Dietary nitrate supplementation increases nitrate and nitrite concentrations in human skin interstitial fluid.

Acute dietary nitrate (NO3-) supplementation can increase [NO3-], but not nitrite ([NO2-]), in human skeletal muscle, though its effect on [NO3-] and [NO2-] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO3--rich beetroot juice (BR; 9.6 mmol NO3-), and 6 young adults ingested 140 mL of a NO3--depleted placebo (PL). Skin dialysate, acquired through intradermal microdialysis, and venous blood samples were collected at baseline and every hour post-ingestion up to 4 h to assess dialysate and plasma [NO3-] and [NO2-]. The relative recovery rate of NO3- and NO2- through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO3-] and [NO2-]. Baseline [NO3-] was lower, whereas baseline [NO2-] was higher in the skin interstitial fluid relative to plasma (both P < 0.001). Acute BR ingestion increased [NO3-] and [NO2-] in the skin interstitial fluid and plasma (all P < 0.001), with the magnitude being smaller in the skin interstitial fluid (e.g., 183 ± 54 vs. 491 ± 62 µM for Δ[NO3-] from baseline and 155 ± 190 vs. 217 ± 204 nM for Δ[NO2-] from baseline at 3 h post BR ingestion, both P ≤ 0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO2-] post BR ingestion was higher, whereas [NO3-] was lower relative to plasma (all P < 0.001). These findings extend our understanding of NO3- and NO2- distribution at rest and indicate that acute BR supplementation increases [NO3-] and [NO2-] in human skin interstitial fluid.

Perilla seed oil improves bone health by inhibiting bone resorption in healthy Japanese adults: A 12-month, randomized, double-blind, placebo-controlled trial.

Accumulating evidence suggests the beneficial effect of omega-3 polyunsaturated fatty acids (PUFAs) on bone mineral density (BMD). However, the effects of perilla (Perilla frutescens) seed oil (PO), a rich source of α-linoleic acid (LNA), on human bone have not yet been elucidated. This randomized, double-blind, placebo-controlled trial investigated the effects of long-term PO intake on bone health in Japanese adults. After screening for eligibility, 52 participants (mean age 54.2 ± 6.4 years) were randomly assigned to placebo (n = 25) and PO (n = 27) groups, which received 7.0 ml of olive oil and PO daily, respectively. At baseline and 12-month, quantitative ultrasound of the right calcaneus was measured with an ultrasound bone densitometer and percentage of the Young Adult Mean (%YAM) was calculated. Serum levels of tartrate-resistant acid phosphatase 5b (TRACP-5b), and bone alkaline phosphatase (BALP) were evaluated. In addition, PUFA levels in the erythrocyte plasma membrane (RBC-PM), serum biological antioxidant potential (BAP), and diacron reactive oxygen metabolites (d-ROM) were evaluated. Compared with the placebo group, %YAM levels increased and serum TRACP-5b levels decreased significantly in the PO group at 12-month, while serum BALP levels remained unchanged. Moreover, RBC-PM LNA levels and BAP/d-ROM ratios increased significantly in the PO compared with the placebo group. These results suggest that long-term PO intake may improve age-related BMD decline by suppressing bone resorption and increasing LNA levels.

Perilla frutescens seed oil combined with Anredera cordifolia leaf powder attenuates age-related cognitive decline by reducing serum triglyceride and glucose levels in healthy elderly Japanese individuals: a possible supplement for brain health.

