Quality Control Of Traditional Chinese Medicine Research Articles

Application of metabolomics in quality control of traditional Chinese medicines: a review

Plant metabolites are the components endowing traditional Chinese medicine (TCM) with therapeutic effects, and, simultaneously, they are the primary targets for quality control. From germplasm selection and origin determination to field management, growth duration, harvesting and processing, and, finally, storage and transportation, each step profoundly influences TCM quality. The complexity of these plant or herb metabolites poses numerous quality control challenges. Metabolomics, as a comprehensive and systematic approach, has demonstrated value in this field. This technique not only meets the requirements for studying the complex mechanisms of TCM but also has significant advantages in identifying the TCM components, including active components. Therefore, in this article, several key factors affecting the chemical characteristics and quality traits of TCM, including their origin, harvesting period, medicinal parts, and processing methods, are researched. Additionally, the current challenges of integrating metabolomics with other omics technologies (transcriptomics, spatial metabolomics, etc.) are discussed. Furthermore, a future development trends and prospects are highlighted. With the continuous deepening of research and ongoing updates in technological capabilities, metabolomics will play an increasingly important role in the quality control of TCM, providing more scientific and robust support for quality assurance and safety evaluation.

Fabrication of amino- and hydroxyl dual-functionalized magnetic microporous organic network for extraction of zearalenone from traditional Chinese medicine prior to the HPLC determination

Efficient enrichment of trace zearalenone (ZEN) from the complex traditional Chinese medicine (TCM) samples is quite difficult, but of great significance for TCM quality control. Herein, we reported a novel magnetic solid phase extraction (MSPE) strategy for ZEN enrichment using the amino- and hydroxyl dual-functionalized magnetic microporous organic network (Fe3O4@MON-NH2-OH) as an advanced adsorbent combined with the high-performance liquid chromatography (HPLC) determination. Efficient extraction of ZEN was achieved via the possible hydrogen bonding, hydrophobic, and π-π interactions between Fe3O4@MON-NH2-OH and ZEN. The adsorption capacity of Fe3O4@MON-NH2-OH for ZEN was 215.0 mg g−1 at the room temperature, which was much higher than most of the reported adsorbents. Under the optimal condition, the developed Fe3O4@MON-NH2-OH-MSPE-HPLC method exhibited wide linear range (5–2500 μg L−1), low limits of detection (1.4–35 μg L−1), less adsorbent consumption (5 mg), and large enhancement factor (95) for ZEN. The proposed method was successfully applied to detect trace ZEN from 10 kinds of real TCM samples. Conclusively, this work demonstrates the Fe3O4@MON-NH2-OH can effectively extract trace ZEN from the complex TCM matrices, which may open up a new way for the application of MONs in the enrichment and extraction of trace contaminants or active constituents from the complex TCM samples.

A comprehensive strategy integrating metabolomics with DNA barcoding for discovery of combinatorial discriminatory quality markers: A case of Cimicifuga foetida and Cimicifuga dahurica

The multiple species characteristics of traditional Chinese medicines (TCMs) are crucial for expanding TCMs sources, meeting the needs of the pharmaceutical industry and ensuring clinical requirements. It’s also one of the significant factors affecting the quality control of TCMs. Systematic differential analysis of original species in TCMs is an important link in achieving comprehensive quality control, ensuring the effectiveness and safety of clinical medication. The study aims to establish a reliable and efficient approach to screen combinatorial discriminatory quality markers for rapid differentiation of original species by metabolomics coupled with DNA barcoding as a case of Cimicifugae Rhizoma. DNA barcoding is used to identify the origin of Cimicifugae Rhizoma. The data-dependent acquisition mode integrated with the computerized intelligent filtering system was established for in-depth characterization of metabolites from Cimicifugae Rhizoma using ultra-high performance liquid chromatography to quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). The untargeted metabolomics combined with multivariate statistical analysis was performed to screen and identify the potential combinatorial discriminatory quality markers. Finally, quantitative analysis and predictive model of these markers were employed to validate the feasibility of this strategy to distinguish the original species. Based on the scores of variable importance in projection greater than 1.0 and t-test (p < 0.05) in chemometric analysis, caffeic acid, cimifugin, ferulic acid and isoferulic acid were authenticated as combinatorial discriminatory quality markers for the two original species of Cimicifugae Rhizoma. In addition, the Fisher discriminant model successfully classified 56 batches of Cimicifugae Rhizoma with an accuracy of 94.4 %, showcased the practicality and scientific validity of this method. This study has provided a comprehensive strategy for efficient discrimination of multiple species of medicinal materials.

