Rearch
Traditional Chine Medicine—Review
Quality Markers of Traditional Chine Medicine:Concept,Progress,and
Perspective
Yazhuo Li a ,Ying Xie b ,Yufei He c ,Wenbin Hou a ,Maoliang Liao a ,Changxiao Liu a ,⇑
a
State Key Laboratory of Drug Delivery Technology and Pharmacokinetics,Tianjin Institute of Pharmaceutical Rearch,Tianjin 300193,China b
State Key Laboratory of Quality Rearch of Chine Medicines,Macau University of Science and Technology,Macao,China c
School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China
a r t i c l e i n f o Article history:
Received 21June 2018
Revid 27December 2018Accepted 7January 2019
Available online 26June 2019Keywords:
Traditional Chine medicine Quality marker Quality control
a b s t r a c t
As the most important complementary medication against a variety of dias,traditional Chine medicines (TCMs)have been extensively applied over thousands of years.Current quality control of herbal medicines,however,is in great dispute.Unlike chemical drugs,which have clear and validated quality standards,the content of only one (or a few)compounds of many herbs and preparations is currently assd as an indicator of quality,even though the assd compound(s)is neither cloly associated with the efficacy nor reprentative of the medicine as a whole.Bad on the clinical u,compatibility of multiple component prescriptions,and manufacturing process of TCM,the new concept of a TCM quality marker that was propod in previous work is discusd further here.In addition,practical technological approaches are described for the qualitative analysis and quantification of TCMs including herbs,procesd products,and preparations,which lead to the discovery and identification of specific chemicals as quality markers and new quality control patterns.The progress that has been made in TCM quality control is also addresd.This work provides uful information for the quality control of herbal medicines in the future.
Ó2019THE AUTHORS.Published by Elvier LTD on behalf of Chine Academy of Engineering and Higher Education Press Limited Company.This is an open access article under the CC BY-NC-N
D licen
(creativecommons/licens/by-nc-nd/4.0/).
1.Introduction
As a conventional therapy,traditional Chine medicines (TCMs)have been extensively applied in the treatment of various kinds of acute and chronic dias.There is no doubt that TCM is of particular importance in terms of efficacy and safety.TCM—which includes but is not limited to herbs,species,decoction,and preparations—provides alternative therapy that is comple-mentary to chemical drugs and biological applications.Over the past decades,a great deal of progress has been made in clarifying the mechanisms and substantial basis of TCM [1–5],while the TCM pharmaceutical industry has rapidly developed.Most impor-tantly,TCM has now been integrated into medical care along with other medications for patients who are already under treatment as well as for people who wish to maintain a better quality of life.TCM has gradually been recognized by developed countries includ-ing the United States and various European countries.Several TCM preparations that have been developed for various indications are currently in clinical trials in the United States [6–9].Once market-ing approval is granted by the authorities,the endeavors will assist in promoting global acceptance of TCM.
However,the quality control system for TCM is insufficient.Although monographs and standards for the quality control of herbs,procesd products,and preparations have been established and recorded in official or private publications such as pharma-copoeia and directives (Table 1)[10,11]—which include definitions,characters,identification,tests,assays,storage information,and more—the information provided in the standards is insufficient to make a clear distinction between species with high similarity.For example,it is difficult to recognize which species Flos Magno-liae is derived from,since it can be obtained from Magnolia biondii Pamp.,Magnolia denudata Desr.,or Magnolia sprengeri Pamp.,according to the Pharmacopoeia of the People’s Republic of China (ChP)2015edition.Similar problems exist in the cas of Zicao and Mutong [12,13];the former may be obtained from Lithosper-mum erythrorhizon (Zicao),Arnebia euchroma (Ruan Zicao),or Onosma paniculatum (Dian Zicao),while the latter can be obtained from both Clematis armandii Franch.(Chuan Mutong)and Aristolochia manshuriensis Kom.(Guan Mutong).
⇑Corresponding author.
E-mail address: (C.Liu).