We have shown that Anredera cordifolia extract improves learning and memory in a senescence-accelerated mouse model, and that α-linolenic acid (ALA)-rich Perilla frutescens seed oil (PO) improves brain function in healthy Japanese adults and elderly individuals. Herein, we present a 12-month, randomised, double-blind, parallel-armed intervention trial examining the effects of PO supplementation alone or in combination with A. cordifolia leaf powder on brain function in healthy elderly Japanese individuals. Participants were randomly divided into two groups: the PO group received 1.47 mL PO (0.88 g ALA) daily via soft gelatine capsules, and the POAC group received 1.47 mL PO and 1.12 g A. cordifolia leaf powder (1.46 mg vitexin and 1.12 mg adenosine) daily. After 12 months of intervention, the POAC group showed generally higher cognitive index scores than the PO group. The beneficial effects of combined supplementation on cognitive function were associated with increased ALA and eicosapentaenoic acid levels in red blood cell plasma membranes, increased serum biological antioxidant potential, and decreased serum triglyceride, glucose, and N-(epsilon)-carboxymethyl-lysine (CML), an advanced glycation end-product and biochemical marker of oxidative stress levels. The effects of combined supplementation on cognitive function also showed a significant negative correlation with serum CML levels after 12 months of intervention. Our findings suggest that combined long-term supplementation with PO and A. cordifolia more effectively ameliorates age-related cognitive decline than PO alone. These findings may serve as a basis for the development of new supplements for brain health. Clinical Trial Registry, UMIN000040863.

Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly.

Perilla (Perilla frutescens) seed oil (PO), rich in α-linolenic acid (ALA), can improve cognitive function in healthy elderly Japanese people. Here, supplements containing either PO alone or PO with nobiletin-rich air-dried immature ponkan powder were examined for their effects on cognitive function in 49 healthy elderly Japanese individuals. Patients were enrolled in a 12-month randomized, double-blind, parallel-armed study. Randomized participants in the PO group received soft gelatin capsules containing 1.47 mL (0.88 g of ALA) of PO daily, and those in the PO + ponkan powder (POPP) group received soft gelatin capsules containing both 1.47 mL of PO and 1.12 g ponkan powder (2.91 mg of nobiletin) daily. At the end of intervention, the POPP group showed significantly higher cognitive index scores than the PO group. The pro-cognitive effects of POPP treatment were accompanied by increases in ALA and docosahexaenoic acid levels in red blood cell plasma membranes, serum brain-derived neurotropic factor (BDNF) levels, and biological antioxidant potential. We demonstrate that 12-month intervention with POPP enhances serum BDNF and antioxidant potential, and may improve age-related cognitive impairment in healthy elderly people by increasing red blood cell ω-3 fatty acid levels. Clinical Trial Registry, UMIN000040863.

Intake of Docosahexaenoic Acid-Enriched Milk Beverage Prevents Age-Related Cognitive Decline and Decreases Serum Bone Resorption Marker Levels.

The pathogenic mechanism of dementia is still unknown, and the fundamental treatment remains to be established. Thus, there is growing interest in preventing dementia through diet. One of the functional ingredients attracting attention is docosahexaenoic acid. We conducted a 12-month, randomized, double-blind, placebo-controlled clinical trial in healthy elderly Japanese individuals with a Mini-Mental State Examination score of 28 or higher at baseline using a docosahexaenoic acid-enriched milk beverage containing 297 mg docosahexaenoic acid and 137 mg eicosapentaenoic acid. Consumption of a docosahexaenoic acid-enriched milk beverage increased the fatty acid levels of docosahexaenoic acid and eicosapentaenoic acid in erythrocyte membranes, which was the primary outcome of this study. Moreover, intake of this beverage prevented age-related cognitive decline and decreased serum bone resorption marker levels. Our data demonstrate that, even at a low dose, long-term daily intake of docosahexaenoic acid prevents dementia and may show beneficial effect on bone health.

Anredera cordifolia extract enhances learning and memory in senescence-accelerated mouse-prone 8 (SAMP8) mice.

