Inhibition of oral carcinogenesis by citrus flavonoids

Six citrus flavonoids were tested for antineoplastic activity. The hamster cheek pouch model was utilized, and the solutions of the flavonoids (2.0-2.5%) and the solution of the carcinogen, 7,12-dimethylbenz[a]anthracene (0.5%), were applied topically to the pouches. The pouches of the positive controls were treated with the solvent used to dissolve the flavonoids and the solution of the carcinogen. The data show that 4 flavonoids (hesperetin, neohesperidin, tangeretin, and nobiletin) were inactive. The results with naringin and naringenin show that both of these flavonoids significantly lowered tumor number [5.00 (control group), 2.53 (naringin group), and 3.25 (naringenin group)]. Naringin also significantly reduced tumor burden [269 mm(3)(control group) and 77.1 mm(3)(naringin group)]. The data suggest that naringin and naringenin, 2 flavonoids found in high concentrations in grapefruit, may be able to inhibit the development of cancer.     

Transformation of flavonoids by intestinal microorganisms

Fruit, vegetables and cereals contain a wealth of secondary plan metabolites which have been implicated in the promotion of health. To understand the mechanism of their action it is necessary to gain more information on their fate in the body following ingestion. A certain proportion of ingested secondary plant constituents may escape absorption in the small intestine and therefore undergo transformation by intestinal microorganisms or enterohepatic circulation. To study the transformation of secondary plant metabolites by bacteria, Eubacterium ramulus was isolated from human feces and incubated with selected flavonoids. E. ramulus is a strictly anaerobic bacterium which was found to be present in the gastrointestinal tract of most individuals investigated. E. ramulus cleaves the ring system of several flavonols and flavones giving rise to the corresponding hydroxyphenylacetic and hydroxyphenylpropionic acids, respectively, as well as acetate and butyrate. Degradation pathways were proposed based on the intermediates detected by high performance liquid chromatography (HPLC) and HPLC coupled with mass spectrometry (LC-MS) and the detection of enzymes that catalyze reactions such as taxifolin isomerization, phloretin hydrolysis and phloroglucinol reduction. The dearomatizing phloroglucinol reductase, presumably part of all flavonoid degradation pathways, was purified and characterized. The gene encoding phloretin hydrolase was cloned from a E. ramulus gene library taking advantage of a newly developed fluorescence test for activity screening. Moreover, a new intermediate was discovered and identified by MS and 1H and 13C NMR analysis as alphitonin. To investigate the degradational potential of E. ramulus under in vivo conditions, germfree rats were associated with E. ramulus. Following the intragastric application of quercetin-3-glucoside, urine and feces of gnotobiotic rats were analyzed for degradational products originating from quercetin-3-glucoside. In feces of rats monoassociated with E. ramulus, 3,4-dihydroxyphenylacetic acid was found, indicating that this organism is able to cleave quercetin under in vivo conditions. To investigate in which way the dietary flavonoid content affects the cell counts of E. ramulus in the human intestinal tract, twelve human subjects consumed a flavonoid-free diet for one week and at one point during this period a large dose of flavonoids. Fecal samples from both phases of the study were analyzed by in-situ hybridization for total bacterial counts and counts of E. ramulus. Total cell counts and the cell counts of E. ramulus decreased significantly during the flavonoid-free period, while there was an increase in the E. ramulus counts of up to 10-fold during the flavonoid-rich period indicating that dietary secondary plant metabolites may have an influence on the intestinal microflora. E. ramulus is also capable of converting the isoflavonoids genistein and daidzein to the products 2-(4-hydroxyphenyl)-propionic acid and O-desmethylangolensin, respectively.     

Intakes of total and individual flavonoids by US adults

Knowing the dietary flavonoid intake of individuals and populations is the first step to clearly understand their health effects. Dietary flavonoid intake studies have been hampered by the lack of flavonoid food composition data. The objectives of this study were to estimate intakes of individual, classes and total flavonoids in the US adults; to evaluate the effects of socio-demographic factors on the flavonoid consumption patterns; and to establish major dietary sources of flavonoids. We calculated flavonoid intakes using the most updated USDA flavonoid and isoflavone databases, and the National Health and Nutrition Examination Survey (NHANES) III 24-h dietary recall (DR). Estimated mean total flavonoid intake by US adults was 344.83?±?9.13?mg/day. The flavan-3-ols (191.99?±?6.84?mg/day) were the most abundant flavonoid class. The three most dominant individual flavonoids were catechin, epicatechin and polymers. Tea, wine, beer, citrus fruits and apples were the most important sources of total flavonoid intakes in the US adults.     

