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PubMed1990

Induction of tumor cytotoxic immune cells using a protein from the bitter melon (Momordica charantia).

The fruit and seeds of the bitter melon (Momordica charantia) have been reported to have anti-leukemic and antiviral activities. This anti-leukemic and antiviral action was associated with an activation of murine lymphocytes. A partially purified protein factor from the bitter melon caused an infiltration and activation of peritoneal exudate cells in C57B1/6J, C3H/HeJ, and C3H/HeN mice. When the extract was injected twice a week at 8 micrograms of protein per ip injection for 0-4 weeks, the peritoneal exudate cells from the treated mice were cytotoxic in a long-term (18-hr) 51Cr-release assay against a range of labeled targets: L1210, P388, and MOLT-4 tumor cells. Cytotoxicity was also observed against YAC-1 targets in a short-term (4-hr) assay. Fractionation of the cytotoxic immune cells implicated a nonadherent cell population which was capable of killing an NK-sensitive cell line in a 4-hr 51Cr-release assay. Unit gravity sedimentation studies indicated that the cytotoxicity was due to either a neutrophil or a large lymphocyte. Antibody depletion experiments using antibody to asialo GM1, an NK cell-specific antibody, depleted cytotoxicity observed in nonadherent, Ficoll/Hypaque-separated PEC. This suggests that at least part of the anti-leukemic activity of the bitter melon extract is due to the activation of NK cells in the host mouse.

Animals↗
PubMed1992

The immobilization of all spermatozoa in vitro by bitter lemon drink and the effect of alkaline pH.

UNLABELLED: This study investigated the effects of increase in temperature and in pH of Coca-Cola, Afri-Cola, Pepsi-Cola and Krest bitter lemon drinks ("soft drinks") produced in Nigeria on the in vitro motility of spermatozoa. Semen was collected from 7 men, average age 28 years, of proven fertility, after 5 days' abstinence from sexual intercourse. The temperature and pH of the drinks were adjusted from 22 degrees C (room) to 37 degrees C, and pH 2.4 (acid) to 7.5 (alkaline), respectively. The mean % motility of spermatozoa in the adjusted and in the unadjusted drinks was compared for significant differences at the 1% level using the student's t-test. The results showed no significant differences in mean % motility in the drinks at 22 degrees C and at 37 degrees C. The mean % motility in all the drinks, except Coca-Cola, was significantly greater at alkaline than at acid pH; for Coca-Cola, motility was significantly greater at acid than alkaline pH. Of the drinks, Krest bitter lemon (unadjusted) immobilized all spermatozoa within 1 minute of addition. CONCLUSION: i) alkalinity decreases the spermicidal action of all drinks except Coca-Cola, and ii) Krest bitter lemon may achieve very high efficacy if used as post-coital douche, especially in the impoverished, densely populated Third World.

Adult↗
PubMed1994

Genetics of bitter perception in mice.

Inbred and congenic strains exhibited several patterns of relative sensitivity to bitter tastants in 48-h, two-bottle preference tests. With segregation analyses of descendents of crosses between contrasting strains, these patterns suggested at least three genetic loci influencing bitter perception. The extensively characterized Soa (sucrose octaacetate) locus underlies one pattern. Variation at this locus had pleiotropic effects on avoidance of other acetylated sugars, plus such structurally dissimilar bitter tastants as brucine, denatonium benzoate, and quinine sulfate. Unlike SOA, however, sensitivity to quinine sulfate was polygenically determined, and produced a second characteristic pattern. At least one, possibly several, additional unlinked loci contributed to quinine differences. Phenylthiocarbamide (PTC) aversion differences exemplified a third pattern. Segregation consistent with monogenic control of PTC aversion has been reported, and within segregating populations PTC aversion did not covary with SOA or quinine sulfate avoidance. Variants of the three major patterns may be useful for analysis of specific mechanisms. While both showed the SOA pattern, strychnine differences were markedly smaller than brucine (dimethoxystrychnine) differences. Likewise, a hop extract containing primarily iso-alpha acids (e.g., isohumulone) produced an SOA-like pattern, while an extract with nonisomerized alpha-acids (e.g., humulone) did not.

Animals↗
PubMed1994

Perceptual interactions in mixtures containing bitter tasting substances.

