Safety evaluation of Tibetan medicine Qishiwei Zhenzhu Pills based on serum pharmacochemistry and network pharmacology / 中国中药杂志

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.

Characterization of Effective Components in Guizhi Jia Gegentang for Intervention of Influenza Virus Pneumonia Based on Serum Pharmacochemistry of Traditional Chinese Medicine / 中国实验方剂学杂志

ObjectiveTo characterize the efficacy components of Guizhi Jia Gegentang（GGT） in intervening influenza virus pneumonia by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）. MethodBALB/c mice were randomly divided into normal group and GGT group（36 g·kg-1·d-1） with six mice in each group. GGT group was continuously administered GGT extract for 5 d， while the normal group was administered an equal amount of ultrapure water. Serum and lung tissue were collected after administration， and UPLC-Q-Exactive Orbitrap MS was used to characterize the prototypical and metabolic components of GGT in serum and lung tissue of mice. The components existed simultaneously in the serum and lung tissue of mice from the GGT group were defined as its functional components， and the targets of efficacy components were searched by SwissTargetPrediction database， and GeneCards database was used to query the target of influenza virus pneumonia， and then the intersection was taken to obtain potential targets of GGT for intervening in the disease. Protein-protein interaction（PPI） network analysis of potential targets was performed by STRING database， and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis on potential targets was performed by Metascape. ResultA total of 29 prototypical components and 28 metabolic components of GGT were detected in the drug-containing serum of mice， of which 11 prototypical components and 4 metabolic components were detected in the lung tissue of mice. The main metabolic pathways included reduction， hydroxylation， methylation， glucuronidation and sulfation. The results of PPI network and KEGG analysis showed that these functional components may act through their effects on targets such as albumin（ALB）， epidermal growth factor receptor（EGFR）， steroid receptor coactivator（SRC）， Toll-like receptor 4（TLR4）， nuclear transcription factor（NF）-κB and adhesion junction. ConclusionThe 11 prototypical components and 4 metabolites present simultaneously in the drug-containing serum and lung tissue of mice may be the potential therapeutic components of GGT in interfering with influenza viral pneumonia， and act through interfering with inflammatory metabolic pathways. This study can provide a reference for the mechanism study of GGT in the treatment of influenza viral pneumonia.

Analysis on Material Basis of Anti-COPD Effect of Euphorbia helioscopia Based on Serum Pharmacochemistry and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo analyze the migrating components absorbed into blood of the aqueous extract of Euphorbia helioscopia， and to explore the pharmacodynamic material basis of the aqueous extract of E. helioscopia against chronic obstructive pulmonary disease（COPD）. MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detecte the migrating components absorbed into blood of rats after intragastric administration of aqueous extract of E. helioscopia. An Agilent RRHD SB-C18 column（3 mm×100 mm， 1.8 μm） was used with 0.1% formic acid aqueous solution（A）-acetonitrile（B） as the mobile phase for gradient elution（0-15 min， 5%-30%B； 15-20 min， 30%-50%B； 20-30 min， 50%-95%B； 30-35 min， 95%-5%B）， and the detection wavelength of 190-800 nm， column temperature of 40 ℃， flow rate of 0.3 mL∙min-1 and injection volume of 4 μL. The electrospray ionization（ESI） was used in positive and negative ion modes， and the detection range was m/z 50-1 250. Network pharmacology was used to screen out the key components and the key targets of COPD through the interaction analysis. Metascape database was used to predict the molecular function， biological process， cellular composition and signal pathways mainly involved in the anti-COPD effect of E. helioscopia. Molecular docking technique was used to determine the affinity of key targets with key components. ResultA total of 29 migrating components absorbed into blood of rats were identified after intragastric administration of aqueous extract of E. helioscopia， 9 of which were prototype components and 20 were metabolites. Network pharmacological analysis showed that luteolin， quercetin， apigenin， naringenin and helioscopinolide C were the key components of E. helioscopia against COPD， and vascular endothelial growth factor A（VEGFA）， albumin（ALB）， protein kinase B1（Akt1）， tumor necrosis factor（TNF） and interleukin-6（IL-6） were the key targets. Molecular docking results showed that one diterpene lactone（helioscopinolide C） and three flavonoids（naringenin， luteolin， apigenin） in the migrating components absorbed into blood all had strong binding activity to the key targets of E. helioscopia against COPD. ConclusionNaringenin， helioscopinolide C， luteolin and apigenin may be the main anti-COPD active substances of E. helioscopia.