Comprehensive multicomponent characterization and quality assessment of Xiaoyao Wan by UPLC-Q-Orbitrap-MS, HS-SPME-GC-MS and HS-GC-IMS

Xiaoyao Wan (XYW) is a prescription medicine of traditional Chinese medicine (TCM) with the effects of “soothing the liver and relieving depression,” and “strengthening spleen and nourishing blood”. XYW has been widely concerned in the treatment of depression and has become one of the commonly used classic formulas in clinical practice. However, the pharmacodynamic substance basis and the quality control studies of XYW are hitherto quite limited. Here, we aim to fully utilize an advanced ultra – performance liquid chromatography-quadrupole – Orbitrap mass spectrometry (UPLC-Q-Orbitrap-MS), headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) technique to deep characterization of the pharmacological substance basis and quantitatively evaluate the quality of XYW. Firstly, 299 compounds were identified or tentatively characterized, including 198 non-volatile organic compounds (n-VOCs) and 101 volatile organic compounds (VOCs). Secondly, principal component analysis (PCA) and hierarchical cluster analysis (HCA) was used to analyze quality differences in XYW at different manufacturers. Thirdly, a parallel reaction monitoring (PRM) method was established and validated to quantify the fourteen major effective substances in different manufacturers of XYW, which were chosen as the benchmarked substances to evaluate the quality of XYW. In conclusion, this study shows that the strategy provides a useful method for quality control of TCM and offers a practical workflow for exploring the quality consistency of TCM.

A rapid localization and analysis method for isoquinoline alkaloids with fluorescence in Coptis chinensis Franch. By fabricating the nano-silver sol as a substrate for surface-enhanced Raman spectroscopy

BackgroundThe quality of traditional Chinese medicines (TCMs) directly impacts their clinical efficacy and drug safety, making standardization a critical component of modern TCMs. Surface-enhanced Raman spectroscopy (SERS) is an effective physical detection method with speed, sensitivity, and suitability for large sample analyses. In this study, a SERS analysis method was developed using a nano-silver sol as the matrix to address the interference of fluorescence components in TCMs and overcome the limitations of traditional detection methods. ResultsThe higher sensitivity and efficiency of SERS was used, enabling detection of a single sample within 30 s. Coptis chinensis Franch. (CCF) was chosen as the model medicine, the nano-silver sol was used as the matrix, and CCF’s fourteen main fluorescent alkaloids were tested as index components. Typical signal peaks of the main components in CCF corresponded to the bending deformation of the nitrogen-containing ring plane outer ring system, methoxy stretching vibration, and isoquinoline ring deformation vibration. Through SERS detection of different parts, the distribution content of the main active components in the cortex of CCF was found to be lower than that in the xylem and phloem. Additionally, rapid quality control analyses indicated that among the nine batches of original medicinal materials purchased from Emei and Guangxi, the main active ingredient showed a higher content. SignificanceA SERS-based method for the rapid localization and analysis of multiple components of TCMs was established. The findings highlight the potential of SERS as a valuable tool for the analysis and quality control of TCMs, especially for fluorescent components.

Chemical index components and quality control of Traditional Chinese Medicine: “Never change a winning team”? -A case study of volatile oil from Bupleuri radix

Chemical index components, especially those defined as quality control (QC) markers through spectrum-effect relationship approach, are commonly suggested and adopted as indicator for quality control of Traditional Chinese Medicines (TCMs). However, are chemical index components and quality control of TCMs “never change a winning team”? In this study, under the ponderation of the applicability of QC markers strategy, spectrum-effect relationship and OPLS-DA between GC×GC-MS fingerprint and inhibitory effect on the expression of extracellular secretory TNF-α of volatile oil from Bupleuri radix (BVO) was studied with the purpose of discovery of QC markers and establish a bioactive compounds-based QC method. 290 compounds of BVO were identified by GC×GC-MS. Besides, BVO had significant inhibitory effects on the expression of extracellular secretory TNF-α in a dose-dependent manner. The potency of different batches of BVOs could be distinguished with this bioassay-based method, which has been validated in terms of intermediate precision, repeatability, linearity, range and credibility tests. The QC markers of BVO were investigated by Spearman’s correlation test and OPLS-DA. It is regrettable that there were no ideal QC markers of BVO could be found. In conclusion, quality control method relayed on chemical QC markers is not feasible for TCMs with complex composition but lack of ingredients that dominate in content, just like BVO. Alternatively, a bioassay-based method established in our study is suitable for quality control of BVO.

