Comprehensive evaluation system for quality of Chinese medicinal decoction pieces based on "experience-ingredients-activity-electronic sensing" / 中国中药杂志

Quality evaluation of Chinese medicinal decoction pieces is vital for the development of the downstream industries, and is an important channel for implementing the strategy of "higher quality, higher price, and priority for the high quality" for traditional Chinese medicine. At the moment, the quality of Chinese medicinal decoction pieces is mainly evaluated based on chemical component examination. Considering the weak preliminary research foundation and poor research conditions, traditional experience-based evaluation is undervalued in the quality rating of Chinese medicinal decoction pieces. However, traditional experience is a summary of the quality of Chinese medicinal materials based on clinical experience, which thus can be a potential basis for the quality evaluation of the decoction pieces. It is a challenge in the evaluation of Chinese medicinal decoction pieces to objectify the traditional experience-based evaluation from multiple aspects such as chemistry, effect, and characterization via modern techniques. Therefore, this study developed the "experience-ingredients-activity-electronic sensing" evaluation system for Chinese medicinal decoction pieces on the basis of experience-based assessment, chemical ingredients that can truly reflect the traditional experience, biological effect assessment, and electronic sensory evaluation, which is expected to quantify the traditional experience of quality evaluation of Chinese medicinal decoction pieces via chemistry, biology, and sensory simulation. The evaluation system can serve as a reference for clinical experience-based quality evaluation of Chinese medicinal decoction pieces.

Structure and identification of immune fragments of acid-degraded oligosaccharides from active Astragalus polysaccharides APS-Ⅱ / 药学学报

We previously reported that active Astragalus polysaccharides APS-Ⅱ generate strong immune activity. Here we establish the optimal method for APS-II acid degradation. After preliminary structural studies and separation and preparation of the degradation products, the oligosaccharide active center with the strongest immune activity was identified by in vitro immune cell culture experiments. The optimum acid degradation conditions for APS-II were determined by a single factor experiment and an orthogonal experiment. Astragalus oligosaccharides prepared under the optimal conditions were subjected to structural analysis by hydrophilic interaction chromatography - electrospray ionization source - high resolution time-of-flight mass spectrometry. The products were separated and oligosaccharide fragments with different degrees of polymerization were isolated by preparative purification chromatography. Finally, fragments of the immunologically active centers were identified by in vitro immune cell cultures from multiple perspectives. The results show that the optimal acid hydrolysis conditions for APS-Ⅱ are hydrolysis temperature 80 ℃, trifluoroacetic acid concentration 1.0 mol·L-1, hydrolysis time 1 h. The degradation conditions have good repeatability. The degradation product is a six-carbon aldehyde glycan structure with the main chain 1→4 connected. The immune activity screening experiment for six oligosaccharide fragments showed that larger molecular weight oligosaccharides have stronger immune-promoting effects. It is speculated that the immunologically active center of Astragalus oligosaccharide is located in the sugar chain of DP9-DP19. The animal welfare and the experimental process in this study follow the requirements of the Animal Ethics Committee of Shanxi University. This result suggests a foundation for the structural characterization and structure-activity relationship research of Astragalus oligosaccharides, and may promote the development of Astragalus oligosaccharide drugs.

Comparative study on different areas of Astragali Radix based on oligosaccharides characteristic map and immunological activity evaluation of partial acid hydrolyzed / 中草药

