Impact of a Rice-Centered Diet on the Quality of Sleep in Association with Reduced Oxidative Stress: A Randomized, Open, Parallel-Group Clinical Trial.

Previously, we found that a Japanese diet was associated with psychological status, and a combination of rice and miso was related to mental and physical health. We hypothesized that the intake of a rice-based diet affected mental and physical health and aimed to investigate the consequences of a dietary intervention with rice. We conducted a randomized, open-label, parallel-group clinical trial that included 60 participants, who were randomly assigned to receive either rice-based meals or meals with other cereals for three daily meals over 2 months. The participants were surveyed for psychological status and biochemical changes. Sleep quality index scores showed significant improvement after the rice-based intervention. Additionally, blood oxidative stress levels were reduced in the rice-diet group compared with the no-rice-diet group. Although the molecular mechanisms should be investigated in detail, our findings suggest that controlling oxidative stress through the intake of a rice-centered diet may be key to improving sleep quality.

Effects of Palmaria palmata on lipid metabolism and glycemic control in participants with hypercholesterolemia in a randomized double-blind placebo-controlled trial.

BACKGROUND: Red algae have been reported to improve lipid and glucose metabolism in rats. We investigated the effects of Palmaria palmata (P. palmata), a red alga from northern Japan, on lipid metabolism and glycemic control in participants with hypercholesterolemia. METHODS: We conducted an 8-week, randomized, double-blind, placebo-controlled, and parallel-group comparison trial. The study enrolled Japanese participants with a serum low-density protein cholesterol (LDL-C) ≥120 mg/dL. The participants were randomly assigned to take either capsules containing P. palmata (2 g/day) or placebo capsules. The primary endpoint was the change in LDL-C from baseline to week 8 and the secondary endpoints were the changes in other lipid parameters and glycemic control. RESULTS: Of the 104 participants completed the study protocol. There were no significant differences in change in LDL-C, body mass index, waist circumference, or glycemic control between the two groups. However, serum triglyceride showed significantly greater improvement in women in the P. palmata group (-9.0 [-25.0, +5.0]) vs. those in the placebo group (-1.0 [-11.0, +19.0]; p = .03). CONCLUSIONS: The present study did not show that P. palmata had significant effect on serum LDL-C nor glycemic control, but hypertriglyceridemia could be ameliorated by administration of P. palmata in women.

Mediators of the effects of rice intake on health in individuals consuming a traditional Japanese diet centered on rice.

Although the Japanese diet is believed to be balanced and healthy, its benefits have been poorly investigated, especially in terms of effects on mental health. We investigated dietary patterns and physical and mental health in the Japanese population using an epidemiological survey to determine the health benefits of the traditional Japanese diet. Questionnaires to assess dietary habits, quality of life, sleep quality, impulsivity, and depression severity were distributed to 550 randomly selected middle-aged and elderly individuals. Participants with any physical or mental disease were excluded. Two-hundred and seventy-eight participants were selected for the final statistical analysis. We determined rice to be one of the most traditional foods in Japanese cuisine. Scores for each questionnaire were computed, and the correlations between rice intake and health indices were assessed. When analyzing the direct correlations between rice intake and health indices, we found only two correlations, namely those with quality of life (vitality) and sleep quality. Path analysis using structural equation modeling was performed to investigate the association between rice intake and health, with indirect effects included in the model. Additional associations between rice intake and health were explained using this model when compared to those using direct correlation analysis. Path analysis was used to identify mediators of the rice-health association. These mediators were miso (soybean paste) soup, green tea, and natto (fermented soybean) intake. Interestingly, these mediators have been major components of the Japanese diet since 1975, which has been considered one of the healthiest diets since the 1960s. Our results indicate that the combination of rice with other healthy foods, which is representative of the traditional Japanese diet, may contribute to improvements in physical and mental health.

The relationship between a low grain intake dietary pattern and impulsive behaviors in middle-aged Japanese people.