A quality-comprehensive-evaluation-index-based model for evaluating traditional Chinese medicine quality

BackgroundEvaluating traditional Chinese medicine (TCM) quality is a powerful method to ensure TCM safety. TCM quality evaluation methods primarily include characterization evaluations and separate physical, chemical, and biological evaluations; however, these approaches have limitations. Nevertheless, researchers have recently integrated evaluation methods, advancing the emergence of frontier research tools, such as TCM quality markers (Q-markers). These studies are largely based on biological activity, with weak correlations between the quality indices and quality. However, these TCM quality indices focus on the individual efficacies of single bioactive components and, therefore, do not accurately represent the TCM quality. Conventionally, provenance, place of origin, preparation, and processing are the key attributes influencing TCM quality. In this study, we identified TCM-attribute-based quality indices and developed a comprehensive multiweighted multi-index-based TCM quality composite evaluation index (QCEI) for grading TCM quality.MethodsThe area of origin, number of growth years, and harvest season are considered key TCM quality attributes. In this study, licorice was the model TCM to investigate the quality indicators associated with key factors that are considered to influence TCM quality using multivariate statistical analysis, identify biological-evaluation-based pharmacological activity indicators by network pharmacology, establish real quality indicators, and develop a QCEI-based model for grading TCM quality using a machine learning model. Finally, to determine whether different licorice quality grades differently reduced the inflammatory response, TNF-α and IL-1β levels were measured in RAW 264.7 cells using ELISA analysis.ResultsThe 21 quality indices are suitable candidates for establishing a method for grading licorice quality. A computer model was established using SVM analysis to predict the TCM quality composite evaluation index (TCM QCEI). The tenfold cross validation accuracy was 90.26%. Licorice diameter; total flavonoid content; similarities of HPLC chromatogram fingerprints recorded at 250 and 330 nm; contents of liquiritin apioside, liquiritin, glycyrrhizic acid, and liquiritigenin; and pharmacological activity quality index were identified as the key indices for constructing the model for evaluating licorice quality and determining which model contribution rates were proportionally weighted in the model. The ELISA analysis results preliminarily suggest that the inflammatory responses were likely better reduced by premium-grade than by first-class licorice.ConclusionsIn the present study, traditional sensory characterization and modern standardized processes based on production process and pharmacological efficacy evaluation were integrated for use in the assessment of TCM quality. Multidimensional quality evaluation indices were integrated with a machine learning model to identify key quality indices and their corresponding weight coefficients, to establish a multiweighted multi-index and comprehensive quality index, and to construct a QCEI-based model for grading TCM quality. Our results could facilitate and guide the development of TCM quality control research.

HPLC fingerprint and total antioxidant capacity of the extracts from the aerial part of Paeonia lactiflora Pall

ABSTRACT High-performance liquid chromatography (HPLC) fingerprinting is a reliable quality control method for traditional Chinese medicine (TCM). As a research method combining fingerprint and pharmacodynamics of TCM, the TCM spectral effect relationship is widely used in the quality control of TCM and its preparations, which can better reflect the intrinsic quality of TCM and is of great significance for the research on the material basis of TCM efficacy. In this study, an HPLC fingerprint of the extracts from the aerial part of Paeonia lactiflora Pall (APPE) was first established. Then, the HPLC fingerprint of APPE was evaluated by stoichiometry analysis methods such as similarity analysis, hierarchical clustering analysis, and principal component analysis. At the same time, the spectral effect relationship between the HPLC pattern and the total antioxidant capacity of APPE was analyzed by Partial Least Squares Regression (PLSR). The results showed that the similarity correlation coefficient of the 12 batches was ≥0.994, and the total antioxidant capacity was stable. In addition, PLSR analysis showed that 13 chemical components were closely related to the antioxidant activity of APPE.

Quality assessment of traditional Chinese medicine using quality biomarkers: Compound DanShen dripping pills as an example.

