Rui-Fang Xie

Bufothionine, a possible effective component in cinobufocini injection for hepatocellular carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE Cinobufacini has been traditionally used in China for the treatment of tumor since hundreds years ago. For recent years, its modern preparation,cinobifucini injection has also obtained satisfactory therapeutic functions for cancer. MATERIALS AND METHODS High performance liquid chromatography (HPLC) analysis was applied to determine the content of cinobufagin, resibufogenin and bufothionine in cinobufacin extract liquid and injection; MTT assay and flow cytometric analysis were also respectively used to study the effect of cinobufacini extract liquid, injection and three chemical structures on cells and cell cycles. RESULTS HPLC results demonstrated that in cinobufacini extract liquid three ingredients (cinobufagin, resibufogenin and bufothionine) were all monitored while in cinofacini injection only bufothinone was detected; MTT assays showed bufothionine could obviously inhibit the proliferation of human hepatocellular carcinoma cell lines such as SMMC-7721 and BEL-7402 in a dose- and time-dependent manner as well as cinobufagin and resibufogenin; further flow cytometric analysis indicated obvious increases in G2/M phase and decrease in G0/G1 phase when SMMC-7721 cell line exposure to bufothionine (480 μg/ml). CONCLUSIONS These results suggested bufothionine could be involved in treatment of human cancer for cinobufacini injection and the mechanism might be relative to induce G2/M phase cell cycle arrest.

Study on Spectrum-Effect Relationship of Rhizoma Rhei, Cortex Magnoliae Officinalis, Fructus Aurantii Immaturus and their Formula

Rhizoma Rhei, cortex Magnoliae Officinalis and fructus Aurantii Immaturus compose dachengqi tang (DCQT), a classical formula of traditional Chinese medicine (TCM) that is used for acute intestinal obstruction and has been proven to be effective and economic. However, the ingredients of TCM are complicated, and it is unclear which ingredients are the most important for its effects. In this paper, the relationship between the spectra and effects is discussed to provide a powerful method and some insights into the quality control of the herbs and their formula. High-performance liquid chromatographic (HPLC) fingerprint analysis was performed to investigate the chemical structures in different batches of rhizoma Rhei, cortex Magnoliae Officinalis, fructus Aurantii Immaturus and DCQT. Hierarchical clustering analysis was employed to evaluate the similarities between fingerprints. Animal model of small intestinal propulsion was established to study the purgative functions of the herbs and DCQT. The relationship between the chemical ingredients and the effects was explored by regression analysis. HPLC fingerprint analysis results demonstrated variations between ingredients in different batches of rhizoma Rhei, cortex Magnoliae Officinalis, fructus Aurantii Immaturus and DCQT. The origin, collection time and preparation process may have contributed to these differences. Small intestinal propulsion results showed that, compared with the control group, the positive and therapeutic groups including single herbs and formula were significantly effective (P < 0.05). Spectrum-effect relationship results indicated that seven peak ingredients, hesperidin, aloe-emodin, honokiol, rhein, magnolol, emodin and sennoside A, were inducted in the regression equation, among which, the influence of sennoside A was the largest and most positively associated with the effects. The data analysis results indicated that many ingredients contributed to the purgative effects, among which, sennoside A might be the most important effective component; therefore, sennoside A should be determined for quality control. Furthermore, the spectrum-effect relationship is simple, operative and suitable for the quality evaluation of TCM.

Optimization of high pressure machine decocting process for Dachengqi Tang using HPLC fingerprints combined with the Box–Behnken experimental design

Using Dachengqi Tang (DCQT) as a model, high performance liquid chromatography (HPLC) fingerprints were applied to optimize machine extracting process with the Box–Behnken experimental design. HPLC fingerprints were carried out to investigate the chemical ingredients of DCQT; synthetic weighing method based on analytic hierarchy process (AHP) and criteria importance through intercriteria correlation (CRITIC) was performed to calculate synthetic scores of fingerprints; using the mark ingredients contents and synthetic scores as indicators, the Box–Behnken design was carried out to optimize the process parameters of machine decocting process under high pressure for DCQT. Results of optimal process showed that the herb materials were soaked for 45 min and extracted with 9 folds volume of water in the decocting machine under the temperature of 140 °C till the pressure arrived at 0.25 MPa; then hot decoction was excreted to soak Dahuang and Mangxiao for 5 min. Finally, obtained solutions were mixed, filtrated and packed. It concluded that HPLC fingerprints combined with the Box–Behnken experimental design could be used to optimize extracting process of traditional Chinese medicine (TCM).