Comparative Analysis of Serum Pharmacochemistry of Alismatis Rhizoma Before and After Salt Processing Based on UPLC-Q-TOF-MS / 中国实验方剂学杂志

ObjectiveBased on serum pharmacochemistry and ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） the transitional components in the serum of rats after intragastric administration of water extract of Alismatis Rhizoma（AR）and salt-processed Alismatis Rhizoma（SAR） were compared. MethodSD rats were randomly divided into blank group, AR group（10 g·kg-1） and SAR group（10 g·kg-1）, 3 rats in each group, the administration groups were given AR and SAR aqueous extracts by gavage, respectively, and the blank group was given an equal volume of drinking water by gavage once in the morning and once in the evening, for 3 consecutive days. Sixty minutes after the last administration, blood was collected from the eye orbits, and the serum samples were prepared. The serum samples were prepared on an ACQUITY UPLC BEH C18 column（2.1 mm×50 mm, 1.7 μm） with the mobile phase of acetonitrile（A）-0.1% formic acid aqueous solution（B） in a gradient elution（0-10 min, 10%-50% A; 10-27 min, 50%-95%A; 27-27.1 min, 95%-10% A; 27.1-30 min, 10%A）, the data were collected at a flow rate of 0.3 mL·min-1 in positive ion mode with a scanning range of m/z 100-1 200. Based on the self-constructed chemical composition library of AR, the total ion flow diagrams and secondary MS fragmentation information of the aqueous extracts of AR and SAR, as well as the administered serum and the blank serum, were compared with each other by UNIFI 1.9.2, so as to deduce the possible blood-migrating constituents and their cleavage patterns in the aqueous extracts, and the response intensity ratios of each chemical component were calculated before and after processing. ResultA total of 20 components, including 5 prototypical components and 15 metabolites, were analyzed and deduced from the serum of rats given aqueous extract of AR. And 14 components, including 5 prototypical components and 9 metabolites, were analyzed and deduced from the serum of rats given aqueous extract of SAR. Of these, 13 components were common to both of them, including 5 prototypical components and 8 metabolites. The 5 prototypical components were 16-oxoalisol A, alisol A 24-acetate, alisol A, alisol B and alisol C. The metabolites were mainly involved in phase Ⅰ metabolism（oxidation） and phase Ⅱ metabolism（glucuronidation）. There was a big change in the intensity of response of the common components before and after salt-processing, and the response intensities of the prototypical components, 16-oxoalisol A, alisol B and alisol C, were elevated, while the type and response intensity of metabolites were generally decreased, and it was hypothesized that the metabolic rate of terpenoids might be slowed down after salt-processing of AR, so that the blood-migrating constituents could participate in the metabolism of the body more in the form of prototypes. ConclusionSalt-processing of AR may promote the absorption of prototypical components into the blood by slowing down the metabolic rate of terpenoids, which can provide support for the research on material basis of AR and SAR.

Q-markers of Yuquan Capsules based on serum pharmacochemistry of Chinese medicine / 中国中药杂志

This study analyzed the quality markers(Q-markers) of Yuquan Capsules(YQC) based on serum pharmacochemistry of Chinese medicine and detected the components and metabolites of YQC absorbed into the blood by UPLC-Q-TOF-MS and UNIFI systems. As a result, 32 components of YQC were detected, including 17 prototype components and 15 metabolized components. Among them, 12 prototype components(ginsenoside Rh_2, genistein, formononetin, puerarin, daidzein, schizandrin A, schizandrin B, schizandrin C, schizandrol A, schizandrol B, gomisin D, and ononin) and 12 metabolized components(ginsenoside Rg_1, ginsenoside Rg_2, ginsenoside Rg_3, ginsenoside Ro, 3'-methoxypuerarin, daidzin, astragaloside Ⅱ, astragaloside Ⅳ, glycyrrhizic acid, liquiritigenin, isoliquiritin, and verbascoside) showed inhibitory effects and pharmacological activities against diabetes, and these 24 blood-entering components against diabetes were identified as Q-markers of YQC.