The quality control of traditional Chinese medicine (TCM) is one of the main topics in TCM modernisation research. To date, the overwhelming majority of research has focused on chemical ingredients in the quality control of TCM. However, detecting a single or multiple chemical components cannot fully demonstrate the specificity and correlation between quality and efficacy. To solve the problem that the association between quality control and efficacy is lacking. The present study was designed to establish a methodology for quality control based on quality biomarkers (Q-biomarkers) and the vasodilatation efficacy of compound DanShen dripping pills (CDDP) as a case. Guided by the basic principles of Q-biomarkers, the compounds in TCM were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Predicted targets were screened through network pharmacology. The potential Q-biomarkers were further screened through proteomics and partial least squares regression analysis. The protein-protein interaction network that combines both predicted targets and potential Q-biomarkers was constructed to screen Q-biomarkers. There were 32 components and 79 predictive targets for CDDP. Proteomic results indicated that the expression of 23 differential proteins changed as pharmacodynamic and componential changes. CPSF6, RILP11, TMEM209, COQ7, VPS18, PPPP1CA, NF2, and ARFRP1 highly correlated with vasodilation. Protein interaction network analysis showed that NF2 and PPPP1CA were closely related to predicted proteins. Thus, NF2 and PPPP1CA could be considered as Q-biomarkers of CDDP. Our preliminary study suggested the feasibility of the Q-biomarkers theory in the quality of TCM. The concept of Q-biomarkers provided a powerful method to strengthen the link between clinical efficacy and the quality of TCM. In conclusion, a novel, more scientific, and standard quality control method was established in this study.

An intelligent extraction approach of feature information from three-dimensional DAD chromatogram for integrated quality control of traditional Chinese medicines: Gardenia jasminoides root as an example.

Traditional Chinese medicine (TCM) fingerprinting, which has the characteristics of holism and ambiguity, is a conventional strategy for the holistic quality control of TCMs. However, the fingerprinting of TCMs at the current stage generally adopts a single wavelength or few wavelengths, lacking the effective utilization of diode-array detector (DAD) chromatogram data. This study proposes an intelligent extraction approach of feature information from a three-dimensional DAD chromatogram to establish a novel bar-form-diagram (BFD) for integrated quality control of TCMs. The BFD was automatically established by the chromatographic and spectral information of a complex hybrid system in a DAD chromatogram. This covered the peak areas of target compositions at the optimal absorption wavelength. Taking 27 batches of Gardenia jasminoides root as samples, the BFD combined with chemometrics was applied for assessing the quality of samples completely, which improved the accuracy of origin classification using hierarchical cluster analysis, principal component analysis, soft independent modeling of class analogy and orthogonal partial least squares discriminant analysis. Single-wavelength fingerprinting and BFD used 23 and 38 common peaks as variables respectively, and the adjusted rand index results of the single wavelength and BFD were 0.559 and 0.819, respectively. Compared with the ergodic methods of each single wavelength, the peak recognition method in this study improved the operation speed from 180 s to 4 s and the computational complexity. The established BFD approach performed more abundant characteristic information of chemical components of TCMs and more accurate origin classification ability, and it had great advantages in the overall quality control of TCMs.

Blending Technology Based on HPLC Fingerprint and Nonlinear Programming to Control the Quality of Ginkgo Leaves.

The breadth and depth of traditional Chinese medicine (TCM) applications have been expanding in recent years, yet the problem of quality control has arisen in the application process. It is essential to design an algorithm to provide blending ratios that ensure a high overall product similarity to the target with controlled deviations in individual ingredient content. We developed a new blending algorithm and scheme by comparing different samples of ginkgo leaves. High-consistency samples were used to establish the blending target, and qualified samples were used for blending. Principal component analysis (PCA) was used as the sample screening method. A nonlinear programming algorithm was applied to calculate the blending ratio under different blending constraints. In one set of calculation experiments, the result was blended by the same samples under different conditions. Its relative deviation coefficients (RDCs) were controlled within ±10%. In another set of calculations, the RDCs of more component blending by different samples were controlled within ±20%. Finally, the near-critical calculation ratio was used for the actual experiments. The experimental results met the initial setting requirements. The results show that our algorithm can flexibly control the content of TCMs. The quality control of the production process of TCMs was achieved by improving the content stability of raw materials using blending. The algorithm provides a groundbreaking idea for quality control of TCMs.

The Application of UHPLC-HRMS for Quality Control of Traditional Chinese Medicine.