Mixtures of Quinine HCl and NaCl elicit heterogeneous taste percepts. Each such percept consists of a bitter and a salt sensation. Using functional measurement in combination with a two-stimulus procedures, it was found that the NaCl suppresses the QHCl bitterness and that QHCl has almost no suppressive effect on NaCl saltiness. In addition, it was shown that the total intensity of the mixture percept is almost identical to the sum of the intensities of the bitterness and saltiness sensations-within-the-percept. As was found in earlier experiments with mixtures of other tastants, central sensory integration within a heterogeneous percept seems to be a fairly simple additive process.

Adult↗
PubMed1996

Characteristics of phosphatidic acid-containing lipoproteins which selectively inhibit bitter taste: high affinity to frog tongue surface and hydrophobic model membranes.

In previous studies (Katsuragi and Kurihara (1993) Nature 365,213--214; Katsuragi et al. (1995) Pharm. Res. 12,658--662) we showed that a lipoprotein composed of phosphatidic acid (PA) and beta-lactoglobulin (LG) selectively suppressed the taste responses to bitter substances without affecting those to other taste stimuli in the frog and man, while complexes composed of other lipids except for phosphatidylserine and LG had little inhibitory activity. In the present study, we found that the lipoproteins having inhibitory activity are adsorbed on the frog tongue surface, while those having no inhibitory activity are not adsorbed. We also examined adsorption of the lipoproteins on model lipid membranes coated on a quartz-crystal microbalance by measuring changes in its frequency. The lipoproteins having inhibitory activity were well adsorbed on the hydrophobic lipid membranes, while the lipoproteins having no inhibitory activity were little adsorbed on the membranes. It seems that receptor sites for bitter substances on the taste cell membranes are hydrophobic and those for other taste stimuli such as salts, acids and sugars are hydrophilic. Hence, the binding of PA-LG to hydrophobic sites of the receptor membranes will lead to selective inhibition of bitterness.

Adsorption↗
PubMed1995

Bitterness of sweeteners as a function of concentration.

Sixteen trained tasters provided sweetness and bitterness intensity ratings for 19 compounds including: acesulfame-K, alitame, aspartame, fructose, glucose, glycine, lactitol, maltitol, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone, neosugar (fructo-oligosaccharide), palatinit (isomalt), rebaudioside-A, sodium cyclamate, sodium saccharin, stevioside, sucralose, sucrose, and thaumatin. With increasing concentration, high-potency sweeteners including acesulfame-K, neohesperidin dihydrochalcone, sodium saccharin, rebaudioside-A, and stevioside tended to become more bitter. Low-potency sweeteners including fructose, sucrose, and lactitol tended to become less bitter with increasing concentration.

Female↗
PubMed2005

The effects of lipopolysaccharide and lithium chloride on the ingestion of a bitter-sweet taste: comparing intake and palatability.

Activation of the immune system with lipopolysaccharide (LPS) has been shown to result in decreased consumption of normally preferred substances while at the same time not affecting palatability. The present study examined the effects LPS administration on both intake and palatability of a relatively unpalatable bitter-sweet taste. Bitter is thought to signal a danger cue to an animal representing a potential toxin-containing food. Using a one-bottle consumption test, voluntary intake of a sucrose-quinine (0.15 M sucrose + 0.00015 M quinine; S-Q) solution was assessed in rats on two conditioning days (days 1 and 4) after a systemic injection with LPS, LiCl, or NaCl. On the test day (day 7), rats were given 1h access to the same solution in the absence of any injection. In a separate experiment, rats fitted with intraoral cannulae received similar testing schedules, however, the solution was delivered intraorally, activating only the consummatory responses of the animal. During conditioning, rats received 5 brief (1 min) intraoral infusions of the taste across a 1h period following injections of LPS, LiCl or NaCl. Individual taste reactivity responses were recorded and analyzed. Both LPS and LiCl resulted in decreased consumption of the unpalatable taste relative to controls on the test day, suggesting typical conditioned taste avoidance. When the consummatory responses were examined, LPS-treatment produced an increase in active oral rejection relative to NaCl- and LiCl-treated groups on both conditioning days. The present study demonstrates that although both LPS- and LiCl-treatment result in similar conditioned avoidance using an intake measure, they do not elicit similar patterns of taste reactivity responding to intraoral infusions of the bitter-sweet taste. Furthermore, the present results suggest that immune activation with LPS-treatment results in increased rejection of a mildly aversive stimulus and supports the hypothesis that reorganization of behavioral priorities occurs during bacteria-induced sickness.

