Simultaneous ingestion of high-methoxy pectin from apple can enhance absorption of quercetin in human subjects.

Chronic ingestion of apple pectin has been shown to increase the absorption of quercetin in rats. The present study was designed to elucidate whether the simultaneous ingestion of quercetin with apple pectin could enhance the absorption of quercetin in humans, and the effects of dose dependency and degree of pectin methylation on quercetin absorption were also investigated. Healthy volunteers (n 19) received 200 ml of 0.5 mg/ml of quercetin drinks with or without 10 mg/ml of pectin each in a randomised cross-over design study with over 1-week intervals; urine samples from all the subjects were collected within 24 h after ingestion of the test drinks, and urinary deconjugated quercetin and its metabolites were determined using HPLC. The sum of urinary quercetin and its metabolites excreted was increased by 2.5-fold by the simultaneous ingestion of pectin. The metabolism of methylated quercetin (isorhamnetin and tamarixetin) was not affected by pectin ingestion. In six volunteers, who received quercetin drinks containing 0, 3 and 10 mg/ml of pectin, the sum of urinary quercetin and its metabolites excreted also increased in a pectin dose-dependent manner. Furthermore, the simultaneous ingestion of quercetin with low-methoxy and high-methoxy pectin, respectively, increased the sum of urinary excretion of quercetin and its metabolites by 1.69-fold and significantly by 2.13-fold compared with the ingestion of quercetin without pectin. These results elucidated that apple pectin immediately enhanced quercetin absorption in human subjects, and that its enhancing effect was dependent on the dose and degree of pectin methylation. The results also suggested that the viscosity of pectin may play a role in the enhancement of quercetin absorption.

p-terphenyl derivatives from the mushroom Thelephora aurantiotincta suppress the proliferation of human hepatocellular carcinoma cells via iron chelation.

A novel 2',3'-dihydroxy-p-terphenyl derivative, thelephantin O (TO), which has cancer-selective cytotoxicity, was isolated. This study investigated the underlying basis of the cytotoxicity of 2',3'-dihydroxy-p-terphenyl compounds in view of their ability to chelate metal ions. FeCl(2) significantly reduced TO-induced cytotoxicity, whereas several other salts of transition metals and alkaline-earth metals did not. A structure-activity relationship study using newly synthesized p-terphenyl derivatives revealed that o-dihydroxy substitution of the central benzene ring was necessary for both the cytotoxicity and Fe(2+) chelation of the compounds. Real-time PCR array and cell cycle analysis revealed that the TO-induced cytotoxicity was attributed to cell cycle arrest at the G1 phase via well-known cell cycle-mediated genes. The TO-induced changes in the cell cycle and gene expression were completely reversed by the addition of FeCl(2). Thus, it was concluded that Fe(2+) chelation occurs upstream in the pivotal pathway of 2',3'-dihydroxy-p-terphenyl-induced inhibition of cancer cell proliferation.

Anticancer activities of thelephantin O and vialinin A isolated from Thelephora aurantiotincta.

Thelephora aurantiotincta is an edible mushroom belonging to the genus Thelephora; it grows in symbiosis with pine trees. Recently, phytochemical investigations have revealed that the genus Thelephora is an abundant source of p-terphenyl derivatives. However, their bioactivity has not yet been well characterized. In screening for natural materials with anticancer activity, a T. aurantiotincta ethanol extract (TAE) was found to decrease cell viability in human hepatocellular carcinoma cells (HepG2). In this study, a new p-terphenyl derivative, thelephantin O, and a known compound, vialinin A, were isolated as the principal bioactive components of TAE. These compounds decreased cell viability in HepG2 and human colonic carcinoma cells (Caco2), but not in noncancerous human hepatocytes. This is the first report of the isolation from T. aurantiotincta of selective cytotoxic agents against cancer cells.

Chronic ingestion of apple pectin can enhance the absorption of quercetin.

The effect of apple pectin (AP) on quercetin and rutin bioavailability was investigated. Rats received a basal (control) or AP-containing diet for 6 weeks followed by orally administered quercetin or rutin. With quercetin administration, the maximum concentration and area under the curve of concentration-time from 0 to 24 h for the sum of quercetin metabolites in the plasma were significantly higher in AP-fed rats than in the control group. However, AP did not significantly affect rutin bioavailability. The crypt depth of the jejunum and ileum and the villus thickness of the ileum of AP-fed rats were significantly greater than those of control rats. These results demonstrate that chronic AP ingestion enhances intestinal absorption of quercetin. This increase in quercetin absorption might be attributed to alteration of the absorptive capacity of the small intestine through AP-induced improvement of its morphological and physiological properties.