Study on critical quality attributes of Qingjin Huatan Decoction based on serum pharmacochemistry / 中国中药杂志

Qingjin Huatan Decoction is a classic prescription with the effects of clearing heat, moistening lung, resolving phlegm, and relieving cough. In order to explore the critical quality attributes of Qingjin Huatan Decoction, we identified the blood components of Qingjin Huatan Decoction by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) under the following conditions, chromatographic column: Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm); mobile phase: 0.1% formic acid acetonitrile(A)-0.1% formic acid in water(B); gradient elution; flow rate: 0.2 mL·min~(-1); column temperature: 30 ℃; injection volume: 5 μL. The electrospray ionization(ESI) source was used to collect data in both positive and negative ion modes under the following conditions, capillary voltage: 3 kV for the positive ion mode and 2 kV for the negative ion mode; ion source temperature: 110 ℃; cone voltage: 30 V; cone gas flow rate: 50 L·h~(-1); nitrogen degassing temperature: 350 ℃; degassing volume flow rate: 800 L·h~(-1); scanning range: m/z 50-2 000. In this experiment, a total of 66 related components of Qingjin Huatan Decoction were identified, including 22 prototype components and 44 metabolites. The results of this study preliminarily revealed the pharmacodynamic material basis of Qingjin Huatan Decoction in vivo, which has provided an experimental basis for the determination of quality markers of Qingjin Huatan Decoction and the development of new drugs.

Comparative study of rat serum pharmacochemistry between Puerariae Lobatae Radix and Puerariae Thomsonii Radix based on UPLC-Q-TOF-MS / 中国中药杂志

UPLC-Q-TOF-MS and serum pharmacochemistry were employed to study the migrating components in rat sera after intragastric administration of the water extracts of Puerariae Lobatae Radix(PLR) and Puerariae Thomsonii Radix(PTR). After the respective intragastric administration of PLR and PTR extracts, blood samples were collected from the orbital vein. The serum samples were treated by protein precipitation method with methanol and acetonitrile at a ratio of 1∶1 and then passed through Agilent ZORBAX RRHD SB-C_(18) column(3 mm×100 mm, 1.8 μm) and Agilent SB-C_(18) pre-column(3 mm×5 mm, 1.8 μm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as the mobile phase. The elution was performed at the flow rate of 0.25 mL·min~(-1), the column temperature of 40 ℃, and the injection volume of 2 μL. By comparison of the total ion chromatogram and secondary fragment ion information of PLR and PTR water extracts, PLR-and PTR-containing sera, and blank serum, we found 42 migrating components(including 17 prototype components and 25 metabolites) in the sera of rats treated with PLR and 35 migrating components(including 15 prototype components and 20 metabolites) in the sera of rats treated with PTR. Thirty-three common components were shared by the two treatments, including 13 prototype components and 20 metabolites. The differences of migrating components in the PLR-and PTR-treated rat sera provide a scientific basis for further study of the active components and quality markers of PLR and PTR.

Analysis of blood components of Yougui Yin in normal rats and rats with kidney deficiency caused by adenine based on UPLC-MS technology / 中国中药杂志

Based on the serum medicinal method, this study aims to investigate the migrating components of Yougui Yin in the blood after intragastric administration, and to provide reference for the basic research of its pharmacodynamics. The kidney deficiency rat model was replicated by adenine method. Normal rats and model rats were administered orally for a single gavage of Yougui Yin. The components in blood were rapidly analyzed and identified by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and multiple reaction monitoring(MRM), and the migrating components in blood of Yougui Yin were explored by multivariate statistical analysis. The results showed that there were 42 characteristic peaks in the plasma of normal rats by UPLC-Q-TOF-MS technology and 13 chemical components were identified, including 6 alkaloids, 2 flavonoids, 2 triterpenoid saponins, 1 iridoid, 1 phenylpropanoid and 1 monoterpenoid. There were 22 characteristic peaks in the plasma of kidney-deficiency rats, and 12 chemical components were identified, including 2 iridoids, 6 alkaloids, 2 flavonoids, 1 monoterpenoid and 1 triterpenoid saponin. Verbascoside, isoacteoside, acteoside, pinoresinoldiglucoside, loganin and morroniside were identified by MRM both in the plasma of normal rats and kidney-deficiency rats. Compared with 85 monomer components in Yougui Yin, 17 common prototype components were found by UPLC-MS in the plasma of normal rats and kidney deficiency rats, including verbascoside, isoacteoside, acteoside, rehmapicrogenin derived from Rehmanniae Radix Praeparata, pinoresinol diglucoside and geniposidic acid from Eucommiea Cortex, loganin and morroniside derived from Corni Fructus, mesaconine, benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, mesaconitine, aconitine derived from Aconiti Lateralis Radix Praeparata, liquiritin, isoliquiritin and glycyrrhizic acid derived from Glycyrrhizae Radix et Rhizoma. Thirty-one metabolites of medicinal ingredients not found in the plasma of adenine-induced kidney deficiency rats were also detected in the plasma of normal rats. Twelve metabolites of medicinal materials not found in the plasma of normal rats were detected in the plasma of kidney deficiency rats. The results of the study provide reference for explaining the material basis and mechanism of Yougui Yin in the treatment of kidney deficiency.

Effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure based on UHPLC-Q-TOF-MS integrated with network pharmacology / 中国中药杂志

This study aimed to elucidate the effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure. Firstly, UHPLC-Q-TOF-MS was established to identify the main chemical constituents in the rat serum after intragastric administration with Shengxian Decoction. Secondly, the absorbed components in serum were then used for the network pharmacology analysis to infer the mechanism and effective components. Targets for constituents in serum were predicted at TCMSP and Swiss-TargetPrediction database. An association network map was drawn by network visualization software Cytoscape 3.6.1. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were carried out for the core target genes. By UHPLC-Q-TOF-MS, 18 prototype compounds were definitely identified, including five compounds from Astragali Radix, four compounds from Anemarrhenae Rhizoma, four compounds from Bupleuri Radix, four compounds from Cimicifugae Rhizoma, and one compound from Platycodonis Radix. Those components of Shengxian Decoction were closely associated with 13 key protein targets, including inflammatory factors, like IL6, IL1 B, TNF, PTGS2, IL10; redox enzymes CAT, HMOX1, and MPO; cardiovascular targets, like VEGFA, NOS3, and NOS2; and transmememial proteins CAV1 and INS. Network pharmacology analysis showed that the 18 compounds could be responsible for the treatment of chronic heart failure by regulating HIF-1 signaling pathways, PI3 K-Akt signaling pathways, cGMP-PKG signaling pathways, cAMP signaling pathways and TNF signaling pathways. This study provided a scientific basis for mechanism and effective ingredients of Shengxian Decoction.

Overview research status in serum spectrum-effect of Chinese materia medica / 中草药

Currently, the domestic and foreign research methods for the qualitative basis of Chinese materia medica (CMM) mainly include phytochemical separation method, pharmacological activity tracer method, chromatography, etc. The above methods have played an active role in elucidating the qualitative basis of CMM. However, how to form a multi-component research model that can better reflect the "holistic view" characteristics of CMM and reflect the effectiveness of CMM has become an important direction for scholars in the industry to explore. Serum spectrum-effect of CMM is based on the theory of spectrum-effect to study the relationship between serum chemical fingerprints and pharmacodynamics in vivo. In this paper, by consulting relevant literature, the research idea of serum spectrum-effect was collected, the research results were summarized, and the research bottleneck was analyzed and discussed, so as to provide reference for revealing the material basis of CMM.

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.

Identification of Prototype Compounds and Their Metabolites in Rat Plasma After Oral Administration of Aurantii Fructus Extract by UPLC-Q-TOF/MS / 中国实验方剂学杂志

Objective:To study the serum pharmacochemistry of Aurantii Fructus （AF）， and to investigate the pharmacological material basis of AF extract in rats. Method:Rapid identification and speculation of the prototype constituents and their metabolites in vivo were carried out according to the relative retention time， accurate relative molecular mass， cleavage fragments of MS/MS and neutral loss of metabolites with ultrahigh performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UPLC-Q-TOF/MS） technique by comparing the differences between different samples such as AF extracts， blank plasma， and administered plasma under the same chromatographic and mass spectrometric conditions. Result:After oral administration of the AF extract， 74 transitional constituents absorbed into the blood were detected in serum， in which 49 compounds were prototype constituents and the other 25 were metabolites. The prototype constituents could be divided into dihydroflavones， polymethoxyflavonoids， limonins， coumarins and alkaloids. The identified metabolites included glucuronic acid conjugates， sulfuric acid conjugates， hydroxylated products of flavonoid glycosides and polymethoxyflavonoids， as well as the simultaneous glucuronidation and sulfation products. Conclusion:The constituents absorbed into the blood and their metabolites may be the pharmacodynamic components of AF. Among them， alkaloids， polymethoxyflavonoids and coumarins are mainly introduced into the blood in the prototype form， while naringin and neohesperidin （the index components） exert effect mainly through hydrolysis into aglycones. This work will help to further elucidate the material basis of AF.

