Chemical Constituent Analysis of Tongxie Yaofang Decoction by UPLC-LTQ-Orbitrap-MS / 中国实验方剂学杂志

ObjectiveTo rapidly identify the chemical constituents in Tongxie Yaofang decoction by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap-MS）. MethodChromatographic conditions were ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm）， mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution （0-4 min， 5%-15%B； 4-10 min， 15%-25%B； 10-15 min， 25%-60%B； 15-20 min， 60%-90%B； 20-25 min， 90%-100%B； 25-27 min， 100%B； 27-30 min， 100%-5%B； 30-32 min， 5%B）， flow rate of 0.3 mL·min-1， column temperature at 35 ℃ and injection volume of 3 μL. UPLC-LTQ-Orbitrap-MS was equipped with an electrospray ionization（ESI）， the MS and MS/MS data were collected in positive and negative ion modes， and detection range was m/z 100-1 250. Combining the reference substance， chemical databases and related literature information， TraceFinder 4.1 and Xcalibur 2.1 were used to identify the chemical constituents of Tongxie Yaofang decoction. ResultA total of 90 compounds， mainly including flavonoids， coumarins， monoterpene glycosides， chromones and lactones， were identified from Tongxie Yaofang decoction. By attributing the sources of Chinese medicines for all identified compounds， 9 of them were found to be derived from Atractylodis Macrocephalae Rhizoma， 21 from Paeoniae Radix Alba， 24 from Citri Reticulatae Pericarpium， 29 from Saposhnikoviae Radix， and 7 from at least two Chinese medicines. ConclusionThe method can effectively， quickly and comprehensively identify the chemical components of Tongxie Yaofang decoction， and clarify the chemical composition. These identified compounds cover the main active ingredients of the four herbs with high abundance， which indicates that the extraction method and the ratio of the medicinal materials of Tongxie Yaofang are scientific， and can provide a reference for the research on the material basis and quality evaluation of this famous classical formula.

Identification of chemical constituents in Zhachong Shisanwei Pills by UPLC-Q-TOF-MS/MS / 中国中药杂志

Zhachong Shisanwei Pills, composed of 13 Chinese medicinal materials, are used for treating the diseases such as hemiplegia, pain of muscles and bones, rheumatism, and joint pain. The chemical composition and pharmacodynamics of Zhachong Shisanwei Pills have not been reported. Ultra-performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to quickly identify the chemical components of Zhachong Shisanwei Pills, which was performed with Shim-pack GIST C_(18) column(4.6 mm×150 mm, 5 μm). The gradient elution was conducted with methanol-0.05% acetic acid as the mobile phase. Electrospray ionization mass spectrometry(ESI-MS) was carried out in both positive and negative ion modes. The compounds were identidied based on accurate relative molecular weight, fragment ion species, and the MS data of reference substances and in literature. In conclusion, a total of 98 compounds were identified, including 19 organic acids, 36 flavonoids, 13 volatile oils, 8 tannins, 5 2-(2-phenylethyl)chromones, 5 amino acids, 3 sesquiterpenoids, 3 alkaloids, and 2 other compounds. This study characte-rized the chemical components of Zhachong Shisanwei Pills rapidly for the first time, laying a foundation for further research on the pharmacodynamic material basis and quality evaluation.

Study on serum pharmacodynamic material basis of Gegen Qinlian Decoction in treatment of ulcerative colitis based on UHPLC-Q-Orbitrap-MS / 中国中药杂志

This study established a mouse model of ulcerative colitis and explored the serum transitional components of Gegen Qinlian Decoction by UHPLC-Q-Orbitrap-MS. Based on the exact relative molecular weight and MS/MS spectrum, 55 prototype components and 59 metabolites were identified from the model group, while 18 prototype components and 35 metabolites from the control group. The prototype components in serum were mainly flavonoids and the characteristic components of the model group were alkaloids. Glucuronidation, sulfonation, and glycosylation have been confirmed to be the main metabolic types in vivo. The results of comparative analysis of differences indicated that puerarin, baicalin, wogonoside, wogonin, chrysin, oroxylin A, berberine, berberrubine, and palmatine were the characteristic components in model state, which at the same time, were confirmed by pharmacological studies to be the serum pharmacodynamic material basis of Gegen Qinlian Decoction in the treatment of ulcerative colitis. This study has provided reference for explaining the metabolic transformation pattern and mechanism of action of Gegen Qinlian Decoction in vivo.