In recent years,the need for a TCM quality control system has become a new hotspot attracting a great deal of rearch interest.
A few years ago,the new concept of a TCM quality marker was pro-pod by Prof.Changxiao Liu et al.[14,15].The prent review dis-cuss new methods and technologies to explore potential quality markers for TCM quality control,considering the complexity of TCM and the factors that affect TCM quality,and may provide insight into rational grounds for the establishment of an appropri-ate TCM quality control and asssment system.This paper also discuss progress that has been made in TCM quality control,with the aim of providing a valuable reference for future investigations.
2.A propod quality marker for TCM
Unlike quality control for chemical drugs,which have clear quality standards for individual pharmaceutical products,investi-gations of TCM quality and the establishment of corresponding TCM quality standards are complicated.The question of how to for-mulate TCM quality standards and what methodology can be implemented for quality studies remains in dispute.Any pharma-ceutical products—including but not limited to chemical entities, herbal medicines,and biological applications—must be demon-strated to have acceptable quality,efficacy,and safety before they are granted approval for marketing and become accessible to clini-cal practitioners and individual patients.The good news is that her-bal medicines are currently being prescribed and applied in regions beyond Asian countries(and particularly beyond East Asia,where TCMs are common),and are gradually beco
ming accepted around the world.For example,TCMs are taken as complementary medici-nes and dietary supplements in European countries and are recog-nized within the European Union’s regulatory framework. Monographs and standards for herbal medicines that are developed through modern technology to provide a modern standard for quali-ty control may promote a more widespread acceptance of TCM.
However,the monographs and standards that have been formulated and are currently recorded in the ChP and other pharmacopoeia/directives—whether published officially or by pri-vate organizations—are unable to fulfill the requirements of quality control.The quality standards that are currently implemented are controversial.For example,the content of only one(or a few)com-pounds of many herbs and preparations is currently assd as an indicator of quality,even though the assd compound(s)is nei-ther cloly associated with the clinical efficacy of the TCM nor reflects its pharmacological actions,due to the limited number of chemicals tested.Thus far,the main focus of TCM quality asss-ment involves distinguishing authentic herbs from adulterants; however,the qualitative analysis and quantification of multiple specific components through modern analytical technologies are fundamental for the establishment of TCM quality standards with specificity and controllability.
Bad on the conventional theory of TCM,the compatibility of multiple component prescriptions,the preparation of herbal medicines,and the clinical application of TCM,Liu et al.[14,15] propod a new concept for a TCM quality marker called the Q-marker.Quality markers of TCM are believed to be intrinsic chemicals that exist in herbs and in products made from herbs—including procesd products,extracts,and pharmaceutical prepa-rations—or that are formed during processing and preparation.In order to be indicators of quality control,the compounds should be associated with the functions and properties of the TCM in question,such that they reflect its safety and efficacy.A TCM quali-ty marker is a compound that may exist in the raw species,in the procesd andfinal product,or even after the TCM has been absorbed into the bloodstream.Most importantly,the chemical structure of the compounds acting as quality markers should be verified,and the compounds should be specific ingredients that can be determined through qualitative and quantitative analysis. Conquently,the molecules that fulfill the requirements,as dis-cusd in Refs.[14,15],are given special consideration before being chon as quality markers.To be specific,a quality maker should be a compound that:①is either intrinsic to the herb or formed during processing;②is cloly related to the functions and prop-erties of the TCM and has a specific structure;③can be identified by qualitative analysis and quantification;and④preferably repre-nts the‘‘king”herb in terms of the theory of TCM compatibility, but may also reprent the minister,guide,and assistant herbs. 3.An exploration of quality markers
The proposal of the new concept of a TCM quality marker trig-gered discussions on how to explore the chemical ingredients of TCMs as potential quality markers.Multidisciplinary strategies, including but not limited to conventional phytochemistry,analyti-cal technology,bionics,system biology,computational approaches,and others have been utilized to identify compounds with characteristics that fulfill the requirements of a quality mar-ker,bad on TCM theory.Zhang et al.[16]elaborated the basic properties of Corydalis Rhizoma(Yanhusuo)and the mechanism of action,with a focus on multiple approaches to explore quality markers.Following the ideas,quality markers for Leonurus japonicus Houtt.,Penthorum chinen Pursh.,and Polygonati Rhizoma have been explored[17,18].