Research Progress on the Effective Substances and the Mechanism of Traditional Chinese Medicine Compound / 中国药学杂志

It is important to elucidate the effective substances and the mechanism of Traditional Chinese Medicine (TCM) compound in revealing the compatibility mechanism of TCM, completing the transformation of large varieties of TCM, modernizing TCM, and gaining international recognition. The research METHODS mainly include: the serum pharmacochemistry, network pharmacology, spectrum-effect relationship, high throughput screening, metabonomics and so on. The main research METHODS reviewed through domestic and foreign related literatures can provide the reference for elucidating the effective substances and the mechanism of TCM compound.

Preliminary discovery of quality marker (Q-marker) of Shenzhiling Oral Liquid based on “fingerprint-efficacy-pharmacokinetics” correlation / 中草药

Objective: To establish a research strategy for discovering quality marker (Q-marker) of Shenzhiling Oral Liquid based on the “fingerprint-efficacy-pharmacokinetics” correlation. Methods: HPLC fingerprints and acetylcholinesterase (AchE) inhibitory activities of 12 batches of Shenzhiling Oral Liquid were analyzed. The correlation analysis between the HPLC fingerprints and AchE inhibitory effects were carried out with orthogonal signal correction-partial least squares regression (OSC-PLSR) method. Combined with network pharmacology, efficacy-related components were determined. By identifying the compounds absorbed and exposed in vivo, pharmacologically active components were determined. Finally, Q-marker could be preliminarily discovered by the comprehensive analysis associated with the integration of efficacy-related components and pharmacologically active ingredients. Results: The results of OSC-PLSR analysis showed that three efficacy-related components were closely related to AchE inhibitory activities. According to mapping the targets of diseases, 61 efficacy-related components were determined. Eleven active compounds in plasma were identified by UHPLC-quadrupole-orbitrap-MS. The Q-markers of Shenzhiling Oral Liquid were liquiritin apioside, albiflorin and azelaic acid preliminarily determined by integrated and comprehensive analysis. Conclusion: The combination of fingerprint-efficacy relationship, network pharmacology and components absorbed in plasma could be an effective way for rapid analysis and discovery of Q-marker in Shenzhiling Oral Liquid, which will be of great significance both to improve the quality control and evaluation, and ensure the safety and effectiveness of traditional Chinese medicines.

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.

An Overview of Methodology and Research Progress on Application of Serum Pharmacochemistry of Traditional Chinese Medicine / 中国实验方剂学杂志

Serum pharmacochemistry of traditional Chinese medicine(TCM) is a new subject based on the identification of migrating components in serum after oral administration of TCM.After more than 20 years of development,serum pharmacochemistry of TCM has been widely recognized and applied by researchers.Based on the references related with the serum pharmacochemistry from these years,the research summarized the methods of serum pharmacochemistry of TCM,for example,selection of experimental animals,preparation of gastric irrigation,design of drug administration scheme,method and time of adoption blood,pretreatment of serum containing drug,as well as analysis of serum sample.In addition,the paper will emphatically introduce the application of serum pharmacochemistryof TCM,which includes clarifying the substance basis of Chinese medicine,establishing the quality standard of TCM,and clarifying the compatibility of compound Chinese medicine.At the same time,we will through some existing problems to look forward to the future of serum pharmacochemistryof TCM,so that people can have a comprehensive understanding of serum pharmacochemistryof TCM,hoping to lay a foundation for the further application of this method in TCM research.

