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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.
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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
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/metabolismoRESUMO
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/químicaRESUMO
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-IdadeRESUMO
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 NeuronalRESUMO
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
Hypercholesterolemia has been implicated as one of the pathomechanistic factors of Alzheimer's disease (AD), the most common neurodegenerative disorder affecting memory and learning abilities. In the present study, ameliorative effect of hot water extract (HWE) of mushroom Ganoderma lucidum to the memory and learning related behavioral performance of hypercholesterolemic and AD rats was investigated using Morris water maze (MWM). Male Wistar rats were randomly grouped into control, extract fed control, hypercholesterolemic, extract fed hypercholesterolemic, AD, and extract fed AD groups, each group containing 8 animals. Hypercholesterolemia was induced in rats by adding 1% cholesterol and 1% cholic acid with the basal diet of the respective group. Alzheimer's disease model rats were prepared through infusion of amyloid ß(1-42) to the right ventricle. Memory and learning related performance of all the rats was tested for 6 consecutive days that included time taken to reach the submerged platform (sec) and distance traveled (m). G. lucidum HWE fed rats took less time and traveled less distance to find the submerged platform, which indicates the spatial learning and memory related behavioral amelioration of the extract fed rats compared with their non-fed counterparts. Thus, usage of G. lucidum seems promising in withstanding hypercholesterolemia-induced Alzheimer's disease pathogenesis.
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Doença de Alzheimer/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Hipercolesterolemia/complicações , Transtornos da Memória/prevenção & controle , Reishi/química , Aprendizagem Espacial , Doença de Alzheimer/fisiopatologia , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Hipercolesterolemia/induzido quimicamente , Masculino , Teste do Labirinto Aquático de Morris , Ratos , Ratos WistarRESUMO
Alzheimer's disease (AD) is the leading neurodegenerative disorder affecting memory and learning of aged people. Hypercholesterolemia had been implicated as one of the stark hallmarks of AD. Recent AD control guidelines have suggested lifestyle modification to slow down the progression of AD. In this regard, medicinal mushroom Ganoderma lucidum seems apt. In the present study, hot water extract of G. lucidum (200 mg/kg body weight) was fed to the hypercholesterolemic and AD model rats for 8 weeks. Nonspatial memory and learning abilities of the model animals was assessed using novel object recognition (NOR) test, rotarod test, and locomotor/open-field test. Then, the animals were sacrificed and transmission electron micrograph (TEM) view of the hippocampal neurons was assessed. In all the nonspatial memory and learning tests, the G. lucidum HWE fed rats performed better indicating improved memory and learning abilities. TEM view showed regular arrangement of the neurons in the G. lucidum HWE fed rats compared with those of the deranged arrangement of the AD rats. G. lucidum might have aided in restoring the memory and learning abilities of the AD model animals through maintaining neuronal structure and function. Thus, G. lucidum could be suggested as a medicotherapeutic agent against AD.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Medicamentos de Ervas Chinesas/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/psicologia , Doença de Alzheimer/fisiopatologia , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Humanos , Hipercolesterolemia/fisiopatologia , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos , Ratos Wistar , ReishiRESUMO
BACKGROUND: The herb, Commelina paludosa (CP) Blume (Family-Commelinaceae) is medicinally used by the traditional practitioners in Bangladesh. However, there is a lack of scientific evidence on this medicinal herb. AIM AND OBJECTIVES: This study aimed to evaluate the phytochemical and pharmacological activities of CP (ethanol [ECP], chloroform [CCP] and n-hexane [NHCP] of whole-plant extracts). MATERIALS AND METHODS: For this antioxidant, antimicrobial, antidiarrheal and antipyretic activities of crude extracts of CP were conducted by 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging, disc diffusion and serial dilution, castor oil-induced diarrhea and yeast powder-induced pyrexia methods respectively. RESULTS AND OBSERVATION: The results suggest that all the fractions significantly scavenged DPPH radicals. In the disc diffusion test, the zones of inhibition were observed within the range of 7 mm to 30.67 mm at 500 mg/disc. The highest zones of inhibition were observed by ECP, CCP and NHCP against Bacillus azotoformans, Lactobacillus coryifomis and Salmonella typhi respectively. NHCP was found to exert stronger antibacterial effect than the ECP and CCP. CONCLUSION: Minimum inhibitory concentrations were detected within the range of 31.25 and 250 µg/ml. Moreover, the crude fractions also showed significant (P < 0.05) antidiarrheal and antipyretic activities in Swiss mice. CP may be a good source of therapeutic components.
