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1.
J Adv Res ; 57: 77-91, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37061218

RESUMO

INTRODUCTION: Nutritional support is potentially considered an essential step to prevent muscle loss and enhance physical function in older adults. OBJECTIVES: This study aimed to assess the role of potential nutritional strategies, i.e., fish oil-derived ω-3 polyunsaturated fatty acids (PUFAs), wheat oligopeptide and their combined intervention, in preventing and reversing sarcopenia in aging process. METHODS: One hundred 25-month-old Sprague-Dawley rats were randomly divided into 10 groups, and 10 newly purchased 6-month-old rats were included in young control group (n = 10). Fish oil (200, 400 or 800 mg/kg body weight), wheat oligopeptide (100, 200 or 400 mg/kg body weight), fish oil + wheat oligopeptide (800 + 100, 400 + 200 or 200 + 400 mg/kg body weight) or the equal volume of solvent were administered daily by gavage for 10 weeks. The effects of these interventions on natural aging rats were evaluated. RESULTS: All intervention groups had a significant increase in muscle mass and grip strength and reduction in perirenal fat weight when compared to the aged control group (P < 0.05). The results of biochemical parameters, magnetic resonance imaging, proteomics and western blot suggested that the combination of wheat oligopeptide and fish oil-derived ω-3 PUFA, especially group WFM 2 (400 + 200 mg/kg body weight fish oil + wheat oligopeptide), was found to be more effective against aging-associated muscle loss than single intervention. Additionally, the interventions ameliorated fatty infiltration, muscle atrophy, and congestion in the intercellular matrix, and inflammatory cell infiltration in muscle tissue. The interventions also improved oxidative stress, anabolism, hormone levels, and inflammatory levels of skeletal muscle. CONCLUSIONS: The combination of fish oil-derived ω-3 PUFA and wheat oligopeptide was found to be a promising nutritional support to prevent and reverse sarcopenia. The potential mechanism involved the promotion of protein synthesis and muscle regeneration, as well as the enhancement of muscle strength.


Assuntos
Ácidos Graxos Ômega-3 , Sarcopenia , Ratos , Animais , Óleos de Peixe/farmacologia , Sarcopenia/prevenção & controle , Triticum , Ratos Sprague-Dawley , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-3/farmacologia , Envelhecimento , Peso Corporal
2.
Adv Nutr ; 14(6): 1644-1655, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37778442

RESUMO

Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia, and hypertension. Alpha-linolenic acid (ALA) is a plant-based essential polyunsaturated fatty acid associated with reduced CVD risks. This systematic review and meta-analysis aimed to investigate the effects of supplementation with ALA compared with the placebo on CVD risk factors in people with obesity or overweight (International Prospective Register of Systematic Reviews Registration No. CRD42023429563). This review included studies with adults using oral supplementation or food or combined interventions containing vegetable sources of ALA. All studies were randomly assigned trials with parallel or crossover designs. The Cochrane Collaboration tool was used for assessing the risk of bias (Version 1). PubMed, Web of Science, Embase, and Cochrane library databases were searched from inception to April 2023. Nineteen eligible randomized controlled trials, including 1183 participants, were included in the meta-analysis. Compared with placebo, dietary ALA supplementation significantly reduced C-reactive protein concentration (standardized mean difference [SMD] = -0.38 mg/L; 95% confidence interval [CI]: -0.72, -0.04), tumor necrosis factor-α concentration (SMD = -0.45 pg/mL; 95% CI: -0.73, -0.17), triglyceride in serum (SMD = -4.41 mg/dL; 95% CI: -5.99, -2.82), and systolic blood pressure (SMD = -0.37 mm Hg; 95% CI: -0.66, -0.08); but led to a significant increase in low-density lipoprotein cholesterol concentrations (SMD = 1.32 mg/dL; 95% CI: 0.05, 2.59). ALA supplementation had no significant effect on interleukin-6, diastolic blood pressure, total cholesterol, or high-density lipoprotein cholesterol (all P ≥ 0.05). Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor.