Inhibitory effect of pine extract on alpha-glucosidase activity and postprandial hyperglycemia

OBJECTIVE: This study investigated the inhibitory effect of pine bark extract (PBE) and needle extract on carbohydrate-hydrolyzing enzymes and the hypoglycemic effect in diabetic mice (Lep(ob) [ob/ob]). METHODS: Pine bark and needle were dried and then placed in ethanol, and the extracts were assayed for the measurement of inhibition mode of PBE against alpha-amylase (EC 3.2.1.1) and alpha-glucosidase (EC 3.2.1.20). We also investigated the effect of long-term treatment with extracts on levels of postprandial blood glucose, body weight, food efficiency ratio, and gene expression of glucose transporter-4 in quadriceps muscle in diabetic mice (Lep(ob) [ob/ob]). RESULTS: The PBE showed competitive inhibition against salivary alpha-amylase and the combination of non-competitive and uncompetitive inhibition against yeast alpha-glucosidase. In animal experiments, PBE effectively suppressed the increase of postprandial blood glucose level by delaying absorption of diet, and body weights of the group that received PBE were significantly lower than that in the group administered 0.5% carboxylmethyl cellulose (control) 21 d after administration. CONCLUSIONS: PBE can be used to suppress postprandial hyperglycemia of diabetic patients. It also can be applied for control of obesity by decreasing the food efficiency ratio, especially carbohydrates.     

Inhibitory activity of Euonymus alatus against alpha-glucosidase in vitro and in vivo

The major goal in the treatment of diabetes mellitus is to achieve near-normal glycemic control. To optimize both fasting blood glucose and postprandial glucose levels is important in keeping blood glucose levels as close to normal as possible. α-Glucosidase is the enzyme that digests dietary carbohydrate, and inhibition of this enzyme could suppress postprandial hyperglycemia. The purpose of this study was to test the inhibitory activity of methanol extract of Euonymus alatus on α-glucosidase in vitro and in vivo to evaluate its possible use as an anti-diabetic agent. Yeast α-glucosidase inhibitory activities of methanol extract of E. alatus were measured at concentrations of 0.50, 0.25, 0.10, and 0.05 mg/ml. The ability of E. alatus to lower postprandial glucose was studied in streptozotocin-induced diabetic rats. A starch solution (1 g/kg) with and without E. alatus extract (500 mg/kg) was administered to diabetic rats by gastric intubation after an overnight fast. Plasma glucose levels were measured at 30, 60, 90, 120, 180, and 240 min. Plasma glucose levels were expressed in increments from baseline, and incremental areas under the response curve were calculated. Extract of E. alatus,which had an IC₅₀ value of 0.272 mg/ml, inhibited yeast α-glucosidase activity in a concentration-dependent manner. A single oral dose of E. alatus extract significantly inhibited increases in blood glucose levels at 60 and 90 min (p<0.05) and significantly decreased incremental response areas under the glycemic response curve (p<0.05). These results suggest that E. alatus has an antihyperglycemic effect by inhibiting α-glucosidase activity in this animal model of diabetes mellitus.     

Antioxidative and antiradical activity of flavonoids

Flavonoids are a major group of phenolic compounds which are important in flavouring and colouring of many fruits and vegetables and derived products such as wine, tea preparations and chocolate. Recently, flavonoids are given much attention due to their excellent antioxidative and antiradical activity. Studies have revealed that flavonoids are good scavengers of free radicals, and consequently, they are much used in pharmaceutical and food industries. Flavonoids also have a gamut of other biochemical activities; some have been found to possess significant anti-cardiovascular disease, anti-inflammatory, anti-allergic, anti-mutagenic, antiviral, anti-tumour and activities.     

