Masanobu Sakono’s research while affiliated with University of Miyazaki and other places

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Publications (62)


Fig. 1. Chemical structures of major polyphenols in the black soybean seed coat extract.
Fig. 2. Effects of the black soybean seed coat extract (BE) on serum biochemical parameters in apolipoprotein E-deficient (ApoE −/− ) mice. ApoE −/− mice and wild-type BALB/c mice were assigned to two diet groups: AIN-93 M based control diet (CN) and CN containing 1% BE diet (CN + BE). Following 8 weeks of consumption of the respective diets, mice were sacrificed without fasting. Data indicate serum biological parameters (means ± SEM, n = 9). (A) Total cholesterol, (B) triglyceride, (C) glucose, and (D) total protein. Different alphabetical superscript letters indicate significant differences (p < 0.05, Tukey-Kramer test).
Fig. 3. Effects of the black soybean seed coat extract (BE) on hepatic lipid levels in apolipoprotein E-deficient (ApoE −/− ) mice. ApoE −/− mice and wild-type BALB/c mice were assigned to two diet groups: AIN-93 M based control diet (CN) and CN containing 1% BE diet (CN + BE). Following 8 weeks of consumption of the respective diets, mice were sacrificed without fasting. Data indicate hepatic lipid levels (means ± SEM, n = 9). (A) Total cholesterol, (B) triglyceride, and (C) phospholipids. Different alphabetical superscript letters indicate significant differences (p < 0.05, Tukey-Kramer test).
Fig. 4. Effects of the black soybean seed coat extract (BE) on lipid metabolismrelated gene expression in apolipoprotein E-deficient (ApoE −/− ) mice. ApoE −/ − mice and wild-type BALB/c mice were assigned to two diet groups: AIN-93 M based control diet (CN) and CN containing 1% BE diet (CN + BE). Following 8 weeks of consumption of the respective diets, mice were sacrificed without fasting. Liver samples were collected, and hepatic lipid metabolism-related gene expression was analyzed. Data indicate fold-change of the Gapdh control (means ± SEM, n = 9). (A) Cyp7a1, (B) Hmgcoar, (C) Pparα, and (D) Fasn. Different alphabetical superscript letters indicate significant differences (p < 0.05, Tukey-Kramer test).
Fig. 5. Effects of the black soybean seed coat extract (BE) on serum adipokine levels in apolipoprotein E-deficient (ApoE −/− ) mice. ApoE −/− mice were assigned to two diet groups: AIN-93 M based control diet (CN) and CN containing 1% BE diet (CN + BE). Following 8 weeks of consumption of the respective diets, mice were sacrificed without fasting. Data indicate serum adipokine levels (means ± SEM, n = 9). (A) Insulin, (B) leptin, (C) resistin, (D) C-peptide 2, and (E) glucose-dependent insulinotropic polypeptide (GIP). Different alphabetical superscript letters indicate significant differences (p < 0.05, Tukey-Kramer test).

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Daily consumption of black soybean (Glycine max L.) seed coat polyphenols attenuates dyslipidemia in apolipoprotein E-deficient mice
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  • Full-text available

September 2020

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242 Reads

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8 Citations

Journal of Functional Foods

Wataru Tanaka

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Hiroki Matsuyama

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Daigo Yokoyama

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[...]

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Hiroyuki Sakakibara

Black soybean (Glycine max L.) seed coat extract (BE) is rich in polyphenols, including epicatechin, procyanidin, and cyanidin-3-glucoside. We evaluated the effects of daily consumption of BE in apolipoprotein E-deficient (ApoE−/−) mice. ApoE−/− and wild-type BALB/c mice were fed a 20% fat diet with or without 1% BE for 8 weeks. Bodyweight was unaffected by BE. BE supplementation significantly lowered serum and hepatic total cholesterol and hepatic triglyceride levels. Hepatic mRNA expression of cholesterol 7α-hydroxylase (Cyp7a1) and peroxisome proliferator-activated receptor α (Pparα) were significantly stimulated in ApoE−/− mice consuming the BE diet. These effects were characteristic in ApoE−/− mice, but not in their corresponding wild type. In conclusion, it is clear that dietary consumption of BE affected blood and hepatic levels of cholesterol and triglyceride in ApoE−/− mice, and consequently exerted preventive effects for dyslipidemia. Putative mechanisms include the upregulation of hepatic Cyp7a1 and Pparα mRNA expression.