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The effects of cholesterol-lowering statins, which substantially benefit future cardiovascular events, on fatty acid metabolism have remained largely obscured. In this study, we investigated the effects of atorvastatin on fatty acid metabolism together with the effects of TAK-085 containing highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl ester on atorvastatin-induced n-3 polyunsaturated fatty acid lowering in SHR.Cg-Leprcp/NDmcr (SHRcp) rats, as a metabolic syndrome model. Supplementation with 10mg/kg body weight/day of atorvastatin for 17 weeks significantly decreased plasma total cholesterol and very low density lipoprotein cholesterol. Atorvastatin alone caused a subtle change in fatty acid composition particularly of EPA and DHA in the plasma, liver or erythrocyte membranes. However, the TAK-085 consistently increased both the levels of EPA and DHA in the plasma, liver and erythrocyte membranes. After confirming the reduction of plasma total cholesterol, 300mg/kg body weight/day of TAK-085 was continuously administered for another 6 weeks. Supplementation with TAK-085 did not decrease plasma total cholesterol but significantly increased the EPA and DHA levels in both the plasma and liver compared with rats administered atorvastatin only. Supplementation with atorvastatin alone significantly decreased sterol regulatory element-binding protein-1c, Δ5- and Δ6-desaturases, elongase-5, and stearoyl-coenzyme A (CoA) desaturase-2 levels and increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression in the liver compared with control rats. TAK-085 supplementation significantly increased stearoyl-CoA desaturase-2 mRNA expression. These results suggest that long-term supplementation with atorvastatin decreases the EPA and DHA levels by inhibiting the desaturation and elongation of n-3 fatty acid metabolism, while TAK-085 supplementation effectively replenishes this effect in SHRcp rat liver.
Assuntos
Atorvastatina/farmacologia , Gorduras na Dieta/farmacologia , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Síndrome Metabólica/metabolismo , Animais , Anticolesterolemiantes/farmacologia , Atorvastatina/administração & dosagem , Gorduras na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Combinação de Medicamentos , Ácido Eicosapentaenoico/administração & dosagem , Interações Alimento-Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Hipercolesterolemia/tratamento farmacológico , Masculino , Síndrome Metabólica/sangue , Ratos , Ratos EndogâmicosRESUMO
The high mortality rate in Bangladesh is related to poverty, which results in protein malnutrition, essential fatty acid deficiency and lacks in adequate vitamins, minerals and calorie. Exploring new food items with improved dietary nutrition factors may, therefore, help to decrease the mortality rate in the poor countries like Bangladesh. Accordingly, the present study was a proximate composition and fatty acid analysis of L. purpureus seed-a legume seed which is given no careful attention locally, though it might be a good source of valuable nutrition factors for both animals and humans. The purpose of the study was, therefore, to generate awareness that L. purpureus could also act as a good source of food components essential for good health. Proximate analysis revealed that the seed powder contained 8.47 ± 0.52% moisture; 3.50 ± 0.0.07% ash; 1.02 ± 0.06% total fat; 23.95 ± 0.15% total protein; 1.21 ± 0.16% total dietary fiber; 61.86 ± 0.70% total carbohydrate and 352.4 ± 2.66 kcal/100 g energy. Phytic acid content (%) was 1.014 ± 0.048. Major fatty acid composition (%): the essential fatty acid linoleic acid (C18:2, ω-6) was 9.50 ± 0.68, while the linolenic acid (C18:3, ω-3) was 1.95 ± 0.18. Palmitic acid (C16:0), stearic acid (C18:0) and oleic acid (C18:1) were, respectively, 2.96 ± 0.19, 0.77 ± 0.04 and 1.10 ± 0.06. Lignoceric acid (C24:0) was 0.11 ± 0.007%. Monounsaturated palmitoleic acid (0.006 ± 0.0), docosapentaenoic acid (DPA, C22:5, ω-3) and nervonic acid (0.002 ± 0.0) were present in trace amounts. Arachidonic acid (AA, C20:4, ω-6), eicosapentaenoic acid (C20:5, ω-3), and docosahexaenoic acid (C22:6, ω-3) were not detected. The fatty acid profile, thus, suggests that essential omega-6 fatty acid linoleic acid (C18:3, ω-6) and omega-3 linolenic acid (C18:3, ω-3) were the major polyunsaturated fatty acids (PUFA) present in L. purpureus seed. In addition, the seed contained high amount of proteins. Finally, these results suggest that L. purpureus seed could be used as a good source of quality food components, including protein and essential fatty acids.