Assuntos
Doenças Cardiovasculares , Adulto , Humanos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológico , Ácido alfa-Linolênico/farmacologia , Ácido alfa-Linolênico/uso terapêutico , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , HDL-Colesterol , Obesidade/complicações , Obesidade/tratamento farmacológico , Suplementos Nutricionais
3.
Pharmacol Res ; 188: 106647, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36638933

RESUMO

Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.


Assuntos
Diabetes Mellitus Tipo 2 , Niacina , Humanos , Vitaminas/uso terapêutico , Metanálise em Rede , Vanádio , Ensaios Clínicos Controlados Aleatórios como Assunto , Suplementos Nutricionais , Minerais/uso terapêutico , Vitamina E , Micronutrientes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Vitamina K , Cromo , Atenção Primária à Saúde , Colesterol
4.
Age Ageing ; 51(12)2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36571774

RESUMO

BACKGROUND: the effects regarding n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on sarcopenia have been explored by several clinical trials. Nonetheless, the use of n-3 PUFA for improving body composition, muscle strength and physical performance in older people is conflicting. OBJECTIVES: our aim was to perform a randomised, double-blind, controlled trial to evaluate the effects of 6-month n-3 PUFA supplementation on body composition, muscle strength and physical performance in older Chinese people. METHODS: in this double-blind, placebo-controlled trial, 200 eligible subjects were randomly assigned to receive 4 g/day fish oil capsules (1.34 g eicosapentaenoic [EPA] + 1.07 docosahexaenoic [DHA]) or 4 g/day corn oil capsules (EPA + DHA <0.05 g) for 6 months. The primary outcomes were the changes of body composition, muscle strength (hand grip strength) and physical performance (Timed Up and Go time). Secondary outcomes were the changes in serum lipid profiles. RESULTS: compared with control group, fish oil-derived n-3 PUFA supplementation resulted in significant increases in thigh circumference (interaction time × group effect P < 0.001), total skeletal muscle mass (interaction time × group effect P < 0.001) and appendicular skeletal muscle mass (interaction time × group effect P < 0.001); the differences were still significant even after height correction. Muscle strength and physical performance including hand grip strength (interaction time × group effect P < 0.001) and Timed Up and Go time (interaction time × group effect P < 0.001) were also improved after a 6-month fish oil-derived n-3 PUFA intervention. In terms of serum lipid profiles, fish oil-derived n-3 PUFA supplementation could significantly reduce serum level of triglyceride (interaction time × group effect P = 0.012) and increase high density lipoprotein cholesterol (interaction time × group effect P < 0.001); while no significant improvement was found in serum concentrations of total cholesterol (interaction time × group effect P = 0.413) and low density lipoprotein cholesterol (interaction time × group effect P = 0.089). CONCLUSIONS: our present trial demonstrated that a 6-month fish oil-derived n-3 PUFA supplementation could beneficially affect the body composition, muscle strength, physical performance and serum lipid profiles in older people, which could be into considerations when making strategies aiming to the primary prevention of sarcopenia.


Assuntos
Ácidos Graxos Ômega-3 , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Sarcopenia/prevenção & controle , Força da Mão , Óleos de Peixe/farmacologia , Força Muscular , Composição Corporal , Desempenho Físico Funcional , Método Duplo-Cego , Suplementos Nutricionais/efeitos adversos
5.
Nutrients ; 14(19)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36235763

