HPLC-Based Activity Profiling for GABA_A Receptor Modulators in <i>Adenocarpus cincinnatus</i>

In a two-microelectrode voltage clamp assay with <i>Xenopus laevis</i> oocytes, a dichloromethane extract of <i>Adenocarpus cincinnatus</i> roots and tubers (Leguminosae) enhanced the GABA-induced chloride current (<i>I</i>_GABA) through receptors of the subtype α₁β₂γ_2s by 126.5 ± 25.1% when tested at 100 μg/mL. By means of HPLC-based activity profiling, 15 flavonoid and isoflavonoid derivatives, including eight new compounds, were identified in the active fractions of the extract. Isoflavone <b>11</b> and pterocarpans <b>2</b> and <b>8</b> showed promising activity in the oocyte assay, with EC₅₀ values between 2.8 ± 1.4 and 18.8 ± 2.3 μM. Maximal potentiation of <i>I</i>_GABA ranged between 490% and 640%. This is the first report of pterocarpans as GABA_A receptor modulators

Antiprotozoal Activity-Based Profiling of a Dichloromethane Extract from <i>Anthemis nobilis</i> Flowers

A dichlomethane extract of <i>Anthemis nobilis</i> flower cones showed promising in vitro antiprotozoal activity against <i>Trypanosoma brucei rhodesiense</i> and <i>Leishmania donovani</i>, with IC₅₀ values of 1.43 ± 0.50 and 1.40 ± 0.07 μg/mL, respectively. A comprehensive profiling of the most active fractions afforded 19 sesquiterpene lactones, including 15 germacranolides, two <i>seco</i>-sesquiterpenes, one guaianolide sesquiterpene lactone, and one cadinane acid. Of these, 13 compounds were found to be new natural products. The compounds were characterized by extensive spectroscopic data analysis (1D and 2D NMR, HRMS, circular dichroism) and computational methods, and their in vitro antiprotozoal activity was evaluated. The furanoheliangolide derivative <b>15</b> showed high potency and selectivity in vitro against <i>T. b. rhodesiense</i> bloodstream forms (IC₅₀ 0.08 ± 0.01 μM; SI 63). In silico calculations were consistent with the drug-like properties of <b>15</b>

Gene expression levels of selected genes in MCF-7 cells after 24 h treatment with black cohosh extract (15 μg/ml), the triterpene glycoside actein (20 μM) or the triterpene aglycon mixture (30 μM)

<p><b>Copyright information:</b></p><p>Taken from "Gene expression profiling reveals effects of (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7"</p><p>http://www.biomedcentral.com/1471-2210/7/11</p><p>BMC Pharmacology 2007;7():11-11.</p><p>Published online 20 Sep 2007</p><p>PMCID:PMC2194763.</p><p></p> For extract treatment results obtained with microarrays () and real-time RT-PCR () are shown. For actein () and the aglycons () expression levels were determined by real-time RT-PCR. Bars represent gene expression levels as fold changes calculated DMSO control. RT-PCR measurements were done at least in triplicate. The data are presented as means ± SD (*p < 0.05, **p < 0.01, ***p < 0.001: gene expression statistically significantly different from DMSO control, calculated by Student's t-test)

Automated Comparative Metabolite Profiling of Large LC-ESIMS Data Sets in an ACD/MS Workbook Suite Add-in, and Data Clustering on a New Open-Source Web Platform FreeClust

The technological development of LC-MS instrumentation has led to significant improvements of performance and sensitivity, enabling high-throughput analysis of complex samples, such as plant extracts. Most software suites allow preprocessing of LC-MS chromatograms to obtain comprehensive information on single constituents. However, more advanced processing needs, such as the systematic and unbiased comparative metabolite profiling of large numbers of complex LC-MS chromatograms remains a challenge. Currently, users have to rely on different tools to perform such data analyses. We developed a two-step protocol comprising a comparative metabolite profiling tool integrated in ACD/MS Workbook Suite, and a web platform developed in R language designed for clustering and visualization of chromatographic data. Initially, all relevant chromatographic and spectroscopic data (retention time, molecular ions with the respective ion abundance, and sample names) are automatically extracted and assembled in an Excel spreadsheet. The file is then loaded into an online web application that includes various statistical algorithms and provides the user with tools to compare and visualize the results in intuitive 2D heatmaps. We applied this workflow to LC-ESIMS profiles obtained from 69 honey samples. Within few hours of calculation with a standard PC, honey samples were preprocessed and organized in clusters based on their metabolite profile similarities, thereby highlighting the common metabolite patterns and distributions among samples. Implementation in the ACD/Laboratories software package enables ulterior integration of other analytical data, and in silico prediction tools for modern drug discovery

