Composition of Algerian Propolis, Plant Origin, and Its Antiangiogenic Activity In Vitro.

The antiangiogenic activity of the ethanol extract of propolis collected from different regions in western Algeria was investigated using in vitro human umbilical vein endothelial cells (HUVECs). The ethanol extract with the strongest activity, i.e., Algerian propolis 1 (EEPA1), inhibited the formation of capillary networks in a dose-dependent manner (6.25-50 µg/mL) within 12 h and induced cell fragmentation of HUVECs at 50 µg/mL after treatment for 24 h. To identify the active compounds in EEAP1, a high-performance liquid chromatography (HPLC) analysis was performed, revealing that EEAP1 contains two major compounds. Both compounds were isolated by repeated column chromatography and identified as ω-hydroxyferulenol (1) and ferulenol (2), which have a coumarin structure conjugated with a farnesyl group according to NMR, high-resolution electrospray ionization mass spectroscopy, and chemical modification. Compounds 1 and 2 inhibited the tube-forming activity of HUVECs, especially 2, which exhibited a stronger antiangiogenic effect even at a low concentration of 3.31 µg/mL. Moreover, 2 suppressed the elongation and induced cell fragmentation at the same dose. The molecular changes in tube-forming HUVECs induced by 2 were found to be related to the activation of the caspase signals. To confirm the plant origin of propolis, an HPLC comparative analysis of the ethanol extracts of some plants near beekeeping areas and that of Algerian propolis (EEAP1) was performed, and similar chromatographic patterns were observed. This result suggests that the plant origin of this Algerian propolis is the resin of Ferula communis.

5-Hydroxyferulic acid methyl ester isolated from wasabi leaves inhibits 3T3-L1 adipocyte differentiation.

To investigate the compounds present in wasabi leaves (Wasabia japonica Matsumura) that inhibit the adipocyte differentiation, activity-guided fractionation was performed on these leaves. 5-Hydroxyferulic acid methyl ester (1: 5-HFA ester), one of the phenylpropanoids, was isolated from wasabi leaves as a compound that inhibits the adipocyte differentiation. Compound 1 suppressed the intracellular lipid accumulation of 3T3-L1 cells without significant cytotoxicity. Gene expression analysis revealed that 1 suppressed the mRNA expression of 2 master regulators of adipocyte differentiation, PPARγ and C/EBPα. Furthermore, 1 downregulated the expression of adipogenesis-related genes, GLUT4, LPL, SREBP-1c, ACC, and FAS. Protein expression analysis revealed that 1 suppressed PPARγ protein expression. Moreover, to investigate the relationship between the structure and activity of inhibiting the adipocyte differentiation, we synthesized 12 kinds of phenylpropanoid analog. Comparison of the activity among 1 and its analogs suggested that the compound containing the substructure that possess a common functional group at the ortho position such as a catechol group exhibits the activity of inhibiting the adipocyte differentiation. Taken together, our findings suggest that 1 from wasabi leaves inhibits adipocyte differentiation via the downregulation of PPARγ.

Binding of Catechins to Staphylococcal Enterotoxin A.

Staphylococcal enterotoxin A (SEA) is a toxin protein, and is the most common cause of staphylococcal food poisoning. Polyphenols, such as catechins, are known to interact with proteins. In this study, we investigated the binding of catechins to SEA using SPR (Biacore), Fourier transform infrared spectroscopy (FT-IR), isothermal titration calorimetry (ITC), and protein-ligand docking. We found that (−)-epigallocatechin gallate (EGCG) could strongly bind to SEA. According to thermodynamic parameters, a negative ΔG indicated that the interaction between EGCG and SEA was spontaneous, and the electrostatic force accompanied by hydrophobic binding forces may play a major role in the binding. Data from Western blot analysis and docking simulation suggest that the hydroxyl group at position 3 of the galloyl group in the catechin structure was responsible for binding affinity with the Y91 of the A-6 region of SEA active sites. Our results provide further understanding of the binding interactions between catechins and SEA, and the inhibition of toxin activities by catechins.

Principal component analysis of molecularly based signals from infant formula contaminations using LC-MS and NMR in foodomics.

