Safety and efficacy of adzuki bean extract in subjects with moderate to high LDL-C: a randomized trial.

The safety and efficacy of polyphenol-containing adzuki bean extract on lipid metabolism were evaluated in human subjects in an 8-week, randomized, double-blind, placebo-controlled, parallel intervention study. No adverse effects were observed in the participants receiving adzuki bean extract. The adzuki bean group showed a significant increase in the ΔHDL-C concentration compared with the placebo group after 4 weeks of intervention (3.76 ± 7.79 mg/dL vs. -0.08 ± 6.03 mg/dL), respectively, and both groups showed reduced ∆HDL-C concentrations, with the adzuki bean extract group showing a return to the baseline levels (0.36 ± 5.36 mg/dL) and the placebo group showing a decrease to below the baseline levels (-3.17 ± 7.79 mg/dL) at week 8. This short-term study represents the first step in establishing the practicality, safety, and plausibility of HDL-C maintaining effects of adzuki bean extract in human subjects.

Effect of a combination of inulin and polyphenol-containing adzuki bean extract on intestinal fermentation in vitro and in vivo.

The effect of a combination of inulin (INU) and polyphenol-containing adzuki bean extract (AE) on intestinal fermentation was examined in vitro using fermenters for 48 h and in vivo using rats for 28 d. The total short-chain fatty acid concentrations in the fermenters were decreased by a combination of INU and AE, but the concentration in the INU + AE group was higher than the cellulose (CEL) and CEL + AE groups. The cecal propionate concentration was increased by a combination of INU and AE compared with their single supplement. The ammonia-nitrogen concentration in the fermenters and rat cecum was decreased by INU and AE. Cecal mucin levels were increased by INU and AE respectively. Therefore, our observations suggested that the combination of INU and AE might be a material of functional food that includes several healthy effects through intestinal fermentation.

Potato powders prepared by successive cooking-process depending on resistant starch content affect the intestinal fermentation in rats.

The effects of resistant starch (RS) in dry potato powders prepared by various processes on intestinal fermentation in rats were assessed. Rats were fed raw potato powder (RP), blanched potato powder (BP), steamed potato powder (SP), or drum-dried potato powder (DP) for 4 weeks. The cecal RS content was significantly higher in the RP group than in the control diet (CN) group and other dry potato powder groups. Cecum pH was significantly lower in the RP group compared to the CN group, and was also significantly lower than that in the SP, BP, and DP groups. Lactic acid bacteria levels in the RP group were significantly higher than those in the CN group, and levels in the SP group also increased relative to the control group. Lactobacillus levels in the RP group were higher than in the CN and other dry potato powder groups. Cecal short-chain fatty acid (SCFA) concentrations in the RP group followed by the SP group exhibited significantly higher levels relative to the control levels. Dry potato powders containing RS produced during the cooking process may represent a useful food material that increases intestinal concentrations of SCFA and enhances the growth of certain lactic acid bacteria.

Comparison of the effect of two types of whole mushroom (Agaricus bisporus) powders on intestinal fermentation in rats.

The effects of two types of mushroom (Agaricus bisporus; white, WM; brown, BM) powders on intestinal fermentation in rats were investigated in terms of the physical characteristics of animals and by bacterial and HPLC analyses of cecal contents. Short-chain fatty acid levels were found to be significantly higher in the WM group than in the BM and the control (CN) groups; coliform bacteria levels in the BM group were significantly lower than those in the CN group, with the WM group inducing an apparent but insignificant decrease in coliforms. Anaerobe levels in the WM group were significantly higher than those in the CN group and, compared with the CN group, the BM and WM groups exhibited significantly increased feces weight and cecum weight, respectively. These results indicate that the mushroom powders, and in particular the WM powder, have beneficial effects on the intestinal environment in rats.

Comparison of the effects of longer chain inulins with different degrees of polymerization on colonic fermentation in a mixed culture of Swine fecal bacteria.