Objective: The characteristic maps and immunological activities of some acid hydrolysates of polysaccharides from Astragali Radix (APS) from different areas were compared. The quality evaluation method of Astragali Radix with oligosaccharide mixture as quality control index was established. Methods: In this study, the polysaccharides from the traditional Chinese medicine Astragali Radix were used as the research object. Firstly, the optimal partial acid hydrolysis conditions were selected by orthogonal test. The polysaccharide was hydrolyzed into oligosaccharides for analysis. The characteristic map of Astragalus oligosaccharides based on partial acid hydrolysis-hydrophilic interaction chromatography was established. Multivariate statistical analysis was performed on the data by SIMCA software to distinguish Mongolian Astragalus from different areas. The partial acid hydrolysis products of Astragalus polysaccharides were characterized by hydrophilic interaction chromatography and mass spectrometry, and the activity was evaluated by mouse peritoneal macrophage phagocytosis neutral red experiment. Results: The optimal hydrolysis conditions obtained by orthogonal experiment were temperature 90 ℃, trifluoroacetic acid concentration 1 mol/L, hydrolysis time 1 h. Under this condition, Astragalus polysaccharide was hydrolyzed into characteristic oligosaccharide fragments, and the method is reproducible. The characteristic map of Astragalus oligosaccharides based on partial acid hydrolysis-hydrophilic interaction chromatography showed that the maps of the same Astragalus oligosaccharides had good consistency, and the maps of different Astragalus oligosaccharides were quite different. PCA showed that three different kinds of Mongolian Astragalus can be distinguished. It was found by mass spectrometry that the extracted Astragalus polysaccharides were mainly 1→4 linear glucan, and gluco-oligosac-charides with the degrees of polymerization 3—8 were obtained after partial acid hydrolysis. The partial acid hydrolysate of the wild Astragalus polysaccharides from Shanxi Hunyuan had higher ability to enhance the phagocytic activity of macrophages than the transplanted Astragalus and higher than the unhydrolyzed total astragalus polysaccharide. Conclusion: This study showed that the characteristics of Astragalus polysaccharides based on partial acid hydrolysis-hydrophilic interaction chromatography and the effects on cellular immune function can be used to evaluate the quality of Astragali Radix in different habitats and different planting methods, and it is also an important supplement to the quality evaluation method of Astragali Radix. At the same time, it has a certain exemplary role in the characterization of other Chinese materia medica polysaccharides.

Establishment of ocular apoptosis model in zebrafish / 中国药理学通报

To establish a model of ocular apoptosis in zebrafish by using dibutyl phthalate(DBP), and accordingly to evaluate the activity of anti-ocular apoptosis drugs. Methods Zebrafish embryos (30 hpf) were treated with DBP(0. 1, 10, 50, 100 jxmol L " 1) for 18 h and 42 h, and the survival rate was calculated. Then zebrafish embryos (30 or 54 hpf) were incubated with DBP(0. 1, 1 , 5 , 10, 50 |j.mol L 1) for 18 h under direct or indirect light conditions, and visualized under microscope, then the ocular apoptosis was assessed by AO staining. Furthermore, modeled zebrafish was treated with N-acetyl-L-cysteine(NAC) or ginsenoside Rgl, and the effects on ocular apoptosis were observed. Results There was no mortality in zebrafish at concentrations below 10 |j,mol L"1 after modeling with DBP for 18 h and 42 h. The survival rate of zebrafish was significantly reduced with a concentration above 50 |xmol L"1 (P < 0 . 0 1) . Furthermore, obvious ocular apoptosis was found at 30 hpf after 18 h with DBP(10 (unol L"1) (P < 0. 0 1) . The zebrafish showed spontaneous apoptosis of the ocular cells at 72 h, which was not associated with light conditions. Effect of NAC or ginsenoside Rgl was observed on decreasing ocular apoptosis in zebrafish (P < 0. 05) . Conclusions DBP can be used to rapidly and efficiently establish a model of ocular apoptosis in zebrafish, which can be used for rapid evaluation of drug activity-.

Establishment of Jinzepaishi Granules fingerprint and evaluation of its anti-inflammatory activity for cyclooxygenase-2 / 中草药

Objective To establish HPLC fingerprints of Jinzepaishi Granules from ten different batches and a preliminary method for its anti-inflammatory biological activity titer detection, and construct a dose-effect relationship between cyclooxygenase-2 (COX-2) and Jinzepaishi Granules for scientific evaluation and effective control of granules quality. Methods The HPLC method was used to analyze the similarity of common peaks in different batches of granules and assigned 19 common peaks to herbs. The fingerprints were further analyzed by the chemometric method of hierarchical clustering analysis and principal component analysis (PCA). The EIA method was used to determine the half-inhibitory concentration (IC50) of Jinzepaishi Granules. Results The similarity of HPLC fingerprints of all the ten batches was ≥ 0.955, which were consistent with the results of cluster analysis and PCA. Jinzepaishi Granules had a significant inhibitory effects on COX-2 with a IC50 of 10.272 mg/mL, which demonstrated a significant dose-effect relationship. Conclusion The multiple quality control system of chemical fingerprinting and biological activity detection has the characteristics of high efficiency, rapidness, accuracy, sensitivity, and good reproducibility. It can effectively evaluate the anti-inflammatory biological activity of Jinzepaishi Granules and achieve more scientific and reasonable control of its quality. It also provides a reference for the establishment of more scientific quality control for other Chinese materia medica preparations.

