[Study on changes of Styrax varieties].

Styrax is a commonly used imported traditional Chinese medicinal material in China. It was introduced to China in the Han Dynasty and was first described as a traditional Chinese medicine in Miscellaneous Records of Famous Physicians(Ming Yi Bie Lu). In this paper, by combing ancient and modern Chinese and foreign herbal medicine books and modern literature, combined with the results of field investigations on the origin of Styrax, the changes of Styrax involving the name, quality evaluation, origin, place of origin, and harvesting and processing were systematically verified. The results show that since ancient times, the origin and place of origin of Styrax have been unclear. The medical scientists of all dynasties in China have evaluated the quality of Styrax from four aspects: texture, viscosity, odor concentration, and color. The varieties of Styrax changed twice. The first change may have occurred during the Sui and Tang Dynasties, and the base changed from Styrax officinalis to Liquidambar orientalis. The second change was in modern times, and the base changed from L. orientalis to L. styraciflua. At the same time, the place of origin changed for the first time, from Turkey, Syria, and other countries in southern Asia Minor to Honduras, Guatemala, and other countries in Central America and southern North America. This paper studied the historical evolution of Styrax in terms of quality evaluation, origin, place of origin, character, and harvesting and processing. At the same time, it summarized the application of Styrax in the western countries, which can provide a historical basis for the further development and utilization of Styrax.

[UPLC-QDA and machine learning for distinguishing different commodity specifications of Fritillariae Cirrhosae Bulbus and application of data augmentation technology].

This study aimed to establish a method based on machine learning technology for accurately predicting the commodity specifications of Fritillariae Cirrhosae Bulbus and explore the application of data augmentation technology in the field of drug analysis. The correlation optimized warping(COW) algorithm was used to perform peak calibration on the UPLC-QDA multi-channel superimposed data of 30 batches of samples, and the data were normalized. Through unsupervised learning methods such as clustering analysis, principal component analysis(PCA), and correlation analysis, the general characteristics of the data were understood. Then, the logistic regression algorithm was used for supervised learning on the data, and the condition tabular generative adversarial networks(CTGAN) was used to generate a large amount of data. Logistic regression classification models were trained separately using the real data and the data generated by CTGAN, and these models were evaluated. The logistic regression model trained with real data achieved cross-validation and test set accuracies of 0.95 and 1.00, respectively, while the logistic regression model trained with both real and CTGAN-generated data achieved cross-validation and test set accuracies of 0.99 and 1.00, respectively. The results indicate that machine learning can accurately predict the classification of Songbei, Qingbei, and Lubeibased on UPLC-QDA detection data. CTGAN-generated data can partially compensate for the lack of data in drug analysis, improving the accuracy and predictive ability of machine learning models.

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

BACKGROUND: Evaluating 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. METHODS: The 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-1ß levels were measured in RAW 264.7 cells using ELISA analysis. RESULTS: The 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. CONCLUSIONS: In 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.

Technical guidelines for risk assessment of heavy metals in traditional Chinese medicines.

BACKGROUND: Heavy metals are considered a global concern because they can deteriorate human health. This guideline aims to scientifically evaluate health risk of heavy metals in TCM and to propose a reference for decision making in developing TCM-related health policies. METHODS: Using a multidisciplinary approach, a steering committee oversaw the development of the guideline. To obtain a reasonable and accurate risk assessment, key exposure assessment parameters for TCM, e.g., exposure frequency (EF), exposure duration (ED), and daily ingestion rate (IR) were obtained from surveys. In addition, transfer rates for heavy metals from Chinese medicinal materials (CMM) to decoctions or preparations were examined. RESULTS: Based on the scientific theory of risk control, the guideline was designed systematically, and principles and procedures for the risk assessment of heavy metals in TCM were identified. The guideline can be utilized to assess the risk of heavy metals in CMM and Chinese patent medicines (CPM). CONCLUSION: This guideline may help standardize the risk assessment of heavy metals in TCM, advance regulatory standards for heavy metals in TCM, and ultimately improve human health through scientific TCM usage in clinic.

Progress in quality control, detection techniques, speciation and risk assessment of heavy metals in marine traditional Chinese medicine.