Research Progress on Chemical Constituents and Pharmacological Effects of Asari Radix et Rhizoma / 中国实验方剂学杂志

Asari Radix et Rhizoma （ARR） is a traditional Chinese medicine for relieving exterior syndrome， and its roots and stems contain rich chemical components， including volatile oils （terpenoids， aromatics and aliphatics）， lignans， flavonoids， etc. Clinically， it has been traditionally used for the treatment of diseases such as phlegm and cough， anemofrigid cold， rheumatic arthralgia due to its ability to spread cold. Modern pharmacological studies have shown that ARR played beneficial roles in analgesic， anti-inflammatory， antitussive， antiasthmatic， antiviral， antibacterial， sedative， antioxidative， and antidepressant responses， antihypertension， as well as tumor suppression. The current studies on the chemical composition of ARR mainly focused on volatile components， and little information is available for the occurrence and pharmacological effects of non-volatile components. In addition， there is a lack of clear classification of chemical components and the distribution of chemical components in medicinal parts and the origin of species. Therefore， in this study， the authors reviewed a large number of literature on the chemical compositions and pharmacological effects of ARR， and hoping to provide a reference for further pharmacological research and the new drug development of ARR.

Pharmacodynamic material basis and mechanism of Fufang Yuxingcao Mixture for the treatment of heat-clearing and detoxification based on network pharmacology / 药学学报

We explored the pharmacodynamic material basis and network regulatory mechanism of Fufang Yuxingcao Mixture (FYM) for the treatment of fever and inflammation. Targets of the 25 compounds in FYM were predicted according to the reverse pharmacophore method and TCMSP, UniProt database. Gene ontology (GO) function enrichment and pathway analysis of the targets was analyzed by Omicsbean software and the Kyoto Gene and Genome Encyclopedia (KEGG) database. A "compound-target-pathway-pharmacological action-effect" network was established with Cytoscape 3.6.1 software. The lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was used to verify the anti-inflammatory effects of FYM and its 10 important components. The network pharmacology experiment showed that 25 compounds affected 97 pathways through 211 targets, of which 15 key targets [including RAC-alpha serine/threonine-protein kinase (AKT1), insulin (INS), vascular endothelial growth factor A (VEGFA), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), tumor necrosis factor (TNF), transcription factor AP-1 (JUN), caspase-3 (CASP3), matrix metalloproteinase-9 (MMP9), interleukin-8 (IL-8), prostaglandin G/H synthase 2 (PTGS2), proto-oncogene c-Fos (FOS), tyrosine-protein kinase SRC (SRC), c-Jun N-terminal kinase 1 (MAPK8), estrogen receptor 1 (ESR1)] and 46 pathways (including NF-kappa B signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, arachidonic acid metabolism, cAMP signaling pathway, T cell receptor signaling pathway, calcium signaling pathway, inflammatory mediator regulation of TRP channels, chemokine signaling pathway, Th1 and Th2 cell differentiation, natural killer cell mediated cytotoxicity, etc.) were related to anti-inflammatory, antipyretic, immune regulation, and analgesia. In vitro cell experiments showed that FYM and the 10 components (including isoquercitrin, luteoloside, baicalein, wogonin, wogonoside, phillyrin, forsythoside A, chlorogenic acid, isochlorogenic acid A, and sweroside) could significantly reduce the expression of nitric oxide (NO), TNF-α and IL-6 in cell supernatants, indicating that the above 10 components may be the key pharmacodynamic material basis of FYM.

