Investigation of Potential Pharmacodynamic Substances and Mechanism of Gardeniae Fructus in Treatment of Ischemic Stroke Based on HPLC-Q-TOF-MS/MS and Network Pharmacology / 中国实验方剂学杂志

Objective:Combined with high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （HPLC-Q-TOF-MS/MS） and network pharmacology， to predict the target and potential mechanism of Gardeniae Fructus in the treatment of cerebral ischemia. Method:HPLC-Q-TOF-MS/MS was used to identify the chemical constituents of Gardeniae Fructus according to the retention time， relative molecular weight， secondary mass spectrometry fragmentation and other information of chromatographic peaks， and combined with literature data. The targets of main active ingredients in Gardeniae Fructus were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and SwissTargetPrediction database. The potential targets of Gardeniae Fructus against cerebral ischemia were obtained through Online Mendelian Inheritance in Man （OMIM）， GeneCards and Kyoto Encyclopedia of Genes and Genomes （KEGG）. Gene ontology （GO） function enrichment and KEGG pathway analysis of potential targets were analyzed with the DAVID 6.8. Cytoscape 3.6.0 software was used to construct the network of active components-targets-pathways. At last， Discovery Studio 2016 software was applied in the molecular docking verification between the key active ingredients and potential protein targets. Result:A total of 40 chemical constituents in Gardeniae Fructus were identified， including iridoids， diterpenoid pigments， organic acids， monoterpenoids and other components. According to the main active ingredients， 208 potential targets were predicted， 560 disease targets related to cerebral ischemia were retrieved， 59 key targets were selected by mapping component targets with disease targets. These targets could act on key target proteins such as tumor necrosis factor （TNF）， Caspase-3 （CASP3） and CASP8， and participate in the regulation of TNF， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， hypoxia inducible factor 1 （HIF-1） and other signal pathways. Molecular docking results showed that geniposide could interact with targets of prostaglandin G/H synthase 2 （PTGS2）， TNF<italic> </italic>and nuclear transcription factor-<italic>κ</italic>B p65 （RELA）， crocin Ⅰ could interact with interleukin-2 （IL-2）. Conclusion:Geniposide， crocin Ⅰ and other ingredients in Gardeniae Fructus can play a role of anti-inflammatory and inhibiting apoptosis to prevent or treat cerebral ischemic diseases by up-regulating protein expression level of RELA and IL-2， down-regulating protein expression level of TNF， CASP8， CASP3 and matrix metalloproteinase 2 （MMP2）， and regulating TNF， PI3K/Akt and HIF-1 signaling pathways.

Analysis on Quality Transfer Law of Rhei Radix et Rhizoma Steamed with Rice-wine During Processing Based on Correlation Between External Appearance Color and Internal Component / 中国实验方剂学杂志

Objective:The correlation between the appearance color of cooked rhubarb samples and the components characterized by high performance liquid chromatography （HPLC） fingerprint was studied to reveal the quality transfer law in the steaming process of processed products with rice-wine. Method:The visual analyzer was used to analyze the change of the appearance color of cooked rhubarb sample powder at different processing time， the common components and their relative peak areas of processed products with rice-wine were identified by HPLC fingerprint， as well as multivariate statistics and Pearson correlation analysis were used to cluster， discriminate and analyze the appearance color and the component variables in HPLC fingerprint. Result:During the processing of cooked rhubarb， the <italic>a</italic>^* （red-green value） of sample powder had no obvious change， but the <italic>L</italic>^* （lightness value）， <italic>b</italic>^*<italic> </italic>（yellow-blue value） and <italic>E</italic>^*<italic>ab </italic>（total chromaticity value） showed a decreasing trend， and the appearance color changed from bright to dark， from yellow to brown. A total of 46 chromatographic peaks in the fingerprint were identified at 254 nm and 280 nm， and 18 of them were identified by comparison with reference standards. The change trend of <italic>L</italic>^*，<italic> b</italic>^*<italic> </italic>and <italic>E</italic>^*<italic>ab </italic>were positively correlated with the contents of tannins （catechin， epicatechin and ethyl gallate）， stilbene glycoside （<italic>trans</italic>-3，5，4′-trihydroxystyryl-4′-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucoside）， phenylbutanone glycoside of 4′-hydroxyphenyl-2-butanone-4′-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-［2ʺ-<italic>O</italic>-gallic-6ʺ-<italic>O</italic>-（4ʺ-hydroxy）-cinnamoyl）-glucoside， conjugated anthraquinones （aloe emodin-8-<italic>O</italic>-glucoside， rhein-8-<italic>O</italic>-glucoside， emodin-8-<italic>O</italic>-glucoside） and <italic>ω</italic>-hydroxyemodin （<italic>P</italic><0.05， <italic>P</italic><0.01）， and negatively correlated with the contents of free anthraquinones （emodin， aloe emodin and physcion）. Compared with 254 nm， the similarities of chromatographic peaks at 280 nm was more obvious， and the number of detected common peaks was more， which could reflect more subtle differences in chemical composition. Conclusion:Tannins， stilbene glycosides and phenylbutanone glycosides are strongly correlated with <italic>L</italic>^*， while anthraquinones are strongly correlated with <italic>b</italic>^*， the decrease of <italic>E</italic>^*<italic>ab</italic> is mainly related to the increase of free anthraquinone content and the decrease of catechins， <italic>ω</italic>-hydroxyemodin， stilbene glycosides， conjugated anthraquinone and phenylbutanone glycosides. The change of appearance color index of process samples can reflect the change trend of the contents of medicinal components in cooked rhubarb to some extent.