Learning and memory impairment may result from age-related decline in synaptic plasticity-related proteins in the hippocampus. Therefore, exploration of functional foods capable of ameliorating memory and cognition decline is an interesting endeavor in neuroscience research. We report the effects of Anredera cordifolia (AC) extract on learning and memory deficits in a senescence-accelerated mouse-prone 8 (SAMP8) mouse model, which demonstrate age-related memory deficits and related pathological changes in the brain. After 8 weeks of oral administration of AC extract, the mice were trained in the Novel Object Recognition (NOR) task, and after 7 more weeks, in the Morris Water Maze (MWM) task. Following the completion of behavioral testing, the blood biochemistry parameters, the hippocampal levels of brain-derived neurotropic factor (BDNF), PSD95, and NR2A, and the p-cAMP-response element binding (p-CREB)/CREB ratio were measured. The AC-treated group spent more time exploring the novel objects in the NOR task, and showed faster acquisition and better retention in the MWM task than the negative control (CN) group. In addition, AC enhanced the levels of the aforementioned neuronal plasticity-related proteins, and did not affect the blood biochemistry parameters. Therefore, our data suggest that the AC extract may improve learning and memory without causing any noticeable side effects in the body.

Dietary Supplementation for Attenuating Exercise-Induced Muscle Damage and Delayed-Onset Muscle Soreness in Humans.

Dietary supplements are widely used as a nutritional strategy to improve and maintain performance and achieve faster recovery in sports and exercise. Exercise-induced muscle damage (EIMD) is caused by mechanical stress and subsequent inflammatory responses including reactive oxygen species and cytokine production. Therefore, dietary supplements with anti-inflammatory and antioxidant properties have the potential to prevent and reduce muscle damage and symptoms characterized by loss of muscle strength and delayed-onset muscle soreness (DOMS). However, only a few supplements are considered to be effective at present. This review focuses on the effects of dietary supplements derived from phytochemicals and listed in the International Olympic Committee consensus statement on muscle damage evaluated by blood myofiber damage markers, muscle soreness, performance, and inflammatory and oxidative stress markers. In this review, the effects of dietary supplements are also discussed in terms of study design (i.e., parallel and crossover studies), exercise model, and such subject characteristics as physical fitness level. Future perspectives and considerations for the use of dietary supplements to alleviate EIMD and DOMS are also discussed.

Intake of Alpha-Linolenic Acid-Rich Perilla frutescens Leaf Powder Decreases Home Blood Pressure and Serum Oxidized Low-Density Lipoprotein in Japanese Adults.

Oxidized low-density lipoprotein (Ox-LDL) is known to be highly atherogenic. Thus, decreasing the blood levels of Ox-LDL through dietary means is an important approach to reduce cardiovascular events in high-risk individuals. In this randomized placebo-controlled human interventional trial, we aimed to evaluate whether Perilla frutescens leaf powder (PLP) ameliorates Ox-LDL and home blood pressure, along with its biological antioxidant potential. Healthy Japanese volunteers aged 30-60 years (n = 60) were randomized to PLP and placebo groups. The PLP group consumed PLP dried using a microwave under reduced pressure, and the placebo group consumed pectin fiber daily for 6 months. Home blood pressure, serum biochemical parameters, and fatty acid profiles of erythrocyte plasma membranes were analyzed. Plasma Ox-LDL levels significantly decreased in the PLP group but not in the placebo group. Mean changes in the biological antioxidant potential and alpha-linolenic acid levels in the erythrocyte plasma membrane were significantly increased in the PLP group than in the placebo group. In subjects with prehypertension (systolic blood pressure [SBP] ³ 120 mmHg), the mean reduction in morning or nocturnal SBP was significantly greater in the PLP group than in the placebo group. Thus, PLP intake may be an effective intervention to prevent cardiovascular diseases.

Effective Timing of Curcumin Ingestion to Attenuate Eccentric Exercise-Induced Muscle Soreness in Men.

