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 , BiomarcadoresRESUMO
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 SinaisRESUMO
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 , TocoferóisRESUMO
Arachidonic acid (ARA), an omega-6 (ω-6) polyunsaturated fatty acid (PUFA), is involved in the development and maintenance of renal functions, whereas docosahexaenoic acid (DHA) is an omega-3 (ω-3) PUFA that has anti-inflammatory effects and attenuates nephropathy. However, their effects on the progression of chronic kidney disease (CKD) remain unknown. The aim of this study was to assess the effects of feeding ARA, DHA, and ARA and DHA-containing diets on rats with 5/6 nephrectomized kidneys. Urine and feces were collected every 4 weeks, and the kidneys were collected at 16 weeks after surgery. Urinary albumin (U-ALB) excretion increased gradually with nephrectomy, but the U-ALB excretion was attenuated by feeding the rats with an ARA + DHA-containing diet. Reactive oxygen species (ROS) levels in the kidneys were lower in the ARA + DHA group than in the other groups. At 4 weeks after surgery, the lipid peroxide (LPO) levels in the plasma of the ARA + DHA groups decreased significantly after surgery compared to the control CKD group, but this did not happen at 16 weeks post-surgery. There was a significant negative correlation between LPO levels in the plasma at 4 weeks and creatinine clearance, and a positive correlation with urinary albumin levels. These results suggest that the combination of ARA and DHA inhibit the progress of early stage CKD.
Assuntos
Gorduras na Dieta/farmacologia , Ácidos Graxos Insaturados/farmacologia , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/dietoterapia , Animais , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Ácidos Graxos Insaturados/administração & dosagem , Testes de Função Renal , Masculino , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/sangueRESUMO
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/químicaRESUMO
BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and the number of AD patients continues to increase worldwide. Components of the germ layer and bran of Brown rice (BR) help maintain good health and prevent AD. Because the germ layer and bran absorb little water and are very hard and difficult to cook, they are often removed during processing. To solve these problems, in this study, we tried to use a high-pressure (HP) technique. METHODS: We produced the highly water pressurized brown rice (HPBR) by pressurizing BR at 600 MPa, and then we fed it to an AD mouse model, senescence-accelerated mouse prone 8, to investigate the therapeutic effects of HPBR on cognitive dysfunction by Y-maze spatial memory test. RESULTS: HP treatment increased the water absorbency of BR without nutrient loss. HPBR ameliorated cognitive dysfunction and reduced the levels of amyloid-ß, which is a major protein responsible for AD, in the brain. CONCLUSIONS: These results suggest that HPBR is effective for preventing AD.
Assuntos
Peptídeos beta-Amiloides/análise , Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Culinária/métodos , Fibras na Dieta/farmacologia , Oryza , Doença de Alzheimer , Animais , Peso Corporal/efeitos dos fármacos , Dieta , Locomoção/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Pressão , ÁguaRESUMO
Abstract: Memory extinction is referred to as a learning process in which a conditioned response (CR) progressively reduces over time as an animal learns to uncouple a response from a stimulus. Extinction occurs when the rat is placed into a context without shock after training. Docosahexaenoic acid (DHA, C22:6, n-3) is implicated in memory formation in mammalian brains. In a two-way active shuttle-avoidance apparatus, we examined whether DHA affects the extinction memory and the expression of brain cognition-related proteins, including gastrin-releasing peptide receptor (GRPR), brain-derived neurotrophic factor receptor (BDNFR) tyrosine kinase receptor B (TrKB), and N-methyl-d-aspartate receptor (NMDAR) subunits NR2A and NR2B. Also, the protein levels of GRP, BDNF, postsynaptic density protein-95 (PSD-95), and vesicular acetylcholine transporter (VAChT), and the antioxidative potentials, in terms of lipid peroxide (LPO) and reactive oxygen species (ROS), were examined in the hippocampus. During the acquisition phase, the rats received a conditioned stimulus (CS-tone) paired with an unconditioned stimulus (UCS foot shock) for three consecutive days (Sessions S1, S2, and S3, each consisting of 30-trials) after 12 weeks of oral administration of DHA. After a three-day interval, the rats were re-subjected to two extinction sessions (S4, S5), each comprising 30 trials of CS alone. During the acquisition training in S1, the shock-related avoidance frequency (acquisition memory) was significantly higher in the DHA-administered rats compared with the control rats. The avoidance frequency, however, decreased with successive acquisition trainings in sessions S2 and S3. When the rats were subjected to the extinction sessions after a break for consolidation, the conditioned response (CR) was also significantly higher in the DHA-administered rats. Interestingly, the freezing responses (frequency and time) also significantly decreased in the DHA-administered rats, thus suggesting that a higher coping capacity was present during fear stress in the DHA-administered rats. DHA treatments increased the mRNA levels of GRPR, BDNF receptor TrKB, and NMDAR subunit NR2B. DHA also increased the protein levels of GRP, BDNF, PSD-95, and VAChT, and the antioxidative potentials in the hippocampus. These results suggest the usefulness of DHA for treating stress disorders.
