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1.
Phytother Res ; 37(6): 2230-2241, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36637040

RESUMO

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.


Assuntos
Densidade Óssea , Reabsorção Óssea , Humanos , Pessoa de Meia-Idade , Fosfatase Ácida Resistente a Tartarato , População do Leste Asiático , Óleos de Plantas/farmacologia , Óleos de Plantas/uso terapêutico , Reabsorção Óssea/tratamento farmacológico , Biomarcadores
2.
Neurochem Res ; 47(4): 933-951, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34855048

RESUMO

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.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Neurogênese , Animais , Benzoquinonas , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Ratos , Transdução de Sinais
3.
Crit Rev Food Sci Nutr ; 62(6): 1502-1520, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33190522

RESUMO

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.


Assuntos
Oryza , Tocotrienóis , Idoso , Animais , Culinária , Fibras na Dieta/análise , Humanos , Tocoferóis
4.
Int J Mol Sci ; 21(3)2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32012687

RESUMO

Salivary immunoglobulin A (IgA) plays a critical role in mucosal immunity. Chronic exposure to moderate heat induces heat acclimation, which modifies salivary functions. However, the changes in salivary IgA secretion in heat-acclimated rats are unclear. In this study, we investigated salivary IgA secretion and the expression of polymeric Ig receptor (pIgR), a key mediator of mucosal IgA secretion, in the submandibular glands (SMGs) of heat-acclimated rats. Following maintenance at an ambient temperature (Ta) of 24 ± 0.1 °C for 10 days, male Wistar rats were subjected to Ta of 32 ± 0.2 °C for 5 days (HE group) for heat acclimation or maintained at Ta of 24 ± 0.1°C (CN group). The rats were then anesthetized, pilocarpine (0.5 mg/kg) was intraperitoneally injected, and saliva was collected. Afterward, the SMGs and plasma were sampled. The salivary IgA concentration and IgA flow rate were significantly higher in the HE group than in the CN group. Similarly, SMG pIgR expression was significantly higher in HE rats. The levels of plasma cytokines, including interleukin (IL)-5, IL-6, and interferon-γ, were significantly greater in HE rats than in CN rats. Heat acclimation may enhance oral immunity through salivary IgA secretion and pIgR upregulation in the SMGs.


Assuntos
Aclimatação/fisiologia , Temperatura Alta , Imunoglobulina A Secretora/metabolismo , Receptores de Imunoglobulina Polimérica/biossíntese , Saliva/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Glândula Submandibular/metabolismo , Animais , Masculino , Ratos , Ratos Wistar
5.
Molecules ; 25(9)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32365849

RESUMO

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.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Lipoproteínas LDL/sangue , Perilla frutescens/química , Folhas de Planta/química , Pós , Ácido alfa-Linolênico/farmacologia , Adulto , Biomarcadores , Composição Corporal , Suplementos Nutricionais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Ácidos Graxos/sangue , Feminino , Humanos , Japão , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Pós/administração & dosagem , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/química
6.
J Biochem Mol Toxicol ; 33(5): e22288, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30672650

RESUMO

The transient receptor potential (TRP) channels are thermo-sensors, and transient receptor potential vanilloid (TRPV)1 and V4 are widely expressed in primary afferent neurons and nonneuronal cells. Although heat acclimation is considered as changes of thermoregulatory responses by thermo-effectors to heat, functional changes of TRP channels in heat acclimation has not been fully elucidated. Here, we investigated whether heat acclimation induces capsaicin tolerance. NIH3T3 cells were incubated at 39.5°C. We determined the expression level of TRPV1 and TRPV4 messenger RNA (mRNA), performed cellular staining of TRPV1 and TRPV4, and investigated actin assembly and activation of the extracellular signal-regulated kinase (ERK). Exposure to moderate heat decreased the levels of TRPV1 but not TRPV4 mRNA. It also induced stress fiber formation and the intensity of TRPV1 seemed to be decreased by chronic heat stimuli. In addition, heat acclimation attenuated the capsaicin-induced activation of ERK. Heat acclimation may induce capsaicin tolerance via the downregulation of TRPV1.