Antidiabetic and antioxidant effects of polyphenols in brown alga Ecklonia stolonifera in genetically diabetic KK-A(y) mice.

The dietary intake and control of blood glucose levels are very important in hyperglycemic patients and alpha-glucosidase inhibitors are a cost-effective means to preventing the progression of diabetes. In search of a natural inhibitor from food materials, alpha-glucosidase inhibitory activity and the anti-hyperglycemic effects of a brown alga, Ecklonia stolonifera, were investigated using non-insulin dependent diabetic mice. Methanolic extract of E. stolonifera (MEE), which contains a high content of polyphenols, showed strong inhibition of alpha-glucosidase in vitro. Male KK-A(y) mice, a genetically non-insulin dependent diabetic model, showed hyperglycemia with aging, but the ingestion of MEE suppressed the increase in plasma glucose and lipid peroxidation levels in unfasted KK-A(y) mice dose dependently. In KK-A(y) mice, which were fed the MEE diet for 4 weeks, MEE moderated the elevation of plasma glucose levels after the oral administration of maltose. The polyphenols in MEE were estimated to be phlorotannins by HPLC-PDA and LC/MS analyses. These results demonstrate that E. stolonifera, seaweed typically used as a health food, has strong antidiabetic and antioxidant effects in vivo, thus, it may have beneficial properties in the prevention of diabetes and could be useful in the development of an antidiabetic pharmaceutical and functional food.

Alpha-glucosidase inhibitory and antihyperglycemic effects of polyphenols in the fruit of Viburnum dilatatum Thunb.

Small crimson fruit of Viburnum dilatatum Thunb. (gamazumi), a wild deciduous low tree belonging to a family of Caprifoliaceae, has strong antioxidant activity, and cyanidin 3-sambubioside (C3S) and 5-caffeoyl quinic acid (5-CQA) are identified as active compounds. The freeze-dried powder of V. dilatatum fruit juice (CEV) was orally administered to streptozotocin-induced diabetic rats for 4 weeks repeatedly. Consequently, the elevation of plasma glucose level after oral administration of 2 g/kg glucose was suppressed by the repeated administration of CEV. The action was dependent on the dose of CEV, and plasma glucose level in rats administered 500 mg/kg of CEV was decreased significantly from that in rats without CEV. Increase of insulin secretion was not found in rats with or without administration of CEV. It was expected that CEV had some effects on glucose uptake. In five compounds identified from V. dilatatum fruit, C3S and 5-CQA showed inhibitory activity on sucrase and maltase. Inhibitory activity of cyanidin 3-glucoside and cyanidin aglycon (Cy) was not found markedly, and so it was thought that the activity was a characteristic property in Cy diglycosides. Moreover, 5-CQA and C3S were main polyphenol in the fruit of V. dilatatum. These results suggest that V. dilatatum fruit has the alpha-glucosidase inhibitory activities and the antihyperglycemic action.

Inhibitory effects of viburnum dilatatum Thunb. (gamazumi) on oxidation and hyperglycemia in rats with streptozotocin-induced diabetes.

The fruit of Viburnum dilatatum Thunb. (gamazumi) was found in a previous study to have strong radical scavenging activity. The present study investigated the antioxidative functions of gamazumi crude extract (GCE) in rats having diabetes induced by the administration of streptozotocin. In rats given water (H(2)O group), plasma levels of glucose, total cholesterol, and lipid peroxide (TBARS) and erythrocyte levels of TBARS increased with time over the experimental period of 10 weeks. These increases were inhibited in rats given GCE (GCE group). After 10 weeks, hepatic, renal, and pancreatic TBARS in the GCE group were significantly lower than those in the H(2)O group. GCE contains a high concentration of polyphenols, and it is expected that they are the active components. These results demonstrate that GCE has an inhibitory effect on the oxidative stress induced by diabetes and suggest that GCE may be useful for the prevention of diabetic complications. Furthermore, as the increase of plasma glucose and total cholesterol was inhibited in the GCE group, GCE may also have anti-hyperglycemic activity in diabetes.

