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Recent data have shown anti-inflammatory effects for trans-resveratrol (RSV) and rosmarinic acid (RA) in various immune-competent cell models through reduction of lipopolysaccharide (LPS)-induced interleukin 6 (IL-6) release. Because both compounds have been reported to taste bitter, we hypothesized an involvement of human bitter taste sensing receptors (TAS2Rs) on IL-6 release in LPS-treated human gingival fibroblasts (HGF-1). First, the bitter taste intensity of RSV and RA was compared in a sensory trial with 10 untrained panelists, of whom 90% rated a 50 ppm of RSV in water solution more bitter than 50 ppm of RA. A mean 19 ± 6% reduction of the RSV-induced bitter taste intensity was achieved by co-administration of 50 ppm of the bitter-masking, TAS2R43 antagonist homoeriodictyol (HED). Mechanistic experiments in a stably CRISPR-Cas9-edited TAS2R43ko gastric cell model revealed involvement of TAS2R43 in the HED-evoked effect on RSV-induced proton secretion, whereas the cellular response to RSV did not depend upon TAS2R43. Next, the IL-6 modulatory effect of 100 μM RSV was studied in LPS-treated immune-competent HGF-1 cells. After 6 h of treatment, RSV reduced the LPS-induced IL-6 gene expression and protein release by -46.2 ± 12.7 and -73.9 ± 2.99%, respectively. This RSV-evoked effect was abolished by co-administration of HED. Because real-time quantitative polymerase chain reaction analyses revealed a regulation of TAS2R50 in RSV with or without HED-treated HGF-1 cells, an siRNA knockdown approach of TAS2R50 was applied to verify TAS2R50 involvement in the RSV-induced reduction of the LPS-evoked IL-6 release in HGT-1 cells.

The cinnamon-derived bioactive aroma compound cinnamaldehyde (CAL) has been identified as a promising antiobesity agent, inhibiting adipogenesis and decreasing lipid accumulation in vitro as well as in animal models. Here, we investigated the antiadipogenic effect of cinnamyl isobutyrate (CIB), another cinnamon-derived aroma compound, in comparison to CAL in 3T3-L1 adipocyte cells. In a concentration of 30 μM, CIB reduced triglyceride (TG) and phospholipid (PL) accumulation in 3T3-L1 pre-adipocytes by 21.4 ± 2.56 and 20.7 ± 2.05%, respectively. CAL (30 μM), in comparison, decreased TG accumulation by 37.5 ± 1.81% and PL accumulation by 28.7 ± 1.83%, revealing the aldehyde to be the more potent antiadipogenic compound. The CIB- and CAL-mediated inhibition of lipid accumulation was accompanied by downregulation of essential adipogenic transcription factors PPARγ, C/EBPα, and C/EBPβ on gene and protein levels, pointing to a compound-modulated effect on adipogenic signaling cascades. Coincubation experiments applying the TRPA-1 inhibitor AP-18 demonstrated TRPA1 dependency of the CAL, but not the CIB-induced antiadipogenic effect.

As a result of their pleasant odor qualities and low odor thresholds, iso- and anteiso-fatty aldehydes represent promising candidates for applications in flavoring preparations. A novel cyanobacter...

Activation of the transient receptor potential (TRP) channel TRPA1 by cinnamaldehyde has been shown to stimulate serotonin release in enterochromaffin QGP-1 cells. However, the impact of cinnamaldehyde on serotonin release in enterocytes is less well understood. In addition, since the neurotransmitter serotonin plays a regulatory role in a large variety of gastrointestinal and metabolic functions, it is of interest to study which structural characteristics determine cinnamaldehyde-induced serotonin release by enterocytes. Thus, the present study analyzed serotonin release in differentiated Caco-2 cells as a model for enterocytes in comparison to enterochromaffin QGP-1 cells after stimulation with cinnamaldehyde and 17 naturally occurring structurally related compounds by means of a serotonin ELISA. Stimulation with cinnamaldehyde induced a dose-dependent increase in serotonin release starting from 0.5 mM in both cell lines, with a larger effect size in Caco-2 enterocytes compared to that in QGP-1 enterochromaffin cells. Serotonin release in Caco-2 cells induced by additional 17 structurally related compounds correlated with serotonin release in QGP-1 cells, showing the highest effects for coniferylaldehyde with a 15.84 ± 3.23-fold increase in Caco-2 cells, followed by the parent compound cinnamaldehyde (13.45 ± 2.15), cinnamyl alcohol (6.68 ± 1.08), and α-methyl-cinnamaldehyde (6.59 ± 0.93). Analysis of structural and molecular characteristics that modulate serotonin release in Caco-2 enterocytes revealed that the ability of a compound to activate TRPA1, demonstrated by means of HEK293 cells transiently expressing hTRPA1, is a decisive factor to stimulate serotonin release in Caco-2 enterocytes, preferring small, electrophilic compounds with a lower polar surface area. In addition, blocking of TRPA1 using 30 μM AP-18 significantly reduced the cinnamaldehyde-induced serotonin release by 30.0 ± 5.24%, confirming a TRPA1-dependent component in serotonin release by Caco-2 cells.

Hortensias (Hydrangea macrophylla L.) are well known as ornamental plants with their impressive flowers. Besides being an ornamental plant, some hortensia species contain constituents of nutritional and pharmaceutical interest. In this context, H. macrophylla subsp. serrata contains dihydroisocoumarins (DHCs), in particular hydrangenol (HG) and phyllodulcin (PD), which determine produce quality. For the successful cultivation of H. macrophylla subsp. serrata, shading may be required. The response of H. macrophylla subsp. serrata as a source for DHCs was investigated in two growing seasons using three different cultivars (‘Amagi Amacha’, ‘Oamacha’ and ‘Odoriko Amacha’) under three different light conditions: no shade (100% photosynthetic active radiation, PAR), partial (72% PAR) and full shading (36% PAR). The shading regimes had no significant effect on dihydroisocoumarin content in leaf dry matter in each single cultivar. However, ‘Amagi Amacha’ and ‘Oamacha’ yielded significantly higher PD content in comparison to ‘Odoriko Amacha’, which showed, in contrast, the significantly highest HG content. The total biomass was not significantly affected by the shading regime, but slightly higher biomass was observed under partially shaded and full-shade conditions. Hyperspectral vegetation indices (VIs) and color measurements indicate less vital plants under no shade conditions. While lighting is an important growth factor for hortensia production, DHC is cultivar dependent.