The effects of inulin with three different degrees of polymerization (DP) on microbial dietary fiber fermentation were compared in an in vitro simulator of the porcine large bowel. The three inulin isolates had a DP of 15 (from chicory grown in Hokkaido, Japan), and 10 and 24 (from Orafti, Belgium), while cellulose was used as a control. The Lactobacillus level in the DP 10 group at 48 h and bifidobacteria levels in the DP 15 and DP 24 groups at 24 and 48 h were significantly higher than in the carbohydrate-free and cellulose groups. The SCFA concentrations in all the inulin groups were significantly higher than in the carbohydrate-free and cellulose groups at 24 and 48 h. Ammonia nitrogen concentrations in all the inulin groups were significantly lower than those in the carbohydrate-free and cellulose groups at 24 and 48 h. The three different inulin types were fermentable by gut microbiota as indicated by substantial increases in SCFA. In particular, inulin DP 15 exhibited a clear potential to be used as a prebiotic with significant increases in Lactobacillus and Bifidobacterium populations, and concomitantly propionate and butyrate productions than cellulose at the early incubation time. There was a negative correlation between SCFA and ammonia nitrogen concentrations. These results indicate DP 15 product has similar potential as a prebiotic to DP 10 or DP 24 product and showed substantial equivalence to DP 10 and DP 24 products.

Inulin-type fructans with different degrees of polymerization improve lipid metabolism but not glucose metabolism in rats fed a high-fat diet under energy restriction.

BACKGROUND: Inulin-type fructan ameliorates metabolic diseases associated with obesity in animals. However, relatively little information is available on the comparative effects of inulins with different degree of polymerization (DP) on the lipid or glucose metabolism. AIM: The objective of this study was to investigate the effect of inulins with various DP on metabolic disorders associated with obesity in rats fed a high-fat diet under food restriction. METHODS: Rats were fed a high-fat diet supplemented with 5 % inulin-GR (Raftiline GR), inulin-Tokachi (Tokachi), or inulin-HP (Raftiline HP) without cellulose for 28 days at normal energy intakes or 14.5 % energy restriction. RESULTS: Under food restriction, the dietary inulin-Tokachi (mean DP 15) and -HP (mean DP 24), but not -GR (mean DP 10), reduced (p < 0.05) the serum cholesterol and triglyceride levels, and liver triglyceride concentration in rats, compared to the control diet. The cecal neutral steroid, bile acid, and propionate concentrations in the Tokachi and HP groups were higher (p < 0.05) than in the CONT group, and the cecal Bifidobacterium count in the Tokachi group was higher (p < 0.05) than in the other groups. CONCLUSIONS: Findings suggest that, depending on DP, dietary supplementation with inulin (DP 15 or DP 24) in rats fed a high-fat diet, regardless of food intake, positively modulates lipid metabolism and fecal microbiota but not glucose metabolism.

Anti-obesity role of adzuki bean extract containing polyphenols: in vivo and in vitro effects.

BACKGROUND: The aim of this work was to evaluate the effects of polyphenol-rich adzuki bean extract on lipid metabolism, triglyceride accumulation and proinflammatory cytokine secretion in vivo and in vitro. RESULTS: For the in vivo study, rats were divided into four groups: group C was fed a control diet, group A was fed the control diet with 1% adzuki bean extract, group CF was fed a high fat diet, and group AF was fed a high fat diet with 1% adzuki bean extract. For the in vitro study, the ability of adzuki bean extract to suppress triglyceride incorporation, glycerol phosphate dehydrogenase activity and inflammatory response was investigated in cultured human adipocytes. Data from the animal study showed that adzuki bean extract improved lipid metabolism in both the normal and high-fat diet groups. Adzuki bean extract treatment in the high-fat group resulted in significant reductions in total hepatic lipid accumulation and lipid secretion into the feces. Incubation of adipocytes with adzuki bean extract significantly decreased triglyceride accumulation, glycerol phosphate dehydrogenase activity and inflammatory responses without affecting cell viability. CONCLUSION: The results of this study demonstrate that adzuki bean extract has high potential to serve as a natural anti-obesity agent.