UHPLC-HRMS (ultra-high-performance liquid chromatography-high resolution mass spectrometry) is a new technique that unifies the application of UHPLC with HRMS. Because of the high sensitivity and good separation ability of UHPLC and the sensitivity of HRMS, this technique has been widely used for structure identification, quantitative determination, fingerprint analysis, and elucidation of the mechanisms of action of traditional Chinese medicines (TCMs) in recent years. This review mainly outlines the advantages of using UHPLC-HRMS and provides a survey of the research advances on UHPLC-HRMS for the quality control of TCMs.

Untargeted metabolomics analysis to unveil the chemical markers for the differentiation among three Gleditsia sinensis-derived herbal medicines by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry

Precise identification and differentiation among those congeneric Traditional Chinese Medicines (TCMs) or derived from the same plant trend to be more challenging, particularly in the absence of appearance characteristics. Three TCMs, involving Gleditsiae Sinensis Fructus (GSF), Gleditsiae Fructus Abnormalis (GFA), and Gleditsiae Spina (GS), recorded in Chinese Pharmacopoeia (2020 edition) are derived from Gleditsia sinensis , but prescribed for different clinical uses. The documents aimed to compare their chemical differences are rare, to date. An untargeted metabolomics approach, based on ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS), was elaborated to unveil the potential chemical markers to differentiate among GSF, GFA, and GS. Good chromatographic separation of all the GSF/GFA/GS components was achieved within 33 min by utilizing a BEH C18 column, while data-independent MS E in the positive mode was selected for profiling the metabolic features. Notably, the high-mass saponins (1300–2500 Da) gave unique protonated precursors ([M + H] + ) in the positive ESI mode, compared with those complicated ion species occurring in the negative mode. Pattern recognition chemometrics analysis of 45 batches of G. sinensis samples could unveil 70 significantly altered ions assigned as 46 potentially differential components. The positive/negative high-accuracy MS 2 data analysis, phytochemical isolation/NMR analysis, and searching of an in-house library of G. sinensis , were utilized for structural elucidation. Three compounds (saikachinoside A, locustoside A, and locustoside B) rich in GSF could be the markers to differentiate from GFA/GS, while four components were characteristic for GS. These results obtained can greatly benefit the quality control of TCMs derived from G. sinensis .

Quality Assessment of Artemisia rupestris L. Using Quantitative Analysis of Multi-Components by Single Marker and Fingerprint Analysis.

The chromatographic fingerprint of 14 batches of Artemisia rupestris L. samples were established in this study. The constituents of ten components in Artemisia rupestris L. were determined using quantitative analysis of multi-components by single marker (QAMS) and the external standard method (ESM). Due to their stability and accessibility, chlorogenic acid and linarin were used as references to calculate the relative correction factors (RCFs) of apigenin-C-6,8-pentoside-hexoside, apigenin-C-6,8-di-pentoside, luteolin, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, chrysosplenetin B, and sbsinthin, based on high-performance liquid chromatography (HPLC). The value calculated by QAMS was consistent with that of the ESM, and the reproducibility of RCFs was found to be reliable. In conclusion, simultaneous determination of the ten components by the QAMS method and chromatographic fingerprint analysis were feasible and accurate in evaluating the quality of Artemisia rupestris L. and can be used as reference in traditional Chinese medicine quality control.

In situ Chemical Profiling and Imaging of Cultured and Natural Cordyceps sinensis by TOF-SIMS.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is a sensitive surface analytical technology, which can simultaneously acquire diverse chemical components and their precise locations on the surfaces of samples without any requirements for chemical damage pretreatments or additional matrices. Commonly, the quality control of TCMs (traditional Chinese medicines) is limited by the qualitative and quantitative evaluations of the specifically extractive constituents. In this study, a practical sample preparation strategy named two-layered media embedding sample preparation was developed to obtain ideal freezing sections of dried materials of Cordyceps sinensis. Meanwhile, the well-established sample preparation method was applied for in situ chemical profiling and imaging of natural (NCS) and cultured Cordyceps sinensis (CCS) by using TOF-SIMS. More than 200 components were tentatively identified and imaged in NCS and CCS at the same time. Mass spectrometry imaging revealed that most components have even distributions in caterpillars of Cordyceps sinensis, while TAGs, DAGs, MAGs, and FAs only have distributions outside caterpillars’ digestive chambers. This is the first time that components were in situ imaged for Cordyceps sinensis to exhibit the chemical distributions which have never been achieved by other analytical techniques so far. In addition, chemometrics was used to simplify and explain the massive TOF-SIMS mass data sets, which revealed the high chemical similarity between CCS and NCS. Furthermore, the relative quantification of TOF-SIMS data showed that CCS has comparable proportions of amino acids, nucleosides, monosaccharides, sphingolipids, sterols and other principles to NCS except for fatty acids, glycerides and glycerophospholipids. The higher amounts of TAGs and DAGs in CCS were confirmed by quantitative 1H-NMR, indicating reliable relative quantification of TOF-SIMS. In general, our research developed a novel approach of TOF-SIMS for in situ chemical analysis of TCMs, and its successful application in comparative study of CCS and NCS suggested that TOF-SIMS is an advanced and promising analytical technology for the research of TCMs.

