Review & Monography

Research progress on quality control of hepatotoxic pyrrolizidine alkaloids in traditional Chinese medicine*

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  • 1. National Institutes for Food and Drug Control,Beijing 100050,China;
    2. Chemistry of Jilin Normal University College,Siping 136000,China;
    3. Siping Institute for Food and Drug Control,Siping 136000,China

Revised date: 2020-05-05

  Online published: 2024-07-15

Abstract

Pyrrolizidine alkaloids are common endogenous substances in plants,which can cause irreversible liver cell damage and have strong hepatotoxicity. In recent years,there have been many studies on the quality control of pyrrolizidine alkaloids,but there are few restrictions on such components in the current quality standards of traditional Chinese medicine,which indicates that there is a certain safety risk of medicine. This paper summarizes the varieties of pyrrolizidine alkaloids that may contain hepatotoxic pyrrolizidine alkaloids and the components of pyrrolizidine alkaloids contained in the current standards of Chinese medicine. It also summarizes the frequentlyused analysis methods and existing problems,and puts forward relevant suggestions for the quality regulation of such components in Chinese medicine.

Cite this article

ZAN Ke, JIANG Huang-hui, JIN Hong-yu, MA Shuang-cheng, ZHAO Lei, SUN Yan-tao . Research progress on quality control of hepatotoxic pyrrolizidine alkaloids in traditional Chinese medicine*[J]. Chinese Journal of Pharmaceutical Analysis, 2021 , 41(4) : 572 -578 . DOI: 10.16155/j.0254-1793.2021.04.02