BACKGROUND: The challenge in developing analytical assessment of unexpected excess contaminations in infant formula has been the most significant project to address the widespread issue of food safety and security. Foodomics based on metabolomics techniques provides powerful tools for the detection of tampering cases with intentional contaminations. However, the safety and risk assessments of infant formula to reveal not only the targeted presence of toxic chemicals, but also molecular changes involving unexpected contaminations, have not been reported. In this study, a huge amount of raw molecularly based signals from infant formula was analysed using reversed phase and hydrophilic interaction chromatography with time-of-flight MS (LC-MS) and (1) H nuclear magnetic resonance (NMR) and then processed by a principal component analysis (PCA). RESULTS: PCA plots visualised signature trends in the complex signal-data batches from each excess contamination of detectable chemicals by LC-MS and NMR. These trends in the different batches from a portion of excess chemical contaminations such as pesticides, melamine and heavy metals and out-of-date products can be visualised from spectrally discriminated infant formula samples. CONCLUSION: PCA plots provide possible attempts to maximise the covariance between the stable lot-to-lot uniformity and excess exogenous contaminations and/or degradation to discriminate against the molecularly based signals from infant formulas. © 2015 Society of Chemical Industry.

Total Synthesis and Structure Determination of JBIR-108-A 2-Hydroxy-2-(1-hydroxyethyl)-2,3-dihydro-3(2H)-furanone Isolated from Streptomyces gramineus IR087Pi-4.

The planar and stereostructures of JBIR-108 isolated from Streptomyces gramineus IR087Pi-4 were determined partly by spectral analysis, and these structural assignments were confirmed and completed by the total synthesis of both 1-epimers. The key stereocenters in JBIR-108 were constructed via a Corey-Bakshi-Shibata (CBS) reduction (C-1), vinylogous Mukaiyama aldol reaction (C-7), and Brown crotylation (C-14 and C-15). Although it was difficult to determine the stereochemistries at the C-1 and C-7 positions in the natural product using the modified Mosher's method, the synthesis of two possible C-1 diastereomers enabled the identification of the configurations at the hitherto unknown stereocenters.

New acylated anthocyanins from purple yam and their antioxidant activity.

Purple yam (Dioscorea alata L.), which is widely distributed in tropical and subtropical regions, is characterized by its color and viscosity. Previous studies have shown that purple yams contain a variety of acylated anthocyanins that exhibit higher levels of antioxidant activity than the corresponding nonacylated compounds. In this study, the pigments found in purple yams from the Philippines (D. alata) were isolated and evaluated in terms of antioxidant activity. Four new acylated anthocyanins, alanins (1-4) were isolated from the MeOH extracts of purple yam, which were subsequently determined to be cyanidin (1, 2, and 4) and peonidin (3) type compounds, along with four known anthocyanins (5-8). The structures of 1-4 were determined by spectroscopic methods, including NMR and MS analyses. The antioxidant activities of anthocyanins 1-8 were investigated using oxygen radical absorbing capacity and ferric reducing antioxidant power assays.

Effects of Roasting on the Quality of Moringa oleifera Leaf Powder and Loaf Volume of Moringa oleifera-Supplemented Bread.

Although a decrease in bread volume on adding nutrient-rich Moringa oleifera leaf powder (MLP) is known, to our knowledge, improving the swelling of MLP-added bread has not been attempted. This study aimed to investigate the effects of MLP and roasted MLP (RMLP) on bread quality. Bread was supplemented with MLP and RMLP treated at varying temperatures and times; the baked bread was then biochemically evaluated relative to the control. The specific volume of MLP-supplemented bread was 2.4 cm3/g, which increased to >4.0 cm3/g on using MLP roasted at 130 °C for ≥20 min, demonstrating remarkable swelling. The specific volume of bread supplemented with MLP roasted at 170 °C for 20 min was 4.6 cm3/g, similar to that of the control. Additionally, MLP interfered with carbon dioxide production in bread, thus decreasing the abundance of yeast cells; however, RMLP had no such effect and allowed normal fermentation. Scanning electron microscopy revealed gluten formation independent of MLP roasting. Thus, MLP-containing breads generally exhibit suppressed fermentation and expansion due to the bactericidal properties of raw MLP, but these effects are alleviated by heat treatment. These findings highlight the importance of heat treatment in mitigating the effects of MLP on bread fermentation and swelling.

