Polysaccharides as Quality Marker to Rapid Profile for Ophiocordyceps sinensis by PXRD.

BACKGROUND: Ophiocordyceps sinensis has long been recognized as a mysterious and valuable traditional Chinese medicine but there has been little research on quality markers for O. sinensis. PURPOSE: This study looked into the potential of using powder X-ray diffractometry (PXRD) to analyze polysaccharides as a quality marker for O. sinensis. STUDY DESIGN: There were 16 different habitats of O. sinensis collected in Qinghai, Gansu, Sichuan, Yunnan, and Tibet. In addition, five different types of Cordyceps species were collected. The characteristic diffraction peaks of O. sinensis were determined and then matched with the characteristic diffraction peaks of intracellular polysaccharides obtained from O. sinensis to determine the attribution relationship of the characteristic diffraction peaks. METHODS: O. sinensis powder's X-ray diffraction pattern is determined by its composition, microcrystalline crystal structure, intramolecular bonding mechanism, and molecular configuration. After fractionation and alcohol precipitation of crude intracellular polysaccharide, mycelium crude intracellular polysaccharide (MCP) and fruiting body crude intracellular polysaccharide (FCP) were obtained and the fingerprint of O. sinensis was identified by the specific characteristic peaks of the X-ray diffraction pattern from intracellular polysaccharide. RESULTS: The results indicated that the PXRD patterns of different populations of O. sinensis were overlaid well with 18 characteristic diffraction peaks obtained by microcrystalline diffraction. Moreover, the powder diffractograms as a fingerprint provided a practical identification of O. sinensis from other Cordyceps species. In addition, we detected that the powder diffractograms of intracellular polysaccharide MCP and MCP75 could be coupled with the PXRD of O. sinensis. Specifically, 18 characteristic diffraction peaks were identified as coming from MCP and MCP75 according to those interplanar crystal spacing, which matched well with those of PXRD of O. sinensis. CONCLUSIONS: PXRD spectra combined with an updated multivariable discriminant model were found to be an efficient and sensitive method for O. sinensis quality control. According to the findings of this study, PXRD should be further investigated for quality control assessments and plant extract selection trials.

A multidimensional strategy for uncovering comprehensive quality markers of Scutellariae Radix based on UPLC-Q-TOF-MS analysis, artificial neural network, network pharmacology analysis, and molecular simulation.

Introduction: Scutellariae Radix (SR), derived from the root of Scutellaria baicalensis Georgi, is a traditional Chinese medicine (TCM) for clearing heat and cooling blood. It has been used as a traditional herbal medicine and is popular as a functional food in Asian countries today. Methods: In this study, UPLC-Q-TOF-MS was first employed to identify the chemical components in the ethanol extract of SR. Then, the extraction process was optimized using star point design-response surface methodology. Fingerprints of different batches and processed products were established, and chemical markers were screened through a combination of various artificial neural network models. Finally, network pharmacology and molecular simulation techniques were utilized for verification to determine the quality markers. Results: A total of 35 chemical components in SR were identified, and the optimal extraction process was determined as follows: ultrasonic extraction with 80% methanol at a ratio of 120:1 for 70 minutes, with a soaking time of 30 minutes. Through discriminant analysis using various artificial neural network models, the samples of SR could be classified into two categories based on their growth years: Kuqin (dried roots of older plants) and Ziqin (roots of younger plants). Moreover, the samples within each category could be further clustered according to their origins. The four different processed products of SR could also be distinguished separately. Finally, through the integration of network pharmacology and molecular simulation techniques, it was determined that baicalin, baicalein, wogonin, norwogonin, norwogonin-8-O-glucuronide, skullcapflavone II, hispidulin, 8, 8"-bibaicalein, and oroxylin A-7-O-beta-D-glucuronide could serve as quality markers for SR. Discussion: The primary factors affecting the quality of SR were its growth years. The geographic origin of SR was identified as a secondary factor affecting its quality. Processing also had a significant impact on its quality. The selected quality markers have laid the foundation for the quality control of SR, and this research strategy also provides a research paradigm for improving the quality of TCM.