References

[1] 张芳,王长虹,王峥涛.植物中吡咯里西啶生物碱的检测与分析[J].天然产物研究与开发,2006,18(6):1057
ZHANG F,WANG CH,WANG ZT.Analysis of pyrrolizidine alkaloids in plants[J].Nat Prod Res Dev,2006,18(6):1057
[2] 孙潇翔,向娥,邱帅凯,等.吡咯里西啶生物碱毒性作用研究进展[J].中国药物警戒,2019,16(2):76
SUN XX,XIANG E,QIU SK,et al.Research progress on toxicity of pyrrolizidine alkaloids[J].Chin J Pharmacov,2019,16(2):76
[3] 高江国,王长虹,李岩,等.吡咯里西啶生物碱的药理作用、毒性及药(毒)物代谢动力学研究进展[J].中国中药杂志,2009,34(5):506
GAO JG,WANG CH,LI Y,et al.Advance on pharmacologic actions,toxicity and pharmacokinetics of pyrrolizidine alkaloids[J].China J Chin Mater Med,2009,34(5):506
[4] 王涛,宋海波.吡咯里西啶类生物碱肝毒性研究进展及风险分析[J].医药导报,2018,37(9):1033
WANG T,SONG HB.Research progress and risk analysis on hepatotoxicity of pyrrolizidine alkaloids[J].Her Med,2018,37(9):1033
[5] 郭严,张世荣,文良志,等.我国吡咯烷生物碱致肝窦阻塞综合征的临床特征分析[J].临床肝胆病杂志,2018,34(6):1277
GUO Y,ZHANG SR,WEN LZ,et al.Clinical features of sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids in China[J].J Clin Hepatol,2018,34(6):1277
[6] 陈阮琴,卓海燕,李孝楼,等.一点红致肝窦阻塞综合征1 例报告[J].临床肝胆病杂志,2019,35(12):2778
CHEN RQ,ZHUO HY,LI XL,et al.Hepatic sinusoidal obstruction syndrome induced by Chinese herb Emilia sonchifolia(L.) DC:a case report[J].J Clin Hepatol,2019,35(12):2778
[7] 汤俊,服部征雄.《中国药典》含吡咯里西啶生物碱的中药品种与用药安全[J].药学学报,2011,46(7):762
TANG J,HATTORI M.Pyrrolizidine alkaloids-containing Chinese medicines in the Chinese Pharmacopoeia and related safety concerns[J].Acta Pharm Sin,2011,46(7):762
[8] World Health Organization.Pyrrolizidine Alkaloids Health and Safety Guide[R].Geneva,1989:26
[9] European Medicines Agency.Public Statement on Contamination of Herbal Medicinal Products/Traditional Herbal Medicinal Products with Pyrrolizidine Alkaloids[EB/OL].[2016-5-31].http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2016/06/WC500208195.pdf
[10] 中华人民共和国药典2020 年版.一部[S].2020:35ChP 2020.Vol Ⅰ[S].2020:35
[11] XIONG AZ,SHAO YL,FANG LX,et al.Comparative analysis of toxic components in different medicinal parts of Gynura japonica and its toxicity assessment on mice[J].Phytomedicine,2019,54:77
[12] ZHOU Y,LI N,CHOI FF,et al.A new approach for simultaneous screening and quantification of toxic pyrrolizidine alkaloids in some potential pyrrolizidine alkaloid-containingplants by using ultra performance liquid chromatography-tandem quadrupolemass spectrometry[J].Anal Chimi Acta,2010,681:33
[13] CHEN L,MULDER PP,PEIJNENBURG A,et al.Risk assessment of intake of pyrrolizidine alkaloids from herbal teas and medicines following realistic exposure scenarios[J].Food Chem Toxicol,2019,130:142
[14] ZHANG F,WANG CH,WANG W,et al.Quantitative analysis by HPLC-MS2 of the pyrrolizidine alkaloid adonifoline in Senecio scandens[J].Phytochem Anal,2008,19(1):25
[15] YANG XJ,YANG L,XIONG AZ,et al.Authentication of Senecio scandens and S.vulgaris based on the comprehensive secondary metabolic patterns gained by UPLC-DAD/ESI-MS[J].J Pharm Biomed Anal,2011,56(2):165
[16] CHEN PH,WANG Y,CHEN LL,et al.Comparison of the antiinflammatory active constituents and hepatotoxic pyrrolizidine alkaloids in two Senecio plants and their preparations by LC-UV and LC-MS[J].J Pharm Biomed Anal,2015,115:260
[17] 乔月,陈丽华,胡宏秀,等.基于UPLC-MS/MS 同时测定款冬花咯里西啶生物碱及其氮氧化物的含量[J].中国实验方剂学杂志,2019,26(1):155
QIAO Y,CHEN LH,HU HX,et al.Simultaneous determination of pyrrolizidine alkaloids and their nitrogen oxides in Farfarae Flos by UPLC-MS/MS[J].Chin J Exp Tradit Med Form,2019,26(1):155
[18] LIU K,ROEDER E,CHEN HL,et al.Pyrrolizidine alkaloids from Eupatorium fortune[J].Phytochemistry,1992,31(7):2573