Physiological effects and active ingredients of Viburnum dilatatum Thunb fruits on oxidative stress.

The fruit of Viburnum dilatatum Thunb, called gamazumi in Japan, showed the strong antioxidant activities, and its preventive effects on oxidative stress and active ingredients were investigated. Male rats were subjected to water immersion restraint stress for 6 hours, after ingestion of the gamazumi crude extract (GCE) for 2 weeks. The formation of gastric ulcer was reduced, and the lipid peroxidation in plasma and organs also lowered in rats ingested GCE. In the streptozotocin-induced diabetic rats given GCE for 10 weeks, inhibition of lipid peroxidation in plasma, erythrocytes and organs was observed, and the increase of plasma glucose level also lowered. On the other hand, two cyanidin glycosides, two chlorogenic acids and quercetin were identified, and especially cyanidin 3-sambubioside (Cy 3-sam) showed the strong radical scavenging activity. It is suggested that Cy 3-sam is a key compound contributing to the physiological effects of V. dilatatum fruit.

Identification and antiradical properties of anthocyanins in fruits of Viburnum dilatatum thunb.

The fruit of Viburnum dilatatum Thunb., called gamazumi, has been shown to prevent oxidative injury in rats given gamazumi crude extract (GCE). Therefore, phenolic compounds in GCE were purified by Sephadex LH-20 column chromatography and preparative high-performance liquid chromatography. Two major anthocyanins were isolated, and their structures were determined by NMR, liquid chromatography/electrospray ionization mass spectrometry/MS and sugar analysis as cyanidin 3-O-(2-O-beta-D-xylopyranosyl)-beta-D-glucopyranoside, namely, cyanidin 3-sambubioside (I) and that of cyanidin 3-O-beta-D-glucopyranoside, namely, kuromanin (II). This is the first identification of these compounds in V. dilatatum fruits, which contain I and II at 141.3 and 4.5 microg/g of fresh fruit, respectively. By the electron spin resonance method, the superoxide anion radical scavenging activities (IC(50)) of I and II were 17.3 and 69.6 microM, and their activities on hydroxyl radicals were 4.3 and 53.2 mM. As a positive control, the activities of ascorbic acid were 74.2 microM on superoxide anion radicals and 3.0 mM on hydroxyl radicals. Our results suggest that these anthocyanins having radical scavenging properties may be key compounds contributing to the antioxidant activity and physiological effects of V. dilatatum fruits.

Inhibitory effect of natto, a kind of fermented soybeans, on LDL oxidation in vitro.

The oxygen radical scavenging activity of natto (fermented soybeans) and its inhibitory effect on the oxidation of rat plasma low-density lipoprotein (LDL) in vitro were investigated to evaluate the usefulness of the antioxidant properties of natto, which has been shown to have antioxidant activity. Natto was separated into three water-soluble fractions: high-molecular-weight viscous substance (HMWVS; Mw > 100 000), low-molecular-weight viscous substance (LMWVS; Mw < 100 000), and soybean water extract (SWE). LMWVS had the strongest radical scavenging activity for hydroxyl and superoxide anion radicals, as assessed by electron spin resonance. The increase of conjugated dienes in LDL oxidized by copper and an azo pigment was depressed by the addition of LMWVS and SWE. These results demonstrate that natto fractions have inhibitory effects on LDL oxidation as a result of their radical scavenging activity.

Antioxidative functions of natto, a kind of fermented soybeans: effect on LDL oxidation and lipid metabolism in cholesterol-fed rats.

Natto water-soluble fractions, low-molecular-weight viscous substance, and soybean water extract, which had an inhibitory effect on the oxidation of low-density lipoproteins (LDL) in vitro, were fed to rats for 3 weeks. These fractions had no influence on the growth of rats, which were fed a basal diet containing 1% cholesterol, but lowered plasma triglyceride and total cholesterol. Inhibition of copper-oxidation of plasma and LDL ex vivo, and a reduction in lipid peroxidation in liver and aorta in vivo, were also observed. The antioxidant enzymes were not induced in rats fed natto fraction diets. These results demonstrate that ingestion of the natto fractions led to inhibition of LDL oxidation, and that the fractions perform direct antioxidant action in the body. It is suggested that natto fractions might help to prevent arteriosclerosis, as they appear to reduce lipid peroxidation and improve lipid metabolism.