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Molecules ; 23(12)2018 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-30513815

RESUMEN

Flavonoids, widely present in medicinal plants and fruits, are known to exhibit multiple pharmacological activities. In this study, we isolated a flavonoid compound, pilloin, from Aquilaria sinensis and investigated its anti-inflammatory activity in bacterial lipopolysaccharide-induced RAW 264.7 macrophages and septic mice. Pilloin inhibited NF-κB activation and reduced the phosphorylation of IκB in LPS-stimulated macrophages. Moreover, pilloin significantly suppressed the production of pro-inflammatory molecules, such as TNF-α, IL-6, COX-2 and iNOS, in LPS-treated RAW 264.7 macrophages. Additionally, pilloin suppressed LPS-induced morphological alterations, phagocytic activity and ROS elevation in RAW 264.7 macrophages. The mitogen-activated protein kinase-mediated signalling pathways (including JNK, ERK, p38) were also inhibited by pilloin. Furthermore, pilloin reduced serum levels of TNF-α (from 123.3 ± 7 to 46.6 ± 5.4 ng/mL) and IL-6 levels (from 1.4 ± 0.1 to 0.7 ± 0.1 ng/mL) in multiple organs of LPS-induced septic mice (liver: from 71.8 ± 3.2 to 36.7 ± 4.3; lung: from 118.6 ± 10.6 to 75.8 ± 11.9; spleen: from 185.9 ± 23.4 to 109.6 ± 18.4; kidney: from 160.3 ± 11.8 to 75 ± 10.8 pg/mL). In summary, our results demonstrate the anti-inflammatory potential of pilloin and reveal its underlying molecular mechanism of action.


Asunto(s)
Antiinflamatorios/farmacología , Flavonoides/farmacología , Thymelaeaceae/química , Animales , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Flavonoides/química , Flavonoides/aislamiento & purificación , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fagocitosis/efectos de los fármacos , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Sepsis/patología
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