This study aimed at identifying whether the bitter-tasting amino acids l-arginine (l-ARG) and l-isoleucine (l-ILE) differentially regulate mechanisms of gastric acid secretion in human parietal cells (HGT-1 cells) via activation of bitter taste sensing receptors (T2Rs). In a first set of experiments, involvement of T2Rs in l-ARG and l-ILE-modulated proton secretion was demonstrated by co-treatment of HGT-1 cells with T2R antagonists. Subsequent whole genome screenings by means of cDNA arrays revealed T2R1 as a prominent target for both amino acids. Next, the functional role of T2R1 was verified by means of a T2R1 CRISPR-Cas9 knock-out approach. Here, the effect of l-ARG on proton secretion decreased by 65.7 ± 21.9% and the effect of l-ILE increased by 93.2 ± 24.1% in HGT-1 T2R1 ko versus HGT-1 wt cells (p < 0.05). Overall, our results indicate differential effects of l-ARG and l-ILE on proton secretion in HGT-1 cells and our molecular docking studies predict distinct binding for these amino acids in the binding site of T2R1. Further studies will elucidate whether the mechanism of differential effects involves structure-specific ligand-biased signaling of T2R1 or additional cellular targets.

Lipid extracts of the fungus Flammulina velutipes were found to contain various scarce fatty acids including dodec-11-enoic acid and di- and tri-unsaturated C16 isomers. A biotechnological approach using a heterologously expressed carboxylic acid reductase was developed to transform the fatty acids into the respective aldehydes, yielding inter alia dodec-11-enal. Supplementation studies gave insights into the fungal biosynthesis of this rarely occurring acid and suggested a terminal desaturation of lauric acid being responsible for its formation. A systematic structure-odor relationship assessment of terminally unsaturated aldehydes (C7-C13) revealed odor thresholds in the range of 0.24-22 μg/L in aqueous solution and 0.039-29 ng/L in air. In both cases, non-8-enal was identified as the most potent compound. All aldehydes exhibited green odor qualities. Short-chained substances were additionally associated with grassy, melon-, and cucumber-like notes, while longer-chained homologs smelled soapy and coriander leaf-like with partly herbaceous nuances. Dodec-11-enal turned out to be of highly pleasant scent without off-notes.

As a result of their pleasant odor qualities and low odor thresholds, iso- and anteiso-fatty aldehydes represent promising candidates for applications in flavoring preparations. A novel cyanobacterial α-dioxygenase from

The noncaloric sweeteners (NCSs) cyclamate (Cycl) and acesulfame K (AceK) are widely added to foods and beverages. Little is known about their impact on gastric acid secretion (GAS), which is stimulated by dietary protein and bitter-tasting compounds. Since Cycl and AceK have a bitter off taste in addition to their sweet taste, we hypothesized they modulate mechanisms of GAS in human gastric parietal cells (HGT-1). HGT-1 cells were exposed to sweet tastants (50 mM of glucose, d-threonine, Cycl, or AceK) and analyzed for their intracellular pH index (IPX), as an indicator of proton secretion by means of a pH-sensitive dye, and for mRNA levels of GAS-associated genes by RT-qPCR. Since the NCSs act via the sweet taste-sensing receptor T1R2/T1R3, mRNA expression of the corresponding genes was analyzed in addition to immunocytochemical localization of the T1R2 and T1R3 receptor proteins. Exposure of HGT-1 cells to AceK or d-threonine increased the IPX to 0.60 ± 0.05 and 0.80 ± 0.04 ( P ≤ 0.05), respectively, thereby indicating a reduced secretion of protons, whereas Cycl demonstrated the opposite effect with IPX values of -0.69 ± 0.08 ( P ≤ 0.05) compared to controls (IPX = 0). Cotreatment with the T1R3-inhibitor lactisole as well as a TAS1R3 siRNA knock-down approach reduced the impact of Cycl, AceK, and d-thr on proton release ( P ≤ 0.05), whereas cotreatment with 10 mM glucose enhanced the NCS-induced effect ( P ≤ 0.05). Overall, we demonstrated Cycl and AceK as modulators of proton secretion in HGT-1 cells and identified T1R3 as a key element in this response.

Advanced glycation end products (AGEs), comprising a highly diverse class of Maillard reaction compounds formed in vivo and during heating processes of foods, have been described in the progression of several degenerative conditions such as Alzheimer's disease and diabetes mellitus. Nϵ-Carboxymethyllysine (CML) represents a well-characterized AGE, which is frequently encountered in a Western diet and is known to mediate its cellular effects through binding to the receptor for AGEs (RAGE). Since very little is known about the impact of exogenous CML and its precursor, glyoxal, on intestinal cells, a genome-wide screening using a customized microarray was conducted in fully differentiated Caco-2 cells. After verification of gene regulation by qPCR, functional assays on fatty acid uptake, glucose uptake and serotonin release were performed. While only treatment with glyoxal showed a slight impact on fatty acid uptake (p

The extensional rheology (ER) of saliva is a property associated with its ability to coat surfaces and is important for the maintenance of a normal mouth feeling. Transient receptor potential (TRP) channels are expressed in the oral cavity and this study investigated how the sensory effects of TRP channel agonists modify the ER of saliva. Healthy volunteers rinsed with solutions containing a TRP agonist. Unstimulated whole mouth saliva (WMS) was collected prior to rinsing and WMS was collected during the first and second minutes after the mouth rinse. The Spinnbarkeit of the collected saliva was measured using a Neva Meter. The nonivamide (TRPV1) mouth rinse increased WMS ER from 37.0 (± 6.3) mm to 49.3 (± 5.1) mm when compared with the vehicle control, which itself had no effect on WMS ER. However, this effect was short-lived and ER of WMS was not increased in the second minute after the nonivamide mouth rinse. The menthol (TRPM8) mouth rinse resulted in an increase up to 57.8 (± 7.8) mm in WMS ER from the vehicle control and returned to control levels in the second minute. The cinnamaldehyde (TRPA1) mouth rinse resulted in no change in WMS ER. It can be concluded that nonivamide and menthol mouth rinsing has a short-term effect of increasing WMS ER, an effect not observed after cinnamaldehyde rinsing. We hypothesize that the activation of some TRP channels in the oral cavity results in changes in the salivary protein composition that in turn alters WMS ER. Practical applications Identifying compounds that modify the physical properties of saliva in a desirable way is important in developing treatments for conditions associated with changes in the physical properties of saliva such as xerostomia (also known as dry mouth). Furthermore, understanding the rheology of saliva contributes to the elucidation of food oral processing which is of importance to food manufacturers.

