Molecules2014, 19(4), 4956-4966; doi:10.3390/molecules19044956 (doi registration under processing) - published online 17 April 2014 Show/Hide Abstract
Abstract: Many recent studies have suggested that activation of the aryl hydrocarbon receptor (AhR) reduces immune responses, thus suppressing allergies and autoimmune diseases. In our continuing study on natural AhR agonists in foods, we examined the influence of 37 health food materials on the AhR using a reporter gene assay, and found that aqueous ethanol extracts of cassia seed and rosemary had particularly high AhR activity. To characterize the AhR-activating substances in these samples, the chemical constituents of the respective extracts were identified. From an active ethyl acetate fraction of the cassia seed extract, eight aromatic compounds were isolated. Among these compounds, aurantio-obtusin, an anthraquinone, elicited marked AhR activation. Chromatographic separation of an active ethyl acetate fraction of the rosemary extract gave nine compounds. Among these compounds, cirsimaritin induced AhR activity at 10–102 μM, and nepitrin and homoplantagenin, which are flavone glucosides, showed marked AhR activation at 10–103 μM.
Molecules2014, 19(4), 4941-4955; doi:10.3390/molecules19044941 (doi registration under processing) - published online 17 April 2014 Show/Hide Abstract
Abstract: Camptothecin-20(s)-O-(2-pyrazolyl-1)acetic ester (CPT6) is a novel semi-synthetic analog of camptothecin. In a previous report, CPT6 possessed higher cytotoxic activity in vitro towards human breast tumor MCF-7 cells than topotecan. In this study, the antitumor activity of CPT6 on the human breast tumor MCF-7 cell line was analyzed using the MTT method. The underlying mechanism of CPT6 action was investigated by analyzing the cell cycle distribution, apoptotic proportion, changes in mitochondrial membrane potential, and intracellular Ca2+ concentration using flow cytometry. Nuclear and mitochondrial morphologies were also observed by laser scanning confocal and transmission electron microscopy. DNA damage was observed in MCF-7 cells treated with CPT6. Low-dose CPT6 had a significant cytotoxic effect and could inhibit proliferation and induce apoptosis in MCF-7 cells, possibly through cell nucleus fragmentation and DNA damage. CPT6 thus appears to display potent antitumor activity against human breast tumor MCF-7 cells via the induction of apoptosis, and may be a useful alternative drug for breast cancer therapy.
Molecules2014, 19(4), 4924-4940; doi:10.3390/molecules19044924 (doi registration under processing) - published online 17 April 2014 Show/Hide Abstract
Abstract: Oleanolic and ursolic acids are natural triterpenic compounds with pentacyclic cholesterol-like structures which gives them very low water solubility, a significant disadvantage in terms of bioavailability. We previously reported the synthesis of inclusion complexes between these acids and cyclodextrins, as well as their in vivo evaluation on chemically induced skin cancer experimental models. In this study the synergistic activity of the acid mixture included inside hydroxypropyl-gamma-cyclodextrin (HPGCD) was monitored using in vitro tests and in vivo skin cancer models. The coefficient of drug interaction (CDI) was used to characterize the interactions as synergism, additivity or antagonism. Our results revealed an increased antitumor activity for the mixture of the two triterpenic acids, both single and in complex with cyclodextrin, thus proving their complementary biologic activities.
Molecules2014, 19(4), 4907-4923; doi:10.3390/molecules19044907 (doi registration under processing) - published online 17 April 2014 Show/Hide Abstract
Abstract: A simple, rapid and sensitive chiral capillary zone electrophoresis coupled with acetonitrile-field-amplified sample stacking method was developed that allows the simultaneous enantioselective separation of the mirtazapine, N-demethylmirtazapine, 8-hydroxymirtazapine and mirtazapine-N-oxide. The separation was achieved on an uncoated 40.2 cm × 75 μM fused silica capillary with an applied voltage of 16 kV. The electrophoretic analyses were carried out in 6.25 mM borate–25 mM phosphate solution at pH 2.8 containing 5.5 mg/mL carboxymethyl-β-cyclodextrin. The detection wavelength was 200 nm. Under these optimized conditions, satisfactory chiral separations of four pair enantiomers were achieved in less than 7 min in vitro. After one step clean-up liquid-liquid extraction using 96-well format, sample was introduced capillary zone electrophoresis with acetonitrile-field-amplified sample stacking to enhance the sensitivity of enantiomers. The method was validated with respect to specificity, linearity, lower limit of quantitation, accuracy, precision, extraction recovery and stability. The lower limit of quantification was 0.5 ng/mL with linear response over the 0.5–50 ng/mL concentration range for each mirtazapine, N-demethylmirtazapine and 8-hydroxymirtazapine enantiomer. The developed and validated method has been successfully applied to the enantioselective pharmacokinetic studies in 12 healthy volunteers after oral administration of rac- mirtazapine.
Molecules2014, 19(4), 4897-4906; doi:10.3390/molecules19044897 (doi registration under processing) - published online 17 April 2014 Show/Hide Abstract
Abstract: Three new ursane triterpenes, 3α,19α-dihydroxy-2-nor-urs-12-en-23,28-dioic acid-23-methyl ester (1), 19α,23-dihydroxy-3-oxo-2-nor-urs-12-en-28-oic acid (2), and 2,3-seco-3-methoxy-3,19α,23-trihydroxy-urs-12-en-2-al-28-oic acid (3), were isolated from the MeOH extract of the branch barks of Davidia involucrata, together with six known compounds. Their structures were elucidated by means of various spectroscopic analyses. The isolated triterpenes provide important evolutionary and chemotaxonomic knowledge about the monotypic genus Davidia. Five of the identified compounds showed moderate cytotoxicities against the cell proliferation of SGC-7901, MCF-7, and BEL-7404 with IC50 range from 7.26 to 47.41 μM.
Molecules2014, 19(4), 4880-4896; doi:10.3390/molecules19044880 (doi registration under processing) - published online 17 April 2014 Show/Hide Abstract
Abstract: The aim of this study was tocompare several methods for measurement of bovine serum albumin (BSA) modification by glycoxidation with reactive dicarbonyl compounds (methylglyoxal ‒ MGO and glyoxal ‒ GO), for studies of the kinetics of this process and to compare the effects of 19 selected compounds on BSA glycation by the aldehydes. The results confirm the higher reactivity of MGO with respect to GO and point to the usefulness of AGE, dityrosine and N′-formylkynurenine fluorescence for monitoring glycation and evaluation of protection against glycation. Different extent of protection against glycation induced by MGO and GO was found for many compounds, probably reflecting effects on various stages of the glycation process. Polyphenols (genistein, naringin and ellagic acid) were found to protect against aldehyde-induced glycation; 1-cyano-4-hydroxycinnamic acid was also an effective protector.