37 research outputs found
Antiprotozoal activity-based profiling of a dichloromethane extract from anthemis nobilis flowers
A dichlomethane extract of Anthemis nobilis flower cones showed promising in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense and Leishmania donovani, 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 seco-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 15 showed high potency and selectivity in vitro against T. b. rhodesiense bloodstream forms (IC50 0.08 ± 0.01 μM; SI 63). In silico calculations were consistent with the drug-like properties of 15
Secondary Metabolites in Allergic Plant Pollen Samples Modulate Afferent Neurons and Murine Tracheal Rings
Plant pollens are strong airborne elicitors of asthma. Their proteinaceous allergens have been studied intensively, but little is known about a possible contribution of pollen secondary metabolites to the nonallergic exacerbation of asthma. Pollen samples originating from 30 plant species were analyzed by HPLC coupled to PDA, ESIMS, and ELSD detectors and off-line NMR spectroscopy. Polyamine conjugates, flavonoids, and sesquiterpene lactones were identified. Polyamine conjugates were characteristic of all Asteraceae species. The presence of sesquiterpene lactones in Asteraceae pollen varied between species and pollen lots. All plant pollen, including those from non-Asteraceae species, contained to some extent electrophiles as determined by their reaction with N-acetyl-l-cysteine. Selected pollen extracts and pure compounds were tested in murine afferent neurons and in murine tracheal preparations. Tetrahydrofuran extracts of Ambrosia artemisiifolia and Ambrosia psilostachya pollen and a mixture of sesquiterpene lactones coronopilin/parthenin increased the intracellular Ca2+ concentration in 15%, 32%, and 37% of cinnamaldehyde-responsive neurons, respectively. In organ bath experiments, only the sesquiterpene lactones tested induced a weak dilatation of naĂŻve tracheas and strongly lowered the maximal methacholine-induced tracheal constriction. A tetrahydrofuran extract of A. psilostachya and coronopilin/parthenin led to a time-dependent relaxation of the methacholine-preconstricted trachea. These results provide the first evidence for a potential role of pollen secondary metabolites in the modulation of the tracheal tone
Acid-Induced Rearrangement of Epoxygermacranolides: Synthesis of Furanoheliangolides and Cadinanes from Nobilin
The acid-induced rearrangement of three epoxyderivatives of nobilin 1, the most abundant sesquiterpene lactone in Anthemis nobilis flowers, was investigated. From the 1,10-epoxyderivative 2, furanoheliangolide 5 was obtained, while the 4,5-epoxy group of 3 did not react. Conversely, when the 3-hydroxy function of nobilin was acetylated (12), the 4,5-epoxy derivative did cyclize into cadinanes (15 and 16) under Lewis acid catalysis. The reactivity of the 4,5- and 1,10-epoxy derivatives of nobilin (2 and 3) was compared with that of parthenolide, and rationalized on the basis of quantum chemical calculations. All isolated reaction products were fully characterized by spectroscopic and computational methods, and their in vitro anti-protozoal activity was evaluated. The paper could provide new insights into the biosynthesis of this class of natural products
Anti-proliferative activity-guided isolation of clerodermic acid from Salvia nemorosa L.: Geno/cytotoxicity and hypoxia-mediated mechanism of action
The adaptation of solid tumors to the low oxygen/nutrient environment is mediated by the pivotal transcription role of hypoxia-inducible factor-1 (HIF-1). Thus, the HIF-1 and its subunits have been considered to be hopeful anti-cancer targets. Various natural compounds were reported to persuade cell cytotoxicity through targeting and downregulation of the HIF-1. The genus Salvia is a rich source of bioactive terpenoids which show promising anti-cancer activities. Here, the identification of natural anti-proliferative compound targeting the HIF-1α expression was reported. A bioassay-guided isolation was employed for the discovery of natural anti-proliferative compounds from Salvia extracts using MTT assay against A549 cells. In this direction, clerodermic acid (CDA) as a potent cytotoxic compound was purified from Salvia nemorosa and identified using 1D and 2D NMR analysis. Results indicated that CDA has anti-proliferation activity (IC50 value of 35 μg/mL) which was confirmed by genotoxicity and apoptosis detection analyses. The quantitative qPCR analysis showed that the expression level of HIF-1 alpha was strongly inhibited in the hypoxic cells treated with CDA compared to the untreated cells tolerated hypoxia. Findings exhibited that S. nemorosa and clerodermic acid have significant potential for reducing HIF-1α expression and could be considered for further studies for cancer therapy
New Acylated Flavonol Glycosides and a Phenolic Profile of Pritzelago alpina, a Forgotten Edible Alpine Plant
