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PubMed2004

1,8-cineole (eucalyptol), a monoterpene oxide attenuates the colonic damage in rats on acute TNBS-colitis.

The monoterpene oxide, 1,8-cineole (cineole, eucalyptol) was examined for its possible influence on the acute phase of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. The test compound, 1,8-cineole (200 and 400 mg/kg) or vehicle (1 ml, 2% Tween 80) was instilled rectally, 24, and 2 h before (pre-treatment) or 2 and 24 h after (post-treatment) the induction of colitis by intracolonic administration of TNBS (0.25 ml of 25 mg of TNBS in 50% ethanol). Rats were killed 48 h after colitis induction and colonic segments were analysed for gross damage scores, changes in wet weights, myeloperoxidase activity, an indicator of neutrophilic infiltration and glutathione level, a major cellular antioxidant. TNBS induced an extensive inflammation and ulceration in the colon. Colonic damage was associated with an increase in myeloperoxidase activity and by a decrease in glutathione. When compared to vehicle-treated TNBS controls, a marked reduction in gross damage scores and wet weights (mg/cm) of colonic segments were evident in animals pre-treated but not post-treated with 1,8-cineole. Cineole also significantly reduced the myeloperoxidase activity, and caused repletion of glutathione. These results confirm the anti-inflammatory action of 1,8-cineole and suggest its potential value as a dietary flavoring agent in the prevention of gastrointestinal inflammation and ulceration.

Acute Disease↗
PubMed2004

Safety assessment of (-)-hydroxycitric acid and Super CitriMax, a novel calcium/potassium salt.

(-)-Hydroxycitric acid (HCA) is a principle constituent (10-30%) of the dried fruit rind of Garcinia cambogia, a plant native to Southeastern Asia. The dried rind has been used for centuries throughout Southeast Asia as a food preservative, flavoring agent and carminative. Extensive experimental studies show that HCA inhibits fat synthesis and reduces food intake. The objective of this review is to systematically review the available safety/toxicity literature on HCA to determine its safety in-use. The primary mechanism of action of HCA appears to be related to its ability to act as a competitive inhibitor of the enzyme ATP-citrate lyase, which catalyzes the conversion of citrate and coenzyme A to oxaloacetate and acetyl coenzyme A (acetyl-CoA), primary building blocks of fatty acid and cholesterol synthesis. Super CitriMax, a novel calcium/potassium-HCA extract (HCA-SX), is considerably more soluble and bioavailable than calcium-based HCA ingredients. Acute oral toxicity studies in animals demonstrate that CitriMax (50% HCA as calcium salt) has a low acute oral toxicity. In a subchronic study in rats, the gavage administration of HCA-SX at doses up to 2500 mg/kg/day for a period of 90 days caused a significant decrease in body weight and reduction in feed consumption without any adverse effects. The structure, mechanism of action, long history of use of HCA and other toxicity studies indicate that HCA-SX is unlikely to cause reproductive or developmental effects. HCA-SX was not mutagenic in the presence or absence of metabolic activation in Ames genotoxicity assays in strains TA98 and TA102. HCA-SX-induced increases in number of revertants in other strains (TA100 and TA1535 in the absence of metabolic activation and in strain TA1537 in the presence of metabolic activation) but these were not considered as biologically indicative of a mutagenic effect. In several, placebo-controlled, double-blind trials employing up to 2800 mg/day HCA, no treatment-related adverse effects were reported. There is sufficient qualitative and quantitative scientific evidence, including animal and human data suggesting that intake of HCA at levels up to 2800 mg/day is safe for human consumption.

Animals↗
PubMed2004

Genotoxicity testing of a fenugreek extract.

Fenugreek seeds have been used in traditional medicines as a remedy for diabetes. Rich in protein, fenugreek seeds contain the unique major free amino acid 4-hydroxyisoleucine (4-OH-Ile), which has been characterized as one of the active ingredients for blood glucose control. Current use of fenugreek in foodstuff has been limited to its role as a flavoring agent, and not as an ingredient to help mitigate the blood glucose response for people with diabetes. As part of a safety evaluation of novel ingredients for use in blood glucose control, the potential genotoxicity of a fenugreek seed extract (THL), containing a minimum of 40% 4-OH-ILE, was evaluated using the standard battery of tests (reverse mutation assay; mouse lymphoma forward mutation assay; mouse micronucleus assay) recommended by US Food and Drug Administration (FDA) for food ingredients. THL was determined not to be genotoxic under the conditions of the tested genetic toxicity battery. The negative assay results provide support that addition of THL to foodstuffs formulated for people with diabetes is expected to be safe. A wide safety margin is established, as anticipated doses are small compared to the doses administered in the assays.

