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1.
Cardiovasc Res ; 117(11): 2365-2376, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-33070172

RESUMO

AIMS: A diet with modified components, such as a ketogenic low-carbohydrate (LC) diet, potentially extends longevity and healthspan. However, how an LC diet impacts on cardiac pathology during haemodynamic stress remains elusive. This study evaluated the effects of an LC diet high in either fat (Fat-LC) or protein (Pro-LC) in a mouse model of chronic hypertensive cardiac remodelling. METHODS AND RESULTS: Wild-type mice were subjected to transverse aortic constriction, followed by feeding with the Fat-LC, the Pro-LC, or a high-carbohydrate control diet. After 4 weeks, echocardiographic, haemodynamic, histological, and biochemical analyses were performed. LC diet consumption after pressure overload inhibited the development of pathological hypertrophy and systolic dysfunction compared to the control diet. An anti-hypertrophic serine/threonine kinase, GSK-3ß, was re-activated by both LC diets; however, the Fat-LC, but not the Pro-LC, diet exerted cardioprotection in GSK-3ß cardiac-specific knockout mice. ß-hydroxybutyrate, a major ketone body in mammals, was increased in the hearts of mice fed the Fat-LC, but not the Pro-LC, diet. In cardiomyocytes, ketone body supplementation inhibited phenylephrine-induced hypertrophy, in part by suppressing mTOR signalling. CONCLUSION: Strict carbohydrate restriction suppresses pathological cardiac growth and heart failure after pressure overload through distinct anti-hypertrophic mechanisms elicited by supplemented macronutrients.


Assuntos
Dieta Rica em Proteínas e Pobre em Carboidratos , Dieta Cetogênica , Carboidratos da Dieta/metabolismo , Insuficiência Cardíaca/prevenção & controle , Hipertrofia Ventricular Esquerda/prevenção & controle , Miócitos Cardíacos/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Ração Animal , Animais , Células Cultivadas , Carboidratos da Dieta/administração & dosagem , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Valor Nutritivo , Ratos Wistar , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Função Ventricular Esquerda , Remodelação Ventricular
2.
J Agric Food Chem ; 57(10): 4313-8, 2009 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-19358605

RESUMO

Commercially available essential oils extracted from Artemisia dracunculus L., Inula graveolens L., Lavandula officinalis Chaix, and Ocimum sanctum L. and the components of these oils were screened by the microplate assay method for determining their acetylcholinesterase (AChE) inhibitory activity. The composition profiles of the oils were characterized by gas chromatography-mass spectrometry (GC-MS) analysis, and the relationships between the oil components and the AChE inhibitory activity of the oils were outlined. The results showed that all of the oils, except that of A. dracunculus from Hungary, exhibited AChE inhibitory activity, and the A. dracunculus oil from France showed the most potent inhibitory activity [50% inhibition concentration (IC(50)) = 0.058 mg/mL]. The AChE inhibitory activity of I. graveolens oil has not been reported to date, and this study is the first to reveal this activity in the oil. Among the essential oil components, five components, namely, 1,8-cineole, α-pinene, eugenol, α-terpineol, and terpinen-4-ol, showed AChE inhibitory activity, with IC(50) values of 0.015, 0.022, 0.48, 1.3, and 3.2 mg/mL, respectively. Eugenol, in particular, was found to be a potent AChE inhibitor along with determination of the IC(50) value, a finding that has been reported for the first time in this study. However, the ratio of the contribution of the active components, including a novel AChE inhibitor, to the observed AChE inhibitory activity of the essential oils was not very high. The results of this study raise concerns about the AChE inhibitory activity of widely produced and readily accessible commercial essential oils.


Assuntos
Inibidores da Colinesterase/análise , Inibidores da Colinesterase/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Artemisia/química , Eugenol/análise , Eugenol/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Lavandula/química , Óleos Voláteis/síntese química , Óleos de Plantas/síntese química , Óleos de Plantas/química , Óleos de Plantas/farmacologia
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