Curcumin is known to have potent anti-inflammatory effects. We have reported that acute curcumin ingestion attenuates eccentric exercise-induced muscle damage. This study aimed to examine the effect of curcumin ingestion timing (before or after exercise) on the changes in muscle damage markers after eccentric exercise. In this randomized, single-blind, parallel design study, 24 healthy young men performed 30 maximal isokinetic (120º/s) eccentric contractions of the elbow flexors using an isokinetic dynamometer. Subjects were randomly assigned to ingest 180 mg/d of oral curcumin either 7 d before (PRE) or 4 d after exercise (POST) or 180 mg/d of oral placebo 4 d after exercise (CON). The maximal voluntary contraction (MVC) torque of the elbow flexors, elbow joint range of motion (ROM), muscle soreness, and serum creatine kinase (CK) activity were measured before, immediately after, and 1-4 d after exercise. Changes in these variables were compared over time. In the POST group, ROM were higher at 3-4 d and muscle soreness was lower at 3 d after exercise compared with the CON group (p<0.05). However, in the PRE group, there were no significant differences compared with the CON group in changes in ROM and muscle soreness. Meanwhile, there were no significant differences among the groups in terms of changes in MVC torque and serum CK activity. Our results suggest that curcumin ingestion after exercise had a more beneficial effect in attenuating muscle soreness.

Effects of oral curcumin ingested before or after eccentric exercise on markers of muscle damage and inflammation.

We examined the effect of curcumin (CUR) ingestion before or after exercise on changes in muscle damage and inflammatory responses after exercise. We conducted two parallel experiments with different CUR ingestion timings using a double-blind crossover. In Exp. 1, ten healthy men ingested 180 mg d-1 of CUR or placebo (PLA) 7 days before exercise. In Exp. 2, ten other healthy men ingested 180 mg d-1 of CUR or PLA 7 days after exercise. They performed 30 maximal isokinetic (120°s-1 ) eccentric contractions of the elbow flexors using an isokinetic dynamometer, and this was repeated with the other arm ≥4 weeks later. Maximal voluntary contraction (MVC) torque of the elbow flexors, elbow joint range of motion (ROM), muscle soreness, and serum creatine kinase (CK) activity were measured before, immediately after, and 1-7 days after exercise. Plasma interleukin-8 (IL-8) was measured before, immediately after, 12 hours after, and 1-7 days after exercise. The changes were compared over time. In Exp. 1, no significant differences were found between CUR and PLA subjects for each parameter. However, increases in IL-8 were significantly reduced 12 hours after exercise when CUR was ingested before exercise. In Exp. 2, compared to the PLA subjects, MVC torque and ROM were higher 3-7 days and 2-7 days after exercise (P < 0.05), respectively, whereas muscle soreness and CK activity were lower 3-6 days and 5-7 days after exercise (P < 0.05), respectively, in CUR subjects. CUR ingestion before exercise could attenuate acute inflammation, and after exercise could attenuate muscle damage and facilitate faster recovery.

Effect of dietary n-3 fatty acids supplementation on fatty acid metabolism in atorvastatin-administered SHR.Cg-Leprcp/NDmcr rats, a metabolic syndrome model.

The effects of cholesterol-lowering statins, which substantially benefit future cardiovascular events, on fatty acid metabolism have remained largely obscured. In this study, we investigated the effects of atorvastatin on fatty acid metabolism together with the effects of TAK-085 containing highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl ester on atorvastatin-induced n-3 polyunsaturated fatty acid lowering in SHR.Cg-Leprcp/NDmcr (SHRcp) rats, as a metabolic syndrome model. Supplementation with 10mg/kg body weight/day of atorvastatin for 17 weeks significantly decreased plasma total cholesterol and very low density lipoprotein cholesterol. Atorvastatin alone caused a subtle change in fatty acid composition particularly of EPA and DHA in the plasma, liver or erythrocyte membranes. However, the TAK-085 consistently increased both the levels of EPA and DHA in the plasma, liver and erythrocyte membranes. After confirming the reduction of plasma total cholesterol, 300mg/kg body weight/day of TAK-085 was continuously administered for another 6 weeks. Supplementation with TAK-085 did not decrease plasma total cholesterol but significantly increased the EPA and DHA levels in both the plasma and liver compared with rats administered atorvastatin only. Supplementation with atorvastatin alone significantly decreased sterol regulatory element-binding protein-1c, Δ5- and Δ6-desaturases, elongase-5, and stearoyl-coenzyme A (CoA) desaturase-2 levels and increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression in the liver compared with control rats. TAK-085 supplementation significantly increased stearoyl-CoA desaturase-2 mRNA expression. These results suggest that long-term supplementation with atorvastatin decreases the EPA and DHA levels by inhibiting the desaturation and elongation of n-3 fatty acid metabolism, while TAK-085 supplementation effectively replenishes this effect in SHRcp rat liver.