Animals↗
PubMed2005

Validation of a rat behavioral avoidance model from a drug delivery perspective.

Conventional taste-masking strategies are used to overcome the bitter taste perception of pharmaceuticals by coating the drug particles and/or adding flavoring agents. However, for certain product categories such as rapid dissolve sublingual tablets, taste-masking is challenging. Programs exploring such formulation strategies in the LO-CS phase or post CS phase possess very little toxicological information available in order to conduct human taste panel studies. The potential of a bitter taste perception can present a significant business risk. The objective of the study was to validate a rat behavioral avoidance model that identifies bitter-tasting compounds. Most classic bitter substances elicit a response in the micromolar concentration range while most drugs elicit a response in the millimolar range, hence a validation exercise was conducted to examine if the existing biological model was sensitive enough to identify known bitter tasting drugs as such. Five compounds: ergotamine tartrate, fluoxetine, sucrose, sumatriptan and povidone were chosen to represent a spectrum of compounds. The bitter tasting compounds were identified as such in the model. Based on these results, the assay may serve as a useful surrogate test to identify compounds that may have bitter taste issues.

Animals↗
PubMed2005

A comparative study of the antioxidant/prooxidant activities of eugenol and isoeugenol with various concentrations and oxidation conditions.

Eugenol (compound in , 4-allyl-2-methyoxyphenol) and isoeugenol (compound in , 4-propenyl-2-methoxyphenol), both used as a flavor agent in cosmetic and food products, have both prooxidant and antioxidant activities. Their adverse effects such as allergic and inflammatory reaction may be due to their prooxidant activity. To clarify the mechanisms of their cytotoxicity and the factors affecting their antioxidant/prooxidant activities, we investigated the cytotoxicity, ROS production, and cellular glutathione (GSH) levels induced by eugenol and isoeugenol in a human submandibular cell line. The cytotoxicity (MTT method) of eugenol was 1 order of magnitude lower than that of isoeugenol (CC50: eugenol, 0.395 mM; isoeugenol, 0.0523 mM); and ROS production (CDF staining) was induced significantly by isoeugenol, but not by eugenol. Under treatment with H2O2 (100 microM) plus horseradish peroxidase (1 microg/ml) for 30 min or with visible light irradiation for 5 min, eugenol caused biphasic ROS production characterized by enhanced at lower eugenol concentrations (5-10 microM) and decreased at higher concentrations (500 microM). In contrast, isoeugenol enhanced ROS production over a wide range of concentrations (5-500 microM). Isoeugenol at 1000 microM significantly reduced GSH levels compared with eugenol at the same concentration. The high cytotoxicity of isoeugenol may be attributed to its induction of high ROS production and low GSH levels, possibly as a result of benzyl radical formation. In contrast, the cytotoxicity of eugenol is likely to be mediated by ROS-independent mechanisms, possibly involving phenoxyl radicals and/or eugenol quinone methide.

Antioxidants↗
PubMed2001

Asafoetida inhibits early events of carcinogenesis: a chemopreventive study.

Ferula (a genus of many species) commonly known as asafoetida is used as a flavoring agent in food and is used as a traditional medicine for many diseases in many parts of world. In the current investigation, we report the antioxidant and anticarcinogenic potential of asafoetida (Ferula narthex) in swiss albino mice. A single dose of TPA (20 nmol/0.2 ml acetone/animal), a known tumor promoter decreased the cellular antioxidant level significantly (p<0.01) when applied topically to mice skin. It also induced the ODC activity, rate of DNA synthesis, hydrogen peroxide level, xanthine oxidase activity and protein carbonyl content in mice skin significantly (p<0.01). These events are early biomarkers of carcinogenesis. However, the pretreatment of animals with asafoetida (300, 400 and 500 microg/200 microl acetone/animal) caused the reversal of all events significantly (p<0.01). The pretreament of animals with asafoetida recovered the antioxidant level and reversed the induced ODC activity and DNA synthesis significantly (p<0.01). We conclude that asafoetida is a potent antioxidant and can afford protection against free radical mediated diseases such as carcinogenesis.

Administration, Topical↗
PubMed2003

Dietary levels of quinine in tonic water do not inhibit CYP2D6 in vivo.