Marine traditional Chinese medicines (MTCMs) hold a significant place in the rich cultural heritage in China. It plays an irreplaceable role in addressing human diseases and serves as a crucial pillar for the development of China's marine economy. However, the rapid pace of industrialization has raised concerns about the safety of MTCM, particularly in relation to heavy metal pollution. Heavy metal pollution poses a significant threat to the development of MTCM and human health, necessitating the need for detection analysis and risk assessment of heavy metals in MTCM. In this paper, the current research status, pollution situation, detection and analysis technology, removal technology and risk assessment of heavy metals in MTCM are discussed, and the establishment of a pollution detection database and a comprehensive quality and safety supervision system for MTCM is proposed. These measures aim to enhance understanding of heavy metals and harmful elements in MTCM. It is expected to provide a valuable reference for the control of heavy metals and harmful elements in MTCM, as well as the sustainable development and application of MTCM.

[Authenticity discrimination of Pulsatillae Radix based on dry-process REIMS fingerprinting combined with machine learning].

In this study, rapid evaporative ionization mass spectrometry(REIMS) fingerprints of 388 samples of roots of Pulsatilla chinensis(PC) and its common counterfeits, roots of P. cernua and roots of Anemone tomentosa were analyzed based on REIMS combined with machine learning. The samples were determined by REIMS through dry burning, and the REIMS data underwent cluster analysis, similarity analysis(SA), and principal component analysis(PCA). After dimensionality reduction by PCA, the data were analyzed by similarity analysis and self-organizating map(SOM), followed by modeling. The results indicated that the REIMS fingerprints of the samples showed the characteristics of variety differences and the SOM model could accurately distinguish PC, P. cernua, and A. tomentosa. REIMS combined with machine learning algorithm has a broad application prospect in the field of traditional Chinese medicine.

Novel compounds discovery approach based on UPLC-QTOF-MS/MS chemical profile reveals birch bark extract anti-inflammatory, -oxidative, and -proliferative effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Betula pendula subsp. Mandshurica (Regel) Ashburner & McAll. Cortex (birch bark) is a globally traditional medicine for treating multiple inflammatory diseases. Its records are included in the Compendium of Materia Medica and other ancient medical literatures. However, uncovering its chemical profile and exploring novel biologically active compounds from birch bark remains a significant challenge. AIM OF THE STUDY: To uncover the anti-inflammatory, -oxidative, and -proliferative mechanisms and potentially effective compounds of birch bark extract by combing chemical profiling, isolation, identification, together with in vivo, in vitro, and silico evaluation. MATERIALS AND METHODS: Ultra-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was used to obtain the chemical profile of birch bark extract. The new compounds were obtained via column chromatography and analyzed using X-ray diffraction and electronic circular dichroism for absolute configuration confirmation. The zebrafish caudal fin inflammation-induced model, qPCR, and Western blot analysis were used to explore the effects and underlying mechanisms of birch bark extract. In vitro cytotoxicity assays and kinases screening conducted to gain preliminary insight into the anti-proliferative effects of birch bark extract and its isolated compounds. In addition, in-silico molecular docking was performed to investigate the putative mechanism. RESULTS: UPLC-QTOF-MS/MS chemical profiles revealed 105 compounds in birch bark extract, with 80 of these were first reported in B. pendula subsp. Mandshurica cortex. We selected five compounds speculated as novel and isolated three ones (one triterpenoid derivative and two lupine series triterpenoids) for further analysis. Birch bark extract exerted antioxidative and anti-inflammatory effects on zebrafish, as shown by the downregulated reactive oxygen species levels and COX-2α, IL-1ß, and TNF-α expression, which occurred through NF-ĸB signaling pathway activation. The in vitro anti-proliferative effects of birch bark extract and compound 44 were also unveiled. Moreover, the putative anti-tumor mechanism of compound 44 was revealed using kinase screening and in-silico molecular docking. CONCLUSIONS: This study provided a predictable chemical profile and demonstrated the pharmacological effects of birch bark extract, elucidated the mechanism of this traditional Chinese medicine and suggested it as a novel anti-cancer candidate.

[Determination of content of nine components in Xinnaojian preparations from different manufacturers by QAMS].