Assuntos
Capsaicina/farmacologia , Temperatura Alta , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Regulação para Baixo/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Camundongos , Células NIH 3T3 , Canais de Cátion TRPV/biossíntese
7.
Crit Rev Biotechnol ; 37(5): 579-597, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27426008

RESUMO

Docosahexaenoic acid (DHA, C22:6, ω-3) is a highly polyunsaturated omega-3 fatty acid. It is concentrated in neuronal brain membranes, for which reason it is also referred to as a "brain food". DHA is essential for brain development and function. It plays an important role in improving antioxidant and cognitive activities of the brain. DHA deficiency occurs during aging and dementia, impairs memory and learning, and promotes age-related neurodegenerative diseases, including Alzheimer's disease (AD). For about two decades, we have reported that oral administration of DHA increases spatial memory acquisition, stimulates neurogenesis, and protects against and reverses memory impairment in amyloid ß peptide-infused AD rat models by decreasing amyloidogenesis and protects against age-related cognitive decline in the elderly. These results demonstrate a robust link between DHA and cognitive health. Rodents that were fed a diet low in ω-3 polyunsaturated fatty acids, particularly those that were DHA-deficient, frequently suffered from anxiety, depression and memory impairment. Although the exact mechanisms of action of DHA in brain functions are still elusive, a host of mechanisms have been proposed. For example, DHA, which inherently has a characteristic three-dimensional structure, increases membrane fluidity, strengthens antioxidant activity and enhances the expression of several proteins that act as substrates for improving memory functions. It reduces the brain amyloid burden and inhibits in vitro fibrillation and amyloid-induced neurotoxicity in cell-culture model. In this review, we discuss how DHA acts as a molecule with diverse functions.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Envelhecimento , Doença de Alzheimer , Peptídeos beta-Amiloides , Animais , Encéfalo , Humanos
8.
Mol Cell Biochem ; 415(1-2): 169-81, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27021216

RESUMO

Myosin heavy chain (MHC) mediates the metabolic and contractile responses of skeletal muscles. MHC displays different isoforms, each of which has different characteristics. To better understand the effect of polyunsaturated fatty acids in skeletal muscles, rats were fed with control-, docosahexaenoic acid (DHA)-, and arachidonic acid (ARA)-oil, and the effects on plasma and muscular fatty acid profile, oxidative stress, mRNA levels of myosin heavy chain isoforms MHC1 of slow-twitch muscle (SO) and MHC2A, MHC2X, and MHCB isoforms of extensor digitorum longus (EDL) of fast-twitch muscle were evaluated. Concomitantly, mRNA levels of anti-oxidative enzymes, such as, catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD were determined. The expressions of MHC1, MHC2A, MHC2X, and MHC2B were lower in the SO of the DHA-fed rats. In the EDL muscles of DHA-fed rats, the expressions of MHC1 and MHC2A increased; however, the expressions of MHC2X increased and that of the MHC2 were not altered. Oxidative stress, as indicated by the levels of LPO, was significantly higher in the plasma of the ARA-fed rats, when compared with that of the DHA-fed rats. The LPO levels were higher both in the SO and EDL muscles of ARA-fed rats. Compared with ARA oil intake, DHA oil showed higher mRNA levels of GPx and SOD. Catalase expression was higher only in the EDL but not in the SO-type muscles. Our studies finally indicate that DHA and ARA differentially affect the regulation of contractile and metabolic properties of slow- and fast-twitch skeletal muscles.


Assuntos
Ácidos Araquidônicos/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos/metabolismo , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Animais , Ácidos Araquidônicos/administração & dosagem , Peso Corporal , Ácidos Docosa-Hexaenoicos/administração & dosagem , Cadeias Pesadas de Miosina/genética , Estresse Oxidativo , Ratos , Ratos Wistar
9.
Int J Biometeorol ; 59(10): 1461-74, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25875447

RESUMO

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.


Assuntos
Temperatura Corporal/efeitos dos fármacos , Ácidos Graxos/sangue , Preparações de Plantas/farmacologia , Zingiber officinale , Administração Oral , Adulto , Cápsulas , Dióxido de Carbono/metabolismo , Humanos , Masculino , Consumo de Oxigênio , Preparações de Plantas/sangue , Preparações de Plantas/farmacocinética , Raízes de Plantas , Pós , Fluxo Sanguíneo Regional/efeitos dos fármacos , Pele/irrigação sanguínea , Sensação Térmica , Adulto Jovem
10.
Food Funct ; 15(10): 5579-5595, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38713055

