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1.
J Biomol Struct Dyn ; 36(3): 609-620, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28132600

RESUMO

The objective of the present study was to evaluate the effects of propolis, pollen, and caffeic acid phenethyl ester (CAPE) on tyrosine hydroxylase (TH) activity and total RNA levels of Nω-nitro-L-arginine methyl ester (L-NAME) inhibition of nitric oxide synthase in the heart, adrenal medulla, and hypothalamus of hypertensive male Sprague dawley rats. The TH activity in the adrenal medulla, heart, and hypothalamus of the rats was significantly increased in the L-NAME group vs. control (p < 0.05). Treatment with L-NAME led to a significant increase in blood pressure (BP) in the L-NAME group compared to control (p < 0.05). These data suggest that propolis, pollen, and CAPE may mediate diminished TH activity in the heart, adrenal medulla, and hypothalamus in hypertensive rats. The decreased TH activity may be due to the modulation and synthesis of catecholamines and BP effects. In addition, the binding mechanism of CAPE within the catalytic domain of TH was investigated by means of molecular modeling approaches. These data suggest that the amino acid residues, Glu429 and Ser354 of TH may play a pivotal role in the stabilization of CAPE within the active site as evaluated by molecular dynamics (MD) simulations. Gibbs binding free energy (ΔGbinding) of CAPE in complex with TH was also determined by post-processing MD analysis approaches (i.e. Poisson-Boltzmann Surface Area (MM-PBSA) method).


Assuntos
Hipertensão/tratamento farmacológico , Hipertensão/enzimologia , Óxido Nítrico Sintase/antagonistas & inibidores , Tirosina 3-Mono-Oxigenase/genética , Medula Suprarrenal/efeitos dos fármacos , Medula Suprarrenal/metabolismo , Animais , Ácidos Cafeicos/administração & dosagem , Domínio Catalítico , Catecolaminas/biossíntese , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Humanos , Hipertensão/genética , Hipertensão/patologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico Sintase/química , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/análogos & derivados , Pólen/efeitos adversos , Própole/administração & dosagem , Ratos , Tirosina 3-Mono-Oxigenase/química
2.
Cell Biochem Funct ; 35(6): 304-314, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28833317

RESUMO

The objective of this study was to evaluate the antioxidant effects of propolis, caffeic acid phenethyl ester (CAPE; active compound in propolis), and pollen on biochemical oxidative stress biomarkers in rat kidney tissue inhibited by Nω -nitro-L-arginine methyl ester (L-NAME). The biomarkers evaluated were paraoxonase (PON1), oxidative stress index (OSI), total antioxidant status (TAS), total oxidant status (TOS), asymmetric dimethylarginine (ADMA), and nuclear factor kappa B (NF-κB). TAS levels and PON1 activity were significantly decreased in kidney tissue samples in the L-NAME-treated group (P < 0.05). The levels of TAS and PONI were higher in the L-NAME plus propolis, CAPE, and pollen groups compared with the L-NAME-treated group. TOS, ADMA, and NF-κB levels were significantly increased in the kidney tissue samples of the L-NAME-treated group (P < 0.05). However, these parameters were significantly lower in the L-NAME plus propolis, CAPE, and pollen groups (P < 0.05) compared with rats administered L-NAME alone (P < 0.05). Furthermore, the binding energy of CAPE within catalytic domain of glutathione reductase (GR) enzyme as well as its inhibitory mechanism was determined using molecular modeling approaches. In conclusion, experimental and theoretical data suggested that oxidative alterations occurring in the kidney tissue of chronic hypertensive rats may be prevented via active compound of propolis, CAPE administration.


Assuntos
Ácidos Cafeicos/farmacologia , Nefropatias/etiologia , Simulação de Dinâmica Molecular , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Própole/farmacologia , Animais , Antioxidantes , Arginina/análogos & derivados , Arginina/metabolismo , Arginina/toxicidade , Arildialquilfosfatase/metabolismo , Sítios de Ligação , Ácidos Cafeicos/química , Ácidos Cafeicos/metabolismo , Glutationa Redutase/química , Glutationa Redutase/metabolismo , Meia-Vida , Hipertensão/metabolismo , Hipertensão/patologia , Nefropatias/metabolismo , Masculino , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Álcool Feniletílico/química , Álcool Feniletílico/metabolismo , Álcool Feniletílico/farmacologia , Pólen/química , Pólen/metabolismo , Própole/metabolismo , Estrutura Terciária de Proteína , Ratos , Ratos Sprague-Dawley
3.
Fertil Steril ; 87(4): 978-81, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17207794

RESUMO

A combination of E and progestogens significantly increased matrix metalloproteinase (MMP)-2 in both T47D cells (E(2)-medroxyprogesteroneacetate [MPA] and E(2)-P) and MCF-7 cells (E(2)-MPA, E(2)-P, and equilin-MPA). All combinations resulted in higher MMP-9 levels in MCF-7 cells, but higher MMP-9 levels resulted only with equilin-norethinderone in T47D cells.


Assuntos
Neoplasias da Mama/enzimologia , Terapia de Reposição de Estrogênios , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Linhagem Celular Tumoral , Equilina/farmacologia , Estradiol/farmacologia , Estrogênios Conjugados (USP)/farmacologia , Feminino , Humanos , Acetato de Medroxiprogesterona/farmacologia , Noretindrona/análogos & derivados , Noretindrona/farmacologia , Acetato de Noretindrona , Progesterona/farmacologia
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