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Figure 1. Effect of time-restricted feeding on body mass gain.
Food consumption.
Body mass gain after 5 weeks of diet consumption.
Suitability of a 10% fat diet for use in time-restricted feeding experiments with C57BL/6 mice

March 2020

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61 Reads

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1 Citation

Bioactive Compounds in Health and Disease

Background: There is growing interest in the possible role of circadian rhythms in feeding behavior and their effect on diet-induced obesity. However, it is unclear whether widely used purified diets are suitable for use as normal control diets for rodents undergoing time-restricted feeding studies. In the present study, we compared the effects of 4% and 10% fat diets on body mass gain and food consumption during time-restricted feeding (TRF).Methods: Ad libitum-fed male C57BL/6J mice had free access to AIN-93M (4% fat) or modified 10% fat diets, whereas TRF groups were only able to consume one of these diets twice daily, at ZT23:00–01:00 and ZT11:00–13:00, for 5 weeks.Results: Total energy consumptions by the TRF-4% and TRF-10% fat groups were 26.5% and 18.6%, respectively, less than that of the ad libitum-fed groups. The body mass gains by the 4% and 10% fat diet groups fed ad libitum were similar, but the gain by the TRF-4% fat group was markedly lower than that of the TRF-10% fat group. In addition, whereas the body mass gain by the TRF-10% fat group was similar to that of its ad libitum equivalent, the gain by the TRF-4% fat group was much lower than that of the equivalent ad libitum-fed group.Conclusion: We showed for the first time that a 10% fat diet (21.9% kcal from fat) is suitable for the maintenance of body mass gain during TRF of C57BL/6 mice.Keywords: ad libitum feeding, fat content, mouse, time-restricted feeding



Fig. 1. Typical blueberry field. (A) General view; (B) close-up view of the leaves. Photographs by H.S.
Fig. 2. Light microscopy of rat thymus tissues stained with hematoxylin and eosin (×10). Blueberry leaf powder was orally administered to male (A-D) and female (E-H) rats daily for 90 days. (A, E) Vehicle solvent (controls); (B, F) 500 mg/kg/day; (C, G) 1000 mg/kg/day; (D, H) 2500 mg/kg/day.
Serum biochemistry parameters in rats administered blueberry leaf powder for 13 weeks.
Urinalysis findings in rats administered blueberry leaf powder for 13 weeks.
Cytokine and corticosterone serum levels in rats administered blueberry leaf powder for 13 weeks.
Subchronic Toxicity Evaluation of Leaves from Rabbiteye Blueberry (Vaccinium virgatum Aiton) in Rats

March 2019

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194 Reads

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8 Citations

Toxicology Reports

Blueberry leaf may contain multiple compounds with beneficial effects. We conducted a 90-day toxicity study in rats to evaluate the safety of consuming the leaves of rabbiteye blueberry (Vaccinium virgatum Aiton; RB species). Powdered leaves were administered daily by oral gavage at doses of 500, 1000, and 2500 mg/kg body weight to male and female Sprague-Dawley rats for 90 days. Treatment did not result in death or changes in the behavior and external appearance of the animals. No alterations were observed in hematological and serum chemical parameters, urinalysis, food consumption, body weight gain, or absolute and relative organ weights at the end of the treatment period, with the exception of some leukocyte percentages in male rats treated with 500 and 1000 mg/kg blueberry leaf powder. The findings indicate that rabbiteye blueberry leaf is safe for consumption and should be investigated as a candidate functional food.