Assuntos
Ácidos Docosa-Hexaenoicos/administração & dosagem , Medo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Medo/fisiologia , Hipocampo/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Memória/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Receptor trkB/metabolismo , Receptores da Bombesina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Proteínas Vesiculares de Transporte de Acetilcolina/metabolismoRESUMO
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 , HumanosRESUMO
Once amyloid ß peptides (Aßs) of the Alzheimer's disease build up in blood circulation, they are capable of binding to red blood cell (RBC) and inducing hemolysis of RBC. The mechanisms of the interactions between RBC and Aß are largely unknown; however, it is very important for the therapeutic target of Aß-induced hemolysis. In the present study, we investigated whether Aß1-42 interacts with caveolin-1-containing detergent-resistant membranes (DRMs) of RBC and whether the interaction could be modulated by dietary pre-administration of docosahexaenoic acid (DHA). DHA pre-administration to rats inhibited hemolysis by Aß1-42. This activity was accompanied by increased DHA levels and membrane fluidity and decreased cholesterol level, lipid peroxidation, and reactive oxygen species in the RBCs of the DHA-pretreated rats, suggesting that the antioxidative property of DHA may rescue RBCs from oxidative damage by Aß1-42. The level of caveolin-1 was augmented in the DRMs of DHA-pretreated rats. Binding between Aß1-42 and DRMs of RBC significantly increased in DHA-rats. When fluorescently labeled Aß1-42 (TAMRA-Aß1-42) was directly infused into the bloodstream, it again occupied the caveolin-1-containing DRMs of the RBCs from the DHA-rats to a greater extent, indicating that circulating Aßs interact with the caveolin-1-rich lipid rafts of DRMs and the interaction is stronger in the DHA-enriched RBCs. The levels of TAMRA-Aß1-42 also increased in liver DRMs, whereas it decreased in plasma of DHA-pretreated rats. DHA might help clearance of circulating Aßs by increased lipid raft-dependent degradation pathways and implicate to therapies in Alzheimer's disease.
Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Dieta , Ácidos Docosa-Hexaenoicos/farmacologia , Eritrócitos/metabolismo , Microdomínios da Membrana/metabolismo , Fragmentos de Peptídeos/metabolismo , Administração Oral , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Animais , Caveolina 1/metabolismo , Forma Celular/efeitos dos fármacos , Colesterol/metabolismo , Detergentes/farmacologia , Ácidos Docosa-Hexaenoicos/administração & dosagem , Eritrócitos/efeitos dos fármacos , Eritrócitos/ultraestrutura , Hemólise/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Microdomínios da Membrana/efeitos dos fármacos , Ratos Wistar , Rodaminas/metabolismo , Soluções , Espectrometria de FluorescênciaRESUMO
We investigated whether a highly purified eicosapentaenoic acid (EPA) and a concentrated n-3 fatty acid formulation (prescription TAK-085) containing EPA and docosahexaenoic acid (DHA) ethyl ester could improve the learning ability of aged rats and whether this specific outcome had any relation with the brain levels of EPA-derived eicosanoids and DHA-derived docosanoids. The rats were tested for reference memory errors (RMEs) and working memory errors (WMEs) in an eight-arm radial maze. Fatty acid compositions were analyzed by GC, whereas brain eicosanoid/docosanoids were measured by LC-ESI-MS-MS-based analysis. The levels of lipid peroxides (LPOs) were measured by thiobarbituric acid reactive substances. The administration of TAK-085 at 300 mg·kg⻹day⻹ for 17 weeks reduced the number of RMEs in aged rats compared with that in the control rats. Both TAK-085 and EPA administration increased plasma EPA and DHA levels in aged rats, with concurrent increases in DHA and decreases in arachidonic acid in the corticohippocampal brain tissues. TAK-085 administration significantly increased the formation of EPA-derived 5-HETE and DHA-derived 7-, 10-, and 17-HDoHE, PD1, RvD1, and RvD2. ARA-derived PGE2, PGD2, and PGF2α significantly decreased in TAK-085-treated rats. DHA-derived mediators demonstrated a significantly negative correlation with the number of RMEs, whereas EPA-derived mediators did not exhibit any relationship. Furthermore, compared with the control rats, the levels of LPO in the plasma, cerebral cortex, and hippocampus were significantly reduced in TAK-085-treated rats. The findings of the present study suggest that long-term EPA+DHA administration may be a possible preventative strategy against age-related cognitive decline.
