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1.
Vaccines (Basel) ; 10(8)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-36016100

RESUMO

Adjuvants and delivery systems are essential components of vaccines to increase immunogenicity against target antigens, particularly for peptide epitopes (poor immunogens). Emulsions, nanoparticles, and liposomes are commonly used as a delivery system for peptide-based vaccines. A Poly(hydrophobic amino acids) delivery system was previously conjugated to Group A Streptococcus (GAS)-derived peptide epitopes, allowing the conjugates to self-assemble into nanoparticles with self adjuvanting ability. Their hydrophobic amino acid tail also serves as an anchoring moiety for the peptide epitope, enabling it to be integrated into the liposome bilayer, to further boost the immunological responses. Polyleucine-based conjugates were anchored to cationic liposomes using the film hydration method and administered to mice subcutaneously. The polyleucine-peptide conjugate, its liposomal formulation, and simple liposomal encapsulation of GAS peptide epitope induced mucosal (saliva IgG) and systemic (serum IgG, IgG1 and IgG2c) immunity in mice. Polyleucine acted as a potent liposome anchoring portion, which stimulated the production of highly opsonic antibodies. The absence of polyleucine in the liposomal formulation (encapsulated GAS peptide) induced high levels of antibody titers, but with poor opsonic ability against GAS bacteria. However, the liposomal formulation of the conjugated vaccine was no more effective than conjugates alone self-assembled into nanoparticles.

2.
Molecules ; 23(4)2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29597336

RESUMO

The current study assesses the antioxidant effects of two similar isoflavonoids isolated from Pueraria lobata, coumestrol and puerarol, along with the cholinergic and amyloid-cascade pathways to mitigate Alzheimer's disease (AD). Antioxidant activity was evaluated via 1,1-diphenyl-2-picryhydrazyl (DPPH) and peroxynitrite (ONOO-) scavenging ability further screened via ONOO--mediated nitrotyrosine. Similarly, acetyl- and butyrylcholinesterase (AChE/BChE) and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities were assessed together with docking and kinetic studies. Considering DPPH and ONOO- scavenging activity, coumestrol (EC50 values of 53.98 and 1.17 µM) was found to be more potent than puerarol (EC50 values of 82.55 and 6.99 µM) followed by dose dependent inhibition of ONOO--mediated nitrotyrosine. Coumestrol showed pronounced AChE and BChE activity with IC50 values of 42.33 and 24.64 µM, respectively, acting as a dual cholinesterase (ChE) inhibitor. Despite having weak ChE inhibitory activity, puerarol showed potent BACE1 inhibition (28.17 µM). Kinetic studies of coumestrol showed AChE and BChE inhibition in a competitive and mixed fashion, whereas puerarol showed mixed inhibition for BACE1. In addition, docking simulations demonstrated high affinity and tight binding capacity towards the active site of the enzymes. In summary, we undertook a comparative study of two similar isoflavonoids differing only by a single aliphatic side chain and demonstrated that antioxidant agents coumestrol and puerarol are promising, potentially complementary therapeutics for AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide , Antioxidantes , Ácido Aspártico Endopeptidases , Cumestrol , Simulação de Acoplamento Molecular , Pueraria/química , Acetilcolinesterase/química , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/química , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/química , Butirilcolinesterase/química , Cumestrol/química , Cumestrol/isolamento & purificação , Electrophorus , Proteínas de Peixes/química , Cavalos , Humanos
3.
Arch Pharm Res ; 40(9): 981-1005, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28840539

RESUMO

The genus Ecklonia (Lessoniaceae, Phaeophyceae), commonly called kelp (brown algae), is abundant on the coasts of Japan and Korea. During the past few decades, Ecklonia species have received tremendous attention for their wide range of therapeutic properties and multiple health benefits, such as great nutritional value and being rich in vitamins, minerals, dietary fiber, proteins, and polysaccharides. Several novel functional ingredients with diversified biological activities have been isolated and possess antimicrobial, antiviral, hepatoprotective, cardioprotective, anti-inflammatory, neuroprotective, anticarcinogenic, immunomodulatory, hypolipidemic, anti-diabetic, and antioxidant therapeutic properties. The present review discusses the phytochemical, pharmacological, therapeutic, nutritional, and health benefits of different species of genus Ecklonia, as well as their use in the prevention of disease and maintenance of good health.


Assuntos
Produtos Biológicos/farmacologia , Medicina Tradicional do Leste Asiático , Phaeophyceae/química , Animais , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Humanos , Japão , República da Coreia
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