A reduction in sugar consumption is desirable from a health point of view. However, the sensory profiles of alternative sweet-tasting compounds differ from sucrose regarding their temporal profile and undesired side tastes, reducing consumers’ acceptance. The present study describes a sensory characterisation of a variety of sweet and sweet taste affecting compounds, followed by a comparison of similarity to sucrose and a multivariate regression analysis, to investigate structural determinants and possible interactions for the temporal profile of the sweetness and side-tastes. The results of the present study suggest a pivotal role for the number of ketones, aromatic rings, double bonds and the M LogP in the temporal profile of sweet and sweet taste affecting compounds. Furthermore, interactions between aggregated physicochemical descriptors demonstrate the complexity of the sensory response, which should be considered in future models to predict a comprehensive sensory profile of sweet and sweet taste affecting compounds.

Scope This study investigates the effect of the sweetness of a sucrose versus an isocaloric glucose solution in dietary concentrations on blood glucose regulation by adjusting the sweetness level using the sweet taste inhibitor lactisole. Methods and Results A total of 27 healthy males participated in this randomized, crossover study with four treatments: 10% glucose, 10% sucrose, 10% sucrose + 60 ppm lactisole, and 10% glucose + 60 ppm lactisole. Plasma glucose, insulin, glucagon‐like peptide 1, and glucagon levels are measured at baseline and 15, 30, 60, 90, and 120 min after beverage consumption. Test subjects rated the sucrose solution to be sweeter than the isocaloric glucose solution, whereas no difference in sweetness is reported after addition of lactisole to the sucrose solution. Administration of the less sweet glucose solution versus sucrose led to higher blood glucose levels after 30 min, as reflected by a lower ΔAUC for sucrose (1072 ± 136) than for glucose (1567 ± 231). Application of lactisole leads to no differences in glucose, insulin, or glucagon responses induced by sucrose or glucose. Conclusion The results indicate that the structure of the carbohydrate has a stronger impact on the regulation of blood glucose levels than the perceived sweetness., The effect of the sweetness of a sucrose versus an iso‐caloric glucose solution on blood glucose regulation by adjusting the sweetness using the sweet taste inhibitor lactisole is investigated. Sucrose is rated sweeter than an iso‐caloric glucose solution. The difference in the structure of glucose and sucrose, but not the perceived sweetness affects the blood glucose regulation in male subjects.

Naturally occurring cinnamon compounds such as cinnamaldehyde (CAL) and structurally related constituents have been associated with antiobesity activities, although studies regarding the impact on intestinal fatty acid uptake are scarce. Here, we demonstrate the effects of CAL and structural analogues cinnamyl alcohol (CALC), cinnamic acid (CAC), and cinnamyl isobutyrate on mechanisms regulating intestinal fatty acid uptake in differentiated Caco-2 cells. CAL, CALC, and CAC (3000 μM) were found to decrease fatty acid uptake by 58.0 ± 8.83, 19.4 ± 8.98, and 21.9 ± 6.55%, respectively. While CAL and CALC at a concentration of 300 μM increased serotonin release 14.9 ± 3.00- and 2.72 ± 0.69-fold, respectively, serotonin alone showed no effect on fatty acid uptake. However, CAL revealed transient receptor potential channel A1-dependency in the decrease of fatty acid uptake, as well as in CAL-induced serotonin release. Overall, CAL was identified as the most potent of the cinnamon constituents tested.

Scope Increasing the intake of satiety‐enhancing food compounds represents a promising strategy for maintaining a healthy body weight. Recently, satiating effects for the capsaicinoid nonivamide have been demonstrated. As various proteins and amino acids have also been demonstrated to decrease energy intake, oral glucose tolerance test (oGTT)‐based bolus interventions of 75 g glucose + 0.15 mg nonivamide (NV control) are tested with/without combination of a wheat protein hydrolysate (WPH: 2 g) and/or l‐arginine (ARG: 3.2 g) for their satiating effects in 27 moderately overweight male subjects. Methods and Results Compared to NV control intervention, ARG and WPH + ARG treatment both reduce (p, A combination of satiating food constituents for enhancing satiety is a promising strategy for maintaining a healthy bodyweight. In this human intervention study, an l‐arginine‐enriched wheat protein hydrolysate is demonstrated to further increase the satiating effect of nonivamide, a pungent pepper constituent, in healthy male volunteers when administered as a protein shake prior to an ad libitum breakfast.

Activation of the transient receptor potential (TRP) channel TRPA1 by cinnamaldehyde has been shown to stimulate serotonin release in enterochromaffin QGP-1 cells. However, the impact of cinnamaldehyde on serotonin release in enterocytes is less well understood. In addition, since the neurotransmitter serotonin plays a regulatory role in a large variety of gastrointestinal and metabolic functions, it is of interest to study which structural characteristics determine cinnamaldehyde-induced serotonin release by enterocytes. Thus, the present study analyzed serotonin release in differentiated Caco-2 cells as a model for enterocytes in comparison to enterochromaffin QGP-1 cells after stimulation with cinnamaldehyde and 17 naturally occurring structurally related compounds by means of a serotonin ELISA. Stimulation with cinnamaldehyde induced a dose-dependent increase in serotonin release starting from 0.5 mM in both cell lines, with a larger effect size in Caco-2 enterocytes compared to that in QGP-1 enterochromaffin cells. Serotonin release in Caco-2 cells induced by additional 17 structurally related compounds correlated with serotonin release in QGP-1 cells, showing the highest effects for coniferylaldehyde with a 15.84 ± 3.23-fold increase in Caco-2 cells, followed by the parent compound cinnamaldehyde (13.45 ± 2.15), cinnamyl alcohol (6.68 ± 1.08), and α-methyl-cinnamaldehyde (6.59 ± 0.93). Analysis of structural and molecular characteristics that modulate serotonin release in Caco-2 enterocytes revealed that the ability of a compound to activate TRPA1, demonstrated by means of HEK293 cells transiently expressing hTRPA1, is a decisive factor to stimulate serotonin release in Caco-2 enterocytes, preferring small, electrophilic compounds with a lower polar surface area. In addition, blocking of TRPA1 using 30 μM AP-18 significantly reduced the cinnamaldehyde-induced serotonin release by 30.0 ± 5.24%, confirming a TRPA1-dependent component in serotonin release by Caco-2 cells.