Effects of dietary supplementation with betaine on a nonalcoholic steatohepatitis (NASH) mouse model.

The effects of betaine supplementation on non-alcoholic steatohepatitis (NASH) model mice were examined by measuring the accumulation of fat in the livers of NASH model mice compared to a control. Betaine from sugar beets was provided to the model mice as a dietary supplement. After 3 wk of dietary supplementation, there were no significant differences in body weight or liver weight between the groups. However, the liver to body weight ratio in the high-fat diet with betaine (HFB) group was significantly (p<0.05) higher than that in the high-fat diet (HF) group. There were no differences in serum triglyceride (TG) concentrations, AST and ALT activities, or hepatic glutathione concentrations between the groups. Hepatic TG level in the HFB group was significantly (p<0.05) lower than that in the HF group. Hepatic cells obtained from the HF group showed increased occurrence of explosive puff and necrosis as compared with those in the HFB group. Betaine supplementation had an inhibitory effect on fat accumulation in the liver: the Oil red-positive area in the HFB group (0.82 ± 0.85%) was significantly (p<0.001) smaller than that in the HF group (9.06 ± 2.24%). These results indicate the potential of betaine to serve as an agent for amelioration of hepatic steatosis in NASH model mice.

Amelioration of D-galactosamine-induced acute liver injury in rats by dietary supplementation with betaine derived from sugar beet molasses.

The effects of betaine supplementation on D-galactosamine-induced liver injury were examined in terms of hepatic and serum enzyme activities and of the levels of glutathione and betaine-derived intermediates. The rats induced with liver injury showed marked increases in serum enzyme activity, but those receiving dietary supplementation of 1% betaine showed enzyme activity levels similar to a control group without liver injury. Administration of betaine also increased both hepatic and serum glutathione levels, even following D-galactosamine injection. The activity of glutathione-related enzymes was markedly decreased following injection of D-galactosamine, but remained comparable to that of the control group in rats receiving 1% betaine. The concentrations of hepatic S-adenosyl methionine and cysteine showed similar trends to that observed for hepatic glutathione levels. These results indicate that 1% betaine has a hepatoprotective effect by increasing hepatic and serum glutathione levels along with glutathione-related enzyme activities in rats.

Invariant Valpha14 natural killer T cell activation by edible mushroom acidic glycosphingolipids.

Invariant natural killer T (iNKT) cells regulate multi-immune response through Th1/Th2 cytokine release triggered by the recognition of CD1d-restricted glycosphingolipid antigens. Here we report that acidic glycosphingolipids (AGLs) of mushroom (Hypsizigus marmoreus and Pleurotus eryngii) presented by murine CD1d-transfected rat basophilic leukocytes induced interleukin-2 (IL-2) release from iNKT hybridoma cells. AGL-1, one of the AGLs, containing mannose at the non-reducing ends, induced CD1d-dependent IL-2 release. Al-though alpha-galactosylceramide (alpha-GalCer) presented by CD11c-positive cells induced both interferon-gamma (IFN-gamma) and IL-4 release, all of AGLs presented by CD11c-positive cells and AGL-1 presented by B cells induced IL-4 release from iNKT hybridoma cells. A single intravenous injection of AGLs into B6 mice induced only a little elevation of IL-4 in serum but repeated intravenous injection of AGLs induced prolonged retention of IL-4 in serum; therefore, these results suggested that edible mushroom AGLs might contribute to the retention of immunohomeostasis through the minimum induction of iNKT cell activation in vivo.

Effect of fermented bean paste on serum lipids in rats fed a cholesterol-free diet.