Animals↗
PubMed2005

Positive selection on a high-sensitivity allele of the human bitter-taste receptor TAS2R16.

BACKGROUND: During periods of human expansion into new environments, recognition of bitter natural toxins through taste may have conferred an important selective advantage. The G protein-coupled receptor encoded by TAS2R16 mediates response to salicin, amygdalin, and many bitter beta-glucopyranosides. beta-glucopyranosides are ubiquitous in nature, with many having a highly toxic cyanogenic activity. RESULTS: We examined evidence for natural selection on the human receptor TAS2R16 by sequencing the entire coding region, as well as part of the 5' and 3' UTRs, in 997 individuals from 60 human populations. We detected signatures of positive selection, indicated by an excess of evolutionarily derived alleles at the nonsynonymous site K172N and two linked sites and significant values of Fay and Wu's H statistics in 19 populations. The estimated age range for the common ancestor of the derived N172 variant is 78,700-791,000 years, placing it in the Middle Pleistocene and before the expansion of early humans out of Africa. Using calcium imaging in cells expressing different receptor variants, we showed that N172 is associated with an increased sensitivity to salicin, arbutin, and five different cyanogenic glycosides. CONCLUSION: We have detected a clear signal of positive selection at the bitter-taste receptor gene TAS2R16. We speculate that the increased sensitivity that is shown toward harmful cyanogenic glycosides and conferred by the N172 allele may have driven the signal of selection at an early stage of human evolution.

Alleles↗
PubMed2004

Acetaminophen-containing chewable tablets with suppressed bitterness and improved oral feeling.

The aim of this study was to develop acetaminophen chewable tablets with suppressed bitterness and improved oral feeling by examination of hard fats as the matrix base and of sweetening agents as corrigents. Witepsol H-15, W-35, S-55, E-75 and E-85, and Witocan H and 42/44 were used as hard fats. Witocan H and 42/44 were selected in view of improved oral feeling. Witocan H/Witocan 42/44 mixture tablets showed different melting characteristics and drug release rates dependent on their ratios, and those with the Witocan H/Witocan 42/44 ratio of 92.5% (w/w) and more showed good drug release. Sucrose, xylitol, saccharin, saccharin sodium, aspartame and sucralose were used as sweetening agents, and applied alone or with Benecoat BMI-40 or cocoa powder. The Witocan H tablet with 1% (w/w) saccharin plus 5% (w/w) Benecoat BMI-40 (Sc1-B5), and the Witocan H/Witocan 42/44 (92.5:7.5, w/w) mixture tablet with 1% (w/w) aspartame plus 5% (w/w) Benecoat BMI-40 suppressed bitterness and sweetness excellently, but the former tablet showed better drug release. Thus, the Witocan H tablet with Sc1-B5 is suggested as the best acetaminophen chewable tablet, exhibiting suppressed bitterness, low sweetness, improved oral feeling and good drug release.

Acetaminophen↗
PubMed2004

Direct characterization of bitter acids in a crude hop extract by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

The applicability of on-line coupling of reversed-phase high-performance liquid chromatography to atmospheric pressure ionization tandem mass spectrometry for the separation and characterization of hop acids mixture from the crude extract of Humulus lupulus was investigated. The solvent system consisting of acetonitrile-aqueous formic acid was used to give proper separation of the six main hop bitter acids within 30 min. Further structural information about the components was acquired by collision-induced dissociation (CID). On the basis of analyses of the fragmentation patterns of the major alpha- and beta-bitter acids respectively, identification of the minor ones was performed using selected reaction monitoring (SRM) with a group of qualitatively relevant selected precursor-product ion transitions for each bitter acid in a single high performance liquid chromatography (HPLC) run. Using this technique, six minor hop acids, including "adprelupulone" observed for the first time in natural resources, were detected along with the six major acids. This hyphenated techniques provides potency for rapid qualitative determination of analogs and homologs in mixtures.

Acids↗
PubMed2006

Intestinal disaccharidases and some renal enzymes in streptozotocin-induced diabetic rats fed sapogenin extract from bitter yam (Dioscorea polygonoides).

