Safety Research in Traditional Chinese Medicine: Methods, Applications, and Outlook

Yue Gao, Aihua Liang, Xiaohui Fan, Limin Hu, Feiran Hao, Yubo Li

Engineering ›› 2019, Vol. 5 ›› Issue (1) : 76-82.

PDF(376 KB)
PDF(376 KB)
Engineering ›› 2019, Vol. 5 ›› Issue (1) : 76-82. DOI: 10.1016/j.eng.2018.11.019
Research
Research Traditional Chinese Medicine—Review

Safety Research in Traditional Chinese Medicine: Methods, Applications, and Outlook

Author information +
History +

Abstract

Traditional Chinese medicine (TCM) is a medical system that has collected and summarized abundant clinical experience over its long history of more than 2000 years. However, the frequent occurrence of TCM-induced adverse reactions has hindered the modernization and internationalization of TCM, while attracting increasing attention from around the world. Unlike chemical drugs and biological agents, the difficulties involved in research on the toxicity and safety of TCM mainly include the complexity of its components and the unpredictability of drug–body interactions. Much of TCM, which has overall therapeutic effects, has the typical mechanisms of multiple components, multiple pathways, and multiple targets. While considering the gradualness and unpredictability of TCM toxicity, the ambiguity of toxicants and safe dosage, and individual differences during long-term TCM administration, we have systematically established key techniques for the toxicity assessment of TCM. These techniques mainly include TCM toxicity discovery in an early phase, based on a combination of drug toxicology genomics and metabolomics; methods to identify dose–toxicity relationships in TCM; and integrated techniques for the exploration of TCM interactions, such as fast-screening tests based on drug-metabolizing enzymes and receptor pathways. In particular, we have developed a new technical system for TCM safety evaluation using molecular toxicology, which has been validated well in research on TCM compatibility contraindication, quality control, and allergen discovery. The application of this key technical platform is introduced here in detail. This application includes model organisms, toxicant biomarkers, a magnetic suspension technique, and the application of network toxicology and computational toxicology in research on the toxicity of Fructus toosendan, Semen cassiae, Polygonum multiflorum, and Fructus psoraleae.

Keywords

Traditional Chinese medicine / Safety / Methods and technical platform / Toxicity / Mechanism

Cite this article

Download citation ▾
Yue Gao, Aihua Liang, Xiaohui Fan, Limin Hu, Feiran Hao, Yubo Li. Safety Research in Traditional Chinese Medicine: Methods, Applications, and Outlook. Engineering, 2019, 5(1): 76‒82 https://doi.org/10.1016/j.eng.2018.11.019