RESUMO

The aim of this study was to examine the association between dietary patterns and high blood glucose in Jiangsu province of China by using structural equation modelling (SEqM). Methods: Participants in this cross-sectional study were recruited through the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance Program in Jiangsu province using a multistage stratified cluster random sampling method. Dietary patterns were defined by exploratory factor analysis (EFA). Confirmatory factor analysis (CFA) was used to test the fitness of EFA. SEqM was used to investigate the association between dietary patterns and high blood glucose. Results: After exclusion, 3137 participants with complete information were analysed for this study. The prevalence of high blood glucose was 9.3% and 8.1% in males and females, respectively. Two dietary patterns: the modern dietary pattern (i.e., high in red meats and its products, vegetables, seafood, condiments, fungi and algae, main grains and poultry; low in other grains, tubers and preserves), and the fruit−milk dietary pattern (i.e., high in milk and its products, fruits, eggs, nuts and seeds and pastry snacks, but low in vegetable oils) were established. Modern dietary pattern was found to be positively associated with high blood glucose in adults in Jiangsu province (multivariate logistic regression: OR = 1.561, 95% CI: 1.025~2.379; SEqM: ß = 0.127, p < 0.05). Conclusion: The modern dietary pattern­high intake of red meats­was significantly associated with high blood glucose among adults in Jiangsu province of China, while the fruit−milk dietary pattern was not significantly associated with high blood glucose.


Assuntos
Glicemia , Hiperglicemia , Adulto , China/epidemiologia , Estudos Transversais , Dieta , Feminino , Humanos , Análise de Classes Latentes , Masculino , Óleos de Plantas , Verduras
6.
J Sci Food Agric ; 102(15): 7172-7185, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35727941

RESUMO

BACKGROUND: The effects of dietary fat on health are influenced by its fatty acid profile. We aimed to determine the effects of monounsaturated fatty acid (MUFA)-rich blended oils (BO) containing a balance of polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFAs) and with a low n-6/n-3 PUFA ratio on the health of rats fed normal or high-fat diets. The BO was obtained by mixing red palm oil, rice bran oil (RO), tea seed oil and flaxseed oil in appropriate proportions. RESULTS: BO consumption reduced the serum low-density lipoprotein cholesterol (LDL-C), non-esterified fatty acid (NEFA), insulin (INS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 (IL-1), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), lipid peroxide (LPO) and oxidized LDL (ox-LDL) concentrations and the homeostasis model assessment of insulin resistance (HOMA-IR); it increased the high-density lipoprotein cholesterol (HDL-C), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) concentrations, and the bone mineral density (BMD) versus control oil-containing normal and high-fat diets. BO also reduced the triglyceride (TG), hs-CRP, MDA, ox-LDL and reactive oxygen species (ROS) concentrations; and increased the serum HDL-C and SOD, and BMD versus RO-containing high-fat diets. Finally, BO reduced the glucose (GLU) and INS, and HOMA-IR; it increased HDL-C, SOD, femoral weight and BMD versus RO-containing normal diets. CONCLUSION: BOs with an appropriate fatty acid profile have beneficial effects on the glucolipid metabolism, inflammation, oxidative stress and bone quality of rats when included in both normal and high-fat diets. © 2022 Society of Chemical Industry.


Assuntos
Ácidos Graxos Ômega-3 , Ácidos Graxos , Ratos , Animais , Proteína C-Reativa/metabolismo , Ácidos Graxos Monoinsaturados , Ácidos Graxos Insaturados , Gorduras na Dieta , HDL-Colesterol , Óleos de Plantas/farmacologia , Superóxido Dismutase/metabolismo
7.
PLoS One ; 16(9): e0256992, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473789

RESUMO

The efficacy of cranberry (Vaccinium spp.) as adjuvant therapy in preventing urinary tract infections (UTIs) remains controversial. This study aims to update and determine cranberry effects as adjuvant therapy on the recurrence rate of UTIs in susceptible groups. According to PRISMA guidelines, we conducted a literature search in Web of Science, PubMed, Embase, Scopus, and the Cochrane Library from their inception dates to June 2021. We included articles with data on the incidence of UTIs in susceptible populations using cranberry-containing products. We then conducted a trial sequential analysis to control the risk of type I and type II errors. This meta-analysis included 23 trials with 3979 participants. We found that cranberry-based products intake can significantly reduce the incidence of UTIs in susceptible populations (risk ratio (RR) = 0.70; 95% confidence interval(CI): 0.59 ~ 0.83; P<0.01). We identified a relative risk reduction of 32%, 45% and 51% in women with recurrent UTIs (RR = 0.68; 95% CI: 0.56 ~ 0.81), children (RR = 0.55; 95% CI: 0.31 ~ 0.97) and patients using indwelling catheters (RR = 0.49; 95% CI: 0.33 ~ 0.73). Meanwhile, a relative risk reduction of 35% in people who use cranberry juice compared with those who use cranberry capsule or tablet was observed in the subgroup analysis (RR = 0.65; 95% CI: 0.54 ~ 0.77). The TSA result for the effects of cranberry intake and the decreased risk of UTIs in susceptible groups indicated that the effects were conclusive. In conclusion, our meta-analysis demonstrates that cranberry supplementation significantly reduced the risk of developing UTIs in susceptible populations. Cranberry can be considered as adjuvant therapy for preventing UTIs in susceptible populations. However, given the limitations of the included studies in this meta-analysis, the conclusion should be interpreted with caution.