This study established the ultra-performance liquid chromatography(UPLC) fingerprint of Xinnaojian preparations. With epicatechin gallate as the internal reference substance, a quantitative analysis of multi-components by single marker(QAMS) method for determining the content of nine components(gallic acid, epigallocatechin, catechin, caffeine, epicatechin, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, and catechin gallate) in Xinnaojian preparations was established. The content determined by the external standard method(ESM) and QAMS method was compared to evaluate the feasibility and accuracy of QAMS method. The results showed that the standard curves of nine components had good linear relationship within the test concentration ranges. The average recoveries were 87.57%-107.4%, and the RSD was 1.5%-2.9%. Except epigallocatechin, the other components showed good repeatability under different experimental conditions. Epigallocatechin could meet the requirements in the same instrument and at the same wavelength. The results generally showed no significant difference between QAMS and ESM. The content of 9 components varied between the samples from different manufacturers, while it showed no significant difference between the samples from the same manufacturer. In summary, the UPLC fingerprint combined with QAMS method is feasible and accurate for determining the content of the nine components, which can be used for rapid quality evaluation of Xinnaojian preparations.

[Spectral characteristics of sesquiterpene pyridine alkaloids from Tripterygium plants].

Sesquiterpene pyridine alkaloids are important components in Tripterygium plants, possessing a wide range of pharmacological activities, such as anti-inflammation immunosuppression, anti-tumor, anti-virus, and deinsectization, and are of great research value. They are composed of highly oxidized dihydro-ß-furansquiterpene and pyridine dicarboxylic acid through ester bonds. According to the structural characteristics of pyridine dicarboxylic acid fragments, they can be divided into various structural subtypes. Up to now, more than 110 sesquiterpene pyridine alkaloids have been isolated and identified from Tripterygium plants. This study reviewed the structural features and spectral(i.e., UV, IR, MS, and NMR) characteristics of sesquiterpene pyridine alkaloids and summarized the structural elucidation process in detail to provide references for their further research and development.

[Toxicokinetics of emodin-8-O-ß-D-glucoside in rats in vivo].

This study aims to establish an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method for the determination of emodin-8-O-ß-D-glucoside(EG) and its metabolites in plasma, and to investigate the toxicokinetics(TK) behavior of them in rats. To be specific, the TK of EG and its metabolites from the first to the last administration in the repeated dose toxicity study was determined, and the kinetic parameters were calculated. The exposure of EG prototype and metabolites in rat plasma after oral administration of different doses of EG was evaluated. The result showed that the prototype of EG and its metabolites aloe-emodin-8-O-ß-D-glucoside, emodin, aloe-emodin, and hydroxyemodin could be detected in rats after oral administration of high-, medium-, and low-dose EG. The area under the curve(AUC) of the prototype and metabolites after the first and last administration was in positive correlation with the dose. The time to the maximum concentration(T_(max)) of EG and metabolites in the three administration groups was <6 h, and the longest in vivo residence time was 12 h. The T_(max) and in vivo residence time of EG were prolonged with the increase in the dose. The metabolites emodin, aloe-emodin, and hydroxyemodin all had two peaks. Both hydroxyemodin and aloe-emodin exhibited increased plasma exposure, slow metabolism, and accumulation in vivo. In addition, aloe-emodin-8-O-ß-D-glucoside and emodin disappeared with the increase in dose, suggesting the change of the metabolic pathway of EG in vivo in the case of high-dose administration. The mechanism of high-dose EG in vivo needs to be further explored. This study preliminarily elucidates the TK behavior of EG in rats, which is expected to support clinical drug use.