Quality markers of Polygala fallax Hemsl decoction based on qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

INTRODUCTION: Polygala fallax Hemsl (PFH) is a widely used herbal medicine in Guangxi, China. At present, research on PFH mainly focuses on extraction technology and cultivation, lacking quality control standards for systematic evaluation. OBJECTIVES: The study aimed to assess the quality of PFH from different sources and to predict markers that would help assess quality. METHODS: Fingerprinting of 15 batches of PFH samples was performed by ultra-high performance liquid chromatography (UPLC) and similarity was assessed using hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares discrimination (OPLS-DA). Differential components were screened by mathematical analysis, and a "component-target-pathway" network map was constructed in combination with network pharmacology, quality markers (Q-markers) of PFH were predicted, and quantitative analysis was performed. RESULTS: Fifteen batches were fingerprinted for PFH, with 11 common peaks, and peak 5 was identified as 4-hydroxybenzoic acid, which was generally consistent with the results of HCA, PCA, and OPLS-DA. Network pharmacology screened 18 potential compounds, 45 core targets, and 20 key pathways, integrating fingerprinting, pattern recognition, and network pharmacology methods. One of the potential Q-markers that can identify the principle of testability, efficacy, and specificity is 4-hydroxybenzoic acid, whose content ranges from 0.0188 to 1.4517 mg/g. CONCLUSION: The potential Q-markers of PFH were predicted by integrating fingerprinting, pattern recognition, and network pharmacological analysis, which provided a scientific basis for the overall control and evaluation of the quality of PFH and a theoretical reference for the study of the quality standard of multi-base traditional Chinese medicine.

Research on quality marker based on the processing from Aconiti lateralis radix praeparata to Heishunpian.

INTRODUCTION: Aconiti lateralis radix praeparata (ALRP), the sub root of Aconitum carmichaelii Debx., is a traditional Chinese medicine with good pharmacological effects. Heishunpian (HSP), prepared through the process of brine immersing, boiling, rinsing, dyeing, and steaming ALRP is one of the most widely used forms of decoction pieces in clinical practice. OBJECTIVES: This study aims to investigate the mechanisms of component changes and transformations during the processing from ALRP to HSP, and to screen for their quality markers through UHPLC-QTOF-MS analysis. METHODS: Samples from ALRP to HSP during processing were prepared and analyzed by UHPLC-QTOF-MS. By comparing the differences between before and after each processing step, the purpose of processing and the transformation of components during processing were studied. In addition, multiple batches of ALRP and HSP were determined, and potential quality markers were screened. RESULTS: Through the analysis of ALRP and five key processing samples, 55 components were identified. Immersing in brine, rinsing, and dyeing were the main factors of component loss, and boiling caused a slight loss of components. Some components were enhanced during the steaming process. Combining the screened differences components between multiple ALRP and HSP, 10 components were considered as potential quality biomarkers. CONCLUSION: This study found that the adjacent hydroxyl groups of the ester group may have a positive impact on the hydrolysis of the ester group, and 10 quality markers were preliminarily screened. It provides a reference for quality control and clinical application of ALRP and HSP.

[Chemical constituents and pharmacological effects of Nauclea officinalis and predictive analysis of its quality markers].

Nauclea officinalis is a Chinese medicinal material with a high medicinal value, which contains various chemical constituents such as alkaloids, pentacyclic triterpenoids and their saponins, organic phenolic acids and their glycosides, iridoids, and flavonoids. It has antiviral, antibacterial, antipyretic, analgesic, anti-inflammatory, and immunoregulatory functions. This article systematically reviewed the reported chemical constituents and pharmacological effects of N. officinalis. According to the concept of quality markers, the quality markers of N. officinalis were predicted and analyzed from the aspects of plant kinship, specificity of chemical constituents, traditional drug efficacy, measurability of chemical constituents, plasma components, and different producing areas and harvest times, in order to provide a basis for the quality evaluation of N. officinalis.