Scope Cinnamon is associated with anti-obesity effects, regulating food intake, improving plasma glucose levels and lipid profiles in vivo. In the present study, the impact of cinnamyl isobutyrate (CIB), one constituent of cinnamon, on ad libitum food intake from a standardized breakfast and outcome measures of hormonal regulation of appetite were investigated. Methods and results In this randomized, short-term crossover intervention study, a 75 g per 300 mL glucose solution solely (control) or supplemented with 0.45 mg CIB was administered to 26 healthy volunteers. Prior to and 2 h after receiving control or CIB treatment, subjective hunger perceptions were rated using a visual analog scale. Food intake from a standardized breakfast was assessed 2 h after treatments. Plasma peptide YY3-36 , glucagon-like-peptide1, ghrelin, and serotonin as well as plasma glucose and insulin were measured in blood samples drawn at fasting and 15, 30, 60, 90, and 120 min after treatment. CIB administration decreased total energy intake and delta area under curve plasma glucose by 4.64 ± 3.51% and 49.3 ± 18.5% compared to control treatment, respectively. Conclusions CIB, administered at a 0.45 mg bolus in 75 g glucose-water solution, decreased ad libitum energy intake from a standardized breakfast and postprandial plasma glucose levels.

Secretion of gastric acid, aimed at preventing bacterial growth and aiding the digestion of foods in the stomach, is chiefly stimulated by dietary intake of protein and amino acids (AAs). However, AAs' key structural determinants responsible for their effects on mechanisms regulating gastric acid secretion (GAS) have not been identified yet. In this study, AAs have been tested in the parietal cell model HGT-1 on GAS and on mRNA expression of genes regulating GAS. AAs' taste intensities from 0 (not bitter at all) to 10 (very bitter) were assessed in a sensory study, in which ARG (l: 6.42 ± 0.41; d: 4.62 ± 0.59) and ILE (l: 4.21 ± 0.43; d: 2.28 ± 0.33) were identified as bitter-tasting candidates in both isomeric forms. Pearson correlation showed that GAS in HGT-1 cells is directly associated with the bitter taste quality ( r: -0.654) in combination with the molecular weight of l-AA ( r: -0.685).

A number of methyl-branched aldehydes impart interesting flavor impressions, and especially 12-methyltridecanal is a highly sought after flavoring compound for savory foods. Its smell is reminiscent of cooked meat and tallow. For the biotechnological production of 12-methyltridecanal, the literature was screened for fungi forming iso-fatty acids. Suitable organisms were identified and successfully grown in submerged cultures. The culture medium was optimized to increase the yields of branched fatty acids. A recombinant carboxylic acid reductase was used to reduce 12-methyltridecanoic acid to 12-methyltridecanal. The efficiency of whole-cell catalysis was compared to that of the purified enzyme preparation. After lipase-catalyzed hydrolysis of the fungal lipid extracts, the released fatty acids were converted to the corresponding aldehydes, including 12-methyltridecanal and 12-methyltetradecanal.

Polyphenol-rich plant extracts have been shown to possess anti-inflammatory activity against oral pathogen-induced cytokine release in model systems of inflammation. Here, it was hypothesized that a flavanone-rich extract of E. angustifolium exhibits an anti-inflammatory potential against endotoxin-induced inflammatory response in human gingival fibroblasts (HGF-1). HGF-1 cells were stimulated with lipopolysaccharide from Porphyromonas gingivalis (pg-LPS) to release pro-inflammatory cytokines. Concentrations of interleukins IL-6 and IL-8 and macrophage chemoattractant protein-1 in the incubation media upon stimulation were determined by means of magnetic bead analysis. A crude ethanol/water extract of E. angustifolium (EE) was fractionated via gel permeation chromatography into a flavanone-rich fraction (FF) and an erionic acid-rich fraction (EF). Individual flavanones and erionic acids as well as EE, EF and FF were tested in the pg-LPS-stimulated HGF-1 cells for their anti-inflammatory potential. The E. angustifolium extract possessed anti-inflammatory potential in this model system, attenuating the pg-LPS-induced release of IL-6 by up to 52.0 ± 15.5%. Of the individual flavanones, eriodictyol and naringenin had the most pronounced effect. However, a mixture of the flavanones did not possess the same effect as the entire flavanoid fraction, indicating that other compounds may contribute to the anti-inflammatory potential of E. angustifolium. For the first time, an anti-inflammatory potential of E. angustifolium and containing erionic acids has been determined.

Capsaicin, the highly pungent principle of red pepper, has been demonstrated to have anti-obesity properties by affecting energy and lipid metabolism. Recent evidence from human intervention trials shows that also less pungent capsaicin analogs, like nonivamide, may help to reduce total body fat, although mechanistic data comparing the effects of capsaicin and nonivamide on outcome measures of energy metabolism are lacking. Here, the tissue-specific effects of capsaicin and nonivamide on parameters of mitochondrial energy metabolism in 3T3-L1 and HepG2 cells are investigated. Lipid accumulation was reduced to a similar extent after treatment with both test substances during the maturation of 3T3-L1 cells by up to 6.91% for capsaicin and up to 4.89% for nonivamide (p < 0.01) at a concentration of 0.1 μM or 1 μM, respectively. Energy-producing pathways, as indicated by the reduced mitochondrial oxygen consumption and reduced glucose and fatty acid uptake, were diminished after incubation with both capsaicinoids at a concentration of 100 μM. The results from HPLC analyses revealed a reduced cellular energy charge potential after a 4 h treatment with nonivamide. In HepG2 cells, similar effects were demonstrated: the glucose uptake was reduced by 18.7% and 25.8% (p < 0.05), after a 24 h incubation with 100 μM capsaicin and nonivamide, respectively. In addition, the fatty acid uptake and oxygen consumption were decreased and the energy charge potential was diminished. These findings provide evidence that concentrations of capsaicin and nonivamide between 0.1 and 100 μM modulate the mechanisms of cellular energy metabolism to a similar extent, independent of the investigated tissue.