Quantities of phenolic compounds in hot-water extracts from blueberry leaves and stems.
Quercetin amounts in livers of rats fed blueberry leaf and stem extracts.
Effects of blueberry leaf and stem extracts on hepatic lipid levels in rats consuming a high-sucrose diet

September 2018

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230 Reads

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9 Citations

Functional Foods in Health and Disease

Background: Blueberry stems, a by-product of blueberry leaf tea production, are typically discarded. We evaluated the effects of hot-water extracts of rabbiteye blueberry (Vaccinium virgatum Aiton; RB species) leaves and stems on hepatic lipid levels in rats consuming a high-sucrose diet. Methods: Male Sprague-Dawley rats were divided into groups that received a control high-sucrose diet alone or supplementation with 2.0% blueberry leaf extract or 0.5% or 2.0% blueberry stem extract. Blood and hepatic lipid levels, hepatic lipogenic enzyme activity, and hepatic quercetin metabolites were evaluated after 28 days of ad libitum consumption. Results: Supplementation with the extracts did not affect body weight gain, food intake, liver and white adipose tissue weights, or serum lipid levels. Hepatic triglyceride and total cholesterol levels were reduced in the groups that received 2.0% supplementation of either extract. Hepatic malic enzyme activity was also reduced in those groups. Quercetin and its glycosides, the major polyphenols identified in the extracts, accumulated in the liver as quercetin aglycone and quercetin metabolites. Conclusion: We demonstrated how daily consumption of blueberry leaf and stem extracts can decrease hepatic lipid levels, potentially downregulating malic enzyme activity. These effects were intensive in leaf extracts. The active compounds existed in both extracts may be quercetin and its glycosides. Therefore, blueberry stems and leaves may be an attractive candidate novel functional food.


Figure 2. Effects of ?-monoglucosyl-rutin (?MR) on body weight gain in mice
Figure 6. Typical high-performance liquid chromatography (HPLC) readouts (370 nm)
Daily consumption of monoglucosyl-rutin prevents high-fat diet-induced obesity by suppressing gastric inhibitory polypeptide secretion in mice

July 2018

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262 Reads

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12 Citations

Functional Foods in Health and Disease

Background: Alpha monoglucosyl-rutin (4G-α-D-glucopyranosyl rutin, αMR) has been shown to stimulate antioxidant defenses and anti-glycation. We evaluated the effects of αMR on body weight gain in mice. Methods: Male C57BL/6J mice were divided into four groups: Control low-fat diet, low-fat diet + 0.5% αMR, high-fat diet, and high-fat diet + 0.5% αMR. Blood chemistry, hepatic lipids, and serum metabolic hormones and cytokines were evaluated after 4 and 13 weeks. Results: After 6 weeks, the high-fat diet group gained more weight than the low-fat diet group. Supplementing the high-fat diet with αMR suppressed weight gain by week 13. Visceral fat weight was higher in the high-fat diet group on weeks 4 and 13, while αMR supplementation inhibited increase on week 13 but not on week 4. Serum levels of gastric inhibitory polypeptide were higher in the high-fat-diet group than in the low-fat-diet group. αMR supplementation inhibited this elevation and regulated levels of serum leptin and hepatic triglycerides. Conclusion: For the first time, we demonstrated how daily consumption of αMR inhibits diet-induced visceral fat accumulation by regulating the secretion of gastric inhibitory polypeptide, which thereby prevents excess weight gain. Therefore, αMR may be a promising potential functional food.


Daily Consumption of Bilberry ( Vaccinium myrtillus L.) Extracts Increases the Absorption Rate of Anthocyanins in Rats

July 2018

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34 Reads

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7 Citations

Journal of Agricultural and Food Chemistry

The effects of daily consumption of anthocyanins on bioavailability was remained unclear. In this study, we evaluated whether daily consumption affects the absorption rate of anthocyanins in rats when consumed during the active and sleep phase. Eighty rats were randomly divided into two groups. The first group consumed AIN-93G control diets and the second group consumed AIN-93G diets containing 1% bilberry extract for 2 weeks. After 12h fast, anthocyanins were not detected in plasma of rats. Bilberry extract (500 mg/kg body weight) was then orally administered at the beginning of the diurnal light period (ZT0, sleep phase) or at the end of the diurnal light period (ZT12, active phase). Blood concentrations of anthocyanins peaked 1 h after administration in both groups. Maximum blood concentration was higher in rats that consumed bilberry extract daily (852 nM) than in control rats (630 nM) when the extract was administered at ZT0, but not at ZT12. Daily consumption of anthocyanins increases their absorption rate, but this effect is limited to the beginning of the sleep phase.