[Progress on historical evolution, clinical application, and pharmacological effects of Dachaihu Decoction and predictive analysis of its quality markers].

Dachaihu Decoction is a classic prescription with the function of harmonizing Shaoyang and purging away internal stasis of heat, which was specially developed by Master ZHANG Zhongjing for the concurrent disease of Shaoyang and Yangming. A large number of international studies have shown that Dachaihu Decoction has liver protection, gallbladder benefit, anti-inflammatory, and other pharmacological effects and is mostly used in modern clinical treatment of acute pancreatitis, acute cholecystitis, cholelithiasis, and other digestive diseases. This paper combined bibliography and statistics and selected the ancient book database and CNKI database to search the relevant literature on Dachaihu decoction, verify the composition and dosage, processing method, main diseases, and modern clinical application, and predict its quality markers(Q-markers) based on the "five principles" of Q-markers. The results suggest that saikosaponin a, baicalin, and 6-gingerol can be selected as potential Q-markers for Dachaihu Decoction, so as to provide a basis for the clinical research of traditional Chinese medicine and the development and application of compound preparations.

AKT, p-AKT, ERK1/2 and p-ERK1/2 in Mural Granulosa Cells Are Not Correlated to Different Ovarian Stimulation Protocols in Patients Undergoing Assisted Reproductive Treatment.

(1) Background: In this paper we aim to study the relationship between the expression levels of molecules involved in apoptotic/survival pathways, considered as molecular markers of oocyte competence (i.e., AKT, p-AKT, ERK1/2, and p-ERK1/2) in mural granulosa cells (MGCs) and the administration of r-FSH alone or combined with exogenous r-LH, in ovarian stimulation protocol. Moreover, we aim to evaluate oocyte competence by comparing normally cleaved embryos that were transferred in the uterus, with embryos that were arrested during in vitro culture. (2) Methods: The study included 34 normo-responder women undergoing ICSI procedures. All subjects were divided into two groups. Group A consisted of 18 women stimulated with r-FSH and used as a control group; Group B consisted of 14 women stimulated with r-FSH combined with r-LH. The MGCs were obtained from individual follicles. Immunoblot analyses were carried out to analyze the AKT, p-AKT, ERK1/2, and p-ERK1/2 levels in MGCs and to correlate them with the ovarian stimulation protocol. Furthermore, the oocyte competence was evaluated, for each follicle, according to the development of the embryo during in vitro culture and the pregnancy outcome. (3) Results: We found no significant difference in the levels of molecules in isolated MGCs between groups A and B. These results, in light of our previous research, suggest for the first time, to our knowledge, that cumulus cells and mural granulosa cells in the same follicle show different expression levels of molecules involved in the apoptotic mechanism. (4) Conclusions: Our results could clarify some controversial data in the literature where cumulative cell pools of cumulus and granulosa were analyzed, described as ovarian follicle cells, and used as markers of oocyte competence. In this paper, we found evidence that cumulus and granulosa cells need to be analyzed separately.

[Research on differential quality markers of medicine herbs for Danggui Buxue Decoction before and after processing based on fingerprint and network pharmacology].