Discovery and molecular elucidation of the anti-influenza material basis of Banlangen granules based on biological activities and ultra-high performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has a wide range of applications, including human healthcare-associated treatments and bioactive compound discovery. However, complex chemical systems present a significant challenge for chemical-material-based research and quality control. For instance, Banlangen (BLG) granules is a well-acknowledged TCM preparation widely used in clinical treatment of virus infection. However, its chemical basis of anti-influenza efficacy remains unclear. AIM OF THE STUDY: In the present study, a systematic discovery strategy for identifying anti-influenza molecules based on biological activities and chemical analysis was established to contribute to the molecular elucidation of the anti-influenza material basis of Banlangen granules. MATERIALS AND METHODS: Hemagglutinase inhibition (HAI) and neuraminidase inhibition (NAI) assays were used to compare the anti-influenza activities of different fractions of BLG granules against H1N1, H5N1 and H7N9 viruses. A comparative qualitative analysis of the chemical constituents in BLG granules and their fractions was performed using ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS), in which a multiple mass spectrometry database platform and three compound identification strategies were used. The association between anti-influenza activities and chemical constituent characteristics was analyzed using multiple stoichiometries and data comparison strategies. RESULTS: The results showed that the chromatography fractions F3 and F4 of the BLG granules had the highest anti-influenza activity. A total of 88 compounds were identified in the BLG granules, including 31 alkaloids, 16 organic acids, 10 nucleosides, 8 phenylpropanoids, 6 sulfur-containing compounds, 5 amino acids, 4 aromatic compounds, 3 aldehydes and ketones, 2 flavonoids, 1 alcohol, 1 carbohydrate, and 1 aliphatic compound. Out of these, 31 characteristic compounds were identified in fractions F3-F4 as candidate compounds with anti-influenza activity. Additionally, 6-methoxyquinoline and 4-guanidinobutanal were identified in BLG granules and its raw material (Isatidis Radix) for the first time. CONCLUSION: In this study, we proposed a systematic discovery strategy to thoroughly investigate the anti-influenza activity, chemical identification, and constituents-activity relationship of BLG granules. These data not only provided a deeper understanding of the molecular mechanism of the activity of BLG granules, but also presented a basis for the discovery of potential novel drug candidates and quality evaluation and control of BLG granules.

Integrated spatially resolved metabolomics and network toxicology to investigate the hepatotoxicity mechanisms of component D of Polygonum multiflorum Thunb.

ETHNOPHARMACOLOGICAL RELEVANCE: The liver toxicity of Reynoutria multiflora (Thunb.) Moldenke. (Polygonaceae) (Polygonum multiflorum Thunb, PM) has always attracted much attention, but the related toxicity materials and mechanisms have not been elucidated due to multi-component and multi-target characteristics. In previous hepatotoxicity screening, different components of PM were first evaluated and the hepatotoxicity of component D [95% ethanol (EtOH) elution] in a 70% EtOH extract of PM (PM-D) showed the highest hepatotoxicity. Furthermore, the main components of PM-D were identified and their hepatotoxicity was evaluated based on a zebrafish embryo model. However, the hepatotoxicity mechanism of PM-D is unknown. AIM OF THE STUDY: This work is to explore the hepatotoxicity mechanisms of PM-D by integrating network toxicology and spatially resolved metabolomics strategy. MATERIALS AND METHODS: A hepatotoxicity interaction network of PM-D was constructed based on toxicity target prediction for eight key toxic ingredients and a hepatotoxicity target collection. Then the key signaling pathways were enriched, and molecular docking verification was implemented to evaluate the ability of toxic ingredients to bind to the core targets. The pathological changes of liver tissues and serum biochemical assays of mice were used to evaluate the liver injury effect of mice with oral administration of PM-D. Furthermore, spatially resolved metabolomics was used to visualize significant differences in metabolic profiles in mice after drug administration, to screen hepatotoxicity-related biomarkers and analyze metabolic pathways. RESULTS: The contents of four key toxic compounds in PM-D were detected. Network toxicology identified 30 potential targets of liver toxicity of PM-D. GO and KEGG enrichment analyses indicated that the hepatotoxicity of PM-D involved multiple biological activities, including cellular response to endogenous stimulus, organonitrogen compound metabolic process, regulation of the apoptotic process, regulation of kinase, regulation of reactive oxygen species metabolic process and signaling pathways including PI3K-Akt, AMPK, MAPK, mTOR, Ras and HIF-1. The molecular docking confirmed the high binding activity of 8 key toxic ingredients with 10 core targets, including mTOR, PIK3CA, AKT1, and EGFR. The high distribution of metabolites of PM-D in the liver of administrated mice was recognized by mass spectrometry imaging. Spatially resolved metabolomics results revealed significant changes in metabolic profiles after PM-D administration, and metabolites such as taurine, taurocholic acid, adenosine, and acyl-carnitines were associated with PM-D-induced liver injury. Enrichment analyses of metabolic pathways revealed tht linolenic acid and linoleic acid metabolism, carnitine synthesis, oxidation of branched-chain fatty acids, and six other metabolic pathways were significantly changed. Comprehensive analysis revealed that the hepatotoxicity caused by PM-D was closely related to cholestasis, mitochondrial damage, oxidative stress and energy metabolism, and lipid metabolism disorders. CONCLUSIONS: In this study, the hepatotoxicity mechanisms of PM-D were comprehensively identified through an integrated spatially resolved metabolomics and network toxicology strategy, providing a theoretical foundation for the toxicity mechanisms of PM and its safe clinical application.

