Selection of chemical markers for identification of different species of Juniperri Caulis et Folium based on UPLC-Q-TOF-MS/MS metabonomics technology / 药学学报

In this study, untargeted metabolomics technology based on ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to analyze and identify the overall chemical components of Juniperri Caulis et Folium. Chemical markers for the identification of different Juniperri Caulis et Folium species were screened by integrated principal component analysis and partial least squares discriminant analysis. A total of 58 chemical components were detected and 46 of them were identified, including 26 flavonoids, 8 organic acids and their derivatives, 4 phenylpropanoids, 3 terpenoids, and 5 other components. Among them, methylsyringin and ekersenin were identified for the first time. In the positive ion mode, 12 markers were screened, and in the negative ion mode, 13 markers were screened for species identification. In summary, UPLC-Q-TOF-MS/MS metabonomics technology combined with chemometrics method can effectively reveal the chemical composition differences of different Juniperri Caulis et Folium species, and provide reference for its species identification and quality control.

Mechanism of Tibetan medicine Pterocephalus hookeri extract in treatment of rheumatoid arthritis based on serum metabonomics / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF/MS) was used to investigate the effect of Pterocephalus hookeri on serum metabolism of adjuvant arthritis(AA) model rats induced by complete Freund's adjuvant. After the AA model was properly induced, the serum of rats was collected 30 days after treatment. UPLC-Q-TOF-MS chromatograms were collected and analyzed by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The results revealed that compared with the control group, the model group showed increased content of 12 biomarkers in the serum(P<0.05) and reduced content of the other nine biomarkers(P<0.05). P. hookeri extract could recover the above-mentioned 19 biomarkers to a certain range. Pathway enrichment showed that these markers mainly involved eight metabolic pathways, including valine, leucine, and isoleucine degradation, arachidonic acid metabolism, arginine and proline metabolism, glycerol phospholipid metabolism, primary bile acid biosynthesis, bile acid biosynthesis, tryptophan metabolism, and unsaturated fatty acid biosynthesis. The findings of this study demonstrate that P. hookeri extract can regulate metabolic disorders and promote the regression of metabolic phenotype to the normal level to exert the therapeutic effect on AA rats. This study is expected to provide a certain scientific basis for the biological research on the treatment of rheumatoid arthritis by P. hookeri.

Comparison of efficacy between laparoscopic and open proximal gastrectomy with double-tract reconstruction for Siewert type Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction / 中华胃肠外科杂志

Objective: To compare the efficacy between laparoscopic and open proximal gastrectomy with double-tract reconstruction for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) 18 to 80 years old; (2) Siewert II and III AEG was confirmed by preoperative gastroscopy and biopsy, which could not be resected by endoscopy; patients undergoing radical proximal gastrectomy with double-tract reconstruction; (3) contrast-enhanced abdominal CT staging was cT1-2N0M0; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, American Association of Anesthesiologists (ASA) grade 1 to 2; (5) patients agreed to perform proximal gastrectomy and signed an informed consent. Those who had undergone neoadjuvant radiochemotherapy, suffered from serious mental diseases and had incomplete data were excluded. According to the above criteria, clinical data of 84 consecutive patients with Siewert II and III AEG undergoing surgery at General Surgery Department of The Affiliated Tumor Hospital of Zhengzhou University from October 2010 to December 2018 were collected and analyzed. Of 84 patients, 61 underwent open proximal gastrectomy with double-tract reconstruction (OPG group), while 23 underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG group). The perioperative complications and postoperative reflux esophagitis of two groups were compared. A P-value of <0.05 was considered to be statistically significant. Results: Among 84 cases, 74 were male and 10 were female. There were 43 cases of Siewert type II and 41 cases of Siewert type III. There were no significant differences in age, gender, body mass index, comorbidities, Siewert type, and tumor staging between the two groups (all P>0.05). As compared to the OPG group, the LPG group had longer operation duration [(223±21) minutes vs. (161±14) minutes, t=15.352, P<0.001], less intraoperative blood loss [195 (150, 215) ml vs. 208 (192, 230) ml, Z=2.143, P=0.032], and shorter time to flatus [(2.8±0.7) days vs. (3.3±0.9) days, t=2.477, P=0.015]. There were no significant differences in the number of harvested lymph nodes, time to the first meal and postoperative hospital stay between the two groups (all P>0.05). Postoperative complications developed in 2 cases (8.7%, 1 case each for anastomotic leakage and intestinal obstruction) in the LPG group and 5 cases (8.2%, 1 case each for anastomotic leakage, anastomotic bleeding, and anastomotic stenosis, 2 cases of incision infection) in the OPG group (χ(2)=5.603, P=0.231). The median follow-up was 41.2 (12.8-110.5) months. One patient (1.6%,1/61) had obvious reflux symptoms in the OPG group, compared with none in the LPG group (χ(2)=0.644, P=0.422). Esophagitis occurred in 1 case (4.8%, 1/21) in LPG group, compared with 4 patients (7.1%, 4/56) in the OPG group, without significant difference between the two groups (χ(2)=0.505, P=0.477). Conclusion: Laparoscopic proximal gastrectomy with double-tract reconstruction is safe and feasible without increasing the risk of postoperative complication and reflux esophagitis.