The different quality markers of Danggui Buxue Decoction before and after processing were studied based on fingerprint and network pharmacological research, and the seven screened index components were quantitatively analyzed, so as to provide an experimental basis for the quality evaluation of Danggui Buxue Decoction before and after processing. HPLC method was used to establish fingerprints of Danggui Buxue Decoction before and after processing, and a multivariate statistical method was used to analyze the cha-racteristic maps and common peak areas of Danggui Buxue Decoction before and after processing. The different characteristic components before and after processing were screened out, and related targets and pathways of their different components were constructed based on network pharmacology. Their components were quantitatively analyzed. A total of 13 common peaks were identified in the fingerprint of the Danggui Buxue Decoction sample, and seven main chemical components were identified, with similarity > 0.911. Further cluster analysis, principal component analysis, and partial least squares discriminant analysis were used to distinguish raw and processed products. According to VIP value, the main difference components 1, 2, 6, 13, and 5 of Danggui Buxue Decoction before and after processing were screened. By combining the "five principles" of TCM Q-marker and network pharmacology, 5-hydroxymethylfurfural, ferulic acid, calycosin-7-O-ß-D-glucoside, calycosin, ligusticolide, formononetin, and ligusticolide I were selected as the signature components of quality difference before and after processing. The results of the quantitative analysis showed that the content of ligustrin I, calycosin, formononetin, and ligusticum decreased after the Danggui Buxue Decoction was processed. The content of calycosin-7-O-ß-D-glucoside and ferulic acid increased. At the same time, a new chemical compound, namely 5-hydroxymethylfurfural was produced. The established fingerprint analysis method is stable and reliable. Combined with network pharmacology and quantitative research, it screens out the differential Q-marker, which provides an experimental basis for further research on processed products of Danggui Buxue Decoction.

Dynamic simulation and experimental studies of molecularly imprinted label-free sensor for determination of milk quality marker.

Bovine serum albumin (BSA) has emerged as a biomarker for mammary gland health and cow quality, being recognized as a significant allergenic protein. In this study, a novel flexible molecular imprinted electrochemical sensor by surface electropolymerization using pyrrole (Py) as functional monomer, which can be better applied to the detection of milk quality marker BSA. Based on computational results, with regard to all polypyrrole (PPy) conformations and amino-acid positions within the protein, the BSA molecule remained firmly embedded into PPy polymers with no biological changes. The molecular imprinted electrochemical sensor displayed a broad linear detection range from 1.0 × 10-4 to 50 ng·mL-1 (R2 = 0.995) with a low detection limit (LOD) of 4.5 × 10-2 pg·mL-1. Additionally, the sensor was highly selective, reproducible, stable and recoverable, suggesting that it might be utilized for the evaluation of milk quality.

An integrated strategy for the discovery of quality marker of Dactylicapnos scandens based on phytochemical analysis, network pharmacology and activity screening.

Dactylicapnos scandens (D. scandens) is an ethnic medicine commonly used for the treatment of analgesia. In this study, an integrated strategy was proposed for the quality evaluation of D. scandens based on "phytochemistry-network pharmacology-effectiveness-specificity" to discover and determine the quality marker (Q-marker) related to analgesia. First, phytochemical analysis was conducted using UPLC-Q-TOF-MS/MS and a self-built compound library, and 19 components were identified in D. scandens extracts. Next, the "compounds-targets" network was constructed to predict the relevant targets and compounds related to analgesia. Then, the analgesic activity of related compounds was verified through dynamic mass redistribution (DMR) assays on D2 and Mu receptors, and 5 components showed D2 antagonistic activity with IC50 values of 39.2 ± 14.7 µM, 5.46 ± 0.37 µM, 17.5 ± 1.61 µM, 7.89 ± 0.79 µM and 3.29 ± 0.73 µM, respectively. Subsequently, nine ingredients were selected as Q-markers in consideration of specificity, effectiveness and measurability, and their content was measured in 12 batches of D. scandens. Furthermore, the hierarchical cluster analysis and heatmap results indicated that the selected Q-marker could be used to discriminate D. scandens and that the content of Q-marker varied greatly in different batches. Our study shows that this strategy provides a useful method to discover the potential Q-markers of traditional Chinese medicine and offers a practical workflow for exploring the quality consistency of medicinal materials.

Jiawei Kongsheng Zhenzhong Pill: marker compounds, absorption into the serum (rat), and Q-markers identified by UPLC-Q-TOF-MS/MS.