Trichostatin analogues JBIR-109, JBIR-110, and JBIR-111 from the marine sponge-derived Streptomyces sp. RM72.

Three new trichostatin analogues, JBIR-109 (1), JBIR-110 (2), and JBIR-111 (3), were isolated from the culture of the marine sponge-derived Streptomyces sp. strain RM72, together with trichostatin A (4) and trichostatic acid (5). The planar structures of 1-3 were determined on the basis of extensive NMR and MS analyses. In addition, the absolute configurations of the amino acid residues were determined by Marfey's method. The histone deacetylase inhibitory activities of 1-5 were examined, and their structure-activity relationships are discussed.

Synthesis and biological evaluation of tubulysin D analogs related to stereoisomers of tubuvaline.

The synthesis and biological evaluation of stereoisomers in tubulysin D are described. The stereoselective synthesis of all possible stereoisomers of C-11 and C-13 positions in tubulysin D was achieved by employing 1'-epi-Tuv-Me, 3'-epi-Tuv-Me, and ent-Tuv-Me and their biological properties were evaluated. It is clear that the stereochemistries of the C-11 and C-13 positions in tubulysin D have no practical impact on the inhibition of tubulin polymerization but play a role in the potent antiproliferative activities.

New antiplasmodial indole alkaloids from Hunteria zeylanica.

Two new indole alkaloids, bisnicalaterine D (1), consisting of an eburnane and a corynanthe type of skeletons, and nicalaterine A (2) were isolated from the bark of Hunteria zeylanica. Their structures were elucidated by various spectroscopic data such as NMR and CD spectra. A series of bisnicalaterines and nicalaterine A showed potent antiplasmodial activity against Plasmodium falciparum 3D7.

Chisomicines A-C, limonoids from Chisocheton ceramicus.

Three new limonoids, chisomicines A-C (1-3), have been isolated from the bark of Chisocheton ceramicus. Their structures were determined by 2D NMR, CD spectroscopic methods, and X-ray analysis. Chisomicine A (1) exhibited NO production inhibitory activity in J774.1 cells stimulated by LPS dose-dependently at high cell viability.

Inhibitors of nitric oxide production from Stemona javanica.

In our screening program for bioactive natural products from our library of tropical plants, the extract prepared from the roots of Stemona javanica inhibited NO production in mouse macrophage-like cell line J774.1 stimulated by lipopolysaccharide (LPS). Bioassay-guided fractionation of the extract from S. javanica led to the isolation of two active compounds, stemofoline (1) and stemanthrene C (2). The inhibition mechanism of 1 was proposed to suppress iNOS expression in J774.1 cells stimulated by LPS, whereas that of 2 was due to potent radical scavenging activity resulting in NO inhibitory activity.

Neolamarckines A and B, new indole alkaloids from Neolamarckia cadamba.

Two new indole alkaloids, neolamarckines A and B (1, 2) were isolated from the leaves of Neolamarckia cadamba (Rubiaceae). Structural elucidation of 1 and 2 was performed by combination of 2D-NMR and circular dichroism (CD) spectra, and chemical correlations. Neolamarckine A (1) showed inhibition of inducible nitric oxide synthase (iNOS) dose dependently.

Phytochemical and anti-inflammatory properties of Senegalese propolis and isolated compounds.

Propolis is a chemically complex resinous product collected from various plant sources by honeybees that has been used historically a traditional folk medicine in many parts of the world. The main constituents of propolis are beeswax and plant resins. We recently obtained Senegalese propolis, which, to our knowledge, has not been previously reported. The purpose of this study was to analyze the composition of Senegalese propolis and evaluate its anti-inflammatory activity. Ten known phenolic compounds with phenanthrene or stilbene skeletons were isolated. Nitric oxide (NO) production assay revealed that Senegalese propolis suppresses lipopolysaccharide (LPS)-stimulated production of NO in J774.1 cells in a dose-dependent manner. The anti-inflammatory potency of Senegalese propolis was higher than that of other previously reported propolis. Furthermore, the eight compounds isolated from Senegalese propolis showed high anti-inflammatory activity by inhibiting the LPS-induced expression of inducible NO synthase (iNOS). These results suggest that Senegalese propolis and its components have potential applications as anti-inflammatory agents.