Assuntos
Envelhecimento/psicologia , Comportamento Animal/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/análogos & derivados , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Nootrópicos/farmacologia , Fatores Etários , Envelhecimento/metabolismo , Animais , Ácido Araquidônico/metabolismo , Córtex Cerebral/metabolismo , Cognição/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/sangue , Combinação de Medicamentos , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/farmacologia , Hipocampo/metabolismo , Peroxidação de Lipídeos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Nootrópicos/metabolismo , Ratos Wistar , Fatores de TempoRESUMO
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 WistarRESUMO
In view of the recent diboson resonant excesses reported by both ATLAS and CMS Collaborations, we suggest that a new weak singlet pseudoscalar particle η(WZ) may decay into two weak bosons while being produced in gluon fusion at the LHC. The couplings to the gauge bosons can arise from a Wess-Zumino-Witten anomaly term and thus we study an effective model based on the anomaly term as a well motivated phenomenological model. In models where the pseudoscalar particle arises as a composite state, the coefficients of the anomalous couplings can be related to the fermion components of the underlying dynamics. We provide an example to test the feasibility of the idea.
RESUMO
BACKGROUND: Identifying agents that inhibit amyloid beta peptide (Aß) aggregation is the ultimate goal for slowing Alzheimer's disease (AD) progression. This study investigated whether the glycoside asiaticoside inhibits Aß1-42 fibrillation in vitro. METHODS: Fluorescence correlation spectroscopy (FCS), evaluating the Brownian diffusion times of moving particles in a small confocal volume at the single-molecule level, was used. If asiaticoside inhibits early Aß1-42 fibrillation steps, more Aßs would remain free and rapidly diffuse in the confocal volume. In contrast, "weaker or no inhibition" permits a greater number of Aßs to polymerize into oligomers, leading to fibers and gives rise to slow diffusion times in the solution. Trace amounts of 5-carboxytetramethylrhodamine (TAMRA)-labeled Aß1-42 in the presence of excess unlabeled Aß1-42 (10 µM) was used as a fluorescent probe. Steady-state and kinetic-Thioflavin T (ThT) fluorospectroscopy, laser-scanning fluorescence microscopy (LSM), and transmission electron microscopy (TEM) were also used to monitor fibrillation. Binding of asiaticoside with Aß1-42 at the atomic level was computationally examined using the Molegro Virtual Docker and PatchDock. RESULTS: With 1 h of incubation time for aggregation, FCS data analysis revealed that the diffusion time of TAMRA-Aß1-42 was 208 ± 4 µs, which decreased to 164 ± 8.0 µs in the presence of asiaticoside, clearly indicating that asiaticoside inhibited the early stages Aß1-42 of fibrillation, leaving more free Aßs in the solution and permitting their rapid diffusion in the confocal volume. The inhibitory effects were also evidenced by reduced fiber formation as assessed by steady-state and kinetic ThT fluorospectroscopy, LSM, and TEM. Asiaticoside elongated the lag phase of Aß1-42 fibrillation, indicating the formation of smaller amyloid species were impaired in the presence of asiaticoside. Molecular docking revealed that asiaticoside binds with amyloid intra- and inter-molecular amino acid residues, which are responsible for ß-sheet formation and longitudinal extension of fibrils. CONCLUSION: Finally, asiaticoside prevents amyloidogenesis that precedes neurodegeneration in patients with Alzheimer's disease.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Centella/química , Fragmentos de Peptídeos/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Doença de Alzheimer/prevenção & controle , Fluorescência , Humanos , Microscopia/métodos , Simulação de Acoplamento Molecular/métodos , Extratos Vegetais/uso terapêutico , Rodaminas/metabolismo , Análise Espectral/métodos , Triterpenos/uso terapêuticoRESUMO
The purpose of patient safety management is to nurture an environment which provides optimal care for each patient through the cooperation of each healthcare staff member based on the idea of team care. This is based on the safety culture of an organization that places value on sharing information. Laboratory medicine is expected to become more important in the areas of staff, patient, and community education.