[Form and valence of arsenic in dry and fresh Cordyceps breeding products based on HPLC-ICP-MS and its risk assessment].

A comparative study was conducted for the first time on the form and valence of arsenic in the dry and fresh Cordyceps breeding products to clarify the specific morphology and valence of arsenic in Cordyceps breeding products and its safety. Arsenic betai-ne(AsB), arsenite(AsⅢ), dimethyl arsenic(DMA), arsenocholine(AsC), monomethyl arsenic(MMA), and arsenate(AsⅤ) in the dry and fresh samples were investigated using a bionic extraction method combined with HPLC-ICP-MS. The HPLC separation was performed on a DioncxIonPac~(TM) AS7 anion exchange column with a mobile phase of 100 mmol·L~(-1) ammonium carbonate-water for gradient elution at room temperature and the flow rate of 0.8 mL·min~(-1). HPLC was coupled with ICP-MS for the determination. The arsenic content was characterized in combination with chemometrics. The health safety risk of inorganic arsenic in the samples was assessed using the margin of exposure(MOE). The results of methodological validation showed that the six arsenic compounds showed good linearity(R~2>0.999) from 10 to 500 ng·mL~(-1), with precision RSDs of 1.8%-3.0%, recoveries(n=6) of 84.15%-98.28%, reproducibility RSDs of 6.4%-7.7%, and sample stability RSDs of 8.3%-14% within 10 h. Trace AsⅢ and AsⅤ were detected in 30 batches of dry and fresh Cordyceps breeding products, while arsenic compounds in other forms and valence were not detected. In the dry products, AsⅢ was 0.019-0.040 mg·kg~(-1) and AsV was 0.024-0.061 mg·kg~(-1), while in the fresh products, AsⅢ was 0.002 3-0.006 1 mg·kg~(-1) and AsⅤ was 0.008-0.016 mg·kg~(-1). The risk assessment results showed that the MOE of inorganic arsenic was much higher than 1 in both dry and fresh products, and the potential health safety risk of inorganic arsenic was low. The HPLC-ICP-MS method established in this study was efficient, rapid, accurate, and stable for the determination of six arsenic compounds in Cordyceps breeding products. The results of this study provide a basis for the safety and quality control of Cordyceps breeding products.

Desorption Electrospray Ionization Mass Spectrometry Imaging Illustrates the Quality Characters of Isatidis Radix.

For a long history, herbal medicines have made significant contributions to human health all around the world. However, the exploration of an effective approach to illustrate their inner quality remains a challenge. So, it is imperative to develop new methods and technologies to characterize and identify quality markers of herbal medicines. Taking Isatidis Radix, the dried root of Isatis indigotica as an example, desorption electrospray ionization (DESI), in combination with quadrupole-time-of-flight mass spectrometry (Q-TOF/MS), was applied in this work for the first time to reveal the comprehensive spatial distribution of metabolites and, further, to illustrate quality characters of this herbal medicine. After simple pretreatment, 102 metabolites including alkaloids, sulfur-containing compounds, phenylpropanoids, nucleosides, amino acids, organic acids, flavonoids, phenols, terpenes, saccharides, peptides, and sphingolipids were characterized, some of which were successfully localized and visualized in the transverse section of the root. Based on the ion images, samples with different quality characters were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 11 major influencing components exerting higher ion intensities in superior samples were identified as the potential quality markers of Isatidis Radix. Desorption electrospray ionization (DESI) mass spectrometry imaging (MSI), together with chemometric analysis could not only improve the understanding of the plant biology of herbal medicines but also be beneficial in the identification of quality markers, so as to carry out better quality control of herbal medicines.