The Application of Electrochemical Oscillation Methods for Identification of Traditional Chinese Medicine Materials

Electrochemical oscillation reflects the overall characteristics of the system under test in terms of redox activity. It has proven to be advantageous in analyzing and processing complex components of herbal systems, such as polysaccharides and proteins. Therefore, it is widely used in the quantitative or qualitative tests of traditional Chinese medicines (TCMs) for identification and quality control. Electrochemical oscillation has several advantages such as high sensitivity, stability and micro sample requirement. Compared with other traditional methods, the interaction of multi-component in the TCMs was taken into account, which provides new ideas for the search of TCMs. Here, we presented a brief introduction on the progress on the topic, which promoted the development of electrochemical oscillation and the standardization of TCMs in the last twenty years. Electrochemical oscillation method is cheap, sensitive, fast, stable and convenient for the identification and quality control of TCMs. Reaction systems and the visualization of the fingerprints can be improved in the future.

Quality markers of Baizhu dispensing granules based on multi-component qualitative and quantitative analysis combined with network pharmacology and chemometric analysis

Ethnopharmacological relevanceThe dispensing granules of traditional Chinese medicines (TCMs) is an innovative form of medicinal material for TCMs decoction, which is gradually recognized in the clinic due to being suitable for production on a large scale and convenient to take for patients. However, the quality control of TCMs dispensing granules is being challenged, because they contain too many unrevealed hydrophilic components. Aim of the studyHere, the dispensing granules produced from the rhizome of Atractylodes macrocephala (Baizhu dispensing granules), were explored as a case to explore the quality markers correlated to the clinical efficacy of TCMs dispensing granules by a comprehensive strategy of integrating chemical profiling, network pharmacology, and chemometric analysis. Materials and methodsFirst, the chemical profiling of Baizhu dispensing granules was characterized by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Subsequently, the potential active components responsible for the efficacy of Baizhu dispensing granules were screened via network pharmacology, and the ultra-performance liquid chromatography coupled with photodiode array detector (UPLC-PDA) method was developed for quantitative analysis of the potential active components in 26 batches of Baizhu dispensing granules. Finally, the quality markers of Baizhu dispensing granules were deciphered based on content variations of potential active components and chemometric analysis. ResultsA total of 69 components were identified from Baizhu dispensing granules. Network pharmacology analysis further revealed that eight of them including five caffeoylquinic acids (31, 32, 36, 42, 44) and three sesquiterpenoids (63, 67, 76) were intimately connected to the core targets of dyspepsia, enteritis, gastritis and immunity. The contents of eight components differed greatly among 26 batches of Baizhu dispensing granules. Chlorogenic acid (31), cryptochlorogenic acid (32) and atractylenolide III (63) have higher concentrations and make great contributions to distinguish different batches of the Baizhu dispensing granules based on principal component analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA), and could be used as the quality markers of Baizhu dispensing granules. ConclusionsOur study defined the quality markers of Baizhu dispensing granules, which will benefit further investigation on the quality evaluation of TCMs dispensing granules containing Baizhu. The strategy used in this study will be helpful for discovering the quality markers of other TCMs dispensing granules.

Validated Quantitative 1H NMR Method for Simultaneous Quantification of Indole Alkaloids in Uncaria rhynchophylla.

