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Subcutaneous infusion of tertiary mu-receptor opioid antagonist naloxone hydrochloride (Nal-HCl) weakens the febrile response of guinea pigs to liposaccharide fever. Nal-HCl exhibits a central hypothermic action, a peripheral thermolytic action and a peripheral antipyretic action. The peripheral antipyretic action of Nal-HCl confirms the necessity to circulate opioids in the fever generation in guinea pigs.

Docosahexaenoic acid (C22:6, n-3), a major n-3 fatty acid of the brain, has been implicated in restoration and enhancement of memory-related functions. Because Alzheimer's disease impairs memory, and infusion of amyloid-β (Aβ) peptide (1–40) into the rat cerebral ventricle reduces learning ability, we investigated the effect of dietary pre-administration of docosahexaenoic acid on avoidance learning ability in Aβ peptide-produced Alzheimer's disease model rats. After a mini-osmotic pump filled with Aβ peptide or vehicle was implanted in docosahexaenoic acid-fed and control rats, they were subjected to an active avoidance task in a shuttle avoidance system apparatus. Pre-administration of docosahexaenoic acid had a profoundly beneficial effect on the decline in avoidance learning ability in the Alzheimer's disease model rats, associated with an increase in the cortico-hippocampal docosahexaenoic acid/arachidonic acid molar ratio, and a decrease in neuronal apoptotic products. Docosahexaenoic acid pre-administration furthermore increased cortico-hippocampal reduced glutathione levels and glutathione reductase activity, and suppressed the increase in lipid peroxide and reactive oxygen species levels in the cerebral cortex and hippocampus of the Alzheimer's disease model rats, suggesting an increase in antioxidative defence. Docosahexaenoic acid is thus a possible prophylactic means for preventing the learning deficiencies of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder and dopaminergic dysfunction in the prefrontal cortex (PFC) may play a role. Our previous research indicated that theobromine (TB), a methylxanthine, enhances cognitive function in rodents via the PFC. This study investigates TB's effects on hyperactivity and cognitive function in stroke-prone spontaneously hypertensive rats (SHR), an ADHD animal model. Male SHRs (6-week old) received a diet containing 0.05% TB for 40 days, while control rats received normal diets. Age-matched male Wistar-Kyoto rats (WKY) served as genetic controls. During the TB administration period, we conducted open-field tests and Y-maze tasks to evaluate hyperactivity and cognitive function, then assessed dopamine concentrations and tyrosine hydroxylase (TH), dopamine receptor D1-5 (DRD1-5), dopamine transporter (DAT), vesicular monoamine transporter-2 (VMAT-2), synaptosome-associated protein-25 (SNAP-25), and brain-derived neurotrophic factor (BDNF) expressions in the PFC. Additionally, the binding affinity of TB for the adenosine receptors (ARs) was evaluated. Compared to WKY, SHR exhibited hyperactivity, inattention and working memory deficits. However, chronic TB administration significantly improved these ADHD-like behaviors in SHR. TB administration also normalized dopamine concentrations and expression levels of TH, DRD2, DRD4, SNAP-25, and BDNF in the PFC of SHR. No changes were observed in DRD1, DRD3, DRD5, DAT, and VMAT-2 expression between SHR and WKY rats, and TB intake had minimal effects. TB was found to have affinity binding to ARs. These results indicate that long-term TB supplementation mitigates hyperactivity, inattention and cognitive deficits in SHR by modulating dopaminergic nervous function and BDNF levels in the PFC, representing a potential adjunctive treatment for ADHD.

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., (© 2023 John Wiley & Sons Ltd.)

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.