Correlation study on Tibetan medicine Pterocephalus hookeri of bitter taste receptors based on molecular docking technology / 中国中药杂志

In order to study the interaction between Pterocephalus hookeri and bitter taste receptors,three-dimensional structural models of bitter taste receptors TAS2 R16,TAS2 R14 and TAS2 R13 were established by homology modeling in this paper. Maestro software was used for docking the chemical constituents of P. hookeri with bitter taste receptors. The results showed that 25 chemical components of P. hookeri can regulate three bitter taste receptors. And these components were mainly iridoid glycosides and phenolic acids.This research focused on the comprehensive application of homology modeling and molecular docking technology to explore the interaction between bitter chemical constituents of P. hookeri and bitter taste receptors. This study provided assistance in revealing pharmacodynamic basis of bitter Tibetan medicine at molecular level. It also provided new ideas and methods for the study of Tibetan medicine.

Investigation on intestinal absorption ingredients and their absorption characteristics in Pterocephali Herba by everted intestinal sac method / 中国中药杂志

The intestinal absorption characteristics of ten iridoid glycosides and phenolic acids in the Pterocephali Herba were evaluated via rat intestinal valgus model. The intestinal sac fluids at different time after administration of high,medium and low concentrations of Pterocephali Herba extract were collected and ten chemical components in fluid samples were detected by UPLC-PDA. Accumulative absorbed doses( Q) and absorption rate constants( Ka) of ten chemical constituents were calculated,while proportions between Pterocephali Herba extract and intestinal absorption liquid were compared. The results showed that the intestinal absorption of 10 chemical components was linear absorption( R2>0. 9) at different concentrations,which accorded with the zero-order absorption rate. The absorption rate constant was related to the concentration of the drug and the intestinal site,which indicated that intestinal adsorption mechanism of the components were passive diffusion and active transport. Proportions of chemical constituents in intestinal sac fluid were different from those in Pterocephali Herba extract. Therefore,those ten chemical components in Pterocephali Herba extract can be absorbed in whole intestine. Everted intestinal sac model can be used to evaluate intestinal absorption characteristics of ingredients in Pterocephali Herba extract effectively.

Study on the Active Components Targets of Tibetan Medicine Pterocephalus hookeri in Anti-rheumatoid Ar-thritis Based on Network Pharmacology / 中国药房

OBJECTIVE:To explore the multi-component,multi-target,multi-channel mechanism of Tibetan medicine Ptero-cephalus hookeri in the treatment of rheumatoid arthritis (RA). METHODS:The selected target compounds (10 chemical struc-tures of P. hookeri)were imported and stored by related software;target prediction and filtering were conducted by PharmMapper and DrugBank databases. The pathways of targets were acquired and analyzed by MAS 3.0 database. Finally P. hookeriactive com-ponent-targeting-pathwaynetwork was constructed by Cytoscape 3.4.0 software. RESULTS:The target information obtained in the PharmMapper database were compared with that of the DrugBank database for inflammation-related drugs,26 potential targets for the treatment of RA were obtained,in which MAPK14,RXRA,ALB,PDE4D,VDR may be the main potential target gene group in the treatment of RA. 57 functional pathways were obtained after 26 functional targets were annotated by pathway. In addition to 27 RA-related pathways,30 other pathways such as endocrine regulation and immune were involved. CONCLUSIONS:Base on the study of network pharmacology,P. hookeri plays the role in the treatment of RA by acting on inflammation,immune,endo-crine and related targets and pathways.