Uncariae Ramulus Cum Uncis, known as “Gou-Teng” in Chinese, is derived mainly from the dried hook-bearing stems of Uncaria rhynchophylla. Quantitative determination of monoterpenoid indole alkaloids is critical for controlling its quality. In the present study, a rapid, accurate, and precise method was developed for the simultaneous quantitation of four characteristic components, namely, rhynchophylline (1), isorhynchophylline (2), corynoxeine (3), and isocorynoxeine (4), through 1H NMR spectrometry techniques. This method was performed on a 600 MHz NMR spectrometer with optimized acquisition parameters for performing quantitative experiments within 14 min. The highly deshielded signal of NH was at δH 10–11 in the aprotic solvent DMSO-d6, which enables satisfactory separation of the signals to be integrated. Validation of the quantitative method was also performed in terms of specificity, linearity, sensitivity, accuracy, and precision. The method is linear in the concentration range of 25–400 μg/mL. The lower limit of quantification is 25 μg/mL. The intra- and interday relative standard deviation across three validation runs over the entire concentration range is less than 2.51%. The accuracy determined at three concentrations was within ±4.4% in terms of relative error. The proposed qNMR method was demonstrated to be a powerful tool for quantifying the alkaloids in traditional Chinese medicines (TCMs) due to its unique advantages of high precision, rapid analysis, and nonrequirement of standard compounds for calibration curve preparation. Moreover, qNMR represents a feasible alternative to high-performance liquid chromatography-based methods for the quality control of TCMs.

A new strategy for quality evaluation and control of Chinese patent medicine based on chiral isomer ratio analysis: With Yuanhuzhitong tablet as an example.

Chiral compounds commonly exist in traditional Chinese medicine (TCM), but little research on the quality control of TCM has been conducted. In this study, a new strategy is proposed, taking Yuanhuzhitong tablet [YHZT, consisting of Radix Angelicae Dahuricae and Rhizoma Corydalis (Yan Hu Suo, YHS)] for example, which is based on chiral isomer ratio analysis to monitor the production process of Chinese patent medicine companies. In the process of content determination for tetrahydropalmatine (THP) in YHZT from different companies, noticeable differences were observed in their chromatographic behaviors. It is known that THP has two enantiomers, naturally coexisting in YHS as a racemic mixture, so we prepared THP twice and subsequently performed chiral separation analysis using supercritical fluid chromatography. As a result, the peak area ratios of two enantiomers from different companies varied remarkably, demonstrating that some companies did not probably manufacture YHZT products in accordance with the prescription proportion, used inferior or extracted YSH crude materials in the production process, and added raw chemical medicine in the production to reach the standard and lower the costs. In conclusion, the peak area ratio of chiral isomers could be taken as a key quality index.

An integrated approach to discriminate the quality markers of Traditional Chinese medicine preparation based on multi-dimensional characteristic network: Shenqi Jiangtang Granule as a case

BackgroundDue to the complexity of traditional Chinese medicine (TCM), the current quality evaluation of TCM are difficult to associate with clinical efficacy. Shenqi Jiangtang Granule (SJG), a classical TCM formula, is proven as a therapy for treatment of type II diabetes mellitus (DM) and complications while the substantial basis of the therapeutic effects is not clear. PurposeThe present study proposed an integrated approach to discriminate the quality markers (Q-markers) based on multi-dimensional characteristic network for quality control of TCM. MethodsThe multi-dimensional characteristic network was established by “Spider-web” mode, which was comprehensively integrating “compatibility-content-activity- efficiency-stability” of the candidate ingredients. The activity dimension was evaluated by the inhibitory activity of SJG on α-glucosidase and aldose reductase. The efficacy dimension was assessed through the association between the compounds and the target pathway of diabetic nephropathy (DN) based on integrated pharmacology platform. Each dimension for the feature network was quantified by multivariate statistical analysis, and regression area of the candidate compounds was constructed in the network. Finally, the candidate compounds were sorted comprehensively by the regression area. ResultsA total of 30 chemical compounds with effective hypoglycemic activity were identified as the potential Q-markers. From the data analysis, three dimensions of activity, efficacy and content performed a greater impact on the regression area of the characteristic network. Among these compounds, ginsenoside Re, ginsenoside Rd, ginsenoside Rg1, calycosin, ginsenoside Rb1, formononetin, astragaloside IV, ginsenoside Rf, ginsenoside Rc, notoginsenoside Fe, schisandrol A, gomisin D were screened out as the candidate Q-markers of SJG. ConclusionThe multi-dimensional characteristic network integrating compatibility, content, activity, efficiency and stability is efficient to discriminate the potential Q-markers of TCM prescription. Our results demonstrated that 12 candidate compounds from Panax Ginseng, Radix Astragali and Schisandrae Chinensis might select as Q-markers for qualitative evaluation of SJG.