Oral intake of encapsulated dried ginger root powder hardly affects human thermoregulatory function, but appears to facilitate fat utilization.

The present study investigated the impact of a single oral ingestion of ginger on thermoregulatory function and fat oxidation in humans. Morning and afternoon oral intake of 1.0 g dried ginger root powder did not alter rectal temperature, skin blood flow, O2 consumption, CO2 production, and thermal sensation and comfort, or induce sweating at an ambient temperature of 28 °C. Ginger ingestion had no effect on threshold temperatures for skin blood flow or thermal sweating. Serum levels of free fatty acids were significantly elevated at 120 min after ginger ingestion in both the morning and afternoon. Morning ginger intake significantly reduced respiratory exchange ratios and elevated fat oxidation by 13.5 % at 120 min after ingestion. This was not the case in the afternoon. These results suggest that the effect of a single oral ginger administration on the peripheral and central thermoregulatory function is miniscule, but does facilitate fat utilization although the timing of the administration may be relevant.

Attenuation of indirect markers of eccentric exercise-induced muscle damage by curcumin.

PURPOSE: Polyphenolic curcumin is known to have potent anti-inflammatory effects; thus the present study investigated the hypothesis that curcumin ingestion would attenuate muscle damage after eccentric exercise. METHODS: Fourteen untrained young men (24 ± 1 years) performed 50 maximal isokinetic (120°/s) eccentric contractions of the elbow flexors of one arm on an isokinetic dynamometer and the same exercise with the other arm 4 weeks later. They took 150 mg of curcumin (theracurmin) or placebo (starch) orally before and 12 h after each eccentric exercise bout in a randomised, crossover design. Maximal voluntary contraction (MVC) torque of the elbow flexors, range of motion of the elbow joint, upper-arm circumference, muscle soreness, serum creatine kinase (CK) activity, and plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration were measured before, immediately after, and 24, 48, 72 and 96 h after each eccentric exercise. Changes in these variables over time were compared between curcumin and placebo conditions by two-way repeated measures ANOVA. RESULTS: MVC torque decreased smaller and recovered faster (e.g., 4 days post-exercise: -31 ± 13 % vs. -15 ± 15 %), and peak serum CK activity was smaller (peak: 7684 ± 8959 IU/L vs. 3398 ± 3562 IU/L) for curcumin than placebo condition (P < 0.05). However, no significant differences between conditions were evident for other variables, and no significant changes in IL-6 and TNF-α were evident after exercise. CONCLUSION: It is concluded that theracurmin ingestion attenuates some aspects of muscle damage such as MVC loss and CK activity increase.