Novel Integrated Tiered Cumulative Risk Assessment of Heavy Metals in Food Homologous Traditional Chinese Medicine Based on a Real-Life-Exposure Scenario.

In order to serve population health better, the first integrated tiered decision tree for cumulative risk assessment of co-exposure of Pb-, Cd-, and As-associated health risks in food homologous traditional Chinese medicine (TCM) was designed, after measuring their concentrations by inductively coupled plasma-mass spectroscopy (ICP-MS). Basically, our three-step decision tree involving hazard quotient (HQ), hazard index (HI), and target-organ toxicity dose (TTD) modification of the HI method was developed to evaluate the potential risks of 949 batches of 15 types of food homologous TCM. To acquire a real-life exposure scenario, the cumulative risk assessment model was established by optimizing key parameters, such as ingestion rates, frequency, and duration of exposure to food homologous TCM based on questionnaire data. As a result, the mean concentrations of Pb, Cd, and As in 949 batches of food homologous TCM were 0.896, 0.133, and 0.192 mg/kg, respectively. The HQ values of As for Angelica sinensis (Oliv.) Diels and Houttuynia cordata Thunb. were 1.04 and 1.01, respectively, for females. Other HQs of Pb, Cd, or As in food homologous TCM were lower than 1 for both males and females. However, after rapid screening of the co-exposure health risks of heavy metals by the HI method, cumulative risk assessment results acquired by TTD modification of the HI method implied that the potential health risks associated with the co-exposure of Pb, Cd, and As in Lonicera japonica Thunb. and Houttuynia cordata Thunb. ingested as both TCM and food were of concern in the clinic. Additionally, the cumulative risks of Pb, Cd, and As in Mentha canadensis L., Chrysanthemum indicum L., and Zaocys dhumnades (Cantor) only used as food exceeded the human tolerance dose. Collectively, our innovation on the tiered strategy of decision tree based on a real-life exposure scenario provides a novel approach engaging in the cumulative risk assessment of heavy metals in food homologous TCM. All in all, such effort attempts to scientifically guide the rational use of TCM in the treatment of the complex diseases and the improvement of population health.

[Panax notoginseng: a review on chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology in recent five years].

As a famous and precious Chinese medicinal material, Panax notoginseng(PN) has been commonly used for a long history in China. As reported, PN exhibits significant pharmacological actions in protecting cardiocerebral vascular system and nervous system and suppressing tumors. In recent years, with the innovation in ideas, as well as the development of methods and equipment, PN has been extensively investigated, and notable progress has been made. This paper reviewed the advancements of PN in recent five years from chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology, in which the application of PN extracts in quality control was first summarized. The present study aims to provide a theoretical basis for quality control, product development, and rational medication of PN.

A strategy for quality control of ginkgo biloba preparations based on UPLC fingerprint analysis and multi-component separation combined with quantitative analysis.

BACKGROUND: Many studies have assessed the fingerprint and quantitative analysis of Ginkgo biloba preparations, but the fingerprint mainly focuses on flavonoid glycosides. However, according to our previous study, the differences among diverse manufacturers mainly involve organic acids. METHODS: A novel reverse-phase liquid chromatography assay using diode array detection was developed for evaluating Ginkgo biloba preparations for quality based on a chromatographic fingerprint allowing the simultaneous assessment of eleven compounds, including four organic acids, six flavonol glycosides and one flavonoid aglycone. And the method was applied to 51 batches of Ginkgo biloba preparations from manufacturers in China. Chemometric approaches were performed for evaluating 51 batches of Ginkgo biloba preparations from various manufacturers. RESULTS: The similarity values among the chromatograms of 51 samples ranged from 0.45 to 1.00, showing that the quality of Ginkgo biloba preparations produced by different manufacturers varied greatly. Data analysis of the 51 batches of GBP samples suggested significant variations of the total contents of all 11 targets, also demonstrating the quality difference of GBP samples. There were significant differences in organic acids in particular. CONCLUSION: Combining the chemical fingerprint and quantitative assessment revealed significant variations in the examined commercial products with regard to organic acids. Thus, this study provided a more comprehensive tool for monitoring the quality consistency of Ginkgo biloba preparations.