Vegetable flavonoids and cardiovascular disease

Studies have suggested that dietary flavonoids are helpful in the prevention of atherosclerosis and cardiovascular disease. Antioxidant activity should be noted as underlying mechanism of their health impact in the vascular system, as atherosclerosis is closely related to oxidative events such as oxidized LDL accumulation in the macrophages. Vegetables contain a variety of flavonoids, such as flavonols, flavones and anthocyanidins. We focused on quercetin (3,3',4',5,7- pentahydroxyflavone), a major flavonoid in onion, and its anti-atherosclerotic effect was examined from the aspect of the bioavailability and translocation to the target site. Although quercetin exists as its glucoside form in onion, it is metabolized into several glucuronides and/or sulfate conjugates with or without methylation during its intestinal absorption. We found that these metabolites circulating in the human blood stream were mostly localized in plasma albumin fraction, but not LDL fraction. Onion consumption failed to enhance the antioxidant activity of plasma fraction against LDL oxidation, indicating that the level of quercetin metabolites bound to albumin is insufficient to exert the antioxidative effect in vivo. In contrast, we discovered that quercetin metabolites accumulate in the aorta tissue and exerted their antioxidant activity, when rabbits were fed with quercetin glucoside and high cholesterol diet. Furthermore, quercetin metabolites were detected in human atherosclerotic aorta exclusively. These imply that quercetin metabolites are incorporated into the atherosclerotic region and act as complementary antioxidants, when oxidative stress is loaded in the vascular system. It is likely that plasma albumin is a carrier for translocation of quercetin metabolites to vascular target.     

Tea flavonoids and cardiovascular disease

Drinking tea could have a significant impact on public health. Health benefits are believed to be largely due to the presence of high levels of flavonoids. Tea is a rich source of flavonoids, and often the major dietary source. Tea intake and intake of flavonoids found in tea have been associated with reduced risk of cardiovascular disease in cross-sectional and prospective population studies. In addition, flavonoids have consistently been shown to inhibit the development of atherosclerosis in animal models. A variety of possible pathways and mechanisms have been investigated. The focus of this review is on the potential of tea and tea flavonoids to improve endothelial function, and reduce blood pressure, oxidative damage, blood cholesterol concentrations, inflammation and risk of thrombosis. There is now consistent data to suggest that tea and tea flavonoids can improve endothelial function. This may be at least partly responsible for any benefits on risk of cardiovascular disease. Additional studies are needed to investigate whether regular consumption of tea can reduce blood pressure, inflammation and the risk of thrombosis. The evidence for benefit on oxidative damage and cholesterol reduction remains weak.     

Antioxidant rich grape pomace extract suppresses postprandial hyperglycemia in diabetic mice by specifically inhibiting alpha-glucosidase

Background

Postprandial hyperglycemia is an early defect of type 2 diabetes and one of primary anti-diabetic targets. Treatment of postprandial hyperglycemia can be achieved by inhibiting intestinal α-glucosidase, the key enzyme for oligosaccharide digestion and further glucose absorption. Grape pomace is winemaking byproduct rich in bioactive food compounds such as phenolic antioxidants. This study evaluated the anti-diabetic potential of two specific grape pomace extracts by determining their antioxidant and anti-postprandial hyperglycemic activities in vitro and in vivo.

Methods

The extracts of red wine grape pomace (Cabernet Franc) and white wine grape pomace (Chardonnay) were prepared in 80% ethanol. An extract of red apple pomace was included as a comparison. The radical scavenging activities and phenolic profiles of the pomace extracts were determined through the measurement of oxygen radical absorbance capacity, DPPH radical scavenging activity, total phenolic content and flavonoids. The inhibitory effects of the pomace extracts on yeast and rat intestinal α-glucosidases were determined. Male 6-week old C57BLKS/6NCr mice were treated with streptozocin to induce diabetes. The diabetic mice were then treated with vehicle or the grape pomace extract to determine whether the oral intake of the extract can suppress postprandial hyperglycemia through the inhibition of intestinal α-glucosidases.