Analysis of Effect of Realgar with Different Compatibility Proportions on Transitional Constituents of Indigo Naturalis in Rat Serum Based on UPLC-Q-TOF-MS/MS / 中国实验方剂学杂志

Objective:To investigate the effect of different dose of Realgar compatible with Indigo Naturalis on the transitional constituents of Indigo Naturalis in rat serum based on the compatibility of Qinghuangsan.Method:Indigo Naturalis test solution, the drug-containing serum of three different proportions of Qinghuangsan (10 g of Indigo Naturalis compatible with 52.5, 105, 210 mg of Realgar for group A, B and C, respectively) and blank serum were detected by UPLC-Q-TOF-MS/MS, in combination with the chemical components identified in Indigo Naturalis test solution, the differences of transitional constituents of Indigo Naturalis in rat serum from the group A, B and C were analyzed. HL-60 cells (human leukemia cells) were treated with the three groups of Qinghuangsan drug-containing serum and the effect of drug-containing serum on the activity of HL-60 cells was detected by cell counting kit-8 (CCK-8) assay.Result:A total of 19, 22, 25 of transitional constituents were detected in Qinghuangsan drug-containing serum from group A, B and C, respectively. The three groups of drug-containing serum all contained 5 prototype components from Indigo Naturalis test solution, including tryptanthrin, indigo, indirubin, 2-aminobenzoic acid and N-phenyl-2-naphthylamine, respectively. The results of CCK-8 assay showed that Qinghuangsan drug-containing serum of group C had the strongest inhibitory effect on HL-60 cells.Conclusion:After fixed Indigo Naturalis dose, with the increase of Realgar dose, the transitional constituents in rat serum increase and the inhibitory effect on HL-60 cells also gradually enhances, which indicates that Realgar may promote the absorption of active components in Indigo Naturali in vivo, thus enhance the efficacy, further explains the compatibility law and pharmacodynamic material basis of different proportions of Realgar and Indigo Naturalis.

Pharmacodynamic Basis of Jinqi Jiangtang Tablets in Treatment of Type 2 Diabetes Based on LC-MS and Molecular Docking Strategy / 中国实验方剂学杂志

Objective::Based on LC-MS and molecular docking strategy, to study the pharmacodynamic material basis of Jinqi Jiangtang tablets in the treatment of type 2 diabetes mellitus(T2DM). Method::UPLC-Q-TOF-MS was used to identify the chemical constituents of Jinqi Jiangtang tablets. On this basis, the disease targets were screened based on the online disease target database and protein-protein interaction(PPI). The molecular docking technology was used to verify the relationship between the chemical constituents and disease targets in Jinqi Jiangtang tablets, so as to find out the potential pharmacodynamic basis of Jinqi Jiangtang tablets in the treatment of T2DM. Result::Based on UPLC-Q-TOF-MS, 51 chemical constituents were identified in Jinqi Jiangtang tablets, including 31 astragalus, 16 coptis and 4 honeysuckle. The key targets of catalase from micrococcus lysodeiktic(CAT) receptor, peroxisome proliferative actived receptor(PPARG) receptor and insulin(INS) receptor were identified by CTD database, topological analysis and related literature. Based on LC-MS and molecular docking technology, we found that magnoflorine, coptisine, epiberberine, astragaloside Ⅳ, caffeic acid, palmatine, berberine, jateorhizine, berberubine, berberastine, groenlandne, lycoranine B, demethyleneberberine, isomucrontolula-7-O-glucoside and calycosin-7-O-glucoside were used to treat type 2 diabetes potential pharmacodynamic material basis of urinary diseases. Conclusion::Protein interaction and network topology analysis are helpful for the rapid localization of core targets. In addition, molecular docking technology can realize large-scale virtual screening of potential candidate compounds. The integration of LC-MS and molecular docking technology can facilitate and quickly find the potential pharmacodynamic substance basis in traditional Chinese medicine prescriptions, and provide a reference for subsequent drug activity screening experiments.

