Antiangiogenic Tocotrienol Derivatives from <i>Garcinia amplexicaulis</i>

Phytochemical investigation of a dichloromethane extract from <i>Garcinia amplexicaulis</i> stem bark led to the isolation of four new tocotrienols (<b>1</b>–<b>4</b>); two known tocotrienols, two triterpenes, and a xanthone were also isolated. Their structures were mainly established using NMR and MS methods. The main compounds isolated, δ-amplexichromanol (<b>1</b>) and γ-amplexichromanol (<b>2</b>), were evaluated on VEGF-induced angiogenesis using a Matrigel assay. Compounds <b>1</b> and <b>2</b> inhibited in vitro angiogenesis of VEGF-induced human primary endothelial cells in the low nanomolar range. Their capacity to inhibit VEGF-induced proliferation of endothelial cells partially explained this activity, although δ-amplexichromanol (<b>1</b>) also prevented adhesion and migration processes

Effect of NPs 1–6 and 8–11 on endothelial cell viability.

<p>Cell viability was assessed on confluent EC monolayers using MTT assay. Cells were incubated with NPs (10 μM) for 48h before analysis. Diluted DMSO (1/1000 –dark dashed line) was used as control for diluent (Dil), as well as a non-treated (NT) control—grey dashed line—and the cytotoxicity positive control glyoxal (Gly) at 4 mM. The cytotoxic activity of the immunosuppressive drug zoledronic acid (ZA, 10 μM) was also assessed. Statistical analysis of values (O.D.) obtained for treated versus non-treated cells were performed using non-parametric ANOVA test.</p

Prenylated polyphenols from <i>Clusiaceae</i> and <i>Calophyllaceae</i> as regulators of inflammation and immunity: Overview and hypothesis.

<p>(1) NPs efficiently inhibit the induction of VCAM-1, an adhesion molecule involved in the firm adhesion of leukocytes on inflamed endothelium and a prerequisite step for leukocyte activation (2) and extravasation in the tissues. (3) NPs strongly impair the expression of MHC molecules expressed on endothelium and involved in innate and adaptive immunity via the activation of NK and CD4T and CD8T cells, respectively.</p

Basal <i>versus</i> IFNγ-modulated expression of MHC class I, MHC class II, HLA-E and MICA on EC cultures.

<p>ECs were treated with or without IFNγ for 48h before analysis. Data shown are representative histograms from Facs analysis showing constitutive <i>versus</i> IFNγ-regulated expression of inflammatory molecules (MHC class I, MHC class II, HLA-E and MICA) at the EC surface. Histograms show the intensity of fluorescence (log, x-axis) <i>versus</i> cell number (y-axis) for untreated (purple line) and cytokine-treated (green line) ECs analyzed by flow cytometry. Immunostaining using an irrelevant isotype-matched IgG (dark line) was used as a negative control.</p

Effect of compounds 1–6 and 8–11 on TNF-induced expression of inflammatory molecules in ECs.

<p><b>(A) Basal <i>versus</i> TNF-induced expression of VCAM-1, ICAM-1 and E-selectin after 6h of incubation.</b> Data shown are representative histograms from fluorescence-activated cell sorting (Facs) analysis showing constitutive <i>versus</i> induced expression of inflammatory molecules (VCAM-1, ICAM-1, E-selectin) at the cell surface of ECs. Histograms show the intensity of fluorescence (log, x-axis) versus cell number (y-axis) for untreated (purple line) and cytokine-treated (green line) ECs analyzed by flow cytometry. Immunostaining using an irrelevant isotype-matched IgG (dark line) was used as a negative control. (<b>B</b>) <b>Inhibitory effects of NPs.</b> Expression of VCAM-1, ICAM-1 and E-selectin was measured by Facs. Each bar represents geometric mean ± SD of fluorescence intensity calculated from three to five independent experiments. Statistical analysis was performed using Kruskal-Wallis test with Dunn’s post-test; *<i>p</i> < 0.05, **<i>p</i> < 0.01, ***<i>p</i> < 0.001 compared with TNF control group. PDTC (200 μM) was used as a positive control for inhibition.</p

Additional Insights into <i>Hypericum perforatum</i> Content: Isolation, Total Synthesis, and Absolute Configuration of Hyperbiphenyls A and B from Immunomodulatory Root Extracts