The application of mass spectrometry imaging in traditional Chinese medicine: a review.

Mass spectrometry imaging is a frontier technique which connects classical mass spectrometry with ion imaging. Various types of chemicals could be visualized in their native tissues using mass spectrometry imaging. Up to now, the most commonly applied mass spectrometry imaging techniques are matrix assisted laser desorption ionization mass spectrometry imaging, desorption electrospray ionization mass spectrometry imaging and secondary ion mass spectrometry imaging. This review gives an introduction to the principles, development and applications of commonly applied mass spectrometry imaging techniques, and then illustrates the application of mass spectrometry imaging in the investigation of traditional Chinese medicine. Recently, mass spectrometry imaging has been adopted to explore the spatial distribution of endogenous metabolites in traditional Chinese medicine. Data collected from mass spectrometry imaging can be further utilized to search for marker components of traditional Chinese medicine, discover new compounds from traditional herbs, and differentiate between medicinal plants that are similar in botanical features. Moreover, mass spectrometry imaging also plays a role in revealing the pharmacological and toxicological mechanisms of traditional Chinese medicine.

Identification of Pulsatilla chinensis (Bge.) Regel and look-alike species by UHPLC-TOF-MS using multivariate statistical analysis.

Pulsatillae Radix, the root of Pulsatilla chinensis (Bge.) Regel, is recorded in the Pharmacopoeia of the People's Republic of China and has been widely used for its pharmacological activities, such as anti-inflammatory, antioxidant, antibacterial, antitumor, and cardiovascular benefits. However, there are several look-alike species that can be marketed as Pulsatillae Radix. To distinguish P. chinensis (Bge.) Regel from its look-alikes, viz. Pulsatilla cernua (Thunb.) Bercht et Opiz., Pulsatilla dahurica (Fisch.) Spreng., Anemone tomeutosa (Maxim.) Pei., and Rhaponticum uniflorum (L.) DC, we used ultra high performance liquid chromatography with time-of-flight mass spectrometry combined with principal component analysis to compare their chemical compositions. Four ions, a (RT 8.98 min, m/z 1381.6671), b (RT 10.64 min, m/z 1219.6143), c (RT 11.52 min, m/z 1217.5978), and d (RT 13.6 min, m/z 749.4463), from P. chinensis (Bge.) Regel were identified as potential chemical markers to distinguish it from look-alike species using an unsupervised statistical model combined with orthogonal partial least-squares discriminant analysis. The results of this study provide an effective method for identifying and distinguishing P. chinensis (Bge.) Regel from similar plants.

A general procedure for establishing composite quality evaluation indices based on key quality attributes of traditional Chinese medicine.

Licorice, a medicinal herb and food flavor ingredient, has been widely used in traditional Chinese medicine (TCM) for the past 4000 years. In this study, we propose a new quality evaluation approach for licorice quality control based on the key quality attributes commonly used in TCM. The high quality of TCM formulations is ensured by verifying the genuine origin and implementing good agricultural and collection practices for each medicinal herb. In our study, the genuine production area, the harvest season, and the number of growth years were considered the key quality attributes of TCM. To ensure the representativeness of our analysis, we obtained a total of 158 licorice sample batches that differed in the number of growth years, the location of the production areas, and the season for harvesting. Initially, the 158 sample batches were subjected to ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS). A preliminary screen identified 11 licorice compounds related to the three key quality attributes of TCM . An analysis by ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-TQ-MS/MS) verified the presence of 34 compounds in all licorice samples. These 34 compounds included the 11 compounds related to the three key quality attributes of the samples, along with other bioactive components identified in previous studies. After using UHPLC-TQ-MS/MS to assess the signal peak intensities of the 34 compounds, we selected 17 licorice compounds to establish sample content evaluation indices, which were determined by high-performance liquid chromatography at four different wavelengths in all 158 licorice sample batches. Finally, the screen identified nine compounds that were closely associated with the quality attributes of licorice based on principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Our results suggested that liquiritin and eight other compounds could be used as quality control indicators of licorice, which provided a foundation to establish the TCM quality composite evaluation index (TCM QCEI). In summary, this research concept can serve as a reference for research on quality markers and the evaluation of TCM.