A particularly interesting and reasonable strategy for exploring TCM quality markers has recently been discusd;a diagram of the workflow is plotted in Fig.1[19].To summarize this strategy,the substantial basis of a specific herb and its related preparations is first clarified.An analysis of as many of the chemical ingredients as possible is then performed by phytochemical investigation (liquid chromatography(LC),nuclear magnetic resonance(NMR) spectroscopy,and liquid chromatography–mass spectrometry (LC–MS))to provide fundamental profiles of the chemical
Table1
Pharmacopoeia and directives of TCMs in different countries or regions.
Pharmacopoeia and directives Authority
The Pharmacopoeia of the People’s Republic of China China Food and Drug Administration, China c
European Pharmacopoeia European Directorate for the Quality of
Medicines&HealthCare,Council of Europe Japane Pharmacopoeia Pharmaceuticals and Medical Devices
Agency,Japan
British Pharmacopoeia British Pharmacopoeia Commission,UK
Australian Regulatory Guidelines for Complementary Medicines Therapeutic Goods Administration, Australia
WHO Monographs on Selected
Medicinal Plants
World Health Organization,United Nations
Hong Kong Chine Materia
Medica Standards
Department of Health,Hong Kong,China Thai Herbal Pharmacopoeia Thai Food and Drug Administration,
Thailand
Korean Pharmacopoeia Ministry of Food and Drug Safety,Republic
猪脚怎么做好吃of Korea
American Herbal
Pharmacopoeia a
American Herbal Pharmacopoeia b,USA British Herbal Pharmacopoeia a British Herbal Medicine Association b,UK
European Directive on Traditional Herbal Medicinal Products European Parliament and Council, European Union
Adapted from Refs.[10,11].
a Unofficial pharmacopoeias.
b Private organizations.
c Rebrande
d and restructured as th
一本正经造句e National Medical Products Administration of
the State Administration for Market Regulation of PRC since2018.
Y.Li et al./Engineering5(2019)888–894889
ingredients.In addition to the structural characterization of chemical ingredients,biosynthetic pathway analysis can offer information on the chemicals attributed to specific components,since the majority
of the chemicals in a TCM are condary metabolites produced via various biosynthetic pathways.Accord-ing to the theory of TCM,the chemical ingredients behind pungent,sweet,sour,bitter,and salty flavors can be identified as property-related ingredients by an integrated study using diver methods such as bionic analysis (i.e.,electronic no and tongue)and com-putational calculations.The next step involves exploring the chemicals that are associated with the efficacy and therapeutic value of a specific herb.Single compounds and/or extracts are screened for their effects using either in vitro or in vivo models.In this procedure,a pharmacokinetic behavior study of the TCM may help to determine the reprentative compounds that reflect the compatibility of a multiple component prescription.