Several studies indicate that dietary habits are associated with mental health. We are interested in identifying not a specific single nutrient/food group but the population preferring specific food combinations that can be related to mental health. Very few studies have examined relationships between dietary patterns and multifaceted mental states using cluster analysis. The purpose of this study was to investigate population-level dietary patterns associated with mental state using cluster analysis. We focused on depressive state, sleep quality, subjective well-being, and impulsive behaviors using rating scales. Two hundred and seventy-nine Japanese middle-aged people participated in the present study. Dietary pattern was estimated using a brief self-administered diet-history questionnaire (the BDHQ). We conducted K-means cluster analysis using thirteen BDHQ food groups: milk, meat, fish, egg, pulses, potatoes, green and yellow vegetables, other vegetables, mushrooms, seaweed, sweets, fruits, and grain. We identified three clusters characterized as "vegetable and fruit dominant," "grain dominant," and "low grain tendency" subgroups. The vegetable and fruit dominant group showed increases in several aspects of subjective well-being demonstrated by the SF-8. Differences in mean subject characteristics across clusters were tested using ANOVA. The low frequency intake of grain group showed higher impulsive behavior, demonstrated by BIS-11 deliberation and sum scores. The present study demonstrated that traditional Japanese dietary patterns, such as eating rice, can help with beneficial changes in mental health.

Arachidonic acid diet attenuates brain Aß deposition in Tg2576 mice.

The amyloid ß-protein (Aß) is believed to play a causative role in the development of Alzheimer's disease (AD). Because the amyloid precursor protein (APP), a substrate of Aß, and ß-secretase and γ-secretase complex proteins, which process APP to generate Aß, are all membrane proteins, it is possible to assume that alterations in brain lipid metabolism modulate APP and/or Aß metabolism. However, the role of polyunsaturated fatty acids in Aß metabolism remains unknown. We report here that 9 months-treatment of Tg2576 mice with arachidonic acid (ARA)-containing (ARA+) diet prevented brain Aß deposition in 17-month-old Tg2576 mice. APP processing to generate soluble APPα, CTF-ß, and Aß synthesis was attenuated in Tg2576 mice fed with the ARA+ diet. These findings suggest that ARA+ diet could prevent Aß deposition through the alteration of APP processing in Tg2576 mice.

Differential effect of arachidonic acid and docosahexaenoic acid on age-related decreases in hippocampal neurogenesis.

Hippocampal neurogenesis affects learning and memory. We evaluated in rats effects of ingestion of arachidonic acid (ARA) and/or docosahexaenoic acid (DHA) on age-related decreases in proliferating neural stem/progenitor cells (NSPCs) or newborn neurons (NNs). Rats were fed with ARA- and/or DHA-containing diet from 2 to 18 months old and then sacrificed 1 day or 4 weeks after 5-bromo-2-deoxyuridine (BrdU) injections at 2, 6 and 18 months. The numbers of NSPCs (SOX2+/BrdU+) and NNs (NeuN+/BrdU+) were determined immunohistochemically. The number of BrdU+ cells 1 day after BrdU injections decreased with age, but increased 65% after ARA ingestion compared to the control at 18 months. The SOX2+/BrdU+ cell ratio was unchanged by aging or ingestion of ARA or DHA. The number of NeuN+/BrdU+ cells 4 weeks after BrdU injections decreased with age, but increased 34% (yet not statistically significant) after DHA ingestion compared to the control at 18 months. These results indicate that ARA ingestion can ameliorate the age-related decrease in the number of NSPCs in rats. The functions of ARA and DHA in hippocampal neurogenesis appear to be different in aged rats; ARA may maintain an NSPC pool, whereas DHA may support NN production and/or survival.

Arachidonic acid-enriched triacylglycerol improves cognitive function in elderly with low serum levels of arachidonic acid.

Arachidonic acid (ARA) is an n-6 PUFA and is thought to have an important role in various physiological and psychological functions. Recently, supplementation with ARA-enriched TAG was shown to improve age-related decreases in cognitive function in healthy elderly men. To investigate the influence of baseline serum ARA status on cognitive function and its improvement, we analyzed cognitive function stratified by serum ARA level. The stratified analysis was also conducted for the effects of ARA-enriched TAG supplementation on cognitive improvement. Cognitive function was evaluated by measuring event-related potentials (ERPs), including P300 latency and amplitude. When participants were stratified by baseline serum ARA level, P300 latency was significantly longer and P300 amplitude was generally lower in the low-ARA group than in the high-ARA group. No significant difference in P300 components was observed when participants were stratified by serum levels of any other fatty acid. ARA-enriched TAG supplementation significantly shortened P300 latency and increased P300 amplitude in the low-ARA group, although no significant differences were observed in the high-ARA group. These findings suggest that lower serum ARA levels were associated with cognitive function in elderly men and that ARA-enriched TAG supplementation is more effective in improving cognitive function in healthy elderly men with low serum ARA levels than in those with high serum ARA levels.