Background: The Jiawei Kongsheng Zhenzhong pill (JKZP), a Chinese herbal prescription comprised of eight Chinese crude drugs, has been historically employed to treat neurological and psychological disorders. Nevertheless, the ambiguous material basis severely hindered its progress and application. Purpose: The current study aimed to establish a rapid analytical method for identifying the chemical components of the JKZP aqueous extract and the components absorbed into the rat serum to investigate the quality markers (Q-markers) responsible for the neuroprotective effects of JKZP. Methods: The qualitative detection of the chemical components, prototype components, and metabolites of the aqueous extracts of JKZP, as well as the serum samples of rats that were administered the drug, was performed using the ultra-performance liquid chromatography- quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) technology. This analysis combined information from literature reports and database comparisons. Moreover, the study was conducted to anticipate the potential Q-markers for the neuroprotective effects of JKZP based on the "five principles" of Q-marker determination. Results: A total of 67 compounds and 111 serum components (comprising 33 prototypes and 78 metabolites) were detected and identified. Combining the principles of quality transmission and traceability, compound compatibility environment, component specificity, effectiveness, and measurability, the study predicted that five key compounds, namely, senkyunolide H, danshensu, echinacoside, loganin, and 3,6'-disinapoyl sucrose, may serve as potential pharmacological bases for the neuroprotective effects of JKZP. Conclusion: To summarize, the UPLC-Q-TOF-MS/MS technique can be employed to rapidly and accurately identify compounds in JKZP. Five active compounds have been predicted to be the Q-markers for the neuroprotective effects of JKZP. This discovery serves as a reference for improving quality, advancing further research and development, and utilizing Chinese herbal prescriptions.

Study on the quality evaluation of the leaves of Croton tiglium from different regions based on quality markers.

METHODOLOGY: The chemical constituents of LCT were identified and quantified using high-performance liquid chromatography with a diode array detector. A characteristic fingerprint was then established and combined with multivariate statistical analysis of 16 common peaks and eight diterpenoids to identify the quality markers. INTRODUCTION: The leaves of Croton tiglium (LCT) have long been used in folk and ethnic medicine in China. Owing to the various regions, the chemical composition and content of LCT may differ, and hence, the quality of medicinal materials may be different. However, quality standards have not yet been established, although some studies have been conducted on their composition. OBJECTIVES: To quantitatively compare the chemical constituents of LCT from different areas and establish a quality evaluation of LCT based on quality markers. RESULTS: Eight quality markers selected based on 16 common peaks and three quality markers selected based on eight diterpenoids can distinguish LCT from three regions. The diterpenoids, including 12-O-acetylphorbol-13-(2-methylbutyrate) (3), 12-O-tiglyl-4-deoxy-4α-phorbol-13-acetate (6), and 12-O-(2-methyl)butyrylphorbol-13-tiglate (8), can be used as potential quality markers for the quality evaluation of LCT. CONCLUSION: Diterpenoids are highly efficient markers for quality evaluation. This study provides robust identification data and lays the foundation for formulating quality standards for LCT.

Fructus mori: An Updated Review on Botany, Phytonutrient, Detection, Bioactivity, Quality Marker, and Application.

BACKGROUND: Fructus mori (mulberry) is not only a delicious fruit with rich phytonutrients and health functions but also a medicinal plant with many clinical therapeutic values for tonifying kidneys and consolidating essence, making hair black and eyes bright. METHODS: The related references about F. mori in this review from 1996 to 2022 had been collected from both online and offline databases, including PubMed, Elsevier, SciFinder, Willy, SciHub, Scopus, Web of Science, ScienceDirect, SpringerLink, Google Scholar, Baidu Scholar, ACS publications, and CNKI. The other information was acquired from ancient books and classical works about F. mori. RESULTS: An updated summary of phytonutrients from F. mori was listed as fellows: flavonoids (1-20) (23.5%), phenolic acids (21-34) 16.5%), alkaloids (35-75) (48.2%), polysaccharides (76- 78) (3.5%), other compounds (79-85) (8.3%). The above chemical components were detected by TLC, UV-Vis, HPLC, GC-MS, and AAS methods for their quality standards. The various bioactivities (hepatoprotective, immunomodulatory, anti-oxidant, hypoglycemic, anti-cancer, and other activities) of mulberry are summarized and discussed in this review, which laid an important basis for analyzing their mechanisms and quality markers. This review summarized its applications for vinegar, wine, yogurt, drink, jelly, and sweetmeat in food fields, and the existing problems and future development directions are also discussed in this review. CONCLUSIONS: This review made a comprehensive description of F. mori, including botany, phytonutrient, detection, bioactivity, quality marker, and application. It will not only provide some important clues for further studying F. mori, but also provide some valuable suggestions for indepth research and development of F. mori.