A pilot study on a quality marker for Corydalis Rhizoma was car-ried out bad on the strategy of establishing a quality marker by integrating all the experimental results obtained from phytochemi-cal analysis,pharmacological analysis,computational calculations of property-related ingredients,and biosynthetic pathway analysis [16].A standard decoction of Corydalis Rhizome after vinegar pro-cessing was characterized by high-pressure liquid chromatography time-of-flight mass spectrometry (HPLC–TOF-MS).Of the 31chemical ingredients,28were identified.All were alkaloids,and were classified into three groups:protoberberine,protopine,and aporphine alkaloids.The alkaloids shared
L -tyrosine as the identi-cal biogenic precursor.Bad on an analysis of the biosynthetic pathway of the alkaloids and the specificity of Corydalis Rhizoma ,tetrahydropalmatine,corydaline,coptisine,palmatine,dehydroco-rydaline,D -tetrahydrojatrorrhizine,and protopine were initially propod as potential quality markers.Protopine and aporphine alkaloids are downstream of biosynthesis and have better speci-ficity,whereas protoberberine (e.g.,tetrahydropalmatine and cory-daline)are main ingredients in terms of content.Further pharmacological studies of extracts of tetrahydropalmatine,both in vivo and in vitro ,confirmed its potent activity in pain relief via significantly prolonged latency in stretching experiments and regu-lation of the critical protein.For example,it caud endorphin to be up-regulated,while 5-hydroxytryptamine (5-HT)and nore-pinephrine were reduced.Network pharmacology analysis pro-vided an additional prediction of tetrahydropalmatine,palmatine,protopine,and glaucine as reprentative ingredients for calcula-tion.Most of the predicted targets and cell-signaling pathways were considered to be associated with analgesic effects in central nervous system at different stages.The chemicals were demon-strated to be bioactive ingredients that correlated with efficacy;glaucine was thus considered to be an additional quality marker.Supportive evidence of property-related ingredients was provided by homology modeling and docking of tetrahydropalmatine,optisine,palmatine,allocryptopine,D -glaucine,and protopine against the bitter taste receptor TAS2R10,and by a binding
affinity
Fig.1.A typical work flow diagram exploring potential quality markers.Reproduced from Ref.[19]with permission of Elvier,Ó2019.
890Y.Li et al./Engineering 5(2019)888–894
study with functional receptors related to pungent and bitter flavors,including5-HT1A receptor,l-opioid receptor(OPRM1), b2adrenergic receptor(ADRB2),thromboxane-prostaglandin receptor(TP/TBXA2R),acetylcholine receptor(M2),and dopamine receptor(D2)[20].Tetrahydropalmatine and protopine are believed to be able to function with the receptors.In addition,a pharma-cokinetic study in rats after oral administration of the Corydalis Rhizoma extract indicated that tetrahydropalmatine,tetrahydroja-trorrhizine,protopine,corybulbine,a-allocryptopine,N-methyl tetrahydrobamarine,corydaline,tetrahydroberberine,dihydrochel-erythrine,and dihydrosanguinarine were absorbed into circulation, and that ven of them were detected in brain tissues.The prence of tetrahydroberberine was attributed to coptisine,since the meta-bolism of coptisine may take place in the intestine,with the prod-ucts then being absorbed in the form of tertiary alkaloids.Bad on the extensive investigations,tetrahydropalmatine,corydaline, coptisine,
palmatine,dehydrocorydaline,D-tetrahydrojatrorrhizine, and protopine were suggested as quality markers for Corydalis Rhizoma.Quantification approaches for the chemical ingredients andfingerprints of the vinegar process for Corydalis Rhizoma were established and extended for the quality control of its preparations, such as Yanhu Zhitong Dropping Pills[21].
4.Application of quality markers in quality asssment
The u of chemical markers as an indicator of the authenticity of herbs and the quality of related preparations is unclear or uncer-tain for most species,although efforts to explore the chemical ingredients of TCMs for the establishment of a quality evaluation and control system are unceasing.This ction expands on the dis-cussion of the progress that has been made in the application of a quality control and asssment system bad on quality markers by providing examples of successful experiences with specific cas.