Bisleuconothine A, an eburnane-aspidosperma bisindole alkaloid from Leuconotis griffithii.

A new bisindole alkaloid, bisleuconothine A (1) consisting of an eburnane-aspidosperma type skeleton, was isolated from the bark of Leuconotis griffithii. The structure including absolute stereochemistry was elucidated on the basis of 2D NMR data and X-ray analysis. Bisleuconothine A (1) showed cell growth inhibitory activity against various human cancer cell lines.

Alpneumines A-H, new anti-melanogenic indole alkaloids from Alstonia pneumatophora.

Eight new indole alkaloids, alpneumines A-H (1-8) were isolated from the Malaysian Alstonia pneumatophora (Apocynaceae) and their structures were determined by MS and 2D NMR spectroscopic methods. Alpneumines E and G (5 and 7), vincamine, and apovincamine showed anti-melanogenesis in B16 mouse melanoma cells.

Eucophylline, a Tetracyclic Vinylquinoline Alkaloid from Leuconotis eugenifolius.

Eucophylline (1), a new tetracyclic vinylquinoline alkaloid, was isolated from the bark of Leuconotis eugenifolius together with leucophyllidine (2). The structure and absolute configuration of 1 were elucidated on the basis of 2D NMR correlations and simulated CD analysis. Leucophyllidine (2) showed iNOS inhibitory activity and decreased the iNOS protein expression dose-dependently.

Papuabalanols A and B, new tannins from Balanophora papuana.

Two new dehydrohexahydroxydiphenoyl (DHHDP) esters of dihydrochalcone glycosides, papuabalanols A (1) and B (2) were isolated from the ethyl acetate extract of Balanophora papuana. Their structures were elucidated on the basis of spectroscopic data and chemical evidences. Papuabalanol A (1) showed moderate vasodilator effect on rat aorta and papuabalanol B (2) showed potent inhibition of mushroom tyrosinase and anti-melanogenesis in B16 mouse melanoma cells.

Synthesis and structure-activity relationships of cassiarin A as potential antimalarials with vasorelaxant activity.

Cassiarin A 1, a tricyclic alkaloid, isolated from the leaves of Cassia siamea (Leguminosae), shows powerful antimalarial activity against Plasmodium falciparum in vitro as well as P. berghei in vivo, which may be valuable leads for novel antimalarials. Interactions of parasitized red blood cells (pRBCs) with endothelium in aorta are especially important in the processes contribute to the pathogenesis of severe malaria. Nitric oxide (NO) reduces endothelial expression of receptors/adhesion molecules used by pRBC to adhere to vascular endothelium, and reduces cytoadherence of pRBC to vascular endothelium. Cassiarin A 1 showed vasorelaxation activity against rat aortic ring, which may be related with NO production. A series of a hydroxyl and a nitrogen-substituted derivatives and a dehydroxy derivative of 1 have been synthesized as having potent antimalarials against P. falciparum with vasodilator activity, which may reduce cytoadherence of pRBC to vascular endothelium. Cassiarin A 1 exhibited a potent antimalarial activity and a high selectivity index in vitro, suggesting that the presence of a hydroxyl and a nitrogen atom without any substituents may be important to show antimalarial activity. Relative to cassiarin A, a methoxy derivative showed more potent vasorelaxant activity, although it did not show improvement for inhibition of P. falciparum in vitro. These cassiarin derivatives may be promising candidates as antimalarials with different mode of actions.

Sucutiniranes C-F, cassane-type diterpenes from Bowdichia nitida.

Four new cassane-type diterpenes, sucutiniranes C-F (3-6), have been isolated from seeds of Bowdichia nitida, and their structures were elucidated by using 2D NMR data, chemical correlations, and X-ray analysis. Sucutiniranes E (5) and F (6) were moderately cytotoxic against human blood premyelocytic leukemia (HL-60), breast adenocarcinoma (MCF-7), and colon cancer (HCT-116) cells.