UPLC-Q-TOF/MS based metabolite profiling and quality marker constituents screening of root, stem and rhizome extracts of Ilex asprella.

OBJECTIVE: The root of Ilex asprella (RIA) is a popular plant resource for treating inflammation-related diseases. The purpose of this study was to identify the secondary metabolites, to compare anti-inflammatory effects and to determine the quality marker components among root, stem and rhizome sections of IA. METHODS: Chemical fingerprints of stem, root and rhizome of IA was determined by high performance liquid chromatography (HPLC). A reliable method using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was established for comprehensively determining the chemical constituents of the plants. Anti-inflammatory activities of IA and its ingredients were screened by in vivo mouse ear swelling and in vitro LPS-induced release of NO from RAW264.7 cells experiments. RESULTS: Root, stem and rhizome of IA have shown high similarity in chemical fingerprints. Totally 149 compounds were characterized in IA, including triterpenoids, triterpenoid saponins, phenolic acids and lignans. 44 of them were identified based on co-occurring Mass2Motifs, including 19 unreported ones, whilst 17 were tentatively confirmed by comparison with reference compounds. No significant anti-inflammatory activity difference among root, stem and rhizome parts of IA was found. Ilexsaponin B2, protocatechualdehyde, isochlorogenic acid B and quinic acid, were screened out as quality marker compounds in IA. CONCLUSION: A sensitive and rapid strategy was established to evaluate the differences on secondary metabolites of different parts of IA for the first time, and this study may contribute to the quality evaluation of medicinal herbs and provide theoretically data support for further analysis of different parts of IA.

Quality markers of Dajianzhong decoction based on multicomponent qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

INTRODUCTION: Dajianzhong decoction (DJZD), a classic famous prescription, has a long history of medicinal application. Modern studies have demonstrated its clinical utility in the treatment of postoperative ileus (POI). But none of the current quality evaluation methods for this compound is associated with efficacy. OBJECTIVES: This study aimed to identify the quality markers (Q-Markers) connected to the treatment of POI in DJZD. METHODOLOGY: Ultra-performance liquid chromatography quadrupole Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) was used to identify the main constituents in DJZD. Based on the qualitative results obtained by fingerprinting, chemical pattern recognition (CPR) was used to analyse the key components affecting the quality and finally to establish the network of the active ingredients in DJZD with POI. RESULTS: A total of 64 chemical components were detected. After fingerprint analysis, 13 common peaks were identified. The fingerprint similarity of 15 batches of samples ranged from 0.860 to 1.000. CPR analysis was able to categorically classify 15 batches of DJZD into two groups. And gingerenone A, methyl-6-gingerdiol, 6-gingerol, and hydroxy-ß-sanshool contributed to their grouping. Twelve common components interact with the therapeutic targets for treating POI. In addition, the mechanism of this prescription for treating POI may be related to the jurisdiction of the neurological system, the immunological system, and the inflammatory response. CONCLUSIONS: This integrated approach can accurately assess and forecast the quality of DJZD, presume the Q-Markers of DJZD for POI, and lay the foundation for studying the theoretical underpinnings and exploring the mechanism of DJZD in the treatment of POI.

Discovery and verification of anti-inflammatory-related quality markers in the aerial part of Bupleurum scorzonerifolium by UPLC-Q-TOF-MS/MS and in RAW 264.7 cells and a zebrafish model.

