The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight). In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca²⁺ action potentials. Determination of the current through ATP-dependent K⁺ channels (K_ATP channels) revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h), the K_ATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes. Full article

New pyrazoline derivatives were synthesized and evaluated for their cytotoxic effects on AsPC-1 human pancreatic adenocarcinoma, U87 and U251 human glioblastoma cell lines. 1-[((5-(4-Methylphenyl)-1,3,4-oxadiazol-2-yl)thio)acetyl]-3-(2-thienyl)-5-(4-chlorophenyl)-2-pyrazoline (11) was found to be the most effective anticancer agent against AsPC-1 and U251 cell lines, with IC₅₀ values of 16.8 µM and 11.9 µM, respectively. Tumor selectivity of compound 11 was clearly seen between Jurkat human leukemic T-cell line and human peripheral blood mononuclear cells (PBMC). Due to its promising anticancer activity, compound 11 was chosen for apoptosis/necrosis evaluation and DNA-cleavage analysis in U251 cells. Compound 11-treated U251 cells exhibited apoptotic phenotype at low concentration (1.5 µM). DNA-cleaving efficiency of this ligand was more significant than cisplatin and was clearly enhanced by Fe(II)-H₂O₂-ascorbic acid systems. This result pointed out the relationship between the DNA cleavage and the cell death. Full article

Pine (Pinus morrisonicola Hay, PM) needles have been used as folk medicine for their antihypertension and lipid-lowering effects. As supercritical fluid extraction (SFE) is considered an ideal technique for the extraction of essential oil from plant materials, the present work investigated the optimal SFE conditions and the protective effects of different resulting fractions of PM needles on lipid peroxidation and foam cell production in macrophages. Nine PM needle extracts (PME1–9) were obtained in 1%–4% yields using different SFE conditions, of which PME1 had the lowest yield (1.1%) and PME3 the highest (3.9%). PME3 exhibited lower cytotoxic effects and stronger inhibition of lipid peroxidation and formation of foam cell in RAW 264.7 macrophages than those of other PME extracts. PME3-1 purified from PME3 by column and thin layer chromatography inhibited LDL oxidation more effectively than did PME3 in a cell-free system oxidized by Cu²⁺. PME3-1 dose-dependently (25–100 μg/mL) decreased conjugated diene levels and foam cell formation induced by ox-LDL. GC/MS analyses revealed that 1-docosene, neophytadiene, and methyl abietate were increased 5.2-, 1.7- and 4.3-fold in PME3-1 relative to PME3. A new hydrocarbon compound, cedrane-8,13-diol, was identified in PME3-1. Overall, the present study demonstrates the optimal extraction conditions of SFE of PM and identifies the most potent antioxidant fractions and possible active compounds in PM. Full article

The thermal influence of carbon nanotubes (CNTs) on the PA12 in the laser sintering process was assessed by physical experiments and a three dimensional simulation model. It appears that, by adding the CNTs into the PA12 matrix, the thermal conductivity increased. A double ellipsoidal heat flux model was applied to input a three dimensional, continuous moving, volumetric laser heat source. The predicted three dimensional temperature distributions suggested that the laser heat was conducted wider and deeper in the PA12-CNT sample than PA12. Greater heat conduction can reduce the interspace between two successive layers, and result in the increase of the parts’ density and properties. Full article

MicroRNAs (miRNAs) represent a family of small non-coding ribonucleic acids that post-transcriptionally inhibits the expression of their target messenger RNAs (mRNAs), thereby acting as general gene repressors. In this study we examined the relative quantity and stability of miRNA subjected to a long period of freezing; we compared the stability of eight miRNAs in the plasma of five human healthy controls before freezing and after six and 12 months of storage at −80 °C. In addition, we examined the plasma frozen for 14 years and the amount of miRNA still available. Using a Life Technologies protocol to amplify and quantify plasma miRNAs from EDTA (Ethylene Diamine Tetraacetic Acid)-treated blood, we analyzed the stability of eight miRNAs, (miR-125b-5p, miR-425-5p, miR-200b-5p, miR-200c-3p, miR-579-3p, miR-212-3p, miR-126-3p, and miR-21-5p). The miRNAs analyzed showed a high stability and long frozen half-life. Full article