Humans perceive bitterness via around 25 different bitter receptors. Therefore, the identification of antagonists remains a complex challenge. We previously demonstrated several bitter-tasting compounds such as caffeine to induce acid secretion in the stomach and in a human gastric tumor cell line (HGT-1). Here, the results of a fluorescent-based in vitro assay using HGT-1 cells and a human sensory panel testing nine selected potential bitter modulators, with or without the bitter compounds caffeine or theobromine, were compared. Of the bitter-modulating compounds tested, eriodictyol, matairesinol, enterolacton, lariciresinol, and homoeriodictyol reduced the effect of caffeine on proton secretion by -163 ± 14.0, -152 ± 12.4, -74 ± 16.4, -58 ± 7.2, and -44.6 ± 16.5%, respectively, and reduced the bitter intensity of caffeine in the human sensory panel. In contrast, naringenin and 5,7-dihydroxy-4(4-hydroxyphenyl)chroman-2-one neither reduced the caffeine-induced proton secretion in HGT-1 cells nor showed an effect on bitter intensity perceived by the sensory panel. Results for theobromine were not as pronounced as those for caffeine, but followed a similar trend. The results demonstrate that the HGT-1 in vitro assay is a useful tool to identify potential bitter-masking compounds. Nevertheless, a sensory human panel is necessary to quantify the bitter-masking potency.

The class of 2-isopropyl-5-methylbicyclo[4.1.0]heptane-7-carboxamides, 1-4, has been identified as potent umami-tasting molecules. A scalable synthesis of this challenging scaffold and new sensory insights will be presented. Interestingly, the umami characteristics differ remarkably, depending on constitutional and stereochemical features of the parent scaffold. During our studies, we could identify the carboxamide moiety as a crucial factor to influence the umami intensity of these scaffolds. In addition, the configuration of the cyclopropyl moiety exerts some influence, whereas the absolute configuration of the menthyl scaffold, at least the tested D- and L-configuration, is less important.

Flavonoide stellen eine grose Gruppe pflanzlicher Sekundarmetabolite dar und haben eine Vielzahl unterschiedlicher biologischer Eigenschaften. Aufgrund dessen stehen sie im Interesse vieler Wissenschaftler, da sie zu vielen industriell interessanten Verbindungen fuhren konnen. Das anaerobe Darmbakterium Eubacterium ramulus kann uber einen bislang unbekannten Abbauweg diese Flavonoide verstoffwechseln. Uber eine Vollgenom-Sequenzierung wurden in dieser Arbeit die entscheidenden Enzyme, eine Chalconisomerase (CHI) und eine Enoatreduktase (ERED), identifiziert, kloniert und funktionell sogar unter aeroben Bedingungen exprimiert. Mittels Biotransformation des Flavanons zum Dihydrochalcon konnte der Flavonoid-Abbauweg bewiesen werden. Der beide Enzyme exprimierende E.-coli-Stamm kann fur die Umsetzung verschiedener Flavanone eingesetzt werden. Dies unterstreicht die Anwendbarkeit des in dieser Arbeit entwickelten biokatalytischen Systems.

Scope Dietary intake of capsaicin has been shown to reduce body weight by increasing energy expenditure, and to enhance alertness and mood by stimulating the brain's reward system. Binding of capsaicin to the vanilloid receptor 1 (transient receptor potential cation channel subfamily V member 1 (TRPV1)) is one of the major cellular mechanisms responsible for these effects. However, strong TRPV1 agonists like capsaicin elicit a sharp, burning pain that limits their dietary intake. The present study aimed to investigate the effect of the less pungent capsaicin-analog nonivamide on dopamine and serotonin release in neural SH-SY5Y cells. Methods and results Nonivamide (1 μM) stimulated the Ca(2+) -dependent release of serotonin (272 ± 115%) and dopamine (646 ± 48%) in SH-SY5Y cells compared to nontreated cells (100%) to a similar extent as capsaicin. qRT-PCR analysis of 1 μM nonivamide-treated SH-SY5Y cells revealed gene regulation of the receptors dopamine D1 and D2, serotonin HTR1A, 1B and 2A, cannabinoid 1, and TRPV1. Co-incubation experiments of SH-SY5Y cells with the TRPV1 inhibitors trans-tert-butylcyclohexanol and capsazepine demonstrated that capsaicin, but not nonivamide, induces serotonin and dopamine release through TRPV1 activation. Conclusion The results indicate a TRPV1-independent signaling pathway for nonivamide that might allow dietary administration of higher doses of nonivamide compared to capsaicin.

cope Anorexia of aging, characterized by a decrease in appetite and/or food intake, is a major risk factor of under-nutrition and adverse health outcomes in elderly people. Recent in vitro evidence suggests homoeriodictyol (HED), a naturally occurring, bitter-masking flavanone, as a promising agent to increase appetite and food intake. Methods and results In two cross-over intervention trials, 30 mg NaHED, either solely (n = 10, Study I) or in combination with a 75g glucose load (n = 17, study II) were administered to healthy adult subjects. Ratings of hunger were assessed at fasting and either 30 min (Study I) or 120 min (Study II) post intervention. Ad libitum energy intake from a standardized breakfast and plasma changes in hunger-/satiety-associated hormones PYY, GLP-1, ghrelin and serotonin were determined after blood drawings. Effects were more pronounced when NaHED was administered in combination with 75g glucose since ad libitum energy (+ 9.52 ± 4.60 %) and protein (+ 7.08 ± 7.97 %) intake as well as plasma ΔAUC ghrelin values increased in study II solely, whereas plasma serotonin concentrations decreased after both interventions. Conclusions NaHED demonstrated appetizing effects in healthy adults when administered with a glucose load. Long-term intervention studies are warranted to verify these effects in compromised subjects. This article is protected by copyright. All rights reserved

cope Inflammation-related diseases are a worldwide problem. The counteraction of inflammation with compounds activating the trigeminal nerve is one strategy to fight these diseases. Known trigeminally active compounds found in black or red pepper are the tingling t-pellitorine, the pungent capsaicin, and the less pungent nonivamide. The presented study compares the anti-inflammatory potential of nonivamide to the two known anti-inflammatory compounds, elucidating the mechanism of action and the role of transient receptor protein (TRP) channels. Methods and results Primary peripheral blood mononuclear cells (PBMCs) and U-937 macrophages were stimulated with 1 μg/mL LPS from Escherichia coli (EC-LPS) to induce inflammation. Nonivamide attenuated the EC-LPS induced release of IL-6 and TNF-α in PBMCs and U-937 macrophages determined by magnetic bead kit analysis. This anti-inflammatory mechanism was independent from nuclear factor-kappa B pathway but mitogen-activated protein kinase (MAPK) pathway may be involved. In addition, cotreatment of U-937 with the trigeminally active compound and an antagonist of TRPV1 or TRPA1 abolished the anti-inflammatory activity. Conclusions Nonivamide possessed similar anti-inflammatory potential as capsaicin and t-pellitorine. In U-937 macrophages, the tested compounds exploited an anti-inflammatory effect by inhibiting the EC-LPS induced activation of the MAPK pathway. In addition, the TRP channel activation plays a role in the anti-inflammatory capacity of capsaicin and nonivamide.