References

[1]
Wang G., Sheng L., Wang X.. Ideas and methods in the research of four properties and five tastes. Chin J Mod Drug Appl. 2013; 7(19): 235-237. Chinese
[2]
Li W., Zhang X., Sui F., Dai L., Huo H., Jiang T.. Study progress on natures and tastes of Chinese herbs. Chin J Exp Tradit Med Formulae. 2015; 21(12): 227-230.
[3]
Ng A.W.T., Poon S.L., Huang M.N., Lim J.Q., Boot A., Yu W., . Aristolochic acid and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia. Sci Transl Med. 2017; 9(412): eaan6446
[4]
Wang Y., Li C., Qiu Q., Guo S., Han J., Wu Y., . Study of collaborative evaluation system on synergistic pharmacological effect of Chinese formula with multi-components and multi-targets. Sci Sin Vitae. 2016; 46(8): 1029-1032. Chinese
[5]
Zhang J.. Chinese traditional medicine is characterized by inducing multi-target effects. Chin J Pharmacol Toxicol. 2015; 29(S1): 3. Chinese
[6]
Zeng K.W., Tu P.F.. Recent progress on the methodology for target study of traditional Chinese medicine. Sci Sin Chim. Epub. 2018; Sep 5. Chinese
[7]
Han L., Wang Y., Yue G.. Application of pregnane X receptor’s regulation of induction of cytochrome P-450 CYP3A to incompatibility of traditional Chinese medicine and toxicity predetermination. Chin J Pharmacol Toxicol. 2015; 6: 967-972. Chinese
[8]
Chao H., Tang X., Jie L., Liang Q., Wang Y., Ma Z., . Metabonomics study of aqueous extract of Fructus psoraleae on serum of rats based on UPLC/QTOF-MS. Pharmacol Clin Chin Materia Medica. 2016; 32(1): 22-26.
[9]
Wang Y., Feng Q., He P., Zhu L., Chen G.. Genomics approach of the natural product pharmacology for high impact diseases. Int J Genomics. 2018; 2018: 9468912.
[10]
Wen L., Wei F.. Relationship among dosage, effect and toxicity of the ingredients in a Chinese herbal formula. Chin J Exp Traditi Med Formulae. 2009; 15(5): 84-87. Chinese
[11]
Ma Z.C., Wang Y.G., Tan H.L., Liang Q.D., Xiao C.R., Tang X.L., . Interactions between drug metabolizing enzymes and traditional Chinese medicine. World Chin J Digestology. 2016; 24(7): 994-1001.
[12]
Zhang X., Wang Y., Liang Q., Ma Z., Xiao C., Tan H., . The correlation between chemical composition, as determined by UPLC-TOF-MS, and acute toxicity of Veratrum nigrum L. and Radix Paeoniae alba. Evid Based Complement Alternat Med. 2014; 892797.
[13]
Lin X., Guo X., Zhang Y., Wei J., Jin H.. Experimental study on acute and repeated dose toxicity of traditional Chinese medicine Kangguan Granule on juvenile rats. Chin J Pharmacovigilance. 2017; 14(11): 653-656. Chinese
[14]
Li H., Wang Y., Ma Z., Tan H., Xiao C., Tang X., . Study on the induction of drug metabolizing enzyme CYP1A1 activity by ginsenoside Rc, Re, Rf and Rg1. Chin Pharmacol Bull. 2016; 32(9): 1217-1223. Chinese
[15]
Bakire S., Yang X., Ma G., Wei X., Yu H., Chen J., . Developing predictive models for toxicity of organic chemicals to green algae based on mode of action. Chemosphere. 2018; 190: 463-470.
[16]
Sanderson D.M., Earnshaw C.G.. Computer prediction of possible toxic action from chemical structure; the DEREK system. Hum Exp Toxicol. 1991; 10(4): 261-273.
[17]
Zhu Y., Ye Z.. Computational toxicology and its application in toxicity study of traditional Chinese medicine. Chin New Drugs. 2011; 20(24): 2424-2429. Chinese
[18]
Valerio L.G.Jr, Arvidson K.B., Chanderbhan R.F., Contrera J.F.. Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling. Toxicol Appl Pharmacol. 2007; 222(1): 1-16.
[19]
Fan X., Zhao X., Jin Y., Shen X., Liu C.. Network toxicology and its application to traditional Chinese medicine. Chin J Chin Materia Medica. 2011; 36(21): 2920-2922.
[20]
Han J., Yi Y., Li C., Zhang Y., Wang L., Zhao Y., . Involvement of histamine and RhoA/ROCK in penicillin immediate hypersensitivity reactions. Sci Rep. 2016; 6(1): 33192.
[21]