We examined the effects of fermented bean pastes derived from bean vinegar by-products on serum cholesterol in rats. The rats were fed boiled paste from adzuki (A), kintoki (K), or tebou (T), or fermented paste from adzuki (AP), kintoki (KP), or tebou (TP) for 4 weeks. The serum non-high-density lipoprotein (HDL) cholesterol levels in all the experimental groups, except for A group, were significantly lower than in the control (CN) group. Likewise, the serum triglyceride levels in K and all the fermented bean groups were significantly lower than in the CN group. The levels of hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase mRNA in all the experimental groups except for A were significantly lower than in the CN group. These findings indicate that fermented bean pastes also suppress cholesterol synthesis, resulting in a reduced serum cholesterol concentration. These effects might be related not only to the resistant starch but also to the protein or peptide in the fermented bean paste.

Effect of white wheat bread containing sugar beet fiber on serum lipids and hepatic mRNA in rats fed on a cholesterol-free diet.

We examined the effects of white wheat bread powder (BP) and white wheat bread powder containing sugar beet fiber (BBP) on serum cholesterol. The total cholesterol (-11%, -16%), HDL-cholesterol (-12%, -11%), non-HDL-cholesterol (-9%, -18%) and triacylglycerol (-44%, -58%) concentrations in the BP and BBP groups, respectively, were significantly different from those in the control group. The fecal excretion of neutral sterols in the BP and BBP groups and of acidic sterols in the BBP group was significantly higher than that in the control group. The hepatic cholesterol 7alpha-hydroxylase (CYP7A1) mRNA level in the BP and BBP groups was significantly higher than that in the control group. The cecal total short-chain fatty acid concentrations in the BBP group were significantly higher than those in the control group. These results indicate that the observed changes in serum lipid levels in the BP and BBP groups were due to the increased fecal lipid and CYP7A1 mRNA levels.

Anti-inflammatory effect of buckwheat sprouts in lipopolysaccharide-activated human colon cancer cells and mice.

In conducting an in vitro screening of ethanol extracts from various natural foods using a human colon cancer cell line (CoLoTC cells), an extract of buckwheat sprouts (ExtBS) was found to express significant anti-inflammatory activity. The anti-inflammatory activity of ExtBS was confirmed by oral administration of lipopolysaccharide (LPS) to mice. Inflammatory cytokines (interleukin 6 and tumor necrosis factor alpha) were markedly up-regulated in the spleen and liver from LPS-administrated mice, and combinatory treatment with LPS and ExtBS decreased up-regulation of them in both cytokines. Both serum cytokine levels corresponded to their gene expressions in tissues, but no anti-inflammatry effect in mice was observed when ExtBS was treated intraperitoneally. ExtBS oral administration also showed protective activity as to hepatic injury induced by galactosamine/LPS treatment. Based on these data, we suggest that ExtBS contains anti-inflammatory compounds.

Mushroom acidic glycosphingolipid induction of cytokine secretion from murine T cells and proliferation of NK1.1 alpha/beta TCR-double positive cells in vitro.

Interferon (IFN)-gamma and interleukin (IL)-4 regulate many types of immune responses. Here we report that acidic glycosphingolipids (AGLs) of Hypsizigus marmoreus and Pleurotus eryngii induced secretion of IFN- gamma and IL-4 from T cells in a CD11c-positive cell-dependent manner similar to that of alpha-galactosylceramide (alpha-GalCer) and isoglobotriaosylceramide (iGb3), although activated T cells by AGLs showed less secretion of cytokine than those activated by alpha-GalCer. In addition, stimulation of these mushroom AGLs induced proliferation of NK1.1 alpha/beta TCR-double positive cells in splenocytes. Administration of a mixture of alpha-GalCer and AGLs affected the stimulation of alpha-GalCer and generally induced a subtle Th1 bias for splenocytes but induced an extreme Th2 bias for thymocytes. These results suggested that edible mushroom AGLs contribute to immunomodulation.

