RESUMO
Honokiol, a small-molecule polyphenol derived and isolated from the Chinese medicinal herb Magnolia officinalis, has been shown to possess a wide range of pharmacological activities. In the present study, we aimed to investigate the effects of honokiol on tumor necrosis factor-α (TNF-α)-induced migration in rat aortic smooth muscle cells (RASMCs). We found that honokiol inhibited TNF-α-induced RASMC proliferation and migration in a dose-dependent manner. At the molecular level, pretreatment with honokiol blocked TNF-α-induced protein expression of matrix metalloproteinase (MMP)-2 and MMP-9, nuclear factor (NF)-κB activation, and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Moreover, NF-κB inhibitor (BAY 11-7028) and ERK inhibitor (U0126) also mimicked the inhibitory effects of honokiol in TNF-α-treated RASMCs. In conclusion, these results indicate that honokiol suppresses TNF-α-induced migration and MMP expression by blocking NF-κB activation via the ERK signaling pathway in RASMCs. Our findings support honokiol as a promising novel agent for the prevention and treatment of atherosclerosis.
Assuntos
Compostos de Bifenilo/farmacologia , Lignanas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Animais , Aorta/efeitos