Thirteen acylated flavonoid glycosides, 1-13, including eleven new congeners, 3-13, were isolated from the aerial parts of Pritzelago alpina (Brassicaceae) by a combination of column chromatography on Sephadex LH-20, and preparative and semi-preparative HPLC. The structures were established by extensive NMR and MS experiments in combination with acid hydrolysis and sugar analysis by GC/MS. The new compounds were shown to be kaempferol and quercetin glycosides acylated for most of them by a branched short chain fatty acid or a hydroxycinnamic acid residue on the sugar portion. As shown by a HPLC-DAD analysis of a MeOH extract, these compounds are the main phenolic constituents in the aerial parts of the plant
Biological activity of constituents of Salvia chamaedryoides
Salvia chamaedryoides Cav. (Lamiaceae) is a Mexican species [1] recently introduced in the Ligurian agricultural market as an ornamental plant, and for extractive purposes [2]. The dichloromethane extract of the aerial parts was investigated for its antimicrobial and hypoglycaemic properties with the aid of bioassay-\uad\u2010oriented fractionation. Six new clerodane diterpenes
along with six known compounds were isolated, and their structures established by extensive 1D and 2D NMR, and HRESI-\uad\u2010TOFMS. For determination of the absolute configuration acetonide derivatives were prepared, and analyzed by comparison
of experimental and calculated ECD spectra. The antimicrobial activity was analyzed on several Gram positive (Staphylococcus
aureus, S. epidermidis, Enterococcus faecium, E. faecalis, Streptococcus pyogenes, S. agalactiae) and Gram negative (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Moraxella catarrhalis) bacteria, including multidrug resistant strains. The total extract displayed the strongest activity (MIC 2-\uad\u20104 \u3bcg/mL), while almost all semi-\uad\u2010purified fractions and one pure compound (MIC 32-\uad\u2010128 were active on both staphylococci and enterococci. The potential hypoglycaemic properties
were evaluated by measuring the inhibitory properties of extract, fractions, and pure compounds against \u3b1-\uad\u2010amylase and \u3b1-\uad\u2010glucosidase. Some of the isolated compounds showed a moderate inhibitory activity against \u3b1-\uad\u2010amylase, while the highest activity was found against \u3b1-\uad\u2010glucosidase. Three compounds showed IC50 values ranging from 0.20 to 0.29 mM and were
stronger inhibitors than the positive control acarbose (IC50=0.45mM). Our results indicate that S. chamaedryoides can be
considered as a plant with activity against important Gram positive human pathogens, and may also be helpful to control
postprandial hyperglycemia. Keywords:
Salvia
chamaedryoides,
antimicrobial
activity,
hypoglycaemic
activity
References
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Metabolite Profile and Antiproliferative Effects in HaCaT Cells of a Salix reticulata Extract
Phenolic constituents of Salix reticulata (Salicaceae) and antiproliferative activity of an extract and individual compounds were investigated in immortalized human non-tumorigenic keratinocytes (HaCaT). A MeOH extract from aerial parts afforded several flavonoids, including luteolin and apigenin glycosides (2–5 and 9) and catechin (1), two procyanidin fractions, and the phenolic glucosides picein (6), triandrin (7), and salicortin (8). In an adenosine triphosphate assay, the MeOH extract reduced cell viability by approximately 60 % at a concentration of 100 µg/mL. Cell proliferation was assessed with a BrdU incorporation ELISA assay. The extract inhibited proliferation of HaCaT cells in a concentration-dependent manner, with approximately 50 % inhibition at 100 µg/mL. In time-lapse assays, the extract showed distinct inhibitory effects on cell migration at concentrations of 12.5, 25, and 50 µg/mL. The activity of selected constituents was also determined. Luteolin-7-O-β-glucuronide (3) significantly inhibited cell proliferation at concentrations of 10 and 50 µM. In contrast, luteolin-7-O-β-glucopyranoside (2) and a procyanidin fraction (P1) had only weak effects, while picein (6) and salicortin (8) did not affect cell proliferation. Luteolin-7-O-β-glucuronide (10 µM) and, to a lesser extent, the procyanidin fraction (10 µg/mL) also inhibited cell migration
Mechanism of chemical degradation and determination of solubility by kinetic modeling of the highly unstable sesquiterpene lactone nobilin in different media
HPLC-Based Activity Profiling for GABA<sub>A</sub> 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><sub>GABA</sub>) through receptors
of the subtype α<sub>1</sub>β<sub>2</sub>γ<sub>2s</sub> 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 EC<sub>50</sub> values between 2.8 ± 1.4 and 18.8
± 2.3 μM. Maximal potentiation of <i>I</i><sub>GABA</sub> ranged between 490% and 640%. This is the first report
of pterocarpans as GABA<sub>A</sub> 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 IC<sub>50</sub> values of 1.43 ± 0.50 and 1.40 ±
0.07 ÎĽg/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 (IC<sub>50</sub> 0.08 ±
0.01 ÎĽM; SI 63). In silico calculations were consistent with
the drug-like properties of <b>15</b>