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Procyanidins, which are flavonoids that are found in a variety of plant species, reduce or prevent immune disorders, such as allergy and autoimmune diseases, through an unknown mechanism. In the present study, we investigated the effects of procyanidins on the T cell receptor (TCR)-mediated responses of CD4⁺ T cells in vitro. Apple procyanidins strongly suppressed the proliferation of splenic CD4⁺ T cells that were stimulated by an anti-CD3ε antibody, as well as splenocytes stimulated by antigen, but did not alter interleukin (IL)-2 secretion from these cells. Furthermore, we found that oligomeric procyanidins strongly suppressed, in a degree of polymerization dependent manner, the proliferation of activated CD4⁺ T cells, as well as their production of effector cytokines, including glycolysis associated-cytokines, without affecting IL-2 secretion. Additionally, we investigated the inhibitory effects of oligomeric procyanidins on the glycolytic activity of activated CD4⁺ T cells. We show that pentameric procyanidin suppressed L-lactate production and glucose uptake in activated CD4⁺ T cells. These results suggest that oligomeric procyanidins suppress the functions of activated CD4⁺ T cells by interfering with glycolysis. Full article

As one of the oldest distillates in the world, flavor compounds of Chinese Baijiu (Chinese liquor) were extremely complex. Propyl lactate was firstly detected by direct injection and gas chromatography-mass spectrometry (GC-MS) in 72 Chinese Baijius. The objectives were to detect the contents of propyl lactate and evaluate its contribution to the aroma of Chinese Baijiu based on odor activity values (OAVs). The levels of propyl lactate in these distillates were determined by internal standard method and selective ion monitoring (SIM), which ranged from 0.050 to 1.900 mg∙L⁻¹ under investigation. Its detection threshold was determined by Three-Alternative Forced-Choice (3-AFC) and curve fitting (CF), which was 0.740 mg∙L⁻¹ in 38% ethanol solution. The contribution of propyl lactate on the aroma of these distillate drinks was evaluated by their odor activity values (OAVs), which varied from 0.066 to 4.440. The OAVs of propyl lactate were found to exceed 1 in 13 Chinese Baijius, including 50° Jingzhi Guniang 5 years (4.440), 52° Jingzhi Guniang 10 years (3.024), Jingyanggang (2.568), Xianghe Ronghe Shaofang (2.313), and 1956 Laolang (1.431), which indicated that propyl lactate was one of odor-active components in these Chinese Baijius. Full article

A rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometric method was developed and validated for the quantification of scopoletin in rat plasma. After the addition of the internal standard xanthotoxin, plasma samples were pretreated by a simple one-step protein precipitation with acetonitrile-methanol (2:1, v/v). Chromatographic separation was achieved on a Diamonsil ODS chromatography column using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. The determination was performed by positive ion electrospray ionization in multiple reaction monitoring mode. The calibration curve was linear over the concentration range of 5–1000 ng/mL (r = 0.9996). The intra- and inter-day precision (RSD%) was less than 6.1%, and the accuracy (RE%) was from −3.0%–2.5%. This method was successfully applied to the pharmacokinetic research of scopoletin in rats after intravenous (5 mg/kg) or oral (5, 10 and 20 mg/kg) administration. The result showed that oral bioavailability with a dose of 5 mg/kg was 6.62% ± 1.72%, 10 mg/kg, 5.59% ± 1.16%, and 20 mg/kg, 5.65% ± 0.75%. Full article