Quality changes of Gardeniae Fructus Praeparatus processed by different frying methods: a color-component correlation analysis / 中国中药杂志

The chromatic values of the broken-fried and single-fried Gardeniae Fructus Praeparatus(GFP) were measured by the color analyzer to analyze the color variation rule, and the contents of 10 main components were determined by ultra-high performance liquid chromatography(UPLC). The multivariate statistical analysis, Pearson correlation analysis, and discriminant analysis were conducted to investigate the color and components of GFP samples. The experimental results revealed that L~*, a~*, b~*, and E~*ab decreased continuously during processing, and the color of samples gradually deepened. The trend and range of chromatic values during broken-frying and single-frying processes were basically identical. Gardenoside, crocin-Ⅰ(C-Ⅰ), and crocin-Ⅱ(C-Ⅱ) showed an obviously downward trend, while the contents of geniposidic acid and 5-hydroxymethylfurfural(5-HMF) increased significantly. Shanzhiside, deacetyl-asperulosidic acid methyl ester, and geniposide(G2) showed a downward trend. Scandoside methyl ester rose first and fell later. Genipin-1-O-gentiobioside(G1) went through a decrease-increase-decrease trend. The change trends of component contents during broken-frying and single-frying processes were generally consistent, but the change range was different. Among all the components, scandoside methyl ester and G1 showed obvious change. Because of different stir-frying time, the change rate of each component content in the process of broken-frying was higher than that in single-frying process. Additionally, geniposidic acid, gardenoside, scandoside methyl ester, C-Ⅰ, C-Ⅱ, and 5-HMF exhibited a higher correlation with apparent color. On the basis of above findings, the discriminant function of two frying processes was established, which could be applied to the discrimination of broken-fried and single-fried samples. This study analyzed the dynamic quality change rule of GFP during broken-frying and single-frying processes based on color-component correlation analysis, and found the two methods showed consistent change trend, yet with slight difference in the quality of samples. This study can provide data support for the processing of GFP.

Brief study on processing characteristics of first batch of classical prescriptions and suggestions on textual research / 中国中药杂志

As an important treasure for the research and development of new Chinese medicines, the classical prescriptions have a long medical history in China and are the summary of the clinical experience of the medical experts in the past dynasties. To support the research and development of classical prescriptions,relevant encouraging policies were issued by the state and relevant administrative departments. It is one of the key problems in the development process of classical prescriptions to verify and determine the processing methods of prescription herbal drugs. At present, there is no consensus or standard on such problems of classical prescriptions. In this paper, we sorted out and analyzed the related content of the herb processing for classical prescriptions, summarized the characteristics of the processing methods in the Catalogue of classical prescriptions(First Batch) and the problems faced in the textual research, and put forward some suggestions on the processing and textual research, including four research strategies: sorting out the mainstream methods for herbs in various periods of classical prescriptions, clarifying histological changes in the processing methods, determining the processing methods based on the drug processing characteristics, determining the processing methods based on the processing functions and identifying the processing methods according to the clinical efficacy and indication, so as to provide ideas and references for the research of processing methods involved in classical prescriptions.