Results

The red grape pomace extract contained significantly higher amounts of flavonoids and phenolic compounds and exerted stronger oxygen radical absorbance capacity than the red apple pomace extract. Both the grape pomace extracts but not the apple pomace extract exerted significant inhibition on intestinal α-glucosidases and the inhibition appears to be specific. In the animal study, the oral intake of the grape pomace extract (400 mg/kg body weight) significantly suppressed the postprandial hyperglycemia by 35% in streptozocin-induced diabetic mice following starch challenge.

Conclusion

This is the first report that the grape pomace extracts selectively and significantly inhibits intestinal α-glucosidase and suppresses postprandial hyperglycemia in diabetic mice. The antioxidant and anti-postprandial hyperglycemic activities demonstrated on the tested grape pomace extract therefore suggest a potential for utilizing grape pomace-derived bioactive compounds in management of diabetes.

     

Improved alpha-amylase and Helicobacter pylori inhibition by fenugreek extracts derived via solid-state bioconversion using Rhizopus oligosporus

The present research investigated the enrichment of fenugreek (Trigonella foenum graceum) seed substrate with phenolic antioxidants and L-DOPA via fungal-based solid-state bioconversion (SSB) system. This approach using food grade fungus Rhizopus oligosporus, was chosen because it has been demonstrated to be effective in other seed and food substrates for improving health-relevant functionality and has long history of use for food processing in Asia. The protein content and beta-glucosidase activity of the substrate which reflects fungal growth, increased with incubation time in conjunction with enhanced phenolic content and also suggested its possible involvement in phenolic mobilization. The antioxidant activity assayed by beta-carotene bleaching and DPPH free radical scavenging methods both indicated high activity during early growth stage (days 4-6) followed by reduced activity during later growth stage (days 8-20). A direct association between higher phenolic contents during early growth stage (days 4-6) and antioxidant activity suggested a link to mobilization of polymeric and hydrophobic phenolic forms. The L-DOPA content of the fenugreek extract fluctuated during the course of bioconversion with higher levels during days 6-10 (1.5-1.7 mg/g DW). The SSB process substantially improved the in vitro porcine alpha-amylase inhibition activity by 75 % on day 4 which correlated to higher levels of total phenolics and related antioxidant activity of the extracts. The high alpha-amylase inhibitory activity also coincided with high L-DOPA content on day 6. These results have implications for diet-based diabetes management. The same bioconversion stage had Helicobacter pylori inhibitory activity, which has implications for ulcer management.     

Inhibition of mast cells by algae

There is a history of use of algae as foods and as food additives, or nutraceuticals. Although algae are a safe component of human foods and animal feeds, the effects of the algae other than as a source of protein are not clear. We examined the prevalence of an antiinflammatory activity in selected algae using, as an assay system, the inhibition of histamine release from mast cells. Methanolic extracts of eleven algae were examined for activity to inhibit the release of histamine from mast cells in vitro. This activity was found widely among the samples tested. The activities of these extracts were not uniformly stable in acid methanol. Selected extracts studied further did not separate with the use of size-exclusion filtration filters. LH-20 chromatography suggested at least two main elution areas of activity of the Chlorella extract. In summary, we saw wide phylogenetic dispersion of mast cell inhibition activity, suggesting that this antiinflammatory property is common in algae. This effect was apparently due to multiple activities within the algal extracts.     

黄酮类化合物的潜在毒性

黄酮类化合物广泛存在于植物类食物中,具有多种生理活性。然而,现在关于黄酮类化合物毒副作用的研究发现,某些黄酮具有遗传毒性,还可能干扰甲状腺激素的合成;异黄酮的雌激素活性可能对动物和人的生长发育带来不良影响;黄酮还可能影响营养物质的吸收、药物代谢及神经行为。本文综述了黄酮类化合物毒性方面的研究进展。     