Li Y., Ju L., Hou Z., Deng H., Zhang Z., Wang L., . Screening, verification, and optimization of biomarkers for early prediction of cardiotoxicity based on metabolomics. J Proteome Res. 2015; 14(6): 2437-2445.
[22]
Li Y., Deng H., Ju L., Zhang X., Zhang Z., Yang Z., . Screening and validation for plasma biomarkers of nephrotoxicity based on metabolomics in male rats. Toxicol Res. 2016; 5(1): 259-267.
[23]
Li Y., Wang L., Ju L., Deng H., Zhang Z., Hou Z., . A systematic strategy for screening and application of specific biomarkers in hepatotoxicity using metabolomics combined with ROC curves and SVMs. Toxicol Sci. 2016; 150(2): 390-399.
[24]
Wang M., Liu C., Dong R., He S., Liu T., Zhao T.C., . Safety evaluation of Chinese medicine injections with a cell imaging-based multiparametric assay revealed a critical involvement of mitochondrial function in hepatotoxicity. Evid Based Complement Alternat Med. 2015; 2015(7): 379586.
[25]
Ma Z., Zhao J., Dong R., Cui Y., Wang M., Zhu Y.. Hepatotoxicity study of extracts and main components in Polygonum multijiorum using high content analysis. Chin Herb Med. 2016; 22: 4021-4029.
[26]
Liang Y., Wang Y., Liang Q., Ma Z., Xiao C., Tan H., . Correlation between changes of alkaloids in combination of Veratrum nigrum and ginseng and animal toxicity. Chin Tradit Herbal Drugs. 2012; 43(08): 1574-1579. Chinese
[27]
Liang Y., Wang Y., Liang Q., Liu H., Ma Z., Xiao C., . UPLC/Q-TOF-MS based the diversity of toxiferous composition of the toxicity of animals and in different combination of Veratrum nigrum and ginseng. J Chin Mass Spectrom Soc. 2012; 33(5): 257-264. Chinese
[28]
Xu H., Hao F., Wang M., Ren S., Li M., Tan H., . Influences of realgar-indigo naturalis, a traditional Chinese medicine formula, on the main CYP450 activities in rats using a cocktail method. Evid-based Compl Alt. 2017; 2017(9): 1-9.
[29]
Chang S.Y., Weber E.J., Sidorenko V.S., Chapron A., Yeung C.K., Gao C., . Human liver-kidney model elucidates the mechanisms of aristolochic acid nephrotoxicity. JCI Insight. 2017; 2(22): e95978.
[30]
Wang K., Feng C., Li C., Yao J., Xie X., Gong L., . Baicalin protects mice from aristolochic acid I-induced kidney injury by induction of CYP1A through the aromatic hydrocarbon receptor. Int J Mol Sci. 2015; 16(7): 16454-16468.
[31]
Feng C., Xie X., Wu M., Li C., Gao M., Liu M., . Tanshinone I protects mice from aristolochic acid I-induced kidney injury by induction of CYP1A. Environ Toxicol Pharmacol. 2013; 36(3): 850-857.
[32]
Levová K., Moserová M., Kotrbová V., Sulc M., Henderson C.J., Wolf C.R., . Role of cytochromes P4501A1/2 in detoxication and activation of carcinogenic aristolochic acid I: studies with the hepatic NADPH:cytochrome P450 reductase null (HRN) mouse model. Toxicol Sci. 2011; 121(1): 43-56.
[33]
Ji L., Liu T., Wang Z.. Pyrrolizidine alkaloid clivorine induced oxidative injury on primary cultured rat hepatocytes. Hum Exp Toxicol. 2010; 29(4): 303-309.
[34]
Wen L., Sun W., Liu K., Wang B., Wei Y., Chen D., . Research progress of pyrrolizidine alkaloids induced liver injury. Infect Dis Info. 2017; 30(4): 209-211.
[35]
Rakba N., Melhaoui A., Rissel M., Morel I., Loyer P., Lescoat G.. Irniine, a pyrrolidine alkaloid, isolated from Arisarum vulgare can induce apoptosis and/or necrosis in rat hepatocyte cultures. Toxicon. 2000; 38(10): 1389-1402.
[36]
Ji L., Chen Y., Liu T., Wang Z.. Involvement of Bcl-xL degradation and mitochondrial-mediated apoptotic pathway in pyrrolizidine alkaloids-induced apoptosis in hepatocytes. Toxicol Appl Pharmacol. 2008; 231(3): 393-400.
[37]
Han J., Liang A., Gao S.. Research progress of especial toxicity and of pyrrolizidine alkaloids. Chin J Chin Materia Medica. 2011; 36(10): 1397-1401. Chinese
[38]
