RESUMEN
BACKGROUND: In the present study, we examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1-4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and TNF-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA). RESULTS: The methanolic extract and dichloromethane fraction exerted potent inhibitory effects on the production of all three pro-inflammatory cytokines, with IC50 values ranging from 0.60 ± 0.01 to 26.19 ± 0.64 µg/mL. Four highly pure steroid derivatives (1-4) were isolated from the dichloromethane fraction and water layer of P. nodosus. Potent inhibitory activities were also observed for (25S) 5α-cholestane-3ß,4ß,6α,7α,8ß,15α,16ß,26-octol (3) on the production of IL-12 p40 and IL-6 (IC50s = 3.11 ± 0.08 and 1.35 ± 0.03 µM), and for (25S) 5α-cholestane-3ß,6α,8ß,15α,16ß,26-hexol (1) and (25S) 5α-cholestane-3ß,6α,7α,8ß,15α,16ß,26-heptol (2) on the production of IL-12 p40 (IC50s = 0.01 ± 0.00 and 1.02 ± 0.01 µM). Moreover, nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6 production. CONCLUSION: This is the first report of the anti-inflammatory activity from the starfish P. nodosus. The main finding of this study is the identification oxygenated steroid derivatives from P. nodosus with potent anti-inflammatory activities that may be developed as therapeutic agents for inflammatory diseases.
Asunto(s)
Antiinflamatorios/análisis , Células Dendríticas/efectos de los fármacos , Subunidad p40 de la Interleucina-12/farmacología , Interleucina-6/farmacología , Estrellas de Mar/química , Factor de Necrosis Tumoral alfa/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Concentración 50 Inhibidora , Subunidad p40 de la Interleucina-12/análisis , Interleucina-6/análisis , Lipopolisacáridos , Ratones Endogámicos C57BL , Cultivo Primario de Células , Esteroides/administración & dosificación , Factor de Necrosis Tumoral alfa/análisis , VietnamRESUMEN
BACKGROUND: In the present study, we examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1-4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and TNF-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA). RESULTS: The methanolic extract and dichloromethane fraction exerted potent inhibitory effects on the production of all three pro-inflammatory cytokines, with IC50 values ranging from 0.60 ± 0.01 to 26.19 ± 0.64 µg/mL. Four highly pure steroid derivatives (1-4) were isolated from the dichloromethane fraction and water layer of P. nodosus. Potent inhibitory activities were also observed for (25S)5α-cholestane-3ß,4ß,6α,7α,8ß,15α,16ß,26-octol (3) on the production of IL-12 p40 and IL-6 (IC50s = 3.11 ± 0.08 and 1.35 ± 0.03 µM), and for (25S) 5α-cholestane-3ß,6α,8ß,15α,16ß,26-hexol (1) and (25S)5α-cholestane-3ß,6α,7α,8ß,15α,16ß,26-heptol (2) on the production of IL-12 p40 (IC50s = 0.01 ± 0.00 and and 1.02 ± 0.01 µM). Moreover, nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6 production. CONCLUSION: This is the first report of the anti-inflammatory activity from the starfish P. nodosus. The main finding of this study is the identification oxygenated steroid derivatives from P. nodosus with potent anti-inflammatory activities that may be developed as therapeutic agents for inflammatory diseases.