INTRODUCTION: The root of Bupleurum scorzonerifolium Willd. (BS) is officially recognized in the Chinese Pharmacopoeia. In contrast, the aerial part of BS (ABS), accounting for 80% of BS, is typically discarded, causing potential waste of medicinal resources. ABS has shown benefits in the treatment of inflammation-related diseases in China and Spain, and the material basis underlying its anti-inflammatory effects must be systematically elucidated for the rational use of ABS. OBJECTIVE: We aimed to screen and validate the anti-inflammatory quality markers (Q-markers) of ABS and to confirm the ideal time for ABS harvesting. METHODS: The chemical components and anti-inflammatory effects of ABS from 10 extracted parts were analyzed by UPLC-Q-TOF-MS/MS and in a lipopolysaccharide (LPS)-induced cell model. Anti-inflammatory substances were screened by Pearson bivariate analysis and gray correlation analysis, and the anti-inflammatory effects were verified in a zebrafish tail-cutting inflammation model. HPLC was applied to measure the Q-marker contents of ABS in different harvesting periods. RESULTS: Ten ABS extracts effectively alleviated the increase in LPS-induced proinflammatory cytokines in RAW 264.7 cells. Forty components were identified from them, among which 27 were common components. Eight components were correlated with anti-inflammatory effects, which were confirmed to reverse the expression of proinflammatory and anti-inflammatory factors in a zebrafish model. Chlorogenic acid, hypericin, rutin, quercetin, and isorhamnetin can be detected by HPLC, and the maximum contents of these five Q-markers were obtained in the sample harvested in August. CONCLUSION: The anti-inflammatory Q-markers of ABS were elucidated by chromatographic-pharmacodynamic-stoichiometric analysis, which served as a crucial basis for ABS quality control.

Identify production area, growth mode, species, and grade of Astragali Radix using metabolomics "big data" and machine learning.

BACKGROUND: Astragali Radix (AR) is a widely used herbal medicine. The quality of AR is influenced by several key factors, including the production area, growth mode, species, and grade. However, the markers currently used to distinguish these factors primarily focus on secondary metabolites, and their validation on large-scale samples is lacking. PURPOSE: This study aims to discover reliable markers and develop classification models for identifying the production area, growth mode, species, and grade of AR. METHODS: A total of 366 batches of AR crude slices were collected from six provinces in China and divided into learning (n = 191) and validation (n = 175) sets. Three ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods were developed and validated for determining 22 primary and 10 secondary metabolites in AR methanol extract. Based on the quantification data, seven machine learning algorithms, such as Nearest Neighbors and Gradient Boosted Trees, were applied to screen the potential markers and build the classification models for identifying the four factors associated with AR quality. RESULTS: Our analysis revealed that secondary metabolites (e.g., astragaloside IV, calycosin-7-O-ß-D-glucoside, and ononin) played a crucial role in evaluating AR quality, particularly in identifying the production area and species. Additionally, fatty acids (e.g., behenic acid and lignoceric acid) were vital in determining the growth mode of AR, while amino acids (e.g., alanine and phenylalanine) were helpful in distinguishing different grades. With both primary and secondary metabolites, the Nearest Neighbors algorithm-based model was constructed for identifying each factor of AR, achieving good classification accuracy (>70%) on the validation set. Furthermore, a panel of four metabolites including ononin, astragaloside II, pentadecanoic acid, and alanine, allowed for simultaneous identification of all four factors of AR, offering an accuracy of 86.9%. CONCLUSION: Our findings highlight the potential of integrating large-scale targeted metabolomics and machine learning approaches to accurately identify the quality-associated factors of AR. This study opens up possibilities for enhancing the evaluation of other herbal medicines through similar methodologies, and further exploration in this area is warranted.