Assuntos
Suplementos Nutricionais , Sucos de Frutas e Vegetais , Frutas/química , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem , Proantocianidinas/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Vaccinium macrocarpon/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cápsulas , Criança , Pré-Escolar , Suscetibilidade a Doenças , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva , Comprimidos , Infecções Urinárias/prevenção & controle , Adulto Jovem
8.
Mol Nutr Food Res ; 65(9): e2001059, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33793078

RESUMO

INTRODUCTION: The purpose of this study is to examine the effects of oat supplementation on serum lipid in a population of adults with mild hypercholesterolemia and reveal the underlying mechanisms with serum untargeted metabolomics. METHODS AND RESULTS: In this placebo-controlled trial, 62 participants from Nanjing, China, with mild elevations in cholesterol are randomly assigned to receive 80 g oats (containing 3 g beta-glucan) or rice daily for 45 days. Fasting blood samples are collected at the beginning, middle, and end of the trial. Compared with the rice group, oat consumption significantly decreases serum total cholesterol (TC) (-8.41%, p = 0.005), low-density lipoprotein cholesterol (LDL-c) (-13.93%, p = 0.001), and non high-density lipoprotein cholesterol (non-HDL-c) (-10.93%, p = 0.017) levels. There are no significant between-group differences in serum triglyceride (TG), apolipoprotein B (Apo B), glycated albumin, or fasting blood glucose levels. An orthogonal partial least squares discriminant analysis (OPLS-DA) suggests a clear separation in metabolic profiles between the groups after the intervention. Twenty-one metabolites in the oat group are significantly different from those in the rice group, among which 14 metabolites show a decreased trend. In comparison, seven metabolites show an increased trend. Correlations analysis from both groups indicate that most metabolites [e.g., sphinganine and phosphatidylcholine (PC)(20:5(5Z,8Z,11Z,14Z,17Z)/20:1(11Z))] have positive correlations with serum cholesterol levels. Kyoto Encyclopedia of Gene and Genomes pathway analysis suggests that oat consumption regulated glycerophospholipid, alanine, aspartate and glutamate, sphingolipid, and retinol metabolism. CONCLUSION: Oat consumption has beneficial effects on serum lipids profiles. The underlying mechanisms involve glycerophospholipid, alanine, aspartate and glutamate, sphingolipid, and retinol metabolism in adults.


Assuntos
Anticolesterolemiantes/farmacologia , Avena , Hipercolesterolemia/dietoterapia , Metabolômica , Adulto , Aminoácidos/metabolismo , Feminino , Humanos , Hipercolesterolemia/metabolismo , Metabolismo dos Lipídeos , Lipídeos/sangue , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Esfingolipídeos/metabolismo , Vitamina A/metabolismo
9.
Nutr Clin Pract ; 36(2): 368-384, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33037694