The value of the signal intensity ratio of the extraocular muscle and the ipsilateral white matter of the MRI in the evaluation of the activity of thyroid-associated ophthalmopathy / 中华内分泌代谢杂志

Objective To investigate the quantitative value of the signal intensity ratio of extraocular muscle and ipsilateral white matter measured by MRI for the evaluation of activity in thyroid-associated ophthalmopathy. Methods A total of 129 patients and 245 eyeballs with thyroid-associated ophthalmopathy were enrolled in this study and this 245 eyeballs were set as thyroid-associated ophthalmopathy group(TAO group). There were 10 patients with newly diagnosed Graves'disease and in the same period and these 20 eyeballs were set as graves'disease group(GD group). 32 normal people from annual physical test excluded thyroid and eye diseases and their 64 eyes were selected randomly for the normal control group(NC group). The signal intensity of the extraocular muscle and the ipsilateral white matter on the MRI images were measured, while did exophthalmos and the width of the inner fat of eyeballs (FWs)measurements in the same time. Results SIR,FWs,and exophthalmos of TAO group were higher than those of the other 2 groups[SIRs:1.71(1.40,2.10)vs 1.26(1.22,1.34)and 1.23(1.14,1.32);FWs:8.04(6.70, 8.71)mm vs 6.16(4.86,7.08)mm and 6.93(6.41,7.65)mm,exophthalmos:20.10(18.56,22.15)mm vs 15.40(14.87,16.60)mm and 14.73(13.40,16.07)mm,all P<0.05]. The reference value of SIR establishing based on SIRs of NC group is less than 1.37. In total 129 TAO patients,55 patients(with 106 eyeballs)have a clinical activity score(CAS). Then,these eyeballs were grouped to activity and non-activity(grouped by CAS≥3),and the baseline group difference of these 2 groups was not statistically significant. The SIRs and exophthalmos of activity group were higher than the non-activity group[SIRs:1.70(1.45,2.33)vs 1.41(1.25,1.75); exophthalmos:(20.38 ± 2.40)mm vs(19.05 ± 3.70)mm,all P<0.05]. But the difference of FWs of these two groups was not statistically significant(P>0.05). The SIRs and CAS had a positive correlation(r=0.580,P=0.000),through the receiver operating characteristic curve(ROC)we get the best diagnostic performance of TAO activity when the SIR≥1.56(sensibility=65.6%,specificity=89.1%,AUC=0.815,P=0.000). Conclusion The signal intensity ratio of extraocular muscle and ipsilateral white matter may discriminate the activity of TAO early as a quantitative indicator, reflecting its efficacy,and is worth clinically generalizing.

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.

Synthesis, stability and activity of the prodrugs of dihydroorotate dehydrogenase inhibitors / 药学学报

This study was conducted to improve structural instability of a highly active DHODH inhibitor A found in our group. Twelve prodrugs were synthesized by modifying the carboxyl group. The enzyme activity test of 12 prodrugs A1−A12 demonstrated that A1−A5 displayed weak inhibitory activity, and A6−A12 displayed no activity, which met the action mechanism of designed prodrug. The structural stability of A1−A12 in methanol and pH 2.0, 9.0 buffers were tested, and the results showed that A12 could avoid intramolecular ring-formation in CH3OH, A1−A8 were easily hydrolyzed under acidic conditions, and A9−A12 were inclined to hydrolyze under alkaline conditions. The cell proliferation inhibitory activity of 12 prodrugs were evaluated, in which compound A12 displayed excellent activity (IC50=0.63 μmol·L−1) similar to brequinar. These results laid a good foundation for conducting further vivo studies.

Evaluation and screening for biological activity of components in Chinese materia medica / 中草药

Biological activity evaluation of Chinese materia medica (CMM) composition is one of the main means to explore the active components of CMM. This paper, from the three aspects of whole animal, cellular, and molecular, discusses systematically the technical progress in this area over the past 10 years and the screening of new active ingredients from CMM and monomer compounds based on new technology. At the same time, the different technical strengths and weaknesses have been analyzed in the hope of providing the information and ideas for the research on the new drugs of CMM.