Manoyloxide Sesterterpenoids from <i>Salvia mirzayanii</i>

Five new manoyloxide-type sesterterpenes were isolated from aerial parts of <i>Salvia mirzayanii,</i> a species endemic to Iran. The planar structures were established by means of 1D and 2D NMR and HRESIMS. Compounds <b>1</b>–<b>3</b> differed only in their configurations at C-13 and C-14. Assignment of relative and absolute configurations was achieved by NOESY experiments and by comparison of experimental and simulated ECD spectra of possible stereoisomers. The absolute configurations of <b>4</b> and <b>5</b> were established in a similar manner

Library-Based Discovery and Characterization of Daphnane Diterpenes as Potent and Selective HIV Inhibitors in <i>Daphne gnidium</i>

Despite the existence of an extended armamentarium of effective synthetic drugs to treat HIV, there is a continuing need for new potent and affordable drugs. Given the successful history of natural product based drug discovery, a library of close to one thousand plant and fungal extracts was screened for antiretroviral activity. A dichloromethane extract of the aerial parts of <i>Daphne gnidium</i> exhibited strong antiretroviral activity and absence of cytotoxicity. With the aid of HPLC-based activity profiling, the antiviral activity could be tracked to four daphnane derivatives, namely, daphnetoxin (<b>1</b>), gnidicin (<b>2</b>), gniditrin (<b>3</b>), and excoecariatoxin (<b>4</b>). Detailed anti-HIV profiling revealed that the pure compounds were active against multidrug-resistant viruses irrespective of their cellular tropism. Mode of action studies that narrowed the site of activity to viral entry events suggested a direct interference with the expression of the two main HIV co-receptors, CCR5 and CXCR4, at the cell surface by daphnetoxin (<b>1</b>)

A nor-diterpene from <i>Salvia sahendica</i> leaves

<p>Phytochemical investigation of <i>n</i>-hexane extract of <i>Salvia sahendica</i> by normal phase column chromatography resulted in the isolation of six compounds. Structures were established by 1D and 2D NMR spectroscopy, and HRMS, as a new norditerpene <b>1</b>, and known terpenoids, sclareol (<b>2</b>), oleanolic acid (<b>3</b>), β-sitosterol (<b>4</b>), salvigenin (<b>5</b>) and 3<i>α</i>-hydroxy-11<i>α</i>,12<i>α</i>-epoxyoleanan-28,13<i>β</i>-olide (<b>6</b>). The absolute configuration of <b>1</b> was confirmed by a combination of X-ray single crystal analysis and electronic circular dichroism spectroscopy. <i>In vitro</i> cytotoxic activity on breast cancer cell line (MDA-MB-231) and also the antimicrobial activity of the pure compounds were tested against <i>Staphylococcus aureus</i>, <i>Bacilus cereus</i> and <i>Escherichia coli</i>.</p

Additional file 1: of Swiss ethnoveterinary knowledge on medicinal plants – a within-country comparison of Italian speaking regions with north-western German speaking regions

Use reports of Swiss farmers in a) Italian speaking regions and b) north western German speaking Cantons. (PDF 185 kb

Additional file 2: of Swiss ethnoveterinary knowledge on medicinal plants – a within-country comparison of Italian speaking regions with north-western German speaking regions

List of all reported plant species used to treat animals in West Alps regions. (PDF 139 kb

Hydrangenone, a New Isoprenoid with an Unprecedented Skeleton from <i>Salvia hydrangea</i>

Hydrangenone, a new heptacyclic isoprenoid with a 6/7/6/5/5 membered carbon ring skeleton, was isolated from the aerial parts of <i>Salvia hydrangea.</i> The structure was established by extensive NMR spectroscopic methods. The relative and absolute configuration of <b>1</b> was assigned by NOESY and X-ray crystallographic analysis and by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compound <b>1</b> showed in vitro antiplasmodial activity, with an IC₅₀ value of 1.4 μM against <i>P. falciparum</i>. A plausible biosynthetic pathway of <b>1</b> was also proposed