Zhao Y., Liang A., Liu T., Li C., Wang X., Yi Y., . Study on embryonic toxicity of Senecio scandens, Qianbai Biyanpian and total alkaloid from S. scandens in rats. Chin J Chin Materia Medica. 2010; 35(3): 373-377. Chinese
[39]
Han J.Y., Yi Y., Liang A.H., Zhang Y.S., Li C.Y., Zhao Y., . Embryotoxicity of Senecionis Scandentis hebra on in vitro cultured mouse embryos. Acta Pharm Sin. 2014; 49(9): 1267-1272. Chinese
[40]
Han J., Liang A.. Toxicity of senecionine on in vitro cultured mouse embryos. Asian J Ecotoxicol. 2011; 6(2): 189-194. Chinese
[41]
Han J., Liang A., Yi Y., Gao S.. Nilsen OG. Toxicity of monocrotaline on in vitro cultured mouse embryos. Asian J Excotoxicol. 2011; 36(4): 484-487. Chinese
[42]
Han J., Liang A., Yi Y.. Developmental toxicity of retrorsine on mouse embryos in vitro. Chin J Chin Materia Medica. 2011; 36(14): 1901-1904. Chinese
[43]
Xia F., Li A., Chai Y., Xiao X., Wan J., Li P., . UPLC/Q-TOFMS-based metabolomics approach to reveal the protective role of other herbs in An-Gong-Niu-Huang Wan against the hepatorenal toxicity of cinnabar and realgar. Front Pharmacol. 2018; 9: 618.
[44]
Yin J., Xie J., Guo X., Ju L., Li Y., Zhang Y.. Plasma metabolic profiling analysis of cyclophosphamide-induced cardiotoxicity using metabolomics coupled with UPLC/Q-TOF-MS and ROC curve. J Chromatogr B Analyt Technol Biomed Life Sci. 2016; 1033–1034: 428-435.
[45]
Li A., Guo X., Xie J., Liu X., Zhang Z., Li Y., . Validation of biomarkers in cardiotoxicity induced by periplocin on neonatal rat cardiomyocytes using UPLC-Q-TOF/MS combined with a support vector machine. J Pharm Biomed Anal. 2016; 123: 179-185.
[46]
Liu C., Sheng X., Wang Y., Yin J., Huang W., Fan Y., . A sensitive approach for simultaneous quantification of carbonyl and hydroxyl steroids using 96-well SPE plates based on stable isotope coded-derivatization-UPLC-MRM: method development and application. RSC Adv. 2018; 8(35): 19713-19723.
[47]
Xu S., Li Z., Li H., Xue C.. Effects of Veleriana extracts on bile acid metabolism and liver injury. Her Med. 2011; 30(3): 298-301. Chinese
[48]
Wang X., Han L., Li G., Peng W., Gao X., Klaassen C.D., . From the cover: identification of natural products as inhibitors of human organic anion transporters (OAT1 and OAT3) and their protective effect on mercury-induced toxicity. Toxicol Sci. 2018; 161(2): 321-334.
[49]
He Y., Ci X., Xie Y., Yi X., Zeng Y., Li Y., . Potential detoxification effect of active ingredients in liquorice by upregulating efflux transporter. Phytomedicine. 2018; 59: 175-182.
[50]
Li Y., Zhang X., Zhou H., Fan S., Wang Y., Wang L., . Toxicity analysis of doxorubicin using plasma metabolomics technology based on rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry. Anal Methods. 2014; 6(15): 5909-5917.
[51]
Li Y., Hou Z., Wang Y., Wang L., Ju L., Zhang Z., . Screening and verification of linearly dependent biomarkers with acute toxicity induced by Aconiti Radix based on liquid chromatography-mass spectrometry-based metabolite profiling. RSC Adv. 2015; 5(126): 103915-103924.
[52]
Li Y., Liu C., Du J., Sheng X., Zhang Y.. Plasma metabolic profiling analysis of Cortex Periplocae-induced cardiotoxicity based on UPLC/Q-TOF-MS. RSC Adv. 2018; 8(9): 4937-4945.
[53]
Li Y., Zhou H., Xie J., Ally M.S., Hou Z., Xu Y., . A novel method for evaluating the cardiotoxicity of traditional Chinese medicine compatibility by using support vector machine model combined with metabonomics. Evid Based Complement Alternat Med. 2016; 2016(3): 6012761.
[54]
Guo X., Gu C., Xu Y., Li Y., Zhang Y.. Applicability of small molecule biomarkers of nephrotoxicity in evaluating toxicity of traditional Chinese medicines. Drug Eval Res. 2017; 40(4): 472-478.

RIGHTS & PERMISSIONS

2019 THE AUTHORS
AI Summary AI Mindmap
PDF(376 KB)

Accesses

Citations

Detail

Sections
Recommended

/