Diversity-oriented synthesis of marine sponge derived hyrtioreticulins and their anti-inflammatory activities.

Diversity-oriented synthesis is aimed to increase the chemical diversity of target natural products for extensive biological activity evaluation. Indole ring is an important functional group in a large number of drugs and other biologically active agents, and indole-containing natural products have been frequently isolated from marine sources in recent years. In this paper, a series of indole-containing marine natural hyrtioreticulin derivatives, including 19 new ones, were designed, synthesized through a key Pictet-Spengler reaction, and evaluated for their inflammation related activity. Compound 13b displayed the most promising activity by inhibiting TNF-α cytokine release with an inhibitory rate of 92% at a concentration of 20 µmol·L-1. A preliminary structure-activity relationship analysis was also discussed. This research may throw light on the discovery of marine indole alkaloid derived anti-inflammatory drug leads.

[Chromatographic Fingerprinting Study of Zhenyuan Granules Dry Extract by HPLC-DAD and HPLC-MS/MS].

OBJECTIVE: To establish a novel, accurate and valid fingerprint method of Zhenyuan granules dry extract by using HPLC-DAD method, to study herbs belonging of fingerprint peaks and to identify some of the chromatographic peaks by HPLC-MS/MS analysis, for providing the basis for scientific evaluation of the quality. METHODS: The sample solutions were analyzed by an Agilent SB C18 (250 mm x 4.6 mm, 5 µm) column, and gradiently eluted with acetonitrile (containing 0.1% formic acid) and aqueous phase (containing 0.1% formic acid) as the mobile phase. The flow rates were 1.2 mL/min (0~70 min) and 0.8 mL/min (70~150 min); the column temperature was 30 °C; and the detection wavelength was 254 nm. RESULTS: 40 peaks were selected as fingerprint peaks under the optimal chromatographic condition, and the similarity coefficients of 10 batches of Zhenyuan granules dry extract were all greater than 0.98. 27 peaks were tentatively identified with reference to literature data based on their mass spectrometry. CONCLUSION: The chromatographic fingerprint of Zhenyuan granules is proved to be a reliable method for comprehensive quality control and assessment.

[Extraction Optimization of Rhizome of Curcuma longa by Response Surface Methodology and Support Vector Regression].

OBJECTIVE: To optimize the optimal microwave-assisted extraction method of curcuminoids from Curcuma longa. METHODS: On the base of single factor experiment, the ethanol concentration, the ratio of liquid to solid and the microwave time were selected for further optimization. Support Vector Regression (SVR) and Central Composite Design-Response Surface Methodology (CCD) algorithm were utilized to design and establish models respectively, while Particle Swarm Optimization (PSO) was introduced to optimize the parameters of SVR models and to search optimal points of models. The evaluation indicator, the sum of curcumin, demethoxycurcumin and bisdemethoxycurcumin by HPLC, were used. RESULTS: The optimal parameters of microwave-assisted extraction were as follows: ethanol concentration of 69%, ratio of liquid to solid of 21 : 1, microwave time of 55 s. On those conditions, the sum of three curcuminoids was 28.97 mg/g (per gram of rhizomes powder). CONCLUSION: Both the CCD model and the SVR model were credible, for they have predicted the similar process condition and the deviation of yield were less than 1.2%.

Feature selection for the identification of antitumor compounds in the alcohol total extracts of Curcuma longa.

Antitumor activity has been reported for turmeric, the dried rhizome of Curcuma longa. This study proposes a new feature selection method for the identification of the antitumor compounds in turmeric total extracts. The chemical composition of turmeric total extracts was analyzed by gas chromatography-mass spectrometry (21 ingredients) and high-performance liquid chromatography-mass spectrometry (22 ingredients), and their cytotoxicity was detected through an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay against HeLa cells. A support vector machine for regression and a generalized regression neural network were used to research the composition-activity relationship and were later combined with the mean impact value to identify the antitumor compounds. The results showed that six volatile constituents (three terpenes and three ketones) and seven nonvolatile constituents (five curcuminoids and two unknown ingredients) with high absolute mean impact values exhibited a significant correlation with the cytotoxicity against HeLa cells. With the exception of the two unknown ingredients, the identified 11 constituents have been reported to exhibit cytotoxicity. This finding indicates that the feature selection method may be a supplementary tool for the identification of active compounds from herbs.

Identification of antitumor constituents in curcuminoids from Curcuma longa L. based on the composition-activity relationship.

Using orthogonal partial least squares (OPLS), based on the Simca-p11.5 software, and canonical correlation analysis (CCA), performed on MatLab r2010 software, the correlation between curcuminoids extracted from Curcuma longa L. and the antitumor activity on HeLa cells was investigated to identify the significantly active constituents. Fingerprints from 31 batches of curcuminoids from C. longa L. were established using high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS), and a total of 26 selected characteristic peaks were quantitatively analyzed. Afterward, the antitumor activities of the curcuminoids on HeLa cells were measured using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. We found that 13 of the curcuminoids (peaks 9, 18, 14, 8, 16, 17, 24, 12, 4, 13, 10, 20 and 11) were significantly correlated with antitumor activity via a Loadings plot and VIP (variable importance in projection) in OPLS and a correlation coefficient in CCA. These results support a method for the discovery of antitumor active constituents.

[Stability of physical state on compound hawthorn dropping pills].

OBJECTIVE: To evaluate the stability of physical state with accelerate test and dropping in process before and after on compound hawthorn dropping pills. METHOD: Scanning electron microscope, TG-DTA, FT-IR and XRD were used. RESULT: The active components presented amorphous, tiny crystal and molecular state in dropping pills, and it had no obvious reaction between PEG 4000 and active components. With time prolonging, a little of active components changed from amorphous state to tiny crystal or molecular state. CONCLUSION: Solid dispersion improved the stability and dissolution of compound hawthorn dropping pills.