Omega-3 fatty acids protect renal functions by increasing docosahexaenoic acid-derived metabolite levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) protect against diabetic nephropathy by inhibiting inflammation. The aim of this study was to assess the effects of highly purified DHA and EPA or EPA only administration on renal function and renal eicosanoid and docosanoid levels in an animal model of metabolic syndrome, SHR.Cg-Lepr(cp)/NDmcr (SHRcp) rats. Male SHRcp rats were divided into 3 groups. Control (5% arabic gum), TAK-085 (300 mg/kg/day, containing 467 mg/g EPA and 365 mg/g DHA), or EPA (300 mg/kg/day) was orally administered for 20 weeks. The urinary albumin to creatinine ratio in the TAK-085-administered group was significantly lower than that in other groups. The glomerular sclerosis score in the TAK-085-administered group was significantly lower than that in the other groups. Although DHA levels were increased in total kidney fatty acids, the levels of nonesterified DHA were not significantly different among the 3 groups, whereas the levels of protectin D1, resolvin D1, and resolvin D2 were significantly increased in the TAK-085-administered group. The results show that the use of combination therapy with DHA and EPA in SHRcp rats improved or prevented renal failure associate with metabolic syndrome with decreasing triglyceride levels and increasing ω-3 PUFA lipid mediators.

Prescription n-3 fatty acids, but not eicosapentaenoic acid alone, improve reference memory-related learning ability by increasing brain-derived neurotrophic factor levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

Metabolic syndrome is implicated in the decline of cognitive ability. We investigated whether the prescription n-3 fatty acid administration improves cognitive learning ability in SHR.Cg-Lepr(cp)/NDmcr (SHR-cp) rats, a metabolic syndrome model, in comparison with administration of eicosapentaenoic acid (EPA, C20:5, n-3) alone. Administration of TAK-085 [highly purified and concentrated n-3 fatty acid formulation containing EPA ethyl ester and docosahexaenoic acid (DHA, C22:6, n-3) ethyl ester] at 300 mg/kg body weight per day for 13 weeks reduced the number of reference memory-related errors in SHR-cp rats, but EPA alone had no effect, suggesting that long-term TAK-085 administration improves cognitive learning ability in a rat model of metabolic syndrome. However, the working memory-related errors were not affected in either of the rat groups. TAK-085 and EPA administration increased plasma EPA and DHA levels of SHR-cp rats, associating with an increase in EPA and DHA in the cerebral cortex. The TAK-085 administration decreased the lipid peroxide levels and reactive oxygen species in the cerebral cortex and hippocampus of SHR-cp rats, suggesting that TAK-085 increases antioxidative defenses. Its administration also increased the brain-derived neurotrophic factor levels in the cortical and hippocampal tissues of TAK-085-administered rats. The present study suggests that long-term TAK-085 administration is a possible therapeutic strategy for protecting against metabolic syndrome-induced learning decline.

Effects of yoga exercise on salivary beta-defensin 2.

PURPOSE: Yoga stretching can be done comfortably and easily by beginners and older adults to compensate for lack of exercise or poor health maintenance. The aim of this study was to determine the effect of yoga stretching on mucosal immune functions, primarily human ß-defensin 2 (HBD-2) in saliva. METHODS: Fifteen healthy adults (age, 60.4 ± 8.0 years) participated in the study. Participants rested for 90 min on the first day and performed yoga for 90 min on the second day. Measurements were carried out before and after rest or yoga. Saliva samples were collected by chewing a sterile cotton at a frequency of 60 cycles per min. Salivary HBD-2 concentration was measured using an enzyme-linked immunosorbent assay. RESULTS: HBD-2 concentration after yoga stretching (165.4 ± 127.1 pg/mL) was significantly higher than that before yoga stretching (84.1 ± 63.4 pg/mL; p < 0.01). HBD-2 expression rate after yoga stretching (232.8 ± 192.9 pg/min) was significantly higher than that before yoga stretching (110.7 ± 96.8 pg/min; p < 0.01). HBD-2 concentration (p < 0.05) and HBD-2 expression rate (p < 0.01) at post on the second day (yoga) was significantly higher than that on the first day (rest). POMS score of anger-hostility was lower after yoga than before. CONCLUSIONS: Yoga stretching for 90 min can increase salivary HBD-2 expression in older adults. Therefore, yoga stretching might be useful for older adults and athletes to maintain their health.

Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women.

Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function.

Protective effects of prescription n-3 fatty acids against impairment of spatial cognitive learning ability in amyloid ß-infused rats.

Deposition of amyloid ß peptide (Aß) into the brain causes cognitive impairment. We investigated whether prescription pre-administration of n-3 fatty acids improves cognitive learning ability in young rats and whether it protects against learning ability impairments in an animal model of Alzheimer's disease that was prepared by infusion of Aß(1-40) into the cerebral ventricles of rats. Pre-administration of TAK-085 (highly purified and concentrated n-3 fatty acids containing eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl ester) at 300 mg kg(-1) day(-1) for 12 weeks significantly reduced the number of reference memory errors in an 8-arm radial maze, suggesting that long-term administration of TAK-085 improves cognitive leaning ability in rats. After pre-administration, the control group was divided into the vehicle and Aß-infused groups, whereas the TAK-085 pre-administration group was divided into the TAK-085 and TAK-085 + Aß groups (TAK-085-pre-administered Aß-infused rats). Aß(1-40) or vehicle was infused into the cerebral ventricle using a mini osmotic pump. Pre-administration of TAK-085 to the Aß-infused rats significantly suppressed the number of reference and working memory errors and decreased the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and hippocampus of Aß-infused rats, suggesting that TAK-085 increases antioxidative defenses. The present study suggests that long-term administration of TAK-085 is a possible therapeutic agent for protecting against Alzheimer's disease-induced learning deficiencies.

Long-term administration of green tea catechins improves spatial cognition learning ability in rats.

Green tea catechins confer potent biological properties including antioxidation and free-radical scavenging. We investigated the effect of long-term oral administration of green tea catechins (Polyphenon E, PE: EGCG 63%; EC 11%; EGC 6%; ECG 6%) mixed with water on the spatial cognition learning ability of young rats. The learning ability of rats administered PE (0%, 0.1%, 0.5%) for 26 wk was assessed in the partially baited 8-arm radial maze. Relative to controls, those administered PE had improved reference and working memory-related learning ability. They also had lower plasma concentrations of lipid peroxides and greater plasma ferric-reducing antioxidation power than controls. Furthermore, rats administered PE had lower hippocampus reactive oxygen species concentrations than controls. We suggest that this improvement in spatial cognitive learning ability is due to the antioxidative activity of green tea catechins.

Chronic administration of docosahexaenoic acid ameliorates the impairment of spatial cognition learning ability in amyloid beta-infused rats.

We investigated whether administration of docosahexaenoic acid (DHA), a major (n-3) fatty acid of the brain, ameliorates the impairment of learning ability in an animal model of Alzheimer's disease (AD), rats infused with amyloid-beta (Abeta) peptide (1-40) into the cerebral ventricle. Inbred 3rd generation male rats (20 wk old) fed a fish oil-deficient diet were randomly divided into 4 groups: a vehicle group, an Abeta peptide-infused group (Abeta group), a DHA group, and an Abeta + DHA group. A mini-osmotic pump filled with Abeta peptide or vehicle was implanted in the rats, and they were tested for learning ability-related reference and working memory in an 8-arm radial maze. The rats were then orally fed DHA dissolved in 5% gum Arabic solution at 300 mg/(kg . d) (DHA and Abeta + DHA groups) or vehicle alone (vehicle and Abeta groups) and tested again for learning ability. DHA administered for 12 wk significantly reduced the increase in the number of reference and working memory errors in the Abeta-infused rats, and increased both the cortico-hippocampal level of DHA and the molar ratio of DHA/arachidonic acid, suggesting an amelioration of the impaired spatial cognition learning ability. Furthermore, DHA suppressed the increases in the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and the hippocampus of Abeta-infused rats, suggesting that DHA increases antioxidative defenses. DHA is thus a possible therapeutic agent for ameliorating learning deficiencies due to Alzheimer's disease.