RESUMO

The purpose of this meta-analysis was to summarize randomized controlled trial (RCT) evidence and evaluate the efficacy and safety of vitamin D (VD) supplementation as an adjunct to antibiotics for the treatment of pneumonia. Data sources published from the inception dates up to January 2020 were searched. RCTs of VD supplementation of any duration, age, and dosing regimen type were eligible for inclusion if data on pneumonia were collected. Thirteen studies (4786 randomized participants) fulfilled eligibility criteria. VD supplementation significantly increased levels of serum 25(OH)D (mean difference = 15.97; 95% CI, 7.49-24.44; P = .002) and reduced incidence of repeat episodes of pneumonia (risk ratio [RR] = 0.68; 95% CI, 0.50-0.93; P = .02). Subgroup analysis revealed VD supplementation had more reducing effects on repeat episodes of pneumonia among participants in trials in which the population were children (RR = 0.66; 95% CI, 0.48-0.90), duration <3 months (RR = 0.55; 95% CI, 0.33-0.91), or dose of VD <300,000 IU (RR = 0.51; 95% CI, 0.29-0.89). Although our results suggested that VD supplementation had a positive effect on recovery rate of pneumonia (RR = 1.28; 95% CI, 0.94-1.74; I2 = 13%), there was no statistical difference (P = .12). High-dose VD intervention may have an effect on reducing the incidence rate of repeat episodes of pneumonia by enhancing immune efficacy, although more population studies are needed to support that VD supplementation has therapeutic effects on pneumonia itself.


Assuntos
Pneumonia , Vitamina D , Criança , Suplementos Nutricionais , Humanos , Pneumonia/tratamento farmacológico , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Vitaminas
10.
Wei Sheng Yan Jiu ; 49(3): 458-462, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32693897

RESUMO

OBJECTIVE: To investigate the effects of mannose, the major component of Lycium barbarum polysaccharide, and its potential target metabolite, inositol, on mouse islet ß-TC6 cells. METHODS: Different concentrations(0, 4. 6875, 9. 375, 18. 75, 37. 5, 75 and 150 µg/mL) of mannose or inositol were used to intervene ß-TC6 cells for 24 hours, and the proliferation activity of cells was determined by CCK-8 method. Enzyme-linked immunosorbent assay was used to detect insulin secretion after the intervention of the ß-TC6 cells from different concentration of the mannose or inositol(0, 18. 75, 75 and 150 µg/mL) combining with glucose stimulation(20 mmol/L) for 60 minutes. Pioglitazone(3. 92 mg/L) was set up as positive group, and after intervention of the mannose or inositol(0, 9. 375, 18. 75, 75 and 150 µg/mL) for 24 h, the expression levels of insulin, glucose kinase(GK), glucose transporter 4(GLUT4) and glycogen synthase(GS) mRNA were detected by real-time quantitative PCR. RESULTS: Compared with the control group, mannose and inositol promoted the proliferation of ß-TC6 cells in a concentration-dependent manner(18. 75-150 µg/mL)(P<0. 05). Although the inositol solution of 4. 6875 µg/mL and 9. 375 µg/mL had a tendency to promote cell proliferation, there was no statistical difference(P>0. 05). After stimulation with 20 mmol/L glucose combining with different intervention concentrations(18. 75, 75 and 150 µg/mL) of mannose or inositol, no significant difference was observed in the insulin secretion of each group(P>0. 05) comparing with the control group. RT-qPCR result showed that 150 µg/mL mannose increased the expression level of GLUT4(P<0. 01) and the expression levels of GK and GLUT4 genes in the 75 µg/mL inositol group were significantly increased(P<0. 01). The expression level of GLUT4 was improved only when the concentration was decreased to 18. 75 µg/mL in inositol group(P<0. 01). CONCLUSION: Mannose and inositol can improve the expression of GLUT4 mRNA, which may help to increase glucose uptake by peripheral cells. In addition, inositol can improve insulin sensitivity and glucose metabolism by increasing the expression level of GK mRNA.