Research progress on application of epigenetics and metabolomics in traditional Chinese medicine / 中草药

Traditional Chinese medicine has multi-component, multi-target, and multi-path action characteristics and complexity, which makes the task of modernizing traditional Chinese medicine arduous, and many medical researchers have made unremitting efforts to this end. The development of systems biology and omics has ushered in an opportunity for the integration of traditional Chinese medicine and modern science. In particular, the characteristics integrity, dynamics, personalization, and interaction with the environment of epigenetics and metabolomics are consistent with function concept of traditional Chinese medicine. The application of popular DNA methylation, histone modifications, miRNA regulation of epigenetic research, and the application of metabolomics in the substance basis, quality control, pharmacodynamic action mechanism in traditional Chinese medicine research are reviewed in this paper. This paper also puts forward the idea that combining the two and innovative application can clarify the scientific connotation of the whole action mechanism of traditional Chinese medicine and the mechanism of multi-component, multi-channel, and multi-target synergistic action at the micro level, and explore a new research model for the scientific connotation of the core thought of traditional Chinese medicine.

Research progress on quality and efficacy evaluation of Rehmanniae Radix Praeparata based on pharmacodynamic material basis / 中草药

The chemical constituents, pharmacological action of active components, and processing of Rehmanniae Radix Praeparata were reviewed in this study to explain its pharmacodynamic material basis and explore the quality and efficacy evaluation of Rehmanniae Radix Praeparata with different processing degrees from the view of the whole. This paper is expected to reveal the scientific connotation of processing, providing new research ideas for the quality and efficacy evaluation and the determination of the possessing end-point of Rehmanniae Radix Praeparata.

Discovery and research advances in quality markers of Chinese materia medica based on holistic characteristics / 中草药

The quality of Chinese material medica (CMM) is an important factor in the application, development, and inheritance of traditional Chinese medicine (TCM). It is also the guarantee of the clinical efficacy of CMM. For a long time, the pharmacodynamics material basis of CMM with the characteristics of complexity and diversity, especially CMM formula composed of many kinds of Chinese materia medica, is still unclear. It limits the scientific formulation of quality standards and affects the process of internationalization of TCM. Quality markers are proposed based on the properties, manufacturing process, and compatibility theory of TCM, which are the indicators of quality evaluation of CMM and its formula. In recent years, the research and application of quality markers has developed rapidly, which provides a more scientific and clear direction for the formulation of quality standards. This paper reviews the discovery of quality markers based on the holistic research system of CMM formula, focusing on its pharmacological activity and related chemical substance basis, integrating the frontier technologies of system biology and network pharmacology, and introduces the relevant experience, methods, and research progress, with a view to discovering the correlation with clinical efficacy. The quality markers of CMM could provide abundant and useful methodological guidance.

The predictive analysis of action mechanism for classic TCM excellent prescriptions of Danggui Buxue decoction on diabetes with TCMIP / 中国药理学通报

To explore the pharmacodynamic material basis and mechanism of the classic TCM excellent prescriptions(cTCMep) Danggui Buxue decoction, so as to provide more choices for the prevention and treatment of diabetes mellitus (DM). Methods With the integrative pharmacology of traditional Chinese medicine (TCMIP) , we predicted the pharmacodynamic material basis and mechanisms of the cTCMep Danggui Buxue decoction for treatment of DM. Results The 50 " Astragalus-Angelica" components in the cTCMep Danggui Buxue decoction directly or indirectly acted on 60 key drug targets. These drug targets restored the disease imbalance network of DM and its complications by acting on 30 major regulatory pathways such as nervous-endocrine system, gap junction, hormone signaling pathways, and cardiovascular circulatory system. The main components of Astragalus membranaceus membranaceus involved in the prevention and treatment of DM were astragalosides, astragalosides and alavonoids. The main components involved in the prevention and treatment of DM in Angelica sinensis were organic acids such as ferulic acid, oil components such as (3-sweet myrrh, stigmasterol-|3-D-glucoside, smbelliferol and scopolamine. Conclusions The 50 " Astragalus-Angelica" components in the cTCMep Danggui Buxue decoction may play a role in preventing and treating DM through the AVPR1A, AVPR1B and AVPR2 (AVPR: Arginine vasopressin receptor, three subtypes), of which Astragalus membranaceu is the key component.