The phytochemical profile of Macropiper excelsum (G.Forst.) Miq. subsp. excelsum (Piperaceae), a shrub which is widespread in New Zealand, was investigated by LC-MS-guided isolation and characterization via HR-ESI-TOF-MS and NMR spectroscopy. The isolated compounds were sensorily evaluated to identify their contribution to the overall taste of the crude extract with sweet, bitter, herbal and trigeminal impressions. Besides the known non-volatile Macropiper compounds, the lignans (+)-diayangambin and (+)-excelsin, four further excelsin isomers, (+)-diasesartemin, (+)-sesartemin, (+)-episesartemin A and B were newly characterized. Moreover, piperine and a number of piperine analogues as well as trans-pellitorine and two homologues, kalecide and (2E,4E)-tetradecadienoic acid N-isobutyl amide were identified in M. excelsum, some of them for the first time. Methyl(2E,4E)-7-(1,3-benzodioxol-5-yl)hepta-2,4-dienoate was identified and characterized for the first time in nature. Sensory analysis of the pure amides indicated that they contributed to the known chemesthetic effects of Macropiper leaves and fruits. Since the pungent piperine has been shown to affect glucose and fatty acid metabolism in vivo in previous studies, piperine itself and four of the isolated compounds, piperdardine, chingchengenamide A, dihydropiperlonguminine, and methyl(2E,4E)-7-(1,3-benzodioxol-5-yl)hepta-2,4-dienoate, were investigated regarding their effects on glucose and fatty acid uptake by enterocyte-like Caco-2 cells, in concentrations ranging from 0.1 to 100 μM. Piperdardine showed the most pronounced effect, with glucose uptake increased by 83 ± 18% at 100 μM compared to non-treated control cells. An amide group seems to be advantageous for glucose uptake stimulation, but not necessarily for fatty acid uptake-stimulating effects of piperine-related compounds.

A methanolic extract of bush tea ( Athrixia phylicoides , Asteraceae) was evaluated sensorially. A High Temperature Liquid Chromatography (HTLC)-coupled sensory-guided analysis was performed on bush tea extract to identify potential taste modulating compounds. One fraction showed bitter enhancing effects on caffeine. Fractionation using Fast Centrifugal Partition Chromatography (FCPC) and preparative HPLC followed by structure elucidation using NMR and LC NMR led to the identification of three polymethoxylated flavones, quercetin-3′- O -glucoside ( 1 ), as well as a methoxylated derivative ( 2 ). In addition, two dicaffeoyl quinic acids and one coumaric acid ester ( 3 ) were isolated. Sensory evaluation of isolated compounds led to the identification of quercetin-3′- O -glucoside as bitterness enhancing principle.

Starting from previous structure-activity relationship studies of taste modifiers based on homoeriodictyol, dihydrochalcones, deoxybenzoins, and trans-3-hydroxyflavones as obvious analogues were investigated for their masking effect against caffeine. The most active compounds of the newly investigated taste modifiers were phloretin, the related dihydrochalcones 3-methoxy-2',4,4'-trihydroxydihydrochalcone and 2',4-dihydroxy-3-methoxydihydrochalcone, and the deoxybenzoin 2-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)ethanone. Starting with the whole set of compounds showing activity22%, a (Q)SAR pharmacophore model for maskers of caffeine bitterness was calculated to explain the structural requirements. After docking of the pharmacophore into a structural model of the broadly tuned bitter receptor hTAS2R10 and docking of enterolactone and enterodiol as only very weakly related structures, it was possible to predict qualitatively their modulating activity. Enterodiol (25 mg L(-1)) reduced the bitterness of the 500 mg L(-1) caffeine solution by about 30%, whereas enterolactone showed no masking but a slight bitter-enhancing effect.

As enzymatic digests of fish proteins were recently reported to enhance salt taste, the fish protein protamine was digested by chymotrypsin and trypsin and subsequently screened for candidate salt taste modulating (STM) peptides. To achieve this, first, a two-step sensory assay was developed and demonstrated to be a rather suitable tool for the detection of salt taste enhancers and the "quantitation" of their salt taste enhancing activity on the basis of isointensities with reference solutions. By means of activity-guided fractionation using ultrafiltration, gel permeation chromatography, and hydrophilic liquid interaction chromatography in combination with the sensory assay for STM activity assessment, a series of arginyl dipeptides, with RP, RA, AR, RG, RS, RV, VR, and RM being the most active, as well as l-arginine were found as salt taste enhancing molecules in fish protamine digests. For the first time, HPLC-MS/MS analysis on a PFP and a HILIC stationary phase, respectively, enabled the quantitative analysis of the arginyl peptides in a series of commercial and laboratory-made protein hydrolysates as well as fermented fish sauces.

The identification of flavor modulating compounds, for example, bitter masking or sweet enhancing compounds, in complex mixtures such as botanical extracts or food preparations is difficult and time- and work-intensive. To accelerate this process, an improved screening method was developed on the basis of the separation of complex matrixes by the so-called LC Taste setup and subsequent comparative sensory analysis. The eluent containing only water and ethanol was diluted with a basic tastant solution (500 mg L(-1) caffeine and 5% sucrose, respectively) and evaluated by a trained panel by duo comparison tests. This novel method was applied to the known flavor and taste modulating substances homoeriodictyol (1), sterubin (2), hesperetin (3), and lactisol (9) as well as to simple mixtures of homoeriodictyol (1), sterubin (2), and hesperetin (3). To evaluate the potential of the method for more complex matrixes, the protocol was applied to plant extracts from Yerba Santa (Eriodictyon californicum) and honeybush tea (Cyclopia intermedia). The flavor modulating activities reported for homoeriodictyol (1), sterubin (2), and hesperetin (3) could be confirmed in these complex mixtures.