The dried root of Salvia miltiorrhiza,known as Danshen in Chine,is widely ud in treatment for cardiovascular and cere-brovascular dias;it acts by improving bloodflow and promot-ing circulation[22].Its major bioactive ingredients have been investigated and classified into two groups:lipophilic tanshinones (tanshinone I,tanshinone IIA,cryptotanshinone)and hydrophilic phenolic
acids(danshensu,salvianolic acid B,protocatechuic acid). Phenolic acids prent bioactivities such as anti-atherosclerosis, anti-phlegmonosis,anti-oxidation,inhibition of platelet aggrega-tion,improving microcirculation,and protecting against myocar-dial damage;while tanshinones are able to inhibit angiogenesis, dilate coronary arteries,enhance coronaryflow,and protect against ischaemia[23–25].Pharmaceutical preparations with Danshen as the main component are applied in clinical usage;for example,compound Danshen Dropping Pills(CDDP)and Compound Danshen Tablet(CDT)are listed in the ChP.The demand for Danshen is therefore increasing remarkably,and the market value of the products is in the millions or more US dollars. Adulterants of the species and raw materials of lower quality have become unavoidable,as they are driven by commercial inter-ests.The establishment of a quality control and asssment system for this species,its extraction,and thefinal pharmaceutical prod-ucts is critical for guaranteeing the safety and efficacy of Danshen.
A large-scalefield investigation of Danshen and related medic-inal plants in China was performed by Li et al.in the early2000s and was published in2008[26].Its goal was to distinguish Salvia miltiorrhiza from other species,in order to meet the official requirements of the ChP,which documents Danshen.A quantita-tive analysis of tanshinones and phenolic acids was performed,in addition to botanical authentication.Bad on the survey,over 20Salvia species were found to have been considered to be
Danshen in local folk medicine,with the collecting locations,grow-ing environment,and distribution of the species genus varying greatly.Samples from different plant species were collected and procesd.The resulting data revealed that phenolic acids were detected in all tested samples;however,the contents were at trace levels,apart from rosmarinic acid and salvianolic acid B,which were the most abundant.For example,salvianolic acid
B ranged from trace to82.52mgÁgÀ1.Levels of tanshinones were demon-strated to be associated with the color of the root bark of the spe-cies.The different natural product profiles were attributed to either genetic or environmental changes;in particular,salvianolic acid B ranged from30.95to55.77mgÁgÀ1in various samples of Salvia miltiorrhiza.In addition,tanshinones and phenolic acids appeared to be less correlated,in terms of concentration,indicating that they might be two independent variables,and that both should be ud as markers for quality control.According to the requirements for the quantification of Danshen recorded in the ChP(2005),the amounts of salvianolic acid B and tanshinone IIA should be no less than30and2mgÁgÀ1,respectively.Several sam-ples of Salvia miltiorrhiza achieved this requirement;the samples were distinguished from other species and concluded to be the official ones.
The quality of Danshen has been shown to be associated with the germplasma and harvest[27],Whe
n harvesting Danshen,it is esntial to wait until the quantity of specific bioactive compounds reaches acceptable levels,rather than harvesting the plant at the root-swelling stage,although the latter is conventionally taken as the harvest time and is when the highest production of this herb occurs.Changes in the levels of cryptotanshinone,tanshinone IIA, danshensu,and salvianolic acid B were continuously examined in the roots of three germplasma,which were cultivated under iden-tical conditions but collected at different harvest times.For exam-ple,the levels of cryptotanshinone and tanshinones IIA in Henan violetflower Danshen continued to decrea,while the levels of danshensu and salvianolic acid B accumulated in a very strange manner,by initially decreasing and subquently increasing[27]. Changes in the levels of the chemical markers indicated the opti-mal harvest time,and provided key evidence in the lection of germplasma lines regarding the contents of the designated bioac-tive compounds.