Potato and soy peptide diets modulate lipid metabolism in rats.

Dietary plant and animal peptides have been shown to reduce serum lipids. However, the potential of food-derived peptides has yet to be fully elucidated. We investigated the physiological importance of potato peptides in rats fed on a cholesterol-free diet containing 20% potato peptides (PP), when compared with two diets containing either 20% casein (CN) or 20% soy peptides (SP). The high-density lipoprotein (HDL)-cholesterol (+13.8%) and serum triglyceride (-38%) concentrations in the PP-fed group, non-HDL-cholesterol level in the PP- (-22.5%) and SP- (-15.7%) fed groups, and serum total cholesterol concentration (-12%) in the SP-fed group, were significantly different from the control group at the end of the experiment. The fecal excretion of neutral and acidic sterols was higher in the PP- and SP-fed groups, respectively, relative to the control group. These results indicate that the observed changes in the serum cholesterol levels in rats fed on soy and potato peptide appear to have been due to different mechanisms.

Some bovine proteins behave as dietary fibres and reduce serum lipids in rats.

We examined the physiological importance of bovine dietary proteins in rats fed diets prepared from bovine Achilles' tendons and arteries. Rats were fed for 4 weeks, with a 20% casein diet (CON), in comparison with two diets containing 15% casein and 5% of either bovine Achilles' tendon (AC) or artery (AR) protein preparations. The serum total cholesterol concentration and non-HDL-cholesterol level in the AR-fed group were significantly lower (P< 0.05) than those in the CON-fed group at the end of the 4-week feeding period. The hepatic mRNA were measured, and the hydroxyl methyl glutaryl-CoA reductase mRNA level was significantly lower (P< 0.05) in the AR-fed group compared with the CON-fed group. Total hepatic cholesterol concentration in AC-fed rats was significantly (P < 0.05) higher than in the CON-fed group. The serum TAG concentration and fatty acid synthase mRNA level in AC- and AR-fed groups were significantly lower (P<0.05) compared with the CON-fed group throughout the feeding period. Faecal neutral sterol excretion was significantly (P<0.05) higher in the AC- and AR-fed groups compared with the CON-fed group. The results of the present study demonstrate that some bovine dietary proteins have similar functions as dietary fibres, lowering serum lipid concentration by enhancing faecal neutral sterol excretion or suppressing lipid synthesis in the liver. Moreover, favourable amino acid compositions in the AR and AC preparations may also have a lowering effect on plasma lipid concentration in bovine protein diet-fed groups.

Adzuki resistant starch lowered serum cholesterol and hepatic 3-hydroxy-3-methylglutaryl-CoA mRNA levels and increased hepatic LDL-receptor and cholesterol 7alpha-hydroxylase mRNA levels in rats fed a cholesterol diet.

We examined the effects of adzuki bean resistant starch on serum cholesterol and hepatic mRNA in rats fed a cholesterol diet. The mRNA coded for key regulatory proteins of cholesterol metabolism. The control rats were fed 15 % cornstarch (basal diet, BD). The experimental rats were fed BD plus a 0.5 % cholesterol diet (CD), or a 15 % adzuki resistant starch plus 0.5 % cholesterol diet (ACD) for 4 weeks. The serum total cholesterol and VLDL + intermediate density lipoprotein + LDL-cholesterol levels in the ACD group were significantly lower than those in the CD group throughout the feeding period. The total hepatic cholesterol concentrations in the CD and ACD groups were not significantly different. The faecal total bile acid concentration in the ACD group was significantly higher than that in the BD and CD groups. Total SCFA and acetic acid concentrations in the ACD group were significantly higher than those in the CD group but there were no significant differences in the concentrations between the ACD and BD groups. The hepatic LDL-receptor mRNA and cholesterol 7alpha-hydroxylase mRNA levels in the ACD group were significantly higher than those in the CD group and the hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase mRNA level in the ACD group was significantly lower than in the CD group. The results suggest that adzuki resistant starch has a serum cholesterol-lowering function via enhancement of the hepatic LDL-receptor mRNA and cholesterol 7alpha-hydroxylase mRNA levels and faecal bile acid excretion, and a decrease in the hepatic HMG-CoA reductase mRNA level, when it is added to a cholesterol diet.

