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Bioorg Med Chem Lett ; 30(12): 127193, 2020 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-32334913

RESUMEN

This study aims to investigate active phytochemicals isolated from Pyrola incarnata Fisch. (P. incarnata) and their protection against neuroinflammation induced by LPS. Betulin, accompanied with other 9 compounds, were isolated from P. incarnata and elucidated by spectroscopic analysis (1H-, 13C NMR). ELISA kits and the measurement of NO production based on Griess reaction showed that betulin (5) (250 µg/mL) could suppress LPS-induced activation of microglial cell BV-2 better than others by inhibiting inflammatory cytokines (TNF-α, IL-6, IL-1ß) expression and NO production. With the guidance of computer-aided drug design and the analysis of biological experiment, we demonstrated betulin could reduce LPS-induced iNOS expression, prevent JNKs pathways, and down-regulate the phosphorylation levels of NF-κB/p65. In conclusion, betulin isolated from P. incarnata possessed outstanding anti-neuroinflammation potential, presumably related to iNOS expression, JNKs and NF-κB/p65 pathways. Therefore, Pyrola incarnata may be a valuable natural resource and betulin is a potential drug for the treatment of neurodegenerative disorders by inhibiting inflammatory mediators.


Asunto(s)
Diseño de Fármacos , Mediadores de Inflamación/farmacología , Inflamación/tratamiento farmacológico , Lipopolisacáridos/antagonistas & inhibidores , Pyrola/química , Triterpenos/farmacología , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Mediadores de Inflamación/química , Mediadores de Inflamación/aislamiento & purificación , Lipopolisacáridos/farmacología , Ratones , Conformación Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estereoisomerismo , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/aislamiento & purificación
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