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.

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.

Ginger facilitates cell migration and heat tolerance in mouse fibroblast cells.

The components of ginger root (Zingiber officinale Roscoe) are widely used for various medicinal purposes. Several bioactive compounds have been identified in ginger, including 6­, 8­ and 10­gingerols, and 6­shogaol, which are agonists of the thermo­sensors transient receptor potential (TRP) cation channel subfamily V member 1 and TRP ankyrin 1. Our previous study demonstrated that ginger powder may affect human metabolism in vivo. However, the effects of the bioactive compounds of ginger on cells have not been completely elucidated. The present study investigated whether ginger powder extracts could modify cell functions in mouse fibroblast cells. The active components of ginger powder extracts were characterized using high­performance liquid chromatography. The activation of protein kinases, actin assembly, cell migration, expression levels of heat shock proteins (HSPs) and cell viability after heat shock were analyzed in NIH3T3 mouse fibroblast cells. Subsequently, 6­, 8­, 10­ and 12­gingerols, as well as 6­, 8­ and 10­shogaols, were detected in ginger powder extracts. The levels of phosphorylated Akt, mTOR, ERK and p38 MAPK increased after a 10­min stimulation with ginger powder extracts. In addition, HSP expression levels, lamellipodia formation occurring at cell edges, cell migration and tolerance against heat shock were facilitated following ginger powder extract stimulation. These results suggest that ginger modified cell functions, including actin assembly and heat tolerance, in vitro.

Theobromine Improves Working Memory by Activating the CaMKII/CREB/BDNF Pathway in Rats.

Theobromine (TB) is a primary methylxanthine found in cacao beans. cAMP-response element-binding protein (CREB) is a transcription factor, which is involved in different brain processes that bring about cellular changes in response to discrete sets of instructions, including the induction of brain-derived neurotropic factor (BDNF). Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been strongly implicated in the memory formation of different species as a key regulator of gene expression. Here we investigated whether TB acts on the CaMKII/CREB/BDNF pathway in a way that might improve the cognitive and learning function in rats. Male Wistar rats (5 weeks old) were divided into two groups. For 73 days, the control rats (CN rats) were fed a normal diet, while the TB-fed rats (TB rats) received the same food, but with a 0.05% TB supplement. To assess the effects of TB on cognitive and learning ability in rats: The radial arm maze task, novel object recognition test, and Y-maze test were used. Then, the brain was removed and the medial prefrontal cortex (mPFC) was isolated for Western Blot, real-time PCR and enzyme-linked immunosorbent assay. Phosphorylated CaMKII (p-CaMKII), phosphorylated CREB (p-CREB), and BDNF level in the mPFC were measured. In all the behavior tests, working memory seemed to be improved by TB ingestion. In addition, p-CaMKII and p-CREB levels were significantly elevated in the mPFC of TB rats in comparison to those of CN rats. We also found that cortical BDNF protein and mRNA levels in TB rats were significantly greater than those in CN rats. These results suggest that orally supplemented TB upregulates the CaMKII/CREB/BDNF pathway in the mPFC, which may then improve working memory in rats.

Effects of hypervolemia by protein and glucose supplementation during aerobic training on thermal and arterial pressure regulations in hypertensive older men.

In Japan, the incidence of heat illness in older people has rapidly increased during midsummer in the last decade, and we suggested that whey-protein+carbohydrate supplementation during aerobic training would increased plasma volume (PV) to enhance thermoregulatory adaptation in older men (J Appl Physiol 107: 725-733, 2009); however, >60% of people age 65 and older suffer from hypertension, and the symptoms may be worsened by hypervolemia. To examine this, we randomly divided 21 older men (∼69 yr) with ∼160 mmHg for systolic and ∼90 mmHg for diastolic blood pressure at rest into two groups: Glc (n = 11) consuming glucose alone (25 g) and Pro-Glc (n = 10) consuming whey protein (10 g) + glucose (15 g), immediately after cycling exercise at 60-75% of peak aerobic capacity (V̇o2 peak) for 60 min/day, 3 days/wk, for 8 wk. Before and after training, we measured PV (dye dilution), baroreflex sensitivity (BRS) of heart rate (Valsalva maneuver), and carotid arterial compliance (CAC) from carotid arterial diameter (ultrasound imaging) responses to pulsatile arterial pressure change (photoplethysmography) at rest. Additionally, we measured esophageal temperature (Tes) and forearm skin blood flow (plethysmography) during exercise at 60% pretraining V̇o2 peak for 20 min in a warm environment. We found that the forearm skin vascular conductance response to increased Tes was enhanced in Pro-Glc with increased PV, but this was not found in Glc; however, despite the increased PV, arterial blood pressures rather decreased with increased CAC and BRS in Pro-Glc. Thus, the prescription was applicable to older men with hypertension to prevent heat illness during exercise.

Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women.

A reduction in exercise efficiency with aging limits daily living activities. We examined whether 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) increased exercise efficiency and voluntary achievement of interval walking training (IWT) in older women. Ten women [65 ± 3(SD) yr] who had performed IWT for >12 mo and were currently performing IWT participated in this study. The study was conducted in a placebo-controlled, double-blind crossover design. All subjects underwent two trials for 7 days each in which they performed IWT with ALA+SFC (100 and 115 mg/day, respectively) or placebo supplement intake (CNT), intermittently with a 2-wk washout period. Before and after each trial, subjects underwent a graded cycling test at 27.0 °C atmospheric temperature and 50% relative humidity, and oxygen consumption rate, carbon dioxide production rate, and lactate concentration in plasma were measured. Furthermore, for the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. We found that, in the ALA+SFC trial, oxygen consumption rate and carbon dioxide production rate during graded cycling decreased by 12% (P < 0.001) and 11% (P = 0.001) at every workload, respectively, accompanied by a 16% reduction in lactate concentration in plasma (P < 0.001), although all remained unchanged in the CNT trial (P > 0.2). All of the reductions were significantly greater in the ALA+SFC than the CNT trial (P < 0.05). Furthermore, the training days, impulse, and time at fast walking were 42% (P = 0.028), 102% (P = 0.027), and 69% (P = 0.039) higher during the ALA+SFC than the CNT intake period, respectively. Thus ALA+SFC supplementation augmented exercise efficiency and thereby improved IWT achievement in older women.