Quinine is a bitter alkaloid that is used as a flavoring agent in tonic water. Studies suggest that quinine can inhibit cytochrome P450 2D6 (CYP2D6) which could have implications for the metabolism of co-ingested drugs. We conducted a study with 11 healthy volunteers (7 men, 4 women; aged 26-54). After urinary void, each subject consumed either 1000 ml of carbonated water or 1000 ml of tonic water containing 80 mg quinine in a crossover design. Following each beverage subjects ingested an oral dose of 30 mg dextromethorphan (DM). Urine was collected for 8 h and analyzed for DM and dextrophran, its CYP2D6 mediated metabolite. The ratio of DM and its metabolite is an established measure of CYP2D6 activity. All subjects metabolized the vast majority of DM to its metabolite after both the carbonated water and the tonic water. The ratio (mean+/-S.D.) of DM to its metabolite was 0.013+/-0.028 after the carbonated water and 0.032+/-0.067 after the quinine containing water. No significant difference in the ratios was observed between the two beverages (P>0.05). We conclude that quinine as consumed in tonic water does not inhibit CYP2D6 activity in vivo. Thus, quinine should not alter the metabolism of CYP2D6 substrates taken concomitantly with tonic water.

Adult↗
PubMed2000

A study on the teratogenic and cytotoxic effects of safflower extract.

In recent years, the use of carthami flos (the flowers of Carthamus tinctorius L.) as a coloring and flavoring agent has increased as a food additive in Iran. In order to evaluate its safety, the teratogenic effects of carthami flos on the central nervous system development in mice was investigated. Furthermore, its cytotoxic effect on the rat nervous cell culture was studied to complete safety evaluations. For teratogenic studies, after natural mating, pregnant mice were divided into test and control groups. The groups were treated with different dosage regimens of aqueous carthami flos extract during 0-8 days of gestation. Embryos were then isolated at the 13th gestation day and evaluated for macroscopic, microscopic and morphometric characteristics. The results showed that in higher doses (1.6 and 2 mg/kg/day) the embryos were absorbed, whereas with lower dose (1.2 mg/kg/day) changes in external, internal and longitudinal diameters, open neuropore, changes in cellular orientation and cellular degeneration were observed. The results obtained from cytotoxic assay also demonstrated a concentration-dependent cytotoxic effect of carthami flos extract. It is concluded that the use of carthami flos as a food additive should be reconsidered.

Animals↗
PubMed2001

Naturally occurring anti-Salmonella agents.

Polygodial and (2E)-hexenal were found to possess antibacterial activity against Salmonella choleraesuis with the minimum bactericidal concentrations (MBC) of 50 microg/mL (0.17 mM) and 100 microg/mL (0.98 mM), respectively. The time kill curve study showed that these two alpha,beta-unsaturated aldehydes were bactericidal against this food-borne bacterium at any stage of growth. However, they showed different effects on the growth of S. choleraesuis. The combination of polygodial and anethole exhibited strong synergism on their bacteriostatic action but only marginal synergism on their bactericidal action.

Aldehydes↗
PubMed2005

Gingerol content of diploid and tetraploid clones of ginger (Zingiber officinale Roscoe).

Ginger (Zingiber officinale Roscoe), a monocotyledonous, sterile cultigen, is widely used as a spice, flavoring agent, and herbal medicine. The pungency of fresh ginger is due to a series of homologous phenolic ketones of which [6]-gingerol is the major one. The gingerols are thermally unstable and can be converted to their corresponding shogaols, which are present in dried ginger. Fresh rhizomes of 17 clones of Australian ginger, including commercial cultivars and experimental tetraploid clones, were assayed by HPLC for gingerols and shogaols. [6]-Gingerol was identified as the major pungent phenolic compound in all samples, while [8]- and [10]-gingerol occurred in lower concentrations. One cultivar known as "Jamaican" contained the highest concentrations of all three gingerols and was the most pungent of the clones analyzed. Gingerols were stable in ethanolic solution over a 5-month period when stored at 4 degrees C. Shogaols were not identified in the extracts prepared from fresh rhizomes at ambient temperature, confirming that these compounds are not native constituents of fresh ginger. In contrast to previous findings, this study did not find significant differences in gingerol concentrations between the tetraploid clones and their parent diploid cultivar.

Australia↗
PubMed2001

Antifungal activities of origanum oil against Candida albicans.

The antimicrobial properties of volatile aromatic oils from medicinal as well as other edible plants has been recognized since antiquity. Origanum oil, which is used as a food flavoring agent, possesses a broad spectrum of in vitro antimicrobial activities attributed to the high content of phenolic derivatives such as carvacrol and thymol. In the present study, antifungal properties of origanum oil were examined both in vitro and in vivo. Using Candida albicans in broth cultures and a micro dilution method, comparative efficacy of origanum oil, carvacrol, nystatin and amphotericin B were examined in vitro. Origanum oil at 0.25 mg/ml was found to completely inhibit the growth of C. albicans in culture. Growth inhibitions of 75% and >50% were observed at 0.125 mg/ml and 0.0625 mg/ml level, respectively. In addition, both the germination and the mycelial growth of C. albicans were found to be inhibited by origanum oil and carvacrol in a dose-dependent manner. Furthermore, the therapeutic efficacy of origanum oil was examined in an experimental murine systemic candidiasis model. Groups of mice (n = 6) infected with C. albicans (5 x LD50) were fed varying amounts of origanum oil in a final vol. of 0.1 ml of olive oil (vehicle). The daily administration of 8.6 mg of origanum oil in 100 microl of olive oil/kg body weight for 30 days resulted in 80% survivability, with no renal burden of C. albicans as opposed to the group of mice fed olive oil alone, who died within 10 days. Similar results were obtained with carvacrol. However, mice fed origanum oil exhibited cosmetically better clinical appearance compared to those cured with carvacrol. The results from our study encourage examination of the efficacy of origanum oil in other forms of systemic and superficial fungal infections and exploration of its broad spectrum effect against other pathogenic manifestations including malignancy.