RESUMO
Identifying dietary alternatives for artificial antioxidants capable of boosting antihemolytic and antioxidative defense has been an important endeavor in improving human health. In the present study, we studied antihemolytic and antioxidative effects of germosprout (i.e., the germ part along with sprouted stems plus roots) extract prepared from the pregerminated rice. The extract contained considerable amounts of antioxidant ß-carotene (414 ± 12 ng/g of extract) and phytochemicals such as total polyphenols (12.0 ± 1.1 mg gallic acid equivalent/g of extract) and flavonoids (11.0 ± 1.4 mg catechin equivalent/g of extract). The antioxidant potential of the extract was assessed by its DPPH- (2,2-diphenyl-1-picrylhydrazyl-) free radical scavenging activity where we observed that germosprout extract had considerable antioxidative potentials. To evaluate antihemolytic effect of the extract, freshly prepared erythrocytes were incubated with either peroxynitrite or Fenton's reagent in the absence or presence of the extract. We observed that erythrocytes pretreated with the extract exhibited reduced degree of in vitro hemolysis. To support the proposition that germosprout extract could act as a good antioxidative agent, we also induced in vitro oxidative stress in erythrocyte membranes and in the aorta, brain, heart, and liver tissue homogenates in the presence of the extract. As expected, germosprout extract decreased oxidative stress almost to the same extent as that of vitamin E, as measured by lipid peroxide levels, in all the mentioned tissues. We conclude that rice germosprout extract could be a good natural source of antioxidants to reduce oxidative stress-induced hemolysis and damage of blood vessels and other tissues.
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We studied the effect of chronic oral exposure to lead acetate (PbA) on the sensitivity of RBC to hemolysis and whether the sensitivity could be decreased by feeding the rats with extract of medicinal mushroom Ganoderma lucidum. Three groups of rats, control, PbA-exposed, and G. lucidum (Gl)+PbA, were used. PbA (3 mM) was administered via drinking water and G. lucidum extract by gavage at 300 mg/Kg BW/day for 12 weeks. Afterwards, the rats were killed and washed RBCs were subjected to hemolysis in the presence of Fenton's reagents. Hemolysis was determined by estimating the amount of released hemoglobin. The levels of lipid peroxide (LPO) and GSH were determined from RBC membranes and whole RBCs, respectively. The levels of TNFα and LPO also were determined from hepatic tissues. The RBCs of PbA-exposed rats displayed significantly higher sensitivity to hemolysis than those of the Gl+PbA rats. The levels of LPO increased and GSH decreased in the RBCs, with concomitant increases in the levels of hepatic TNFα and LPO in the PbA-exposed rats. The degree of hemolysis was significantly low in the RBCs of Gl+PbA rats, concurrently with amelioration of hepatic parameters. Finally, the study suggests that PbA-induced-hemolysis and related oxidative-toxicity might be minimized by consumption of G. lucidum.
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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
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
Aloe vera is a semi-tropical plant of Liliaceae family which has a wide range of applications in traditional medicine. In the present study, we sought to investigate the heptaoprotective potential of Aloe vera gel as a diet supplement. To achieve this goal, we have designed in vitro and in vivo experimental models of chemical-induced liver damage using male Sprague-Dawley rat. In the in vitro model, its effect was evaluated on Fenton's reaction-induced liver lipid peroxidation. Co-incubation with gel significantly reduced the generation of liver lipid peroxide (LPO). Next, to see the similar effect in vivo, gel was orally administered to rats once daily for 21 successive days. Following 1 hour of the last administration of gel, rats were treated with intra-peritoneal injection of CCl4. Dietary gel showed significant hepatoprotection against CCl4-induced damage as evident by restoration of liver LPO, serum transaminases, alkaline phosphatase, and total bilirubin towards near normal. The beneficial effects were pronounced with the doses used (400 and 800 mg/kg body weight). Besides, we did not observe any significant drop in serum albumin, globulin as well as total protein levels of gel-administered rats. Histopathology of the liver tissue further supported the biochemical findings confirming the hepatoprotective potential of dietary gel.