Study on pharmacodynamic material basis of Naomaitong to protect neuronal cells based on PK-PD model / 中国中药杂志

The PK-PD correlation models by using pharmacodynamics and pharmacokinetics were applied to study the material basis of Naomaitong,a clinical empirical prescription for the treatment of cerebral apoplexy,in inhibiting the death of PC12 nerve cells induced by Na_2S_2O_4 and Glu. In this experiment,PC12 cell death models induced by Na_2S_2O_4 and Glu were established respectively.With LDH lateral leakage and NO content as pharmacodynamic indexes,PK-PD model was established by SVM algorithm to evaluate the effective components of Naomaitong in inhibiting neural cell death. The results showed that the positive correlation of emodin methyl ether-8-O-β-D-glucopyranoside,aloe emodin,chrysophanol,rhein,emodin,ginsenoside Rg1,ginsenoside Rc,3'-methoxypuerarin and ligustilide was significant,obviously improving the LDH release and NO content. The results indicated that the contribution of Radix Puerariae Lobatae Radix and Rhei Radix et Rhizoma in Naomaitong could protect the nerve cell death induced by Na_2S_2O_4 and Glu respectively. PK-PD model was used to screen the neuroprotective components in Naomaitong,revealing the possible pharmacodynamic material basis of Naomaitong in the treatment of cerebral ischemia injury.

Material Basis and Action Mechanism of Wendantang in Treatment of Nervous System Diseases / 中国实验方剂学杂志

Wendantang (WDT) is a classical traditional Chinese medicine prescription composed of Pinelliae Rhizoma, Bambuseae Caulis in Taenias, Aurantii Fructus Immaturus, Citri Reticulatae Pericarpium, Zingiberis Rhizoma Recens, Glycyrrhizae Radix et Rhizoma, with the effect in regulating Qi-movement and phlegm and relieving stomach and gallbladder. The clinical studies have proved that WDT has significant therapeutic effects on depression, insomnia, schizophrenia, Alzheimer's disease and other nervous system diseases, but wihtout systematic understanding of material basis and compatibility principle because of the complex chemical composition and the scattered research results. Focusing on the neurological diseases and based on the origin of ancient recipes and modern research examples, the author sorted out and summarized the active ingredients constituting the recipe, paid attention to the effect of the compatibility on the composition and efficacy transmission, and judged the rationality of composition intention and selection. On this basis, it comprehensively identifies the potential components and effective paths that can well treat the nervous system diseases, and had the overall understanding about mutual relationship between composition and efficiency. In this article, we expect to find its scientific basis of effective materials and the key technology of quality standards, and define the direction of future research, so as to provide valuable reference for secondary development and new preparations designed of classic prescriptions.

Serum Pharmacochemical Analysis of Periploca forrestii Rhizomes Based on UPLC-Q-TOF-MS / 中国实验方剂学杂志

Objective:To study the serum pharmacochemistry of Periploca forrestii rhizomes,and to investigate the pharmacological material basis of extract of P. forrestii rhizomes in rats. Method:Rapid identification of constituents absorbed into blood was carried out by UPLC-Q-TOF-MS,according to retention time,accurate relative molecular mass and standard substance comparison,these constituents were identified and speculated by Data Analysis,Metabolite Detect and other softwares,then preliminary determination of constituents absorbed into blood of rats after oral administration of extract of P. forrestii rhizomes was investigated. Result:Totally 17 constituents absorbed into blood were detected in serum,ten of them were prototype constituents and the other were metabolites.Seven of the prototypes were identified as 5-O-caffeoylquinic acid,4-O-caffeoylquinic acid,3-O-caffeoylquinic acid,3,4-di-O-caffeoylquinic acid,3,5-di-O-caffeoylquinic acid,4,5-di-O-caffeoylquinic acid and periplocin. Conclusion:These constituents absorbed into blood may be substances that act directly in vivo of P. forrestii rhizomes,and it is helpful to clarify pharmacological material basis and mechanism of this herb.