In this study, the effects of bitter yam sapogenin extract or commercial diosgenin on intestinal disaccharidases and some renal enzymes in diabetic rats were investigated. Diabetic male Wistar rats were fed diets supplemented with 1% sapogenin extract or commercial diosgenin for 3 weeks. Plasma glucose, intestinal disaccharidases and the activities of transaminases, acid phosphatase, glucose-6-phosphatase, ATP citrate lyase, glucose-6-phosphate dehydrogenase and pyruvate kinase were assessed for the level of metabolic changes in the kidney of diabetic rats. Sapogenin extract or commercial diosgenin supplementation resulted in a significant decrease in lactase and maltase activities in all three regions of the intestine compared to the diabetic control group. However, the test diets significantly reduced intestinal sucrase activity in the proximal and mid regions. Test diets supplementation resulted in a significant decrease in the activities of the transaminases compared to the normal and diabetic control groups. The activity of glucose-6-phosphatase was significantly increased while the activities of ATP citrate lyase, pyruvate kinase and glucose-6-phosphate dehydrogenase were significantly reduced in the kidney of the diabetic control rats compared to the normal group. Test diets supplementation did not significantly alter glucose-6-phosphatase, ATP citrate lyase and pyruvate kinase activities compared to the diabetic control. However, there was a significant increase in glucose-6-phosphate dehydrogenase activity toward the normal group. In conclusion, the consumption of bitter yam sapogenin extract or commercial diosgenin demonstrated hypoglycemic properties, which are beneficial in diabetes by reducing intestinal disaccharidases activities; however, bitter yam sapogenin extract may adversely affect the integrity of kidney membrane.

Animals↗
PubMed2003

Effects of repeated exposure and health-related information on hedonic evaluation and acceptance of a bitter beverage.

The influence of exposure and information on sensory evaluation and acceptance of bitter flavor was assessed. Following sensory testing in the laboratory, subjects consumed a commercially-available bittersweet beverage once daily for 7days in a setting of their choosing, then returned to the laboratory for post-exposure tests. Hedonic ratings for the beverage increased by 68%, whereas ratings for control stimuli sampled only in the laboratory did not change. Following exposure, relationships of hedonic ratings with intensity and familiarity varied according to the context in which evaluations were made: hedonic ratings were correlated with intensity in a familiar setting and with familiarity in an unfamiliar setting. Health-related information had no effect on perceptual changes that accompanied exposure, but did tend to increase a behavioral measure of acceptability, suggesting that information may have a greater effect on behavior than on hedonics. Together, the data suggest that repeated exposure can enhance hedonic evaluation of a bittersweet beverage, perhaps through a learned association of flavor with post-ingestive consequences. Context may mediate this effect and studies addressing the influence of information on bitter food acceptance should include measures of consumption and evaluate information strategies, as bitter foods may be particularly resistant to cognitively-based appeals.

Adult↗
PubMed1998

The bitter with the sweet: the taste/stress/temperament nexus.

Is the tongue a window to the psyche? In rats, stress alters taste, and individual differences in taste are related to measures of emotion. The present study concerned stress-induced changes in taste and its modulation by temperament in people. College students rated saccharin's bitterness and sweetness and a tone's loudness after exposure to a mild stressor. Temperament (trait arousability, pleasure, and dominance) was assessed separately. When individual differences were ignored, stress appeared to selectively increase sensitivity to saccharin's bitterness. However, the stressor's impact was modulated by temperament: Stress nonselectively augmented stimulus magnitude ratings among highly arousable individuals; relative to high-pleasure counterparts, low-pleasure individuals gave higher bitterness ratings and lower sweetness ratings after stress. Taste does seem to provide a glimpse of the emotional life of humans and other animals and opens new avenues to the study of the biological bases of affect.

Adult↗
PubMedDate not supplied

Does a reduced sensitivity to bitter taste increase the risk of becoming nicotine addicted?

Cigarette smoking appears to be on the increase in adolescents. The initiation of regular smoking nearly always begins before adulthood. It is therefore crucial to find ways of identifying those children most vulnerable to nicotine addiction and prioritizing them for preventive measures. We hypothesized that individuals who, in a simple taste test, perceive phenylthiocarbamide (PTC) as bitter may find the taste of cigarettes aversively bitter and could therefore have a reduced vulnerability to nicotine addiction compared to nontasters, who would be the group at greater risk of addiction. We studied 242 Plains American Indians, 136 women and 106 men aged 18-59 years, and found that (allowing for gender differences and the possible direct effects of smoking on taste) the proportion of PTC nontasters to tasters in smokers, even light smokers, was significantly greater than in both nonsmokers and social smokers (chi2= 15.875, 4 df; P=.003), suggesting that nontasters, who are not aversive to the bitter taste of cigarettes, may be more at risk for heavy smoking and therefore more vulnerable to nicotine addiction.