Assuntos
Aloe , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Suplementos Nutricionais , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Fosfatase Alcalina/sangue , Animais , Bilirrubina/metabolismo , Proteínas Sanguíneas/metabolismo , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Géis , Globulinas/metabolismo , Peróxido de Hidrogênio , Ferro , Fígado/metabolismo , Fígado/patologia , Masculino , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Albumina Sérica/metabolismo , Transaminases/sangueRESUMO
The serum phosphorus level is recently considered as one of the foretelling markers for the severity of cardiovascular diseases (CVD). We therefore investigated whether the serum phosphorus level in the diabetic patients against healthy individuals could act as a possible marker for identification of vulnerability to cardiovascular disease. One hundred and thirty two human subjects were involved in the study among which one hundred and four subjects are CVD patients and twenty eight were healthy individuals. The levels of the lipid profile and the glycemic status were significantly increased in the patients than those of the control subjects (Fasting glucose, FS=8.3 ± 0.3 vs. 6.1 ± 0.0 mmol/L; blood glucose 2 h after breakfast (STAB)=12.0 ± 0.5 vs. 8.5 ± 0.7, mmol/L; HbA1c (%),6.7 ± 0.2 vs. 5.4 ± 0.3; and Total cholesterol (TC)=189 ± 4.0 vs. 162 ± 7.0; low density lipoprotein cholesterol (LDL-C), 111 ± 3.8 vs. 96 ± 5.0; triacyglycerol (TG), 202 ± 9.0 vs. 118 ± 5.3 mg/dL, respectively. The serum phosphorus level was significantly increased in CVD patients (mg/dL, patient vs. control, 5.1 ± 0.10 vs. 3.7 ± 0.1). Simple regression analyses revealed a highly significant positive correlation between serum phosphorus and TC, TG and FG. Thus the results demonstrate that the serum phosphorus level might be another parameter which is closely associated with diabetes and could also be used as a possible marker for the risk of CVD.
Assuntos
Doenças Cardiovasculares/complicações , Complicações do Diabetes/complicações , Hiperfosfatemia/complicações , Idoso , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Estudos de Casos e Controles , Complicações do Diabetes/sangue , Jejum/sangue , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperfosfatemia/sangue , Lipídeos/sangue , Pessoa de Meia-Idade , Fósforo/sangue , Fatores de RiscoRESUMO
The in vitro oxidative stress induced by ethanol/Fenton's reaction in rat liver homogenates decreased significantly in the presence of Syzygium cumini seed extract, suggesting the protective effect of the seed extract against the oxidative stress in liver. To corroborate the in vitro effects by an in vivo experiment, 24 rats were divided into four groups: control, S. cumini seed-extract-administered (SE), 15% ethanol-fed (Alc) and Alc+SE rats. The oral administration of the extract (400 mg/kg BW.day) for 7 weeks significantly decreased the levels of liver LPO in the Alc+SE rats, suggesting that S. cumini seed not only obstructed the in vitro free radical production and subsequent oxidative stress, but also inhibited their in vivo formation. The oral administration of extract also reduced the enzyme activities of serum gammaglutamyl transferase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase and the levels of serum creatinine and blood urea nitrogen, serum/liver triglycerides and total cholesterol of the alcoholic rats. The levels of fecal cholesterol were increased by the extract. Fatty degenerations in liver and kidney were absent with S. cumini seed extract treatment. The results suggest that S. cumini seed may be a potential therapy for alcoholics and related dysfunctions by restraining oxidative stress.
Assuntos
Antioxidantes/farmacologia , Fígado Gorduroso Alcoólico/prevenção & controle , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Syzygium , Alcoolismo/complicações , Alcoolismo/fisiopatologia , Animais , Nitrogênio da Ureia Sanguínea , Técnicas In Vitro , Rim/efeitos dos fármacos , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Testes de Função Hepática , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Long-Evans , SementesRESUMO
Twenty 5-week-old male Wistar rats were divided into two groups: one group was fed a fish oil-deficient diet and the other group was fed the same diet supplemented with per orally administered docosahexaenoic acid (DHA) for 12 weeks. Six weeks after the start of the administration of DHA, rats were trained for 6 weeks to acquire a reward at the end of each of four arms of an eight-arm radial maze. On completion of the radial maze task, the Fos expression in the hippocampus was examined immunohistochemically. Chronic DHA administration significantly reduced the number of reference and working memory errors. The number of Fos-positive neurons in the CA1 hippocampus significantly increased in DHA-treated rats compared with control rats, demonstrating a statistically significant negative correlation with the number of reference memory errors. These results suggest that the DHA-induced improvement in spatial cognition is associated with increased Fos expression in the CA1 hippocampus.
Assuntos
Dieta , Ácidos Docosa-Hexaenoicos/farmacologia , Genes fos/efeitos dos fármacos , Hipocampo/metabolismo , Memória/efeitos dos fármacos , Percepção Espacial/efeitos dos fármacos , Animais , Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos WistarRESUMO
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-beta (Abeta) 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 Abeta peptide-produced Alzheimer's disease model rats. After a mini-osmotic pump filled with Abeta 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.