[19] HSIEH CH,CHEN HW,LEE CC,et al.Hepatotoxic pyrrolizidine alkaloids in Emilia sonchifolia from Taiwan[J].J Food Compost Anal,2015,42:1
[20] LUO ZM,LI X,WANG L,et al.Development of UPLC-Q-TOF-MS coupled with cation-exchange solid-phase extraction method for the determination of ten pyrrolizidine alkaloids in herbal medicines[J]. Anal Sci,2019,35(10):1317
[21] CHEN LH,WANG JC,HUO QL,et al.Simultaneous determination and risk assessment of pyrrolizidine alkaloids in Artemisia capillaris Thunb.by UPLC-MS/MS together with chemometrics[J]. Molecules,2019,24(6):1077
[22] ROEDER E,RENGEL-MAYER B.Pyrrolizidine alkaloids from Arnebia euchroma[J].Planta Med,1993,59(2):192
[23] SMYRSKA-WIELEBA N,WOJTANOWSKI K K,MROCZEK T.Comparative HILIC/ESI-QTOF-MS and HPTLC studies of pyrrolizidine alkaloids in flowers of Tussilago farfara and roots of Arnebia euchroma[J].Phytochem Lett,2017,20:339
[24] ROEDER E,RENGEL B.Pyrrolizidine alkaloids from Lithospermum erythrorhizon[J].Phytochemistry,1990,29(2):690
[25] 陈丽华,王钧篪,乔月,等.基于UPLC-MS/MS 同时测定番泻叶中吡咯里西啶生物碱的含量[J].中国现代中药,2019,21(7):931
CHEN LH,WANG JC,QIAN Y,et al.Simultaneous determination of pyrrolizidine alkaloids in Sennae Folium by UPLC-MS/MS[J]. Mod Chin Med,2019,21(7):931
[26] ZHU L,WANG ZT,WONG LL,et al.Contamination of hepatotoxic pyrrolizidine alkaloids in retail honey in China[J].Food Control, 2018,85:484
[27] LETSYO E,JERZ G,WINTERHALTER P,et al.Incidence of pyrrolizidine alkaloids in herbal medicines from German retail markets:risk assessments and implications to consumers[J]. Phytother Res,2017,31(12):1903
[28] QI XY,WU B,CHENG YY,et al.Simultaneous characterization of pyrrolizidine alkaloids and N-oxides in Gynura segetum by liquid chromatography/ion trap mass spectrometry[J].Rapid Commun Mass Spectrom,2009,23(2):291
[29] FANG LX,XIONG AZ,YANG X,et al.Mass-spectrometrydirected analysis and purification of pyrrolizidine alkaloid cis/trans isomers in Gynura japonica[J].J Sep Sci,2014,37(15):2032
[30] 王琼,张朝凤,张勉,等.大黄橐吾的化学成分研究Ⅱ[J].中国中药杂志,2008,33(9):1018
WANG Q,ZHANG CF,ZHANG M,et al.Study on chemical constituents in roots and rhizomes of Ligularia duciforms Ⅱ[J].China J Chin Mater Med,2008,33(9):1018
[31] TANG J,AKAO T,NAKAMURA N,et al.In vitro metabolism of isoline,a pyrrolizidine alkaloid from Ligularia duciformis,by rodent liver microsomal esterase and enhanced hepatotoxicity by esterase inhibitors[J].Drug Metab Dispos,2007,35(10):1832
[32] XIA QS,CHOU MW,LIN G,et al.Metabolic formation of DHP-Derived DNA adducts from a representative otonecine type pyrrolizidine alkaloid clivorine and the extract of Ligularia hodgsonnii Hook[J].Chem Res Toxicol,2004,17(5):702
[33] ZHANG W,HUAI WB,ZHANG Y,et al.Ultra-performance liquid chromatography hyphenated with quadrupole-orbitrap mass spectrometry for simultaneous determination of necine-core-structure pyrrolizidine alkaloids in Crotalaria sessiliflora L.without all corresponding standards[J].Phytochem Anal,2017,28(5):365
[34] R ÖDER E,LIANG XT,KABUS KJ.Pyrrolizidine alkaloids from the seeds of Crotalaria sessiliflora[J].Planta Med,1992,58(3):283
[35] RAVIKUMAR R,LAKSHMANAN AJ.Isoechinatine,a pyrrolizidine alkaloid from Cynoglossum furcatum[J].Indian J Chem,2004,35(22):406
[36] RAVI S,RAVIKUMAR R,LAKSHMANAN AJ.Pyrrolizidine alkaloids from Cynoglossum furcatum[J].J Asian Nat Prod Res, 2008,10(3-4):349
[37] RAVI R,LAKSHMANAN AJ.Neo coramandaline,a pyrrolizidine alkaloid from Cynoglossum furcatum[J].Indian J Chem,2000, 39B:80
[38] 王建华,王跃虎,司红丽,等.狗舌草生物碱成分分析[J].西北农林科技大学学报(自然科学版),2004,32(1):93
WANG JH,WANG YH,SI HL,et al.Analysis on alkaloids from Tephroseri skirilowii[J].J Northwest Sci-Tech Univ Agric Forest (Nat Sci Ed),2004,32(1):93