Simultaneous determination of ten major compounds including iridoid glycosides and phenolic acids in Pterocephalus hookeri by UPLC-PDA / 中国中药杂志

This study is to develop an UPLC-PDA method for determination of 10 major components in Pterocephalus. The UPLC-PDA assay was performed on a Waters Acquity UPLCR BEH C₁₈（2.1 mm ×100 mm,1.7 μm）, and the column temperature was at 30 ℃. The mobile phase consists of water containing 0.2% phosphoric acid (A) and acetonitrile (B) in gradient elution at a flow rate of 0.4 mL•min⁻¹. The detection wave length was set at 237 and 325 nm, and the injection volume was 1 μL in the UPLC system. The linear range of 10 detected compounds were good (r≥0.999 7), and the overall recoveries ranged from 96.30% to 103.0%, with the RSD ranging from 0.72% to 2.9%. The method was simple, accurate and reproducible, which can be used for the simultaneous determination of the content of ten major components in P. hookeri.

Content Determination of Oleanolic Acid and Ursolic Acid from Different Medicinal Parts in Tibetan Medi-cine Pterocephalus hookeri by UPLC-PDA / 中国药房

OBJECTIVE:To establish the method for the determination of oleanolic acid and ursolic acid in different medicinal parts of Tibetan medicine Pteocephalus hookeri,and compare the differences among the different parts. METHODS:The contents of oleanolic acid and ursolic acid from different medicinal parts(whole plant,aerial part,underground part)of P. hookeri were de-termined by UPLC-PDA. The separation was performed on Acquity UPLC HSS T3 column(150 mm×2.1 mm,1.8 μm)with mobile phase consisted of methanol-0.1 mol/L ammonium acetate(88:12,V/V)at the flow rate of 0.2 mL/min. The detection wavelength was set at 210 nm,and column temperature was 30 ℃. The sample size was 5 μL. RESULTS:The linear ranges of oleanolic acid and ursolic acid were 10.65-1065 μg/mL (r=0.9996) and 18.8-1880 μg/mL (r=0.9994),separately. The recoveries were 96.95%(RSD=1.24%,n=9) and 98.12%(RSD=2.13%,n=9),separately. RSDs of precision,stability and reproducibility tests were all less than 3%. The contents of oleanolic acid and ursolic acid from different medicinal parts in P. hookeri were in de-scending order of aerial part>whole plant>underground part;the average total content of oleanolic acid and ursolic acid from whole plants was 0.35%,the aerial part reached 0.56% and underground part was 0.09%. CONCLUSIONS:The method is rapid, accurate and reproducible,and it is suitable for the content determination of oleanolic acid and ursolic acid in different medicinal parts of Tibetan medicine P. hookeri. The contents of oleanolic acid and ursolic acid from aerial part of P. hookeri are higher than whole plant and underground part. It is suggested to use aerial parts of medicine.

Medication rules for prescriptions containing Pterocephali Herba based on data mining / 中国中药杂志