Assuntos
Lycium , Manose , Animais , Medicamentos de Ervas Chinesas , Glucose , Inositol , Insulina , Camundongos , Polissacarídeos
11.
Nutrients ; 10(11)2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30463386

RESUMO

The objective of this study is to investigate and compare the prevalence, knowledge, and attitudes of Chinese university students with respect to nutritional supplements. We conducted a cross-sectional study in several universities around China from January to December 2017, and enrolled a total of 8752 students. Of these, 4252 were medical students and 4500 were non-medical students. The use of nutritional supplements was reported by 58.9% in universities students, with a higher rate for medical students as compared to non-medical students. It was found 24.2% of participants had taken supplements in the past year. Medical students had a higher level of knowledge on nutritional supplements than non-medical students (p < 0.001). The most commonly used nutritional supplements were vitamin C, calcium, and vitamin B. Gender (p < 0.001), household income (p < 0.001), and health status (p < 0.001) were related to the nutritional supplement use after adjustment for related factors. In conclusion, in China, nutritional supplement use was found to be more common in medical students than those studying other disciplines, and was associated with sex, income, and health status. The attitude towards nutritional supplements by medical students was positive. Students' knowledge levels about nutritional supplements need to be improved.


Assuntos
Suplementos Nutricionais , Conhecimentos, Atitudes e Prática em Saúde , Estudantes de Medicina/psicologia , Estudantes/psicologia , Adulto , China , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Renda , Masculino , Inquéritos e Questionários , Universidades , Adulto Jovem
12.
ACS Chem Neurosci ; 7(11): 1499-1507, 2016 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-27504670

RESUMO

Currently, anti-AD drug discovery using target-based approaches is extremely challenging due to unclear etiology of AD and absence of validated therapeutic protein targets. Neuronal death, regardless of causes, plays a key role in AD progression, and it is directly linked to neuroinflammation. Meanwhile, phenotypic screening is making a resurgence in drug discovery process as an alternative to target-focused approaches. Herein, we employed microglia-based phenotypic screenings to search for small molecules that modulate the release of detrimental proinflammatory cytokines. The identified novel pharmacological inhibitor of neuroinflammation (named GIBH-130) was validated to alter phenotypes of neuroinflammation in AD brains. Notably, this molecule exhibited comparable in vivo efficacy of cognitive impairment relief to donepezil and memantine respectively in both ß amyloid-induced and APP/PS1 double transgenic Alzheimer's murine models at a substantially lower dose (0.25 mg/kg). Therefore, GIBH-130 constitutes a unique chemical probe for pathogenesis research and drug development of AD, and it also suggests microglia-based phenotypic screenings that target neuroinflammation as an effective and feasible strategy to identify novel anti-AD agents.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/imunologia , Microglia/efeitos dos fármacos , Microglia/imunologia , Fármacos Neuroprotetores/farmacologia , Piperazinas/farmacologia , Piridazinas/farmacologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/patologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Modelos Animais de Doenças , Donepezila , Relação Dose-Resposta a Droga , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos , Feminino , Indanos/farmacologia , Masculino , Memantina/farmacologia , Memória/efeitos dos fármacos , Memória/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/patologia , Neuroimunomodulação/efeitos dos fármacos , Neuroimunomodulação/fisiologia , Fragmentos de Peptídeos , Fenótipo , Piperidinas/farmacologia , Distribuição Aleatória , Ratos Sprague-Dawley
13.
Artigo em Inglês | MEDLINE | ID: mdl-24078824

RESUMO

Qiliqiangxin capsule (QL) was developed under the guidance of TCM theory of collateral disease and had been shown to be effective and safe for the treatment of heart failure. The present study explored the role of and mechanism by which the herbal compounds QL act on energy metabolism, in vivo, in pressure overload heart failure. SD rats received ascending aorta constriction (TAC) to establish a model of myocardial hypertrophy. The animals were treated orally for a period of six weeks. QL significantly inhibited cardiac hypertrophy due to ascending aortic constriction and improved hemodynamics. This effect was linked to the expression levels of the signaling factors in connection with upregulated energy and the regulation of glucose and lipid substrate metabolism and with a decrease in metabolic intermediate products and the protection of mitochondrial function. It is concluded that QL may regulate the glycolipid substrate metabolism by activating AMPK/PGC-1 α axis and reduce the accumulation of free fatty acids and lactic acid, to protect cardiac myocytes and mitochondrial function.

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