Phytochemical investigation of the root extracts of <i>Hypericum perforatum</i> led to the isolation of two biphenyl derivatives named hyperbiphenyls A and B (<b>1</b> and <b>2</b>) and four known xanthones (<b>3</b>–<b>6</b>). These structures were elucidated by spectroscopic and spectrometric methods including UV, NMR, and HRMS. The absolute configuration of the biphenyl derivatives was defined by two different approaches: biomimetic total synthesis of racemic hyperbiphenyl A followed by ¹H and ¹⁹F NMR Mosher’s esters analysis and stereoselective total synthesis of hyperbiphenyl B, permitting assignment of the <i>S</i> absolute configuration for both compounds. The bioactivity of compounds <b>1</b>–<b>6</b> toward a set of biomolecules, including major histocompatibility complex (MHC) molecules expressed on vascular endothelial cells, was measured. The results showed that the major xanthone, i.e., 5-<i>O</i>-methyl-2-deprenylrheediaxanthone B (<b>3</b>), is a potent inhibitor of MHC that efficiently reduces HLA-E, MHC-II, and MICA biomolecules on cell surfaces

Chemical Composition, Antioxidant and Anti-AGEs Activities of a French Poplar Type Propolis

Accumulation in tissues and serum of advanced glycation end-products (AGEs) plays an important role in pathologies such as Alzheimer’s disease or, in the event of complications of diabetes, atherosclerosis or renal failure. Therefore, there is a potential therapeutic interest in compounds able to lower intra and extracellular levels of AGEs. Among them, natural antioxidants (AO) with true anti-AGEs capabilities would represent good candidates for development. The purpose of this study was to evaluate the AO and anti-AGEs potential of a propolis batch and then to identify the main compounds responsible for these effects. In vivo, protein glycation and oxidative stress are closely related. Thus, AO and antiglycation activities were evaluated using both DPPH and ORAC assays, respectively, as well as a newly developed automated anti-AGEs test. Several propolis extracts exhibited very good AO and anti-AGEs activities, and a bioguided fractionation allowed us to identify pinobanksin-3-acetate as the most active component

Range of symptoms observed on leaves 13 days after inoculation.

<p>The symptom number was assessed at 7, 9 and 13(see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101008#pone-0101008-t001" target="_blank">Table 1</a>). The leaves shown here show a symptom severity representative of the plant partial resistance level. <b>A</b>: H1, <b>B</b>: Presto, <b>C</b>: K3, <b>D</b>: H4, <b>E</b>: Bolero, <b>F</b>: I2. H1, K3, H4 and I2 are breeding lines, while Presto and Bolero are widely cultivated Nantaise type carrot cultivars.</p

Range of embryogenic activity observed in cell suspensions 3 weeks after treatment.

<p>In order to assess carrot cell resistance to fungal toxins, carrot cell suspensions were tested for embryogenesis in the presence of fungal extracts and toxins. Embryogenesis was assessed 3 weeks after treatment, and compared to negative controls. Four levels of embryogenic activity were noted. <b>A</b>: (−) no embryogenesis was visible, cells were damaged, <b>B</b>: (+) early-stage embryogenic masses were visible, <b>C</b>: same as B, but after 6 weeks. <b>D</b>: (++) embryos were present, and <b>E</b>: (+++) embryogenesis was profuse.</p

Correlation coefficients for esterase activity ratios.

<p>Carrot cell suspensions with five different genotypes were tested for esterase relative specific activity in the presence of fungal extracts and toxins. The treatments were as follows: rA: <i>A. dauci</i> (strain FRA017) fungal culture raw extract; rM: uninoculated medium raw extract; aA: <i>A. dauci</i> fungal culture aqueous extract; aM, uninoculated medium aqueous extract; oA: <i>A.dauci</i> fungal culture organic extract; oM: uninoculated medium organic extract; DMSO: DMSO solution at a concentration corresponding to oM, z1, z2 and z3 treatments; z1: 0.025 µM zinniol; z2: 10 µM zinniol; z3: 500 µM zinniol. Correlation coefficients corresponding to significant (α = 0.05) linear regressions are in bold.</p