RESUMO

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.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Dopamina , Memória de Curto Prazo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Teobromina , Animais , Masculino , Ratos , Teobromina/farmacologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Memória de Curto Prazo/efeitos dos fármacos , Dopamina/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Lobo Frontal/metabolismo , Lobo Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Modelos Animais de Doenças , Proteína 25 Associada a Sinaptossoma/metabolismo
11.
J Neural Transm (Vienna) ; 120(10): 1397-409, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23588349

RESUMO

cAMP/PKA/ERK/CREB signaling linked to CRE-mediated transcription is crucial for learning and memory. We originally found nobiletin as a natural compound that stimulates this intracellular signaling and exhibits anti-dementia action in animals. Citrus reticulata or C. unshiu peels are employed as "chinpi" and include a small amount of nobiletin. We here provide the first evidence for beneficial pharmacological actions on the cAMP/PKA/ERK/CREB cascade of extracts from nobiletin-rich C.reticulata peels designated as Nchinpi, the nobiletin content of which was 0.83 ± 0.13% of the dry weight or 16-fold higher than that of standard chinpi extracts. Nchinpi extracts potently facilitated CRE-mediated transcription in cultured hippocampal neurons, whereas the standard chinpi extracts showed no such activity. Also, the Nchinpi extract, but not the standard chinpi extract, stimulated PKA/ERK/CREB signaling. Interestingly, treatment with the Nchinpi extract at the concentration corresponding to approximately 5 µM nobiletin more potently facilitated CRE-mediated transcriptional activity than did 30 µM nobiletin alone. Consistently, sinensetin, tangeretin, 6-demethoxynobiletin, and 6-demethoxytangeretin were also identified as bioactive substances in Nchinpi that facilitated the CRE-mediated transcription. Purified sinensetin enhanced the transcription to a greater degree than nobiletin. Furthermore, samples reconstituted with the four purified compounds and nobiletin in the ratio of each constituent's content in the extract showed activity almost equal to that of the Nchinpi extract to stimulate CRE-mediated transcription. These findings suggest that above four compounds and nobiletin in the Nchinpi extract mainly cooperated to facilitate potently CRE-mediated transcription linked to the upstream cAMP/PKA/ERK/CREB pathway in hippocampal neurons.


Assuntos
Citrus/química , Medicamentos de Ervas Chinesas/farmacologia , Flavonas/farmacologia , Hipocampo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Células Cultivadas , Cromatografia Líquida de Alta Pressão , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Frutas/química , Hipocampo/fisiologia , Aprendizagem/fisiologia , Medicina Kampo , Memória/fisiologia , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Transfecção
12.
Cell Physiol Biochem ; 30(2): 450-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22814242

RESUMO

The heat shock response has been extensively studied by a number of investigators to understand the molecular mechanism underlying the cellular response to severe heat stress (higher than 42°C). But, body or tissue temperature increases by only a few degrees Celsius during physiological events. Therefore, the physiological cellular response to mild heat stress rather than severe heat stress is likely to be more important. Repeated exposure to hyperthermia for consecutive 5 days induces heat acclimation which is an adaptive physiological process in humans and animals. However, thus far, the effect of continuous exposure to heat stress on cells has not been fully evaluated. In this study, we investigated an adaptive physiological process that is induced in culture cells by continuous exposure to mild heat stress for 5 days. Exposure to heat activated p38-mitogen-activated protein kinase; inhibited cell growth without apoptosis; and increased the levels of HSPs and HSF-1 in mouse fibroblast cells. Interestingly, exposure to heat regulated the expression of aquaporins and induced morphological change. In a physiological sense, these results suggested that continuous exposure to mild heat stress for 5 days, in which heat acclimation is attained in humans and animals, might induce molecular adaptation to heat in cells.


Assuntos
Aquaporinas/metabolismo , Fibroblastos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Animais , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Fatores de Transcrição de Choque Térmico , Temperatura Alta , Humanos , Camundongos , Células NIH 3T3 , Estresse Fisiológico , Fatores de Transcrição/metabolismo , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Nutrients ; 14(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35565814

RESUMO

As life expectancy increases, age-associated diseases such as Alzheimer's disease (AD) become a major health problem. The onset of AD involves neurological dysfunction due to amyloid-ß accumulation, tau hyperphosphorylation, oxidative stress, and neuroinflammation in the brain. In addition, lifestyle-related diseases-such as dyslipidemia, diabetes, obesity, and vascular dysfunction-increase the risk of developing dementia. The world population ages, prompting the development of new strategies to maintain brain health and prevent the onset of dementia in older and preclinical patients. Citrus fruits are abundant polymethoxylated flavone and flavanone sources. Preclinical studies reported that these compounds have neuroprotective effects in models of dementia such as AD. Interestingly, clinical and epidemiological studies appear to support preclinical evidence and show improved cognitive function and reduced associated disease risk in healthy individuals and/or patients. This review summarizes the recent evidence of the beneficial effects of citrus peels and extracts on human cognition and related functions.