Clinical Application and Quality Analysis of Classical Formula Xiaoyaowan： A Review / 中国实验方剂学杂志

Xiaoyaowan has the effects of soothing the liver， invigorating the spleen， regulating menstruation， and nourishing blood. It is often used to treat the distending pain of the chest and hypochondriac， loss of appetite， dizziness， and irregular menstruation caused by liver depression and spleen deficiency. The formula originated from the Sinisan of Treatise on Cold Damage（《伤寒论》） in the Han dynasty and was officially formulated in the Song dynasty's Taiping Royal Prescriptions（《太平惠民合计局方》）. In the Ming and Qing dynasties， it was developed into more comprehensive formulas such as modified Bazhentang， modified Xiaoyaowan， and other formulas. In recent years， Xiaoyaowan has become a classic formula for treating many symptoms of liver depression. The Pharmacopoeia of the People's Republic of China（《中华人民共和国药典》）， 2020 edition， records Xiaoyaowan and modified Xiaoyaowan. Modern clinical research has further expanded the therapeutic range of this formula. Through literature research， it is found that there are certain reports on the clinical application and quality analysis of Xiaoyaowan， but the relevant literature lacks collation so far. Therefore， relevant literature was consulted and sorted out. The paper summarized the treatment of mammary hyperplasia， depression， irregular menstruation， melasma， menopausal syndrome， and polycystic ovary syndrome with Xiaoyaowan， as well as the quality analysis of paeoniflorin， ferulic acid， and glycyrrhizinic acid of Xiaoyaowan. It is expected to lay a foundation for further research on clinical application， pharmacodynamic mechanism， and quality control of this classic formula.

Research progress in chemical compositions and pharmacological effects of Dachengqi Decoction and predictive analysis on its quality marker / 国际中医中药杂志

Dachengqi Decoction is a classic prescription attacked by Yangming excessive syndromes in clinic, which has the effects of relieving heat, softening and dispersing knots, etc., and is often used in the treatment of gastrointestinal dysfunction caused by various diseases. This article reviewed the recent studies on the chemical compositions and pharmacological effects of Dachengqi Decoction in recent years. On this basis, combined with the "five principles" of TCM quality markers, the quality markers of Dachengqi Decoction were predicted and analyzed. It is suggested that emodin, Rhein, chrysophanol, aloe-emodin, synephrine, hesperidin, naringin, magnolol and magnolol can be used as quality markers of Dachengqi Decoction.

Pharmacodynamic Substances and Action Mechanisms of Chaihu Shugansan in Antidepressant Treatment： A Review / 中国实验方剂学杂志

Depression is a kind of complex mental illness， which is mainly treated by western medicine at present， but the effect of western antidepressant drugs is not good due to the combined influence of side effects and individual differences of patients. Depression is a "stagnation syndrome" in traditional Chinese medicine， and its treatment principle is to disperse stagnated liver Qi for relieving Qi stagnation. The classic traditional Chinese medicine formula Chaihu Shugansan （CHSGS） has a long history of treating depression and demonstrates significant therapeutic efficacy. Clinically， the addition and subtraction of CHSGS is flexible， but the properties of the active ingredients are vague， and the mechanism and function are unclear. In order to elucidate the pharmacodynamic basis and antidepressant mechanism of CHSGS， this article reviews the pharmacodynamic material basis of CHSGS， clinical research and antidepressant mechanism research progress. Clinically， CHSGS can treat various types of depression such as primary depression， post-stroke depression， and postpartum depression. This article summarizes 32 main ingredients of CHSGS， among which albiflorin， ferulic acid， naringin， hesperidin， saikosaponin a， glycyrrhetinic acid， tangeretin， meranzin hydrate， nobiletin and glycyrrhizic acid are the quality markers （Q-markers） for the antidepressant effect of CHSGS. The antidepressant mechanism of CHSGS is complex， including regulating monoamine neurotransmitters， hypothalamic-pituitary-adrenal （HPA） axis， neurotrophic factors， inflammatory response， cell damage-related pathways， oxidative stress， etc. This article helps to deeply understand the pharmacodynamic basis and mechanism of CHSGS in treating depression， and provides a theoretical basis for the clinical application of CHSGS in treating depression and the development of antidepressant drugs.