COMPARISON OF THREE WEIGHING METHODS FOR EVALUATION OF THE HPLC FINGERPRINTS OF CORTEX FRAXINI

Three weighing methodological approaches, including Analytic Hierarchy Process (AHP), Criteria Importance Through Intercriteria Correlation (CRITIC), and synthetic method (AHP combined with CRITIC), were proposed to handle the relative importance of different constituents in the HPLC fingerprints of cortex fraxini. The consistency and rationale of the three methods have been analyzed and compared. Results showed satisfying consistency in all three methods; the synthetic method reflected both the analysts subjective judgments and the objective data itself and was, therefore, more representative than either of the other two methods alone. We conclude that the synthetic method is a reliable and appropriate method to evaluate the HPLC fingerprint of Traditional Chinese Medicine (TCM).

Compatibility Study of Danggui Buxue Tang on Chemical Ingredients, Angiogenesis and Endothelial Function

Danggui Buxue Tang (DBT) is a classic Chinese herbal formula which consists of Astragali mongholici Radix and Angelica sinensis Radix (ASR). For chemical ingredients, HPLC were performed. Results showed compared with single herbs, DBT decoction could promote the dissolution of ingredients such as ferulic acid and calycosin. Furthermore, when ratio of AMR to ASR was 5 to 1, synthetic score was the best. For angiogenesis, normal and injured zebrafish model were applied. Results showed DBT and its ingredients had angiogenesis effects on Sub Intestinal vessels (SIVs) of normal zebrafish. Meanwhile, DBT and its single herbs could also recover Inter-Segmental Vessels (ISVs) injured by VRI. Angiogenesis effects of DBT on ISVs were better than single herbs. AMR extract, Total Saponins of AMR, Polysaccharide of ASR, ferulic acid, calycosin and calycosin-7-glucoside could be effective ingredients for angiogenisis. For endothelium functions, Lysoph-Osphatidyl choline was used to damage rat endothelial function of thoracic aorta. The results showed DBT and its single herbs could improve endothelial dysfunctions in dose-dependence. Both ferulic acid and calycosin-7-glucoside could also improve endothelium dysfunction in dose dependence. Therefore, compatibility of DBT was reasonable. Compared with single herbs, DBT could promote dissolution of effective ingredients, enhance angiogenesis and relieve endothelial dysfunction.

Study on the HPLC Chromatograms and Pro-Angiogenesis Activities of the Flowers of Panax notoginseng

Panax notoginseng is often used to promote blood circulation for the intervention of cardiovascular diseases (CVDs), while the flower of Panax notoginseng (PF) is used in folk remedies for the amelioration of hypertension in the Yunnan Province of China as a tea and is increasing in popularity throughout Asia. Previous studies on the Panax notoginseng were mainly focused on the root such that limited research on the flower cannot feed the need of increasing consumption and the products quality and pharmacological profile remains to be well characterized. In this study, chromatographic fingerprints and angiogenesis activities of different batches of commercial PF decoction were determined and then multiple regression analysis was performed to analyze their spectrum-effect relationships. The results of chromatographic fingerprints and zebrafish angiogenesis bioassay indicated the significant heterogeneities in the twelve batches of commercial PF products. Multiple regression analysis on the spectrums-activities relationship provided clues on the bioactive chemical markers of PF that may be developed as quality standards of PF.

Cost-effectiveness Assessment of Commonly-used Drugs for Hepatoprotection and Enzymes Reduction Based on Decision Tree and Multi-utility Theory

Abstract Objective Drugs for hepatoprotection and enzymes reduction are widely used in China but their economic analysis has been ignored in a rather long period of time. A suitable protocol for hepatoprotection and enzymes reduction was recommended in Longhua Hospital. Methods This study was conducted as a retrospective piece. Three therapeutic protocols (compound glycyrrhizic glycoside combined with aspartic ornithine injection, compound glycyrrhizic glycoside combined with phosphatidylcholine, and compound glycyrrhizic glycoside combined with tiopronin) were selected. Seventy inpatient cases from January 2011 to February 2012 were enrolled and divided into three groups according to different regimens. The cost effectiveness of the three groups was respectively evaluated by incremental cost-effectiveness ratios (ICERs). A decision tree model and multi attribution utility theory were also adopted to analyze the data. Results All the three regimens exhibited good effects on protecting liver functions and reducing the levels of enzymes. Among them, the protocol of compound glycyrrhizic glycoside combined with tioproni expressed the least ICER, the lowest cost but the highest score in the multi-utility. Conclusion The therapeutic method of compound glycyrrhizic glycoside combined with tiopronin is the most cost-effective option in this study.