Intake of flavonoids and risk of dementia

It has been postulated that oxidative stress may play a key role in dementia. This is substantiated by the recent discovery of the protective effect of wine. In wine, the flavonoids – powerful antioxidant substances also contained in tea, fruits and vegetables – have been thought to offer such protection. We investigated whether flavonoid intake could be associated with a lower incidence of dementia in a cohort of 1367 subjects above 65 years of age (Paquid). A questionnaire was used to evaluate their intake of flavonoids and subjects were followed-up for 5 years between 1991 and 1996: 66 incident cases of dementia were observed. We estimated the relative risk (RR) of dementia according to tertiles of flavonoid intake using a Cox model. The age-adjusted RR of dementia was 0.55 for the two highest tertiles compared to the lowest (95% CI: 0.34–0.90; p = 0.02). After additional adjustment for gender, education, weight and vitamin C intake, the RR was 0.49 (95% CI: 0.26–0.92; p = 0.04). We conclude that the intake of antioxidant flavonoids is inversely related to the risk of incident dementia.     

紫外分光光度法测定银杏制品中黄酮的研究

目的:建立银杏制品中黄酮含量的紫外分光光度的测定方法。方法:样品经干燥后用甲醇超声提取,聚酰胺粉吸附,G3垂融漏斗过滤,甲醇洗脱,以芦丁为标准对照品,测定360 nm处的吸光度。结果:标准对照品在0μg~250μg范围内与吸光度呈良好的线性关系,y=0.0165+0.0026x,r=0.9998,平均回收率93.8%,RSD2.4%。结论:紫外分光光度法灵敏、快速、准确、成本低,适用于银杏制品中黄酮含量的测定。     

The nutraceutical role of the Phaseolus vulgaris alpha-amylase inhibitor

The present review assesses the potential of the Phaseolus vulgaris alpha-amylase inhibitor isoform 1 (alpha-AI1) starch blockers as a widely used remedy against obesity and diabetes. Consumption of the alpha-amylase inhibitor causes marginal intraluminal alpha-amylase activity facilitated by the inhibitor's appropriate structural, physico-chemical and functional properties. As a result there is decreased postprandial plasma hyperglycaemia and insulin levels, increased resistance of starch to digestion and increased activity of colorectal bacteria. The efficacy and safety of the amylase inhibitor extracts, however, depend on the processing and extraction techniques used. The extracts are potential ingredients in foods for increased carbohydrate tolerance in diabetics, decreased energy intake for reducing obesity and for increased resistant starch. Research developments in the distribution and biosynthesis of the alpha-amylase inhibitor, relevant physico-chemical properties, the molecular starch-blocking mechanism, anti-obesity and anti-diabetes effects, safety of extracts and the need for research into their potential anti-colorectal cancer effect are discussed.     

Exposure-response relations of alpha-amylase sensitisation in British bakeries and flour mills

OBJECTIVES: To describe the levels of exposure to fungal alpha-amylase in British bakeries and flour mills, and to describe the relation between exposure to alpha-amylase and sensitisation to fungal alpha- amylase. METHODS: 495 personal flour dust samples were taken in seven British bakeries and flour mills and analysed for alpha-amylase with an immunoassay. Workers at the sites were asked to fill out questionnaires on work related symptoms, smoking history, and work history, and they were skin prick tested with common allergens and fungal alpha-amylase to assess sensitisation. RESULTS: Exposure to high concentrations of alpha-amylase occur in a few areas of British bakeries and flour mills, and there can be considerable differences in exposures to alpha-amylase between sites and between exposure groups, and even within similar exposure groups from different sites. Exposure to the highest concentrations of alpha-amylase was found in the dispensing and mixing areas of the bakeries (geometric mean (GM) 39.7 ng/m3). Exposure to alpha-amylase showed only a moderate correlation with concentrations of dust (r = 0.42) and flour aeroallergen (r = 0.46). The results also showed a relation between exposure to alpha-amylase and sensitisation to fungal alpha-amylase (prevalence ratio (PR) for medium exposure 3.9, 95% confidence interval (95% CI) 0.8 to 20.2, PR for high exposure 9.9, 95% CI 2.8 to 34.6) compared with the low exposure category). Atopic subjects had an increased risk of sensitisation, but this was not significant. CONCLUSION: This study suggests that exposure to alpha- amylase is a considerable health risk in British bakeries and flour mills. A small proportion of workers are exposed to alpha-amylase at concentrations that result in high rates of sensitisation. A reduction in exposure to alpha-amylase is likely to reduce this risk.