Chemical markers were ud as an indicator of the quality con-trol of raw materials such as species and slices;the compounds were further applied as markers for the quality control of pharma-ceutical preparations,with a particular focus on consistency.Bad on the combined u of chromatographic paration and chemo-metric methods,quality investigations were performed on Danshen preparations[28–32].Protocatechuic aldehyde,salvianolic acid B,cryptotanshinone,and tans
hinone IIA were lected as markers for the quality control of CDT,in addition to ginnoside Rg,ginnoside Rb,and notoginnoside R.The resulting data showed that salvianolic acid B was the most abundant compound in the samples manufactured by different companies,whereas the other three compounds were prent in low concentrations in the tablets.Moreover,the content varied in the samples tested,with the variation being attributed to the quality of the raw materials that were ud[29].Similarly,the content of eight phenolic acids and tanshinones was examined in order to asss the quality of a granule of Danshen extract produced by different manufacturers [30].Of the15batches of granules assd,salvianolic acid B and rosmarinic acid were found to be the phenolic acids that were prent in the greatest amounts,while tanshinone I,cryptotanshi-none,and tanshinone IIA were found to be the hydrophobic com-ponents that were prent in the greatest amounts.The content of salvianolic acid B,however,varied up to30-fold by comparison. Most importantly,the contents that were identified did not align with the labeling of the granules,indicating a potential risk to
Y.Li et al./Engineering5(2019)888–894891
efficacy and safe u.HPLCfingerprints were combined with a similarity evaluation to investigate the quality of danshen and its preparations[33].Danshen,CDT,CDDP,and Danshen injection (DSI)were a
nalyzed by a similarity evaluation of their chromato-graphicfingerprints.The peaks of the chemical ingredients were identified by comparing with a reference.The correlation coeffi-cients of the standard samples,including Danshen,CDT,and CDDP, were over0.9,whereas tho of the random samples and DSI had low correlation values and high variation,suggesting inconsistent quality.
A simple and rapid proton NMR(1H NMR)technique for the qualitative and quantitative analysis of compound Danshen extract (CDE)and CDDP was established and was demonstrated to be a good supplement to the LC approach[31].A total of32batches of CDE were studied by NMR;three phenolic acids(danshensu,sal-vianolic acid B,and protocatechuic aldehyde)were simultaneously determined and cross-tested by the LC approach.No significant dif-ferences were found in terms of the contents of three phenolic acids determined by both approaches.The established method was applied to12batches of CDDP.Again,the determined levels of the phenolic acids exhibited good consistency,indicating that this method provides an alternative method for the quality control of thefinal product.
With the development of nsitive analytical approaches and a more comprehensive understanding of the substantial basis/phar-macological action of TCM medicines,the criteria for quality con-trol covering species,extracts,and preparations have been enhanced step by step.In the2000version of t
he ChP,danshensu and tanshinone IIA were lected as single markers for the quality control of CDDP and CDT,respectively.Today,multiple ingredients have emerged as quality markers of Danshen and its related prepa-rations.Cryptotanshinone,tanshinone I,tanshinone IIA,and sal-vianolic acid B have been combined as integrative markers for Danshen.Although tanshinone IIA and salvianolic acid B have been chon as markers for CDT,compound Danshen granule,and com-pound Danshen capsule,the specified contents are highly variable depending on the formulations and specifications in the2015ver-sion of the ChP,since different processing and manufacturing may lead to content change.Thus,the quality control system for Danshen may require further optimization.Other chemical ingredi-ents in Danshen should not be ignored.For example,rosmarinic acid is an abundant chemical in the roots with a concentration ranging from0.59to34.44mgÁgÀ1and diver bioactivities;it has been suggested as an optional marker[26].A pair of atropisomeric trimeric caffeic acid derivatives,salvianolic acid T and U,were recently isolated from Salvia miltiorrhiza and provide an alternative and beneficial complement to the current quality control system of Danshen that can be considered in future[34].An experimental approach to explore quality markers by utilizing salvianolic acids for injections has also been reported[35].
5.Optional approaches for quality control教育案例怎么写
In the identification of herbs,bioassays are an important com-plement to the u of chemical ingredients as indicators for the authentication of species and preparations.The potential of the DNA barcode in distinguishing authentic species from their adul-terants has been explored.For example,ITS2has been investigated as a potential DNA barcode in a large-scale study[36].A total of61 commonly ud herbs and cloly related species or adulterants were investigated,with over4000samples being collected in this experiment.The resulting data was positive with high rates of suc-cess.For the datat containing34herbs and111adulterants,all the herbs were successfully distinguished from the adulterants; ITS2was able to parate48herbs from cloly related species in a datat with51herbs and2382cloly related species.DNA barcode technology is still in a very early stage of development today;however,it should be given special consideration for its potential for quality control.