Grapevine training systems determine the suitability for grape varieties in a specific growing region. We evaluated the influence of three training systems, Single Guyot (SG), Spur-pruned Vertical Shoot-Positioned (VSP), and Four-Arm Kniffin (4AK), on the performance of grapes and vines of Vitis vinifera L. cv. Cabernet Sauvignon in the 2012 and 2013 growing seasons in a wet region of central China. 4AK was the most productive system in comparison to SG and VSP. SG and VSP had lower disease infections of leaves and berries, especially in the mid- and final stage of berry ripening. Three training systems had no impact on berry maturity. PLS-DA (Partial Least Squares-Discriminant) analysis showed that the relatively dry vintage could well discriminate three training systems, but the wet vintage was not. A wet vintage of 2013 had more accumulation of 3′5′-substituted and acylated anthocyanins, including malvidin-3-O-(6-O-acetyl)-glucoside, malvidin-3-O-glucoside, and petunidin-3-O-(cis-6-O-coumaryl)-glucoside, etc. With regard to the effect of training systems, 4AK grapes had the lowest concentrations of total anthocyanins and individual anthocyanins, SG and VSP differed according to the different vintages, and showed highest concentration of total individual anthocyanins in 2012 and 2013, respectively. Generally, VSP benefited the most, contributing to significantly highest levels of total individual anthocyanins, and major anthocyanin, including malvidin-3-O-glucoside and malvidin-3-O-(6-O-acetyl)-glucoside, and the grapes obtained from VSP presented significantly highest proportion of 3′5′-substituted anthocyanins. With regard to the ratios of 3′5′/3′-substituted, methoxylated/non-methoxylated and acylated/non-acylated anthocyanins, the significantly higher levels were also shown in VSP system. In summary, VSP was the best training system for Cabernet Sauvignon to accumulate relatively stable individual anthocyanins in this wet region of China and potentially in other rainy regions. Full article

In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and antioxidant drugs. As well as these membrane-acting drugs, bioactive plant components, phytochemicals, with amphiphilic or hydrophobic structures, are presumed to interact with biological membranes and biomimetic membranes prepared with phospholipids and cholesterol, resulting in the modification of membrane fluidity, microviscosity, order, elasticity, and permeability with the potencies being consistent with their pharmacological effects. A novel mechanistic point of view of phytochemicals would lead to a better understanding of their bioactivities, an insight into their medicinal benefits, and a strategic implication for discovering drug leads from plants. This article reviews the membrane interactions of different classes of phytochemicals by highlighting their induced changes in membrane property. The phytochemicals to be reviewed include membrane-interactive flavonoids, terpenoids, stilbenoids, capsaicinoids, phloroglucinols, naphthodianthrones, organosulfur compounds, alkaloids, anthraquinonoids, ginsenosides, pentacyclic triterpene acids, and curcuminoids. The membrane interaction’s applicability to the discovery of phytochemical drug leads is also discussed while referring to previous screening and isolating studies. Full article

Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels. Full article

Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress. Full article

Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks) and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate the importance of the upper-unit of 4–8 condensed dimeric flavan-3-ols for antimicrobial activity against Saccharomyces cerevisiae (S. cerevisiae) and cervical epithelioid carcinoma cell line HeLa S3 proliferation inhibitory activity. To clarify the important constituent unit of proanthocyanidin, we synthesized four dimeric compounds, (−)-epigallocatechin-[4,8]-(+)-catechin, (−)-epigallocatechin-[4,8]-(−)-epigallocatechin, (−)-epigallocatechin-[4,8]-(−)-epigallocatechin-3-O-gallate, and (+)-catechin-[4,8]-(−)-epigallocatechin and performed structure–activity relationship (SAR) studies. In addition to antimicrobial activity against S. cerevisiae and proliferation inhibitory activity on HeLa S3 cells, the correlation of 2,2-diphenyl-l-picrylhydrazyl radical scavenging activity with the number of phenolic hydroxyl groups was low. On the basis of the results of our SAR studies, we concluded that B-ring hydroxyl groups of the upper-unit of the dimer are crucially important for strong and effective activity. Full article

Two new maleimide derivatives have been synthesized, prone to self-assemble and react with graphene as dienophiles. Both compounds bear a long alkyl chain on the carbon-carbon double bond position 3. The maleimide 1 bears a second alkyl chain at the nitrogen, while in compound 2, three maleimide functionalities are linked to a triethynylbenzene core. Full article