[39] WANG YH,WANG JH,HE HP,et al.Norsesquiterpenoid glucosides and a rhamnoside of pyrrolizidine alkaloid from Tephroseris kirilowii[J].J Asian Nat Prod Res,2008,10(1):25
[40] JOSHI S.Pyrrolizidine alkaloids in some species of Senecio Linnaeus (Senecioneae:Asteraceae)[J].Pharma Innov,2016,5(9):106
[41] WIEDENFELD H,RODER E.Pyrrolizidine alkaloids from Ageratum conyzoides[J].Planta Med,1991,57:578
[42] FAQUETI LG,SANDJO LP,BIAVATTI MW.Simultaneous identification and quantification of polymethoxyflavones,coumarin and phenolic acids in Ageratum conyzoides by UPLC-ESI-QToF-MS and UPLC-PDA[J].J Pharm Biomed Anal,2017,145:621
[43] DESTA T,AFEWORK M,UNNITHAN CR,et al.Isolation and structural elucidation of toxic pyrrolizidine alkaloids from Ageratum conyzoides collected from VOD disease affected communities[J]. Int J Pharm Technol,2014,6(1):6281
[44] LUO ZM,CHEN GN,LI X,et al.Molecularly imprinted polymerssolid phase microextraction coupled with ultra high performance liquid chromatography-tandem mass spectrometry for rapid analysis of pyrrolizidine alkaloids in herbal medicine[J].J Sep Sci,2019, 42(1):3352
[45] SMYRSKA-WIELEBA N,WOJTANOWSKI KK,MROCZEK T.Comparative HILIC/ESI-QTOF-MS and HPTLC studies of pyrrolizidine alkaloids in flowers of Tussilago farfara and roots of Arnebia euchroma[J].Phytochem Lett,2017,20:339
[46] CLAUS MP.Co-occurrence of 2-pyrrolidineacetic acid with the pyrrolizidines tussilaginic acid and isotussilaginic acid and their 1-epimers in Arnica species and Tussilago farfara[J]. Phytochemistry,1992,31(12):4135
[47] XIONG AZ,YANG L,ZHANG F,et al.Determination of total retronecine esters-typehepatotoxic pyrrolizidine alkaloids in plant materials by pre-column derivatization high-performance liquid chromatography[J].Biomed Chromatogr,2009,23(6):665
[48] MROCZEK T,GLOWNIAK K,WLASZCZYK A.Simultaneous determination of N-oxides and free bases of pyrrolizidine alkaloids by cation-exchange solid-phase extraction and ion-pair highperformance liquid chromatography[J].J Chromatogr A,2002,949(1-2):249
[49] 张波,南铁贵,孙晴,等.免疫检测技术在中药质量快速评价中的应用[J].中国中药杂志,2017,42(3):420
ZHANG B,NAN TG,SUN Q,et al.Application of immunoassay in fast quality evaluation of traditional Chinese medicine[J].China J Chin Mater Med,2017,42(3):420
[50] SAKAMOTO S,NAGAMITSU R,YUSAKUL G,et al.Ultrasensitive immunoassay for monocrotaline using monoclonal antibody produced by N,N′-carbonyldiimidazole mediated hapten-carrier protein conjugates[J].Talanta,2017,168:67
[51] YUSAKUL G,SAKAMOTO,CHANPOKAPAIBOON K,et al.Preincubation format for a sensitive immunochromatographic assay for monocrotaline,a toxic pyrrolizidine alkaloid[J].Phytochem Anal,2019,30(6):653
[52] YU LJ,LI SF.Dynamic pH junction-sweeping capillary electrophoresis for online preconcentration of toxic pyrrolizidine alkaloids in Chinese herbal medicine[J].Electrophoresis,2005, 26(22):4360
[53] CAO K,XU Y,MU XN,et al.Sensitive determination of pyrrolizidine alkaloids in Tussilago farfara L.by field-amplified, sample-stacking,sweeping micellar electrokinetic chromatography
[J].J Sep Sci,39(21):4243
[54] KEMPF M,BEUERLE T,BUHRINGER M,et al.Pyrrolizidine alkaloids in honey:risk analysis by gas chromatography-mass spectrometry[J].Mol Nutr Food Res,2008,52(10):1193
[55] HAMA J R,STROBEL BW.Pyrrolizidine alkaloids quantified in soil and water using UPLC-MS/MS[J].RSC Adv,2019,9(52): 30350
[56] ROEDER E.Medicinal plants in china containing pyrrolizidine alkaloids[J].Pharmazie,2000,55(10):711
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