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Int J Mol Sci ; 21(17)2020 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-32825797

RESUMEN

Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis, although the underlying aggregation mechanism has not been elucidated. Since SAA aggregation is a key step in this pathogenesis, inhibitors are useful to prevent and treat AA amyloidosis, serving as tools to investigate the pathogenic mechanism. In this study, we showed that rosmarinic acid (RA), which is a well-known inhibitor of the aggregation of amyloid ß (Aß), displayed inhibitory activity against SAA aggregation in vitro using a microliter-scale high-throughput screening (MSHTS) system with quantum-dot nanoprobes. Therefore, we evaluated the amyloid aggregation inhibitory activity of blood and the deposition of SAA in organs by feeding mice with Melissa officinalis extract (ME) containing RA as an active substance. Interestingly, the inhibitory activity of ME-fed mice sera for SAA and Aß aggregation, measured with the MSHTS system, was higher than that of the control group. The amount of amyloid deposition in the organs of ME-fed mice was lower than that in the control group, suggesting that the SAA aggregation inhibitory activity of serum is associated with SAA deposition. These results suggest that dietary intake of RA-containing ME enhanced amyloid aggregation inhibitory activity of blood and suppressed SAA deposition in organs. This study also demonstrated that the MSHTS system could be applied to in vitro screening and to monitor comprehensive activity of metabolized foods adsorbed by blood.


Asunto(s)
Amiloidosis/dietoterapia , Cinamatos/farmacología , Depsidos/farmacología , Proteína Amiloide A Sérica/metabolismo , Péptidos beta-Amiloides/metabolismo , Amiloidosis/metabolismo , Amiloidosis/patología , Animales , Suplementos Dietéticos , Modelos Animales de Enfermedad , Femenino , Ensayos Analíticos de Alto Rendimiento/métodos , Proteína Antagonista del Receptor de Interleucina 1/genética , Masculino , Melissa/química , Ratones Noqueados , Imagen Molecular/métodos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Puntos Cuánticos , Proteína Amiloide A Sérica/análisis , Ácido Rosmarínico
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