This study was aimed to discuss and analyze the medication rules for prescriptions containing Pterocephali Herba in Chinese Medical Encyclopedia - Tibetan Medicine, Tibetan Medicine Prescription Modern Research and Clinical Application, and Interpretation of Common Tibetan Medicines based on the collection of Pterocephali Herba and by using the "Traditional Chinese Medicine Inheritance Support system(V2.0.1)",with the use of association rules, apriori algorithm and other data mining methods. The frequency of single drug, the frequency of drug combination, the association rule and the combination of core drugs were analyzed. Through collection of the prescriptions, a total of 215 prescriptions were included, involving a total of 376 herbs. Through the "frequency statistics", the prescriptions containing Pterocephali Herba were commonly used to treat cold fever, distemper virus and arthritis. The highest frequently (frequency≥15) used drugs were Corydalis Herba, Lagotidis Herba, and Gentianae Macrophyllae Radix, et al. The most frequently used drug combinations were "Pterocephali Herba, Corydalis Herba","Pterocephali Herba, Lagotidis Herba", and "Pterocephali Herba, Gentianae Macrophyllae Radix" et al. The prescriptions containing Pterocephali Herba were used to primarily treat disease for Tourette syndrome caused by the dampness heat toxin, fever, arthritis etc, such as pestilent toxicity, pneumonia and influenza, rheumatoid arthritis etc. The drugs in the prescriptions mostly had the effects of heat-clearing and detoxifying, anti-inflammatory, dispelling wind and dampness, often in compatible use with heat-clearing drugs. The drug use was concentrated and reflected the clear thought of prescription statutes.

Potential distribution of the traditional Tibetan herb Pterocephalus hookeri by Maxent model / 中国中药杂志

In order to study the ecology suitability of Pterocephalus hookeri, and provide a reference for GAP planting location and regional development, the Maxent model and GIS technology were used to investigate ecology suitability regions for P. hookeri based on the distribution points collected from Chinese virtual herbarium, the references and field trips. The potential distribution areas mainly concentrated in the eastern Tibet, western Sichuan, southern Qinghai, northwest Yunnan, and southern Gansu. There were 7 major environmental factors to have obvious influence on ecology suitability distributions of P. hookeri, including altitude (contribution rate of 62%), precipitation of warmest quarter (contribution rate of 14.4%), coefficient of variation of precipitation seasonality (contribution rate of 7.2%), mean temperature of driest quarter (contribution rate of 3.5%), the electrical conductivity of top and sub-soil (contribution rate of 3%), the total exchangeable bases in the top- and subsoil (contribution rate of 2.4%) and SD of temperature seasonality (contribution rate of 2.2%). The study of the ecological suitability regionalization of P. hookeri based on Maxent model can provide scientific basis for the selection of artificial planting base and GAP planting location.

Optimization on Extraction Technology of Polysaccharide from Rhizoma Coptidis by Box-Behnken Design-Response Surface Methodology / 世界科学技术-中医药现代化

This study was aimed to optimize the extraction conditions of polysaccharides from Rhizoma Coptidis.With the R.Coptidis of extraction yield,polysaccharide yield and uronic acid yield as evaluation indexes,the impact of extraction temperature,extraction times,extraction duration and liquid-to-solid ratio on the process of R.Coptidis polysaccharides reflux extraction were investigated by the Box-Behnken design-response surface methodology.The results showed that the optimal extraction conditions were achieved and listed as follows:extraction temperature at 100℃,extracted 3 times with 3.8 h per each time,liquid-to-solid ratio of 1:15.7.It was concluded that the Box-Behnken design-response surface methodology was accurate,rational and feasible to optimize the extraction method of polysaccharides fromR.Coptidis.

Research on Quality Evaluation Method of Geo-authentic Medicinal Herb Rhizoma Coptidis for the Reflection of Outstanding Feature of TCM / 世界科学技术-中医药现代化

This study took geo-authentic medicinal material Rhizoma Coptidis as an example and analyzed soil characteristics of the growing environment of Rhizoma Coptidis . The methods of ISSR, HPLC, 1H-NMR and NIR were respectively used for exploring its genotype and investigating on its chemitype . In the respects of an-ti-endotoxin, anti-bacterial activities and insulin resistance that was related to the treatment of diabetes, the pharmacodynamic type was studied and the relationship was comprehensively analyzed . The quality evaluation of geo-authentic medicinal materials was preliminarily established based on ecotype , genotype chemitype and phar-macodynamic type of Rhizoma Coptidis . Simultaneously, quality standards of Rhizoma Coptidis were set up in combination with genuine character , which provided the scientific basis for establishing Chinese medicine char-acteristic methods of quality evaluation of Rhizoma Coptidis .