Consumption of Salted Pickles of Sun-dried Radish Roots (Raphanus sativus cv. YR-Hyuga-Risou) Attenuates Blood Pressure in Spontaneously Hypertensive Rats

October 2017

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38 Reads

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3 Citations

Food Science and Technology Research

The effects of γ-amino butyric acid (GABA)-rich salted radish pickles on blood pressure were evaluated. Raw radish roots were dehydrated under the sun, then pickled with salt. GABA concentrations in the radish roots dramatically increased during dehydration, and decreased slightly after pickling. Male spontaneously hypertensive rats (SHR/Izm) consumed AIN-76 based diets containing 0.3% salted pickle powder or equivalent amounts of GABA (0.002%) and sodium chloride (0.055%). After two weeks, the increased systolic blood pressure observed in the control SHR group was significantly prevented in both sample groups at similar potencies, indicating that the consumption of salted pickles lowered blood pressure. Furthermore, one of the active compounds might be GABA, while sodium chloride in the salted pickles might not affect the positive effects on blood pressure observed in SHR fed salted pickles. In conclusion, the daily consumption of GABA-rich salted pickles may be ideal for lowering blood pressure.


Whey Protein-hydrolyzed Peptides Diminish Hepatic Lipid Levels in Rats Consuming High-sucrose Diets

October 2016

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39 Reads

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9 Citations

Food Science and Technology Research

Whey protein consumption is reported to reduce serum lipids, however the responses to derived peptides havenot yet been fully characterized. In this study, we evaluated the effects of whey protein-hydrolyzed pepides (WPP) on serum and hepatic lipid levels, as well as hepatic lipogenic gene expression in SD rats consuming a high-sucrose AIN-76 based diet. After a 14-day ad libitum consumption of diet containing WPP, serum and hepatic triglycerides, and total cholesterol levels were significantly decreased when compared with the control group. A similar trend was observed in the time-restricted feeding groups, in which food was provided for 2 h at the beginning and the end of the dark period cycle during the 14-day treatment period. Additionally, hepatic gene expression linked to triglyceride and cholesterol biosynthesis, and their enzymatic activities were downregulated in the WPP group. In conclusion, daily consumption of WPP appears to decrease lipid levels in the blood and liver, and potentially protect against dyslipidemia.



Citations (51)


... However, because the effect can be expected with at least 8 g of egg white protein ingested daily [73], the effect cannot be expected by the small amount contained in mayonnaise. Cholesterol-lowering effects have also been reported for egg yolk lecithin, but the amount in mayonnaise is so small that it has been thought to have no effect [74,75]. The effect of mayonnaise on serum cholesterol concentrations is the result of edible vegetable oil, but the study did not appear to show any effect of edible vegetable oil. ...

Reference:

Vegetable Salad Improves Lipid and Glucose Metabolism and Enhances Absorption of Specific Nutrients in Vegetables
Influence of Saturated and Polyunsaturated Egg Yolk Phospholipids on Hyperlipidemia in Rats
  • Citing Article
  • September 1989

Agricultural and Biological Chemistry

... The correlation between the black soybean polyphenol intake and reduction of vascular dysfunction and oxidative stress was reported in women by increased urinary excretion of nitric oxide (NO 2 and NO 3 ) with a concomitant decrease in oxidative stress markers (8-hydroxy-2′-deoxyguanosine, hexanoyl-lysine, and myeloperoxidase) . On a similar note, dietary supplementation of black seed coat polyphenolic extract (1%) to high fat-fed (20%) apolipoprotein E (ApoE −/− ) deficient mice for 8 weeks resulted in a marked reduction in serum and hepatic cholesterol and triglyceride levels with activation in hepatic mRNA expression of Cyp7a1 and Pparα thereby attenuating dyslipidemia symptoms (Tanaka et al., 2020). ...

Daily consumption of black soybean (Glycine max L.) seed coat polyphenols attenuates dyslipidemia in apolipoprotein E-deficient mice

Journal of Functional Foods

... We used 10% (w/w) soybean oil containing the AIN-93G-based formula as a controlled low-fat diet, as previously described (Table 4) [27]. We used three high-fat diets containing 30% (w/w) fat, composed of soybean oil (SOY), lard (LARD), or fish oil (FISH). ...