To unambiguously identify their structures and to evaluate their organoleptic properties, several constitutional und configurational isomers of dialkyl-tetrathianes and dialkyl-pentathiepanes were synthesized by two different synthetic protocols, and separated by preparative gas chromatography. Raman and NMR spectroscopy were used to differentiate between the constitutional 3,6-dialkyl-1,2,4,5-tetrathiane and the 4,6-dialkyl-1,2,3,5-tetrathiane isomers. Furthermore, cis- and trans-isomers of 3,6-dialkyl-1,2,4,5-tetrathianes were distinguished by temperature-dependent NMR experiments. Static, quantum-chemical simulations of the NMR spectra for these cis- and trans-isomers were calculated in the gas layer in order to confirm our experimental assignments. In addition, the assignment of 4,7-alkyl-1,2,3,5,6-pentathiepanes were deducted from their Raman spectra. Dialkyl-tetrathianes and dialkyl-pentathiepanes are interesting components to be used in flavor applications due to their unique olfactory impact and facets.

Sensory screening of a series of naturally occurring N-cinnamoyl derivatives of substituted phenethylamines revealed that rubemamine (9, from Chenopodium album) and rubescenamine (10, from Zanthoxylum rubsecens) elicit strong intrinsic umami taste in water at 50 and 10 ppm, respectively. Sensory tests in glutamate- and nucleotide-containing bases showed that the compounds influence the whole flavor profile of savory formulations. Both rubemamine (9) and rubescenamine (10) at 10-100 ppm dose-dependently positively modulated the umami taste of MSG (0.17-0.22%) up to threefold. Among the investigated amides, only rubemamine (9) and rubescenamine (10) are able to directly activate the TAS1R1-TAS1R3 umami taste receptor. Moreover, both compounds also synergistically modulated the activation of TAS1R1-TAS1R3 by MSG. Most remarkably, rubemamine (9) was able to further positively modulate the IMP-enhanced TAS1R1-TAS1R3 response to MSG ∼ 1.8-fold. Finally, armatamide (11), zanthosinamide (13), and dioxamine (14), which lack intrinsic umami taste in vivo and direct receptor response in vitro, also positively modulated receptor activation by MSG about twofold and the IMP-enhanced MSG-induced TAS1R1-TAS1R3 responses approximately by 50%. In sensory experiments, dioxamine (14) at 25 ppm in combination with 0.17% MSG exhibited a sensory equivalent to 0.37% MSG.

The antioxidative and radical scavenging activity of the 3,4-dihydroxymandelic acid (DHMA) amides of hexylamine, 2-ethylhexylamine, octylamine, and cyclohexylamine was determined by several physicochemical test systems. The amides were synthesized by protecting group-free coupling of in situ prepared N-hydroxysuccinimidylester of DHMA and the amines. The radical scavenging activity was determined using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method and by quenching superoxide anions generated using a horse radish peroxidase/H 2 O 2 system. In the DPPH assay, all amides show higher radical scavenging activity (EC 50 0.09-0.12 mol/mol DPPH ) compared to the standard antioxidants ascorbic acid (EC 50 0.27 mol/mol DPPH ) and tocopherol (EC 50 0.25 mol/mol DPPH ). The amides are also more potent superoxide radical scavengers (IC 50 0.9, tocopherol 0.08). The DHMA octylamide in combination with ascorbic acid shows a synergistic antioxidative effect in the emulsion model. In conclusion, the new alkylamides of DHMA are easy to synthesize, potent radical scavengers and protect lipids, in particular the highly unsaturated, both in bulk and in emulsions against autoxidation.

The decarboxylated noradrenaline metabolite 3,4-dihydroxymandelic acid [DHMA, 2-(3,4-dihydroxyphenyl)-2-hydroxyacetic acid] occurs in different mammalian tissues, especially in the heart. To elucidate the physiological function of DHMA, the antioxidative and radical scavenging activity was determined by physicochemical and cell-based test systems. In the 2,2-diphenyl-1-picrylhydrazyl assay it shows a 4-fold higher radical scavenging activity compared to the standard antioxidants ascorbic acid, tocopherol, and butylated hydroxytoluene. DHMA is also a very potent superoxide radical scavenger and shows a 5-fold smaller IC(50) value compared to standard ascorbic acid. Again, in most cases the antioxidative power of DHMA against bulk lipid oxidation determined by accelerated autoxidation of oils is much higher than for the standard antioxidants. In soybean oil and squalene a DHMA/alpha-tocopherol mixture (1:1 w/w) shows a synergistic effect. Last but not least, 0.001 and 0.0005% levels of DHMA protect human primary fibroblasts against H(2)O(2)-induced oxidative stress as determined by the 2',7'-dichlorofluorescein assay.

Several oximes and oximeethers of hydroxylated benzaldehydes and acetophenones were investigated for their antioxidative potential and compared with further standards. Radical scavenging activity was determined using a photometric assay based on the colored radical 2,2-diphenyl-1-picrylhydrazyl and a superoxide anion quenching assay using luminol amplified chemiluminescence. The activity against lipid autoxidation was measured by accelerated autoxidation of soybean oil, evening primrose oil, and squalene. All tested catecholoximes show good to excellent antioxidative properties. 3,4-Dihydroxybenzaldoxime shows the best overall performance and is a very powerful radical scavenger and lipid antioxidant. Le potentiel antioxydant de quelques oximes et ethers-oximes de benzaldehydes et d'acetophenones hydroxyles est etudie. Les catecholoximes 1-8 presentent une activite elevee d'interception de radicaux et sont des intercepteurs puissants de superoxydes ainsi que des antioxydants tres puissants par rapport a l'acide ascorbique, le tocopherol et le BHT.

cope A bolus administration of 0.15 mg nonivamide has previously been demonstrated to reduce energy intake in moderately overweight men. This 12-week intervention investigated whether a daily consumption of nonivamide in a protein-based product formulation promotes a reduction in body weight in healthy overweight subjects and affects outcome measures associated with mechanisms regulating food intake, e.g. plasma concentrations of (an)orexigenic hormones, energy substrates as well as changes in fecal microbiota. Methods and results Nineteen overweight subjects were randomly assigned to either a control (C) or a nonivamide (NV) group. Changes in the body composition and plasma concentrations of satiating hormones were determined at fasting and 15, 30, 60, 90, and 120 min after a glucose load. Participants were instructed to consume 0.15 mg nonivamide per day in 450 mL of a milk shake additionally to their habitual diet. After treatment, a group difference in body fat mass change (–0.61 ± 0.36% in NV and +1.36 ± 0.38% in C) and an increase in postprandial plasma serotonin were demonstrated. Plasma metabolome and fecal microbiome read outs were not affected. Conclusions A daily intake of 0.15 mg nonivamide helps to support to maintain a healthy body composition.