Effect of an adzuki bean extract on hepatic anti-oxidant enzyme mRNAs in D-galactosamine-treated rats.

In acute hepatic injury tests, an adzuki bean extract decreased D-galactosamine (GalN)-induced alterations in the serum alanine aminotransferase and aspartate aminotranferase activities to about 37% and 25%, respectively, although there were no significant differences in these activities between the GalN-treated group with the adzuki bean extract and the GalN-treated group without the adzuki bean extract. Furthermore, the hepatic glutathione peroxidase, glutathione reductase, and Mn- and Cu,Zn-superoxide dismutase mRNA levels in the GalN-treated group with the adzuki bean extract were higher than those in the control group and GalN-treated group without the adzuki bean extract.

Resistant starch fraction prepared from kintoki bean affects gene expression of genes associated with cholesterol metabolism in rats.

Feeding rats beans with resistant starch reduces the serum cholesterol concentration; however, the mechanism is not fully understood. We examined the effects of resistant starch of kintoki (Phaseolus vulgaris, variety) bean on serum cholesterol and hepatic mRNAs in rats. Male F344/Du Crj rats were fed a cholesterol-free diet either with 5 g of cellulose powder (control)/100 g or 5 g of pancreatin-resistant fraction prepared from kintoki bean (kintoki)/100 g diet for 4 weeks. There were no differences in the body weight gain, food intake, liver weight, and mass of cecum contents between the groups. Serum total cholesterol, very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL)-cholesterol, and high density lipoprotein (HDL)-cholesterol levels in the kintoki group were significantly (at least P < 0.05) lower than in the control group throughout the feeding period. There was no difference in the serum triglyceride concentration between two groups throughout the feeding period. Total hepatic cholesterol in the control group was significantly (P < 0.01) lower than in the kintoki groups. Fecal bile acid, cecal acetate, propionate and n-butyrate concentrations in the kintoki group all were significantly (P < 0.05) higher than in the control group. Likewise, hepatic cholesterol 7alpha-hydroxylase, LDL receptor, and SR-B1 mRNA levels in the kintoki group were significantly (P < 0.05) higher than in the control group. The results suggest that resistant starch of kintoki bean reduces serum cholesterol level by increasing hepatic LDL receptor, SR-B1, and cholesterol 7alpha-hydroxylase mRNAs.

Hepatoprotective effects of the water extract from adzuki bean hulls on acetaminophen-induced damage in rat liver.

We examined the hepatoprotective effect of water-extract from adzuki bean (Vigna angularis) hulls on acetaminophen (AAP)-induced damage in rat liver. F344/DuCrj rats of 8 weeks of age were fed diets without and with 0.5% AAP or besides it 5% adzuki extract (lyophilized) on a daily basis over a period of 4 wk. At that time, serum aspartate aminotransferase activity in only AAP-treated group was higher than in both control and AAP plus adzuki extract (AAPA)-treated groups, while hepatic glutathione content and hepatic glutathione reductase and catalase activities in the AAP-treated group were lower than in the control group in contrast to the reverse in the AAPA-treated group. Hepatic phosphatidylcholine hydroperoxide and phosphatidylethanolamine hydroperoxide concentrations were higher in the AAP-treated group than in the control group, and were lower in the AAPA-treated group than in the AAP-treated group. Hepatic glutathione peroxidase activity was higher in the AAP-treated group than in the control group, although there was no significant difference between both AAP- and AAPA-treated groups in this respect. These findings suggest that the adzuki extract will serve as a prophylactic against oxidative damage to the liver.