Assuntos
Educação em Saúde , Disseminação de Informação , Laboratórios , Segurança do Paciente , Gestão da Segurança , Humanos , JapãoRESUMO
Increasing evidence from the fields of neurophysiology and neuropathology has uncovered the role of polyunsaturated fatty acids (PUFA) in protecting neuronal cells from oxidative damage, controlling inflammation, regulating neurogenesis, and preserving neuronal function. Numerous epidemiological studies have shown that deficits in the dietary PUFA docosahexaenoic acid and eicosapentaenoic acid are associated with the onset and progression of neuropsychiatric illnesses such as dementia, schizophrenia, depression, and posttraumatic stress disorder (PTSD). Recent clinical trials have offered compelling evidence that suggests that n-3 PUFA could reduce depressive, psychotic, and suicidal symptoms, as well as aggression. Although many studies have had the validity of their results questioned because of small sample size, several studies have indicated that n-3 PUFA are useful therapeutic tools for the treatment of dementia, major depression, bipolar disorder, and PTSD. These findings suggest that the pharmacological and nutritional actions of n-3 PUFA may be beneficial in certain neuropsychiatric illnesses. This review article outlines the role of PUFA in neurodevelopment and the regulatory mechanisms in neuronal stem cell differentiation and also the possible use of PUFA as a prescription medicine for the prophylaxis or treatment of neuropsychiatric illnesses such as dementia, mood disorder, and PTSD.
Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/prevenção & controle , Diferenciação Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Demência/tratamento farmacológico , Demência/prevenção & controle , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/fisiologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/fisiologia , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/fisiologia , Humanos , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/prevenção & controle , Células-Tronco Neurais/citologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/prevenção & controleRESUMO
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.
Assuntos
Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Síndrome Metabólica/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/análogos & derivados , Eicosanoides/metabolismo , Ácidos Graxos Ômega-3/química , Rim/patologia , Testes de Função Renal , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Endogâmicos SHRRESUMO
Docosahexaenoic acid, the most abundant omega3 fatty acid in the brain, plays a role in cognitive development, learning ability, neuronal membrane plasticity, synaptogenesis, and neurogenesis, all of which are involved in synaptic transmission and the well-being of normal brain functions, and search on the functionality is still in progress. Establishment of prevention and treatment of neuropsychiatric illnesses, such as dementia is not easy, but from numerous basic and epidemiological studies, increase of omega3 fatty acid dietary intake is reported likely to prevent the onset of dementia. This paper is outlined the relevance of cognitive function and omega3 fatty acids, especially docosahexaenoic acid, and the possibility of preventive effect of the fatty acid on dementia.
Assuntos
Cognição/fisiologia , Demência/prevenção & controle , Ácidos Graxos Ômega-3/fisiologia , Ácidos Graxos Ômega-3/uso terapêutico , HumanosRESUMO
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/metabolismoRESUMO
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.
Assuntos
Córtex Cerebral/metabolismo , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/análogos & derivados , Ácidos Graxos Ômega-3/farmacologia , Hipocampo/metabolismo , Síndrome Metabólica/tratamento farmacológico , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/sangue , Combinação de Medicamentos , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos/sangue , Ácidos Graxos Ômega-3/uso terapêutico , Hipocampo/efeitos dos fármacos , Peróxidos Lipídicos/sangue , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHRRESUMO
Cardanol (ginkgol) extracted from Ginkgo biloba leaves and cashew nutshell liquid enhances the growth of NSC-34 immortalized motor neuron-like cells and, when chronically administered to young rats, improves working memory-related learning ability as assessed by eight-arm radial maze tasks. These findings suggest that cardanol is one of the components in Ginkgo biloba leaves that improves cognitive learning ability.