Thymoquinone is a pharmacologically active component of Nigella sativa Linn. seeds. Despite the diverse neuropharmacological attributes of TQ, limited reports related to adult neurogenesis and memory research are available. In this study, we investigated the effects of TQ on the proliferation and neural differentiation of cultured neural stem/progenitor cells (NSCs/NPCs). We also investigated the effect of TQ chronic administration on neurogenesis and memory in adult rats. Under proliferation conditions, TQ (0.05-0.3 μM) significantly increased NSCs/NPCs viability, neurosphere diameter, and cell count. TQ treatment under differentiation conditions increased the proportion of cells positive for Tuj1 (a neuronal marker). Furthermore, chronic oral administration of TQ (25 mg/kg/day for 12 weeks) to adult rats increased the number of bromodeoxyuridine (BrdU)-immunopositive cells double-stained with a mature neuronal marker, neuronal nuclei (NeuN), and a proliferation marker, doublecortin (Dcx), in the dentate gyrus of the hippocampus. TQ-administered rats showed a profound beneficial effect on avoidance-related learning ability, associated with an increase in the hippocampal mRNA and protein levels of brain-derived neurotrophic factor (BDNF), as measured by both real-time PCR and ELISA. Western blot analysis revealed that TQ stimulates the phosphorylation of cAMP-response element-binding protein (CREB), the upstream signaling molecule in the BDNF pathway. Furthermore, chronic administration of TQ decreased lipid peroxide and reactive oxygen species levels in the hippocampus. Taken together, our results suggest that TQ plays a role in memory improvement in adult rats and that the CREB/BDNF signaling pathways are involved in mediating the actions of TQ in hippocampal neurogenesis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Although brown rice (BR) contains significantly higher levels of nutrients than the traditionally used polished white rice (WR), its consumption among the population is still not noteworthy. WR and BR are essentially same grain. The only difference between the two is the application of an exhaustive milling procedure during the processing of WR that removes all other layers of the grain except the portion of its white endosperm. BR, on the other hand, is prepared by removing only the outer hull of the rice seed. Thus, in addition to its inner endosperm, the bran and germ are also left on the BR. Hence, BR retains all its nutrients, including proteins, lipids, carbohydrates, fibers, vitamins, minerals, tocopherols, tocotrienols, γ-oryzanol, and γ-aminobutyric acid (GABA) packed into the bran and germ of the seed. Since BR tastes nutty and takes longer to cook than WR, it is not appreciated by the consumers. However, these problems have been circumvented using non-thermal ultra-high hydrostatic pressure (UHHP)-processing for the treatment of BR. A superior modification in the physicochemical and functional qualities of UHHPBR, along with its ability to curb human diseases may make it a more palatable and nutritious choice of rice over WR or the untreated-BR. Here, we have reviewed the mechanism by which UHHP treatment leads to the modification of nutrients such as proteins, lipids, carbohydrates, and fibers. We have focused on the effects of rice on cell and animal models of different conditions such as hyperlipidemia, diabetes, and hypertension and the possible mechanisms. Finally, we have emphasized the effects of UHHPBR in human cases with rare conditions such as osteoporosis and brain cognition - two age-related degenerative diseases of the elderly population.

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.

Oxidative stress plays an important role in age-associated cognitive decline. We recently reported that dietary intake of perilla seed oil (PO), a rich source of α-linolenic acid (LNA, C18:3, ω-3), helps in maintaining good mental health in adults. This study aimed to investigate the impacts of dietary PO intake on cognitive functions and mental health in healthy, elderly Japanese individuals. Seventy-five healthy volunteers aged 64-84 years were randomly divided into two groups: a control group and a PO-administered group. At baseline and at 12 months of intervention, cognitive function, mental health condition, fatty acid profile of the red blood cell plasma membranes (RBC-PM), and serum biochemical parameters were evaluated. Results showed that serum biological antioxidant potential and LNA levels in the RBC-PM at 12 months after the trial were significantly higher in the PO group compared to the control group. Further, both the cognitive function measures, as evaluated by the Frontal Assessment Battery test and the apathy scores, tended to be improved after 12 months in the PO group. Our results demonstrate that dietary PO intake enhances the antioxidant potential and prevents the age-related cognitive and mental decline in healthy elderly individuals by enhancing the blood LNA levels.