Research Progress on Pharmacodynamic Material Basis and Quality Control of Danggui Buxue Tang / 中国实验方剂学杂志

Danggui Buxue Tang(DBT) is a famous classical formula of traditional Chinese medicine(TCM) for invigorating Qi and activating blood circulation.It is composed of Angelicae Sinensis Radix and Astragali Radix.It has the effect of enriching blood,invigorating Qi and regulating immunity,and has a high application value in clinical treatment.Because of its definite curative effect and simple compatibility,it has become a hot spot in the research field of TCM.This paper summarized and analyzed the research status of DBT from the pharmacological action,pharmacodynamic material basis,pharmacokinetics,quality control,compatibility and decoction process,so as to provide reference for the development of DBT and formulating its quality standard.

Research progress on pharmacological effects and clinical application of single Astragali Radix and classical formulae containing Astragali Radix in treatment of kidney disease / 中草药

Astragali Radix with the functions of promoting pus discharge and tissue regeneration, tonifying qi and elevating yang, inducing diuresis to alleviate edema, and replenishing wei and consolidating exterior, has been widely used in clinics. The study of Astragali Radix and the classical formulae containing Astragali Radix in kidney disease is a hot topic in recent years. According to vast information from literatures in the last five years, this paper systematically reviewed the pharmacological activities and clinical applications of Astragali Radix and the classical formulae containing Astragali Radix, aiming at understanding the effect and mechanism of Astragalus Radix on kidney disease in different compatibilities. This study is expected to provide the theoretical basis for the reasonable evaluation of Astragalus Radix resources based on the effectiveness and promote the modernization of Astragali Radix in the field of kidney disease.

Discovery of quality markers of Chinese materia medica based on Chinmedomics / 中草药

The quality of Chinese materia medica (CMM) has become an important factor affecting the inheritance and development of traditional Chinese medicine. However, due to the complexity of CMM ingredients and the specificity of prescription application, the current quality standards of CMM are difficult to guarantee clinical efficacy. Academician Changxiao Liu proposed the concept of the quality marker (Q-marker) of CMM and its basic attributes, which provided a direction for the study of CMM quality standards. Chinmedomics, integrating serum pharmacochemistry and metabolomics technology, under the conditions of correspondence of prescription-syndrome with therapeutic effect, can be used to find the Q-markers of CMM which are related to the clinical efficacy, and reflect the compatibility of prescriptions, and trace the in vivo metabolism and preparation process. The research strategy based on Chinmedomics is an effective method for discovering the Q-markers of CMM, it has been applied to discovery Q-markers of Yinchenhao Decoction, Liuwei Dihuang Pill, NanShi Capsule, AS1350, and other CMM formula as well as the health products.

Research ideas and progress on screening and identification of pharmacodynamic substance of Chinese materia medica / 中草药

Study on the pharmacodynamic material basis of Chinese materia medica (CMM) is the key and difficult points of CMM research due to its complicated components and synergistic effect of multiple pathways and multiple targets in pharmacological action. Currently, research ideas and research methods of the pharmacodynamic material basis of CMM are being constantly innovated. In this review, research ideas and progress on screening and identification of pharmacodynamic substance of CMM were summarized. It suggested that the research model of interdisciplinarity, multi-dimensional screening and evaluation should be established, in order to provide references for further and comprehensively revealing the mechanism of action of CMM and the law of compatibility, and establishing quality evaluation system of CMM.

Modern research progress of traditional Chinese medicine based on integrative pharmacology / 中国中药杂志

Integrative pharmacology (IP) is a discipline that studies the interaction, integration and principle of action of multiple components with the body, emphasizing the integrations of multi-level and multi-link, such as "whole and part", " and ", " process and activity evaluation". After four years of development and practice, the theory and method of IP has received extensive attention and application.In order to better promote the development of IP, this paper systematically reviews the concepts, research contents, research methods and application fields about IP.

Research progress on material basis of Guilingji based on pharmacodynamical effect / 中草药

The functional components of Guilingji in nervous system diseases, reproductive system diseases, and digestive system diseases were found by the study of functional components and modern pharmacological of main medicinal materials in Guilingji. The relationship among them was analyzed, which provided scientific basis and research ideas for explaining pharmacodynamic material basis of Guilingji, formulating Guilingji quality evaluation criteria, and carrying out the second development.