Another alternative is bioactivity assay of herbal medicines.For example,Qin et al.[37]attempted to distinguish aconitum herbs by toxicity.The u of bioassays to evaluate toxicity by the deter-mination of minimum lethal dos was established,and toxic exposure was calculated and compared.The experimental condi-tions were optimized in order to ensure reliability,although the study failed to explain the overall toxicity of the herbs,since the total toxicity of the extract was much higher than tho
of three toxic alkaloids measured by the LC approach in parallel.Even though it was not a successful application of bioassay,this approach is a promising tool for the safety asssment of herbs and requires further improvement.
6.Perspective
In summary,the efficacy and safety of TCMs are strongly asso-ciated with the chemical ingredients of many structurally diver compounds.As TCMs are an important therapy against dia, their quality is of particular importance in guaranteeing their value in treatment and their safety for patients.Current quality control and standards for most herbs,procesd herbal products,and TCM preparations are unsatisfactory,since either the quality asssment is insufficiently correlated with the efficacy,or the chemicals chon for quality control are not reprentative of the medicine as a whole.Moreover,quality studies of herbs,procesd products,and preparations are fragmented rather than integral.
There is a need to determine potential solutions to the issue of the quality of TCMs,which is a very rious problem for pharma-ceutical industries.In past years,scientists have intensively dis-cusd rearch strategies and technological approaches in detail by hosting high-end minars,and the co
ncept of quality markers and related studies has been given special consideration by central funding bodies such as the National Natural Science Foundation of China.Several major rearch projects in this newfield are sched-uled to receivefinancial support for investigating the scientific rationale of this concept.Recently,a special issue on quality mark-ers was organized and published by the leading journal Phy-tomedicine.New methodologies,rearch patterns,and rearch efforts were reported.In addition to a discussion on the concept of quality markers[38],it was propod that biological activity—and particularly biological respon[39]—and intelligent quality management with near-infrared spectroscopy[40]be integrated into the evaluation of TCM quality.Pharmacokinetic studies of ingredients in herbs were also reviewed for the discovery and iden-tification of quality markers[41,42].Along with discussions of methods,investigational studies of quality markers using multiple approaches have been reported[43–48].The studies cover a molecular connectivity index,an effect-constituent index, quality-marker-bad chemical manufacturing and control,inte-grative pharmacology,and relevant data mining.Meanwhile,mod-ern analytical technologies,including MS and chemometrics,have been applied to identify potential quality markers for coix eds [49],ginng[50,51],and pharmaceutical preparations[51–54]. All of the studies have greatly expanded the range of TCM quality control,guided by the concept of quality markers.
The concept of quality markers for TCMs was propod on the basis of a combination of the biological properties,manufacturing process,and compatibility principle of TCMs in order to integrate studies of TCM quality by emphasizing the relationship between the efficacy,substantial basis,and reprentative components of TCM.The propod concept and—most importantly—the novel rearch pattern that resulted,with its focus on the traceability
892Y.Li et al./Engineering5(2019)888–894
and transitivity of quality throughout the entire quality control procedure,will eventually be beneficial to the establishment of a TCM quality control system.
川贝冰糖雪梨Acknowledgements
The authors are grateful forfinancial support from the National Key Rearch and Development Program of China (2016YFE0121400),the National Natural Science Foundation of China(81430096),the Program for Changjiang Scholars and Innovative Rearch Team in University(IRT_14R41),the Macau Science and Technology Development Fund,Macau SAR (006/2015/AMJ)to Y.Xie,and the Tianjin Natural Science Foundation(15JCYBJC29500).
Compliance with ethics guidelines
Yazhuo Li,Ying Xie,Yufei He,Wenbin Hou,Maoliang Liao,and Changxiao Liu declare that they have no conflict of interest or financial conflicts to disclo.
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