Suitability of a 10% fat diet for use in time-restricted feeding experiments with C57BL/6 mice

Bioactive Compounds in Health and Disease

... Blueberries have been suggested to prevent cancer and improve lifestyle-related diseases and are used in functional foods and medicines to maintain and improve health [2]. Recently, functional compounds contained in the leaves and branches of blueberries-in additional to those in the fruit-have attracted attention [3,4]. ...

Effects of blueberry leaf and stem extracts on hepatic lipid levels in rats consuming a high-sucrose diet

Functional Foods in Health and Disease

... Blueberry (Vaccinium corymbosum) is a popular fruit worldwide, in part due to the health benefits associated with its rich flavonoid compounds, particularly anthocyanins [27,28]. The fruits of the Vaccinium species are the main commercial products, whereas the leaves have been used mainly for medicinal purposes [29][30][31][32]. In the wild lowbush blueberry (V. ...

Subchronic Toxicity Evaluation of Leaves from Rabbiteye Blueberry (Vaccinium virgatum Aiton) in Rats

Toxicology Reports

... Several studies have reported that healthy dietary patterns such as traditional Japanese diet are associated with low LDL-C levels[32][33]. Quercetin, the aglycone released from MR in the intestinal track, binds to C/EBPβ and suppresses ApoB, the major apoprotein of LDL-C[34].An in vitro study by Suganya et al.[35] revealed the antidyslipidemic property of rutin, mediated by its inhibition of HMG-CoA reductase. Therefore, MR is predicted to inhibit cholesterol synthesis and reduced serum LDL cholesterol levels via an inhibitory effect on HMG-CoA reductase. ...

Daily consumption of monoglucosyl-rutin prevents high-fat diet-induced obesity by suppressing gastric inhibitory polypeptide secretion in mice

Functional Foods in Health and Disease

... Accordingly, diurnal variations have been observed for many biological phenomena. For example, compounds such as polyphenols, which are absorbed into the body via transporters with diurnal variations, have different patterns of absorption depending on the time of intake (13). Toxicological expression also differs depending on the time of administration of chemicals, such as ethylnitrosourea (14). ...

Daily Consumption of Bilberry ( Vaccinium myrtillus L.) Extracts Increases the Absorption Rate of Anthocyanins in Rats
  • Citing Article
  • July 2018

Journal of Agricultural and Food Chemistry

... For example, sun-dried radishes contain approximately three times the amount of γ-amino butyric acid (GABA), a non-proteinogenic amino acid compared with raw radishes (Kato et al., 2015). Consumption of GABA-rich sun-dried radishes, but not raw radishes, significantly decreased blood pressure in a spontaneously hypertensive rat model (Tashiro et al., 2017), which indicates that sundried radishes and raw radishes may have different effects on health. ...

Consumption of Salted Pickles of Sun-dried Radish Roots (Raphanus sativus cv. YR-Hyuga-Risou) Attenuates Blood Pressure in Spontaneously Hypertensive Rats
  • Citing Article
  • October 2017

Food Science and Technology Research

... Histidine, with its imidazole group, and cysteine, with its thiol group, act as scavengers of hydroxyl radicals, further improving the antioxidant properties of FPHs. Additionally, the indole group in tryptophan (Trp) is crucial for scavenging hydroxyl radicals, enhancing the antioxidant capacity of FPHs (Mignone et al., 2015;Zhu et al., 2021) (Yokoyama et al., 2016;Zhang et al., 2014Zhang et al., , 2015. In β-pleated sheets, two or more segments of a peptide chain align side by side, forming a sheet-like structure held together by hydrogen bonds. ...

Whey Protein-hydrolyzed Peptides Diminish Hepatic Lipid Levels in Rats Consuming High-sucrose Diets
  • Citing Article
  • October 2016

Food Science and Technology Research

... The reason for enhanced hepatic synthesis of taurine during CR remains undetermined. One intriguing possibility is that since taurine stimulates the production of BA [40][41][42][43], this may be its primary function in CR liver, and its release in the intestine is only a derivative of this process. This hypothesis fits with the increased clearance of taurine as the side product of the physiological circumstances by secretion in CR mice urine. ...

Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high cholesterol-fed rats
  • Citing Article
  • December 2015

Clinical and Experimental Pharmacology and Physiology