Animals↗
PubMed2003

Chemomodulatory influence of Ferula asafoetida on mammary epithelial differentiation, hepatic drug metabolizing enzymes, antioxidant profiles and N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats.

The present study was conducted to ascertain the modulatory influences of Ferula asafoetida L. (asafoetida, flavoring agent) on the mammary epithelial tissue differentiation, hepatic drug metabolizing enzymes, antioxidant profiles and N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in Sprague-Dawley rats. Feeding with two doses of asafoetida (1.25 and 2.5% w/w in diet) showed a remarkable increase in the development and differentiation of ducts/ductules (p < 0.01-0.005), lobules (p < 0.005) and a decrease in terminal end buds (p < 0.05-0.005) as compared to both normal and MNU-treated control animals. To assess the biochemical parameters, effect of asafoetida on drug-metabolizing enzymes was evaluated in the liver of rats. Asafoetida treatment significantly reduced (p < 0.05) the levels of cytochrome P450 and b5. There was an enhancement in the activities of glutathione S-transferase (p < 0.05-0.005), DT-diaphorase (p < 0.05-0.01), superoxide dismutase (p < 0.01-0.005) and catalase (p < 0.05-0.005) and in the level of reduced glutathione (p < 0.05-0.005), followed by asafoetida treatment. Also, asafoetida significantly restored the level of antioxidant system, depleted by MNU-treatment. The strengthening of antioxidant system by the lower and higher doses of asafoetida in the presence and absence of MNU was further substantiated by a significant inhibition (p < 0.005) in lipid peroxidation as measured by thiobarbituric acid-reactive substances (TBARS) in the liver of rat. Further, in long-term animal studies, where MNU was used to induce mammary carcinogenesis, asafoetida treatment resulted in a significant reduction in the multiplicity (p < 0.001) and size of palpable mammary tumors (p < 0.005-0.001) and a delay in mean latency period of tumor appearance (p < 0.005). Together, these findings indicate the chemopreventive potential of asafoetida against MNU-induced mammary carcinogenesis. Thus, asafoetida needs further investigation with regard to identification and characterization of its active principle(s) and mechanism of action, for this compound to be developed as a potential chemopreventive agent for human cancers.

Animals↗
PubMed1972

Foood additives.

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Coloring Agents↗
PubMed1982

Foods, and food and drug combinations, responsible for head and neck pain.

The literature has been reviewed to uncover the existence of head and neck pain syndromes caused by foods and food and drug combinations. Knowledge of the etiology of such syndromes may help in their treatment. At least twenty-five syndromes have been described. These include those induced by coloring and flavoring agents, alcoholic products, chocolate, coffee and tea, foods containing tyramine, vitamins, minerals, pesticides, and several others. Where possible, the active ingredients and the minimal amounts responsible for the induction of pain have been identified.

Adult↗
PubMed2001

Attractive and defensive functions of the ultraviolet pigments of a flower (Hypericum calycinum).

The flower of Hypericum calycinum, which appears uniformly yellow to humans, bears a UV pattern, presumably visible to insects. Two categories of pigments, flavonoids and dearomatized isoprenylated phloroglucinols (DIPs), are responsible for the UV demarcations of this flower. Flavonoids had been shown previously to function as floral UV pigments, but DIPs had not been demonstrated to serve in that capacity. We found the DIPs to be present in high concentration in the anthers and ovarian wall of the flower, suggesting that the compounds also serve in defense. Indeed, feeding tests done with one of the DIPs (hypercalin A) showed the compound to be deterrent and toxic to a caterpillar (Utetheisa ornatrix). The possibility that floral UV pigments fulfill both a visual and a defensive function had not previously been contemplated. DIPs may also serve for protection of female reproductive structures in other plants, for example in hops (Humulus lupulus). The DIPs of hops are put to human use as bitter flavoring agents and preservatives in beer.

Animals↗