CY, Wen CC, et al. Nephroprotective role of resveratrol and ursolic acid in aristolochic acid intoxicated zebrafish[J]. Toxins (Basel), 2015, 7:97-109.
[87] Wang SF, Fan JJ, Mei XB, et al. Interleukin-22 attenuated renal tubular injury in aristolochic acid nephropathy via suppressing activation of NLRP3 inflammasome[J]. Front Immunol, 2019, 10:2277.
[88] Hamano Y, Aoki T, Shirai R, et al. Low-dose darbepoetin alpha attenuates progression of a mouse model of aristolochic acid nephropathy through early tubular protection[J]. Nephron Exp Nephrol, 2010, 114:e69-81.
[89] Xie XC, Zhao N, Xu QH, et al. Relaxin attenuates aristolochic acid induced human tubular epithelial cell apoptosis in vitro by activation of the PI3K/Akt signaling pathway[J]. Apoptosis, 2017, 22:769-776.
[90] Zeniya M, Mori T, Yui N, et al. The proteasome inhibitor bortezomib attenuates renal fibrosis in mice via the suppression of TGF-β1[J]. Sci Rep, 2017, 7:13086.
[91] Wu TK, Wei CW, Pan YR, et al. Vitamin C attenuates the toxic effect of aristolochic acid on renal tubular cells via decreasing oxidative stress-mediated cell death pathways[J]. Mol Med Rep, 2015, 12:6086-6092.
[92] Wu T, Pan Y, Wang H, et al. Vitamin E (α tocopherol) ameliorates aristolochic acidinduced renal tubular epithelial cell death by attenuating oxidative stress and caspase3 activation[J]. Mol Med Rep, 2018, 17:31-36.
[93] Priestap HA, Barbieri MA. Conversion of aristolochic acid I into aristolic acid by reaction with cysteine and glutathione:biological implications[J]. J Nat Prod, 2013, 76:965-968.
[94] Liu XX, Wu XF, Pan Y, et al. Analysis of aristolochic acid derivates in Aristolochia debilis and its fermented product by HPLC-ESI-TOF-MS[J]. Chin J Nat Med, 2010, 8:456-460.
[95] Xiao Y, Xiao R, Tang J, et al. Preparation and adsorption properties of molecularly imprinted polymer via RAFT precipitation polymerization for selective removal of aristolochic acid I[J]. Talanta, 2017, 162:415-422.
[96] Li WW, Chan CK, Wong YL, et al. Cooking methods employing natural anti-oxidant food additives effectively reduced concentration of nephrotoxic and carcinogenic aristolochic acids in contaminated food grains[J]. Food Chem, 2018, 264:270-276.
相关文献:
1.宋迪, 陈帅帅, 李朋彦, 张乐, 柏兆方, 肖小河, 秦旭华, 王伽伯.补骨脂潜在肝毒性的修制减毒方法研究:酒浸水漂法[J]. 药学学报, 2020,55(2): 276-282
2.王伽伯, 崔鹤蓉, 柏兆方, 肖小河.精准医学下的中药安全性评价策略和方法:病证毒理学[J]. 药学学报, 2016,51(11): 1681-1688
3.王伽伯 马永刚 张萍 金城 孙玉琦 肖小河 赵艳玲 周灿平.炮制对大黄化学成分和肝肾毒性的影响及其典型相关分析[J]. 药学学报, 2009,44(8): 885-890