Fingerprint of serum containing rhubarb bound anthraquinones / 中国药学杂志

OBJECTIVE: To establish the fingerprint of the serum containing rhubarb bound anthraquinones, and to analyze the drug-originated constituents in serum containing drugs by serum pharmacochemistry. METHODS: Rat serum containing drugs were prepared after intragastric administration of the extract of rhubarb bound anthraquinones. Fingerprints of 10 batches serum containing drugs were determined by HPLC, and the common mode was established. Comparing the chromatogram of serum containing drugs with the one of blank serum, the common peaks of drug-originated constituents in blood were identified. Comparing the retention time and spectrum of the chromatographic peaks of serum containing drugs with the ones of extract, the sources of drug-originated constituents were analyzed. Comparing the retention time and spectrum of the chromatographic peaks of serum containing drugs with the ones of mixed reference substances, some drug-originated constituents were identified. RESULTS: There are 20 common peaks of drug-originated constituents in 10 batches serum containing drugs, 14 of them were in vitro prototype, and the other 6 were metabolites in vivo. Thirteen out of 14 prototype constituents were identified as aloe emodin-8-O-glucopyranoside, rhein-8-O-glucopyranoside, emodin-1-O-glucopyranoside, chrysophanol-1-O-glucopyranoside, chrysophanol-8-O-glucopyranoside, emodin-8-O-glucopyranoside, aloe emodin-3-CH2-O-glucopyranoside, physcion-8-O-glucopyranoside, aloe emodin, rhein, emodin, chrysophanol, and physcion, respectively. Other 1 prototype constituent and 6 metabolites possessed the same UV absorption character as that of anthraquinones. CONCLUSION: The method established in this study is accurate and feasible, and can be used for the analysis of the drug-originated constituents in serum containing rhubarb bound anthraquinones.

Overview on main research method of effective material basis of Chinese materia medica / 中草药

Studies on the effective material basis of Chinese materia medica (CMM), which is critical for clarifying the mechanism of action and control quality. The main research methods on the effective material basis of CMM were reviewed through consulting relevant literature in this paper. It mainly includes the serum pharmaceutical chemistry, spectrum-effect and PK/PD model research.

Studies on serum pharmacochemistry of effective parts of modified Xiaochaihu Tang for treatment of gastric ulcer / 中国中药杂志

To conduct the studies on serum pharmacochemistry of effective parts of modified Xiaochaihu Tang for treatment of gastric ulcer by using chromatography-mass spectrometry. Absolute ethyl alcohol induced-gastric ulcer model of mouse was used in this study to investigate the pharmacology of modified Xiaochaihu Tang and its effective parts. Both groups could significantly decrease the absolute ethyl alcohol induced-ulcer. Gasphase-mass spectrometry (GC-MS) was used to detect chemical compositions of volatile fractions and the drug components after gastric administration. A total of 63 compounds were identified in extracts, accounting for more than 93% of the all volatile oil, including 23.51% α-curcumene, 11.96% zingiberene, 9.56% curzerene, 6.54% β-sesquinene, 4.77% camphene, and 6 prototype components were also detected in serum for gastric ulcer model. In liquid chromatography-mass spectrometry (LC-MS), a total of 17 compounds were identified in extracts, 6 prototype components and 2 metabolites (3,5-O-feruloylquinic acid and palmatine) were obtained in serum. In a conclusion, this study provides an important scientific basis for identifying the active ingredients in modified Xiaochaihu Tang, and also helps to reveal the pharmacological effect of modified Xiaochaihu Tang for treatment of gastric ulcer.

Analysis of components in plasma from effective fractions of Inula cappa based on UHPLC/Q-TOF/MS / 中国药理学通报

Aim To analyze the main components of effective fractions of Inula cappa in rat plasma with UHPLC/Q-TOF/MS technology and serum pharmacochemistry theory.Methods After gavage administration with Inula cappa extracts,blood was collected from abdominal aorta,and the protein in plasma sample was precipitated by methanol.Eclipse Plus C18 RRHD (2.1 mm × 100 mm,1.8 μm) was used,with 0.1％ formic acid agueous solution (A)-0.1％ formic acid and acetonitrile (B) as the mobile phase for gradient elution,and the flow rate was 0.3 mL ·min-1 Detected at negative ion mode,and with the help of Metabolite Tools software from Bruker Corporation,components in plasma were defined.Results A total of 16 compounds were identified,including 9 prototypes and 7 metabolites.Main metabolites were isomerization,methylation,glucuronidation and recombination of caffeoylquinic acid.Conclusions Therefore,our study has comprehensively expounded Inula cappa extracts' constituents migrating to rat plasma,and provided a reference for further studies for in vivo metabolic process and effective material base of Inula cappa.