Assuntos
Doença de Alzheimer , Citrus , Idoso , Doença de Alzheimer/metabolismo , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Citrus/metabolismo , Humanos , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
14.
Food Funct ; 13(13): 7226-7239, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35722977

RESUMO

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.


Assuntos
Disfunção Cognitiva , Perilla frutescens , Idoso , Animais , Encéfalo/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Suplementos Nutricionais , Glucose/metabolismo , Humanos , Japão , Camundongos , Perilla frutescens/metabolismo , Folhas de Planta/metabolismo , Óleos de Plantas/metabolismo , Pós/metabolismo , Triglicerídeos/metabolismo
15.
Food Funct ; 13(5): 2768-2781, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35171190

RESUMO

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.


Assuntos
Antioxidantes/farmacologia , Cognição/efeitos dos fármacos , Disfunção Cognitiva/prevenção & controle , Suplementos Nutricionais , Flavonas/farmacologia , Perilla frutescens , Ácido alfa-Linolênico/farmacologia , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/administração & dosagem , Antioxidantes/química , Método Duplo-Cego , Ácidos Graxos Ômega-3/metabolismo , Feminino , Flavonas/administração & dosagem , Flavonas/química , Humanos , Masculino , Óleos de Plantas/administração & dosagem , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Resultado do Tratamento , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/química
16.
Nutrients ; 13(1)2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33406641

RESUMO

The number of patients with central nervous system disorders is increasing. Despite diligent laboratory and clinical research over the past 30 years, most pharmacologic options for the prevention and long-term treatment of central nervous system disorders and neurodegenerative disorders have been unsuccessful. Therefore, the development of drugs and/or functional foods to prevent the onset of neurodegenerative disorders is highly expected. Several reports have shown that polymethoxylated flavones (PMFs) derived from citrus fruit, such as nobiletin, tangeretin, and 3,3',4',5,6,7,8-heptamethoxyflavone, are promising molecules for the prevention of neurodegenerative and neurological disorders. In various animal models, PMFs have been shown to have a neuroprotective effect and improve cognitive dysfunction with regard to neurological disorders by exerting favorable effects against their pathological features, including oxidative stress, neuroinflammation, neurodegeneration, and synaptic dysfunction as well as its related mechanisms. In this review, we describe the profitable and ameliorating effects of citrus-derived PMFs on cognitive impairment and neural dysfunction in various rat and murine models or in several models of central nervous system disorders and identify their mechanisms of action.


Assuntos
Doenças do Sistema Nervoso Central/tratamento farmacológico , Citrus/química , Flavonas/farmacologia , Animais , Humanos , Inflamação , Lipopolissacarídeos/efeitos adversos , Modelos Animais , Esclerose Múltipla
17.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537806

RESUMO

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.


Assuntos
Fibroblastos/metabolismo , Resposta ao Choque Térmico/efeitos dos fármacos , Temperatura Alta , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Zingiber officinale/química , Animais , Movimento Celular , Camundongos , Células NIH 3T3 , Extratos Vegetais/química
18.
Foods ; 10(5)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069601

RESUMO

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.

19.
Food Funct ; 12(9): 3992-4004, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977955

RESUMO

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.


Assuntos
Envelhecimento , Aprendizagem/efeitos dos fármacos , Magnoliopsida , Memória/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Camundongos , Plasticidade Neuronal
20.
J Oleo Sci ; 70(12): 1829-1838, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34759112

RESUMO

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.


Assuntos
Fosfatase Alcalina/sangue , Reabsorção Óssea/diagnóstico , Reabsorção Óssea/prevenção & controle , Envelhecimento Cognitivo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Demência/prevenção & controle , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ingestão de Alimentos/fisiologia , Leite , Fosfatase Ácida Resistente a Tartarato/sangue , Idoso , Animais , Povo Asiático , Biomarcadores/sangue , Demência/etiologia , Ácidos Docosa-Hexaenoicos/sangue , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Membrana Eritrocítica/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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