The effect of the sympathetic nervous system on splenic natural killer cell activity in mice administered the Lactobacillus pentosus strain S-PT84.

Splenic sympathetic nerve activity (SNA) modulates cellular immune functions such as splenic natural killer cell activity. Lactobacillus pentosus strain S-PT84 enhances splenic natural killer cell activity. Here, we examined whether S-PT84 affects splenic natural killer activity through splenic SNA in BALB/c mice. Splenic SNA was significantly decreased following the administration of S-PT84. This phenomenon was inhibited by pretreatment with thioperamide (histamine H3 receptor antagonist), suggesting that S-PT84 directly affected splenic SNA. Thioperamide also inhibited the increase in splenic natural killer activity by S-PT84. Thus, the change in splenic natural killer activity by S-PT84 may be partially modulated through SNA.

Effects of heat-killed Lactobacillus pentosus S-PT84 on postprandial hypertriacylglycerolemia in rats.

The effect of Lactobacillus pentosus strain S-PT84 (S-PT84) on postprandial hypertriacylglycerolemia was investigated in rats. S-PT84 dose-dependently inhibited the hydrolysis of triacylglycerols by pancreatic lipase in vitro. Intragastric administration of S-PT84 significantly reduced the lymphatic recovery of (3)H-trioleoylglycerol up to 8 h. The oral administration of a fat emulsion, with or without S-PT84, resulted in the concentration of plasma triacylglycerol 2 h and 3 h after administration being significantly lower in the S-PT84 group than in the group without S-PT84 (control group). These results suggest that S-PT84 alleviated postprandial hypertriacylglycerolemia by delaying triacylglycerol absorption in the intestine through the inhibition of pancreatic lipase.

Evaluation of antioxidative effects of sesamin on the in vivo hepatic reducing abilities by a radiofrequency ESR method.

Antioxidative effects of sesamin (a mixture of sesamin and episesamin) were evaluated in the liver, kidney and inferior vena cava of living rats using a radiofrequency ESR method. TEMPOL, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl, was used as an in vivo redox probe, the half-life of which is believed to be correlated with the antioxidant status. The oral administration of sesamin (250 mg/kg rat weight) 3 h before ESR measurements shortened the half-life of TEMPOL in the liver by 10 - 15% as compared with the controls, but did not affect the other organs. This effect was maintained for at least 3 h after the administration, and then disappeared at 24 h, corresponding to the results of our preliminary pharmacokinetic studies. Changes in the reducing ability were observed only in the hepatic sites of the sesamin-treated rats. These findings suggest that sesamin exhibits effective antioxidant activity in the liver via modulation of the intracellular redox status related to TEMPOL reduction.

Identification of the metabolites of episesamin in rat bile and human liver microsomes.

Episesamin is an isomer of sesamin, resulting from the refining process of non-roasted sesame seed oil. Episesamin has two methylendioxyphenyl groups on exo and endo faces of the bicyclic skeleton. The side methylendioxyphenyl group was metabolized by cytochrome-P450. Seven metabolites of episesamin were found in rat bile after treatment with glucuronidase/arylsulfatase and were identified using NMR and MS. The seven metabolites were (7α,7'ß,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane (EC-1-1), (7α,7'ß,8α,8'α)-3,4-methylenedioxy-3',4'-dihydroxy-7,9':7',9-diepoxylignane (EC-1-2) and (7α,7'ß,8α,8'α)-3,4:3',4'-bis(dihydroxy)-7,9':7',9-diepoxylignane (EC-2), (7α,7'ß,8α,8'α)-3-methoxy-4-hydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane (EC-1m-1), (7α,7'ß,8α,8'α)-3,4-methylenedioxy-3'-methoxy-4'-hydroxy-7,9':7',9-diepoxylignane (EC-1m-2), (7α,7'ß,8α,8'α)-3-methoxy-4-hydroxy-3',4'-dihydroxy-7,9':7',9-diepoxylignane (EC-2m-1) and (7α,7'ß,8α,8'α)-3,4-dihydroxy-3'-methoxy-4'-hydroxy-7,9':7',9-diepoxylignane (EC-2m-2). EC-1-1, EC-1-2 and EC-2 were also identified as metabolites of episesamin in human liver microsomes. These results suggested that similar metabolic pathways of episesamin could be proposed in rats and humans.