Flavanoids and related polyphenols, among them hesperitin, have been shown to modulate cellular glucose transport by targeting SGLT-1 and GLUT-2 transport proteins. We aimed to investigate whether homoeriodictyol, which is structurally related to hesperitin, affects glucose uptake in differentiated Caco-2 cells as a model for the intestinal barrier. The results revealed that, in contrast to other polyphenols, the flavanon homoeriodictyol promotes glucose uptake by 29.0 ± 3.83% at a concentration of 100 μM. The glucose uptake stimulating effect was sensitive to phloridzin, but not to phloretin, indicating an involvement of the sodium-coupled glucose transporter SGLT-1, but not of sodium-independent glucose transporters (GLUT). In addition, in contrast to the increased extracellular serotonin levels by stimulation with 500 mM D-(+)-glucose, treatment with 100 μM homoeriodictyol decreased serotonin release by -48.8 ± 7.57% in Caco-2 cells via a phloridzin-sensitive signaling pathway. Extracellular serotonin levels were also reduced by -57.1 ± 5.43% after application of 0.01 μM homoeriodictyol to human neural SH-SY5Y cells. In conclusion, we demonstrate that homoeriodictyol affects both the glucose metabolism and the serotonin system in Caco-2 cells via a SGLT-1-meditated pathway. Furthermore, the results presented here support the usage of Caco-2 cells as a model for peripheral serotonin release. Further investigations may address the value of homoeriodictyol in the treatment of anorexia and malnutrition through the targeting of SGLT-1. ispartof: PLOS ONE vol:12 issue:2 ispartof: location:United States status: published

Red pepper and its major pungent component, capsaicin, have been associated with hypolipidemic effects in rats, although mechanistic studies on the effects of capsaicin and/or structurally related compounds on lipid metabolism are scarce. In this work, the effects of capsaicin and its structural analog nonivamide, the aliphatic alkamide trans-pellitorine and vanillin as the basic structural element of all vanilloids on the mechanisms of intestinal fatty acid uptake in differentiated intestinal Caco-2 cells were studied. Capsaicin and nonivamide were found to reduce fatty acid uptake, with IC50 values of 0.49 μM and 1.08 μM, respectively. trans-Pellitorine was shown to reduce fatty acid uptake by 14.0 ± 2.14% at 100 μM, whereas vanillin was not effective, indicating a pivotal role of the alkyl chain with the acid amide group in fatty acid uptake by Caco-2 cells. This effect was associated neither with the activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1) or the epithelial sodium channel (ENaC) nor with effects on paracellular transport or glucose uptake. However, acetyl-coenzyme A synthetase activity increased (p < 0.05) in the presence of 10 μM capsaicin, nonivamide or trans-pellitorine, pointing to an increased fatty acid biosynthesis that might counteract the decreased fatty acid uptake.

Astringency is an everyday sensory experience best described as a dry mouthfeel typically elicited by phenol-rich alimentary products like tea and wine. The neural correlates and cellular mechanisms of astringency perception are still not well understood. We explored taste and astringency perception in human subjects to study the contribution of the taste as well as of the trigeminal sensory system to astringency perception. Subjects with either a lesion or lidocaine anesthesia of the Chorda tympani taste nerve showed no impairment of astringency perception. Only anesthesia of both the lingual taste and trigeminal innervation by inferior alveolar nerve block led to a loss of astringency perception. In an in vitro model of trigeminal ganglion neurons of mice, we studied the cellular mechanisms of astringency perception. Primary mouse trigeminal ganglion neurons showed robust responses to 8 out of 19 monomeric phenolic astringent compounds and 8 polymeric red wine polyphenols in Ca(2+) imaging experiments. The activating substances shared one or several galloyl moieties, whereas substances lacking the moiety did not or only weakly stimulate responses. The responses depended on Ca(2+) influx and voltage-gated Ca(2+) channels, but not on transient receptor potential channels. Responses to the phenolic compound epigallocatechin gallate as well as to a polymeric red wine polyphenol were inhibited by the Gαs inactivator suramin, the adenylate cyclase inhibitor SQ, and the cyclic nucleotide-gated channel inhibitor l-cis-diltiazem and displayed sensitivity to blockers of Ca(2+)-activated Cl(-) channels.

Six hydroxymandelic acid amides of phenolic amines were synthesized by condensation of 3,4-dihydroxymandelic or 4-hydroxy-3-methoxymandelic acid N-succinimidyl esters and several phenolic benzylamino and phenethylamino hydrochlorides in moderate to good yield. The radical scavenging activities determined by 2,2-diphenyl-1-picrylhydrazyl assay and superoxide trapping assay were superior compared to standards l -ascorbic acid, α-tocopherol, and butylated hydroxytoluene (BHT). The antioxidative activities tested by accelerated autoxidation of bulk lipids were 2–3.5 times more potent compared to standards α-tocopherol and BHT. 3,4-Dihydroxymandelic acid dopamide (4b) and 4-hydroxy-3-methoxymandelic acid dopamide (4a) showed the best overall performance as antioxidants.

Sensory-guided analysis of an aqueous-ethanolic extract of Mondia whitei indicated sweetness enhancing effects of 2-hydroxy-4-methoxybenzaldehyde (HMBA). Further sensory tests confirmed these findings at low concentrations (0.5 mg/L). Higher concentrations did not show the desired effect, probably due to the strong coumarin-like flavor of HMBA. Similar to vanillin, the enhancement mainly results from a congruent flavor effect. Trials with nose clamps clearly reduced the observed effects. In a simple sugar reduced beverage application, however, HMBA was able to partly restore the sweetness of the beverage.