Adolescent↗
PubMed2000

Bitter and sweet components of ethanol taste in humans.

This study examined taste descriptions elicited by ethanol and by other tastants in humans. All subjects described 10% ethanol as bitter and approximately 30% of the subjects described it as sweet and/or sour. Highly significant correlations were found between sweetness of some sucrose solutions (0.6-1%) and intensity of the taste of ethanol. In another experiment, quinine (bitter) solutions were rated as similar to 10% ethanol taste and this effect was potentiated by the addition of sucrose. In contrast, citric acid (sour) tended to decrease similarity ratings when added to the quinine solutions. Taken together, these findings suggest that: (1) in humans ethanol tastes both bitter and sweet; and (2) the relationship between sucrose and ethanol intakes previously found in animals and humans may result, at least partially, from similar taste responses elicited by sucrose and ethanol.

Adolescent↗
PubMed2001

Determination of taste-active compounds of a bitter Camembert cheese by omission tests.

The taste-active compounds of a Camembert cheese selected for its intense bitterness defect were investigated. The water-soluble fraction (WSE) was extracted with pure water and fractionated by successive tangential ultrafiltrations and nanofiltration. The physicochemical assessment of these fractions led to the construction of a model WSE which was compared by sensory evaluation to the crude water-soluble extract, using a panel of 16 trained tasters. As no significant difference was perceived, this model WSE was then used directly or mixed with other cheese components for omission tests. Among the main taste characteristics of the WSE (salty, sour, umami and bitter), bitterness was found to be due to small peptides whose mass distribution was obtained by RPHPLC-MS (400-3000 Da) and whose taste properties are discussed.

Amino Acids↗
PubMed2001

Evolution of the composition of a selected bitter Camembert cheese during ripening: release and migration of taste-active compounds.

The aim of this study was to add to the understanding of changes in taste that occur during the ripening of a bitter Camembert cheese by the evolution of its composition. Physicochemical analyses were performed on rind, under-rind, and center portions of a Camembert cheese selected for its intense bitterness. At each of the six steps of ripening studied organic acids, sugars, total nitrogen, soluble nitrogen, phosphotungstic acid soluble nitrogen, non-protein nitrogen, Na, K, Ca, Mg, Pi, Cl, and biogenic amines were quantified in each portion. Changes in cheese composition seemed to mainly result from the development of Penicillium camemberti on the cheese outer layer. Migration phenomena and the release of potentially taste-active compounds allowed for the evolution of saltiness, sourness, and bitterness throughout ripening to be better understood. Apart from taste-active compounds, the impact of the cheese matrix on its taste development is discussed.

Carbohydrates↗
PubMed2002

Reinvestigation of the chemical structure of bitter-tasting quinizolate and homoquinizolate and studies on their Maillard-type formation pathways using suitable (13)C-labeling experiments.

Very recently, application of taste dilution analysis to heated xylose/alanine solutions led to the isolation of two bitter-tasting compounds exhibiting extraordinarily low detection thresholds of 0.00025 and 0.001 mmol/kg of water, respectively. On the basis of LC-MS and NMR spectroscopy, the structures of these compounds, named quinizolate and homoquinizolate, were proposed as 1-oxo-1H,4H-quinolizinium-7-olates. Since recent experiments in our laboratory shed some doubt on the entire correctness of their structures, labeling experiments with mixtures of multiply (13)C-labeled and nonlabeled pentoses were performed to follow the joint transfer of several (13)C atoms en bloc into the bitter compounds by LC-MS and NMR isotopomer diagnosis. The site-specific visualization of the mosaics assembled from (13)C-labeled and (12)C-labeled carbon modules in both bitter compounds demonstrated the structures of quinizolate and homoquinizolate to be the previously unknown (2E)-7-(2-furylmethyl)-2-(2-furylmethylidene)-3-(hydroxymethyl)- and (2E)-7-(2-furylmethyl)-2-(2-furylmethylidene)-3,8-bis(hydroxymethyl)-1-oxo-2,3-dihydro-1H-indolizinium-6-olate.

Carbon Isotopes↗