Oral supplementation with dihomo-γ-linolenic acid (DGLA)-enriched oil increases serum DGLA content in healthy adults.

Dihomo-γ-linolenic acid (DGLA) is one of the polyunsaturated fatty acids, and is expected to show anti-allergic activity. We examined the effects of supplementation with DGLA-enriched oil (450 mg as free DGLA) for 4 weeks in healthy adults in a randomized controlled study. The DGLA composition in the total fatty acids of serum phospholipids increased from 2.0 to 3.4%, and returned to the initial level after a 4-week washout. No side effects or changes in blood biochemical parameters were observed. These results indicate that serum DGLA content can be safely increased by supplementation with 450 mg DGLA under these conditions.

Role of L-carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the circadian clock and histamine.

L-carnosine (ß-alanyl-L-histidine; CAR) is synthesized in mammalian skeletal muscle. Although the physiological roles of CAR have not yet been clarified, there is evidence that the release of CAR from skeletal muscle during physical exercise affects autonomic neurotransmission and physiological functions. In particular, CAR affects the activity of sympathetic and parasympathetic nerves innervating the adrenal glands, liver, kidney, pancreas, stomach, and white and brown adipose tissues, thereby causing changes in blood pressure, blood glucose, appetite, lipolysis, and thermogenesis. CAR-mediated changes in neurotransmission and physiological functions were eliminated by histamine H1 or H3 receptor antagonists (diphenhydramine or thioperamide) and bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN), a master circadian clock. Moreover, a carnosine-degrading enzyme (carnosinase 2) was shown to be localized to histamine neurons in the hypothalamic tuberomammillary nucleus (TMN). Thus, CAR released from skeletal muscle during exercise may be transported into TMN-histamine neurons and hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of CAR on neurotransmission and physiological function. Thus, CAR appears to influence hypoglycemic, hypotensive, and lipolytic activity through regulation of autonomic nerves and with the involvement of the SCN and histamine. These findings are reviewed and discussed in the context of other recent reports, including those on carnosine synthetases, carnosinases, and carnosine transport.

Interrelated effects of dihomo-γ-linolenic and arachidonic acids, and sesamin on hepatic fatty acid synthesis and oxidation in rats.

Interrelated effects of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (ARA), and sesamin, a sesame lignan, on hepatic fatty acid synthesis and oxidation were examined in rats. Rats were fed experimental diets supplemented with 0 or 2 g/kg sesamin (1:1 mixture of sesamin and episesamin), containing 100 g/kg of maize oil or fungal oil rich in DGLA or ARA for 16 d. Among the groups fed sesamin-free diets, oils rich in DGLA or ARA, especially the latter, compared with maize oil strongly reduced the activity and mRNA levels of various lipogenic enzymes. Sesamin, irrespective of the type of fat, reduced the parameters of lipogenic enzymes except for malic enzyme. The type of dietary fat was rather irrelevant in affecting hepatic fatty acid oxidation among rats fed the sesamin-free diets. Sesamin increased the activities of enzymes involved in fatty acid oxidation in all groups of rats given different fats. The extent of the increase depended on the dietary fat type, and the values became much higher with a diet containing sesamin and oil rich in ARA in combination than with a diet containing lignan and maize oil. Analyses of mRNA levels revealed that the combination of sesamin and oil rich in ARA compared with the combination of lignan and maize oil markedly increased the gene expression of various peroxisomal fatty acid oxidation enzymes but not mitochondrial enzymes. The enhancement of sesamin action on hepatic fatty acid oxidation was also confirmed with oil rich in DGLA but to a lesser extent.

Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate and quercetin glycosides on symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Oral glucosamine and chondroitin sulfate, alone and in combination, have been used worldwide for the treatment of osteoarthritis (OA), but their efficacy is controversial. This clinical study was aimed at investigating the potential of a dietary supplement containing glucosamine and chondroitin sulfate in combination with derivatives of quercetin, a naturally occurring flavonoid, (GCQ supplement) for knee OA care. RESULTS: A randomized, double-blind, placebo-controlled study was conducted in 40 Japanese subjects with symptomatic knee OA. Subjects were randomly assigned to GCQ supplement (1200 mg glucosamine hydrochloride, 60 mg chondroitin sulfate and 45 mg quercetin glycosides per day) or placebo and the treatment and follow-up were continued for 16 weeks. The results of symptomatic efficacy assessment based on Japanese Orthopaedic Association criteria showed that scores for two of the four symptom/function subscales, as well as the aggregate scores, were significantly improved at week 16 or earlier in the GCQ group compared to the placebo group. Moreover, analyses of cartilage metabolism biomarkers showed a trend of improvement in type II collagen synthesis/degradation balance in the GCQ group during follow-up. CONCLUSION: GCQ supplement was thought to be more effective than placebo in decreasing the intensity of knee OA-associated clinical symptoms.

Supplementation of arachidonic acid-enriched oil increases arachidonic acid contents in plasma phospholipids, but does not increase their metabolites and clinical parameters in Japanese healthy elderly individuals: a randomized controlled study.

BACKGROUND: The importance of arachidonic acid (ARA) among the elderly has recently gained increased attention. The effects of ARA supplementation in the elderly are not fully understood, although ARA is considered to be associated with various diseases. We investigate whether ARA supplementation to Japanese elderly subjects affects clinical parameters involved in cardiovascular, inflammatory, and allergic diseases. We also examine the levels of ARA metabolites such as prostanoids during intervention. METHODS: We conducted a randomized, double-blind and placebo-controlled parallel group intervention trial. ARA-enriched oil (240 or 720 mg ARA per day) or placebo was administered to Japanese healthy men and women aged 55-70 years for 4 weeks followed by a 4-week washout period. The fatty acid contents of plasma phospholipids, clinical parameters, and ARA metabolites were determined at baseline, 2, 4, and 8 weeks. RESULTS: The ARA content in plasma phospholipids in the ARA-administrated groups increased dose-dependently and was almost the same at 2 weeks and at 4 weeks. The elevated ARA content decreased to nearly baseline during a 4-week washout period. During the supplementation and washout periods, no changes were observed in eicosapentaenoic acid and docosahexaenoic acid contents. There were no changes in clinical blood parameters related to cardiovascular, inflammatory and allergic diseases. ARA supplementation did not alter the level of ARA metabolites such as urinary 11-dehydro thromboxane B2, 2,3-dinor-6-keto prostaglandin (PG) F1α and 9,15-dioxo-11α-hydroxy-13,14-dihydro-2,3,4,5-tetranor-prostan-1,20-dioic acid (tetranor-PGEM), and plasma PGE2 and lipoxin A4. ARA in plasma phospholipids was not correlated with ARA metabolite levels in the blood or urine. CONCLUSION: These results indicate that ARA supplementation, even at a relatively high dose, does not increase ARA metabolites, and suggest that it does not induce cardiovascular, inflammatory or allergic diseases in Japanese elderly individuals.

Associations between dietary n-6 and n-3 fatty acids and arachidonic acid compositions in plasma and erythrocytes in young and elderly Japanese volunteers.

BACKGROUND: We reported that the compositions of arachidonic acid (ARA) in erythrocytes and plasma phospholipids (PL) in the elderly were lower than those in the young, though the ARA intake was nearly identical. OBJECTIVE: We further analyzed data in four study groups with different ages and sexes, and determined that the blood ARA levels were affected by the kinds of dietary fatty acids ingested. METHODS: One hundred and four healthy young and elderly volunteers were recruited. Dietary records together with photographic records from 28 consecutive days were reviewed and the fatty acid composition in plasma lipid fractions and erythrocyte PL was analyzed. RESULTS: No correlations for ARA between dietary fatty acids and blood lipid fractions were observed. A significant negative correlation between eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) intake and ARA composition in erythrocyte PL was observed. ARA composition in erythrocyte PL was significantly lower in elderly subjects than in young subjects, because EPA and DHA intake in elderly subjects was higher than in young subjects. However, after removing the effect of dietary EPA+DHA intake, the ARA composition in erythrocyte PL in elderly subjects was significantly lower than that in young subjects. CONCLUSIONS: Changes in physical conditions with aging influenced the low ARA composition of erythrocyte in elderly subjects in addition to the effects of dietary EPA and DHA.

The mechanism underlying the synergetic hypocholesterolemic effect of sesamin and α-tocopherol in rats fed a high-cholesterol diet.

Sesamin is a major lignan in sesame seed. We confirmed that ingestion of sesamin and α-tocopherol synergistically reduced the concentration of blood cholesterol in rats given a high-cholesterol diet. To elucidate the molecular mechanism behind this effect, we analyzed the gene-expression profiles in rat liver after co-ingestion of sesamin and α-tocopherol. Six-week-old male Sprague-Dawley rats were fed a 1% cholesterol diet (HC) or HC containing 0.2% sesamin, 1% α-tocopherol or sesamin + α-tocopherol for 10 days. Blood samples were collected on days 1, 3, 7, and 10 and livers were excised on day 10. The gene expressions of ATP-binding cassette, sub-family G (WHITE), members 5 (ABCG5) and 8 (ABCG8) were significantly increased, while the gene expression of apolipoprotein (Apo) A4 was significantly decreased. ABCG5 and ABCG8 form a functional heterodimer that acts as a cholesterol efflux transporter, which contributes to the excretion of cholesterol from the liver. ApoA4 controls the secretion of ApoB, which is a component of low-density-lipoprotein cholesterol. These studies indicate that the cholesterol-lowering mechanism underlying the effects of co-ingestion of sesamin and α-tocopherol might be attributable to increased biliary excretion of cholesterol and reduced ApoB secretion into the bloodstream.

Pharmacology in health foods: effects of arachidonic acid and docosahexaenoic acid on the age-related decline in brain and cardiovascular system function.

Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are major constituents of cell membranes and play important roles in preserving physiological and psychological function. Recently, data from several studies have indicated that impairments in long-term potentiation (LTP), the process underlying plasticity in synaptic connections, are associated with a decrease in membrane ARA and DHA in aged rats; and treatment of aged rats with either of these polyunsaturated fatty acids (PUFAs) reverses age-related decrease in LTP and the decrease in membrane fatty acid concentration. This review focuses on our recent findings concerning the effects of ARA and DHA on the age-related decline in the function of the brain and cardiovascular system. ARA supplementation decreased P300 latency and increased P300 amplitude of event-related potentials in healthy elderly men. Cognitive impairments in patients with mild cognitive impairment (MCI) and patients with organic brain lesions were significantly improved with ARA and DHA supplementation. ARA and DHA supplementation also increased coronary flow velocity reserve in elderly individuals; this suggests beneficial effects of PUFAs on coronary microcirculation. In conclusion, ARA and DHA may be beneficial in preventing and/or improving age-related declines in brain and cardiovascular system function.

Pharmacology in health foods: improvement of vascular endothelial function by French maritime pine bark extract (Flavangenol).

Flavangenol is the French maritime pine bark extract (PBE). It consists of a concentrate of pine bark constituents such as catechin, taxifolin, and proanthocyanidins. Recent studies have shown that PBE has a strong antioxidant effect and exerts ameliorative effects on cardiovascular, skin, cognitive, and menstrual disorders, as well as in the context of other diseases and disease processes such as diabetes and inflammation. We have also obtained evidence that Flavangenol suppresses nuclear factor-kappa B (NF-κB) activation and the subsequent various NF-κB-induced gene expressions such as those of adhesion molecules and endothelin-1 in cultured vascular endothelial cells and that the antihypertensive effect of Flavangenol on deoxycorticosterone acetate-salt hypertensive rats is attributable to both its antioxidative property-related protective effects against endothelial dysfunction and the endothelium-dependent vasorelaxant effect, which is mediated by endothelial nitric oxide synthase activation. Furthermore, Flavangenol showed a renoprotective effect on ischemia/reperfusion-induced acute kidney injury in rats. These findings suggest that Flavangenol supplementation may be a promising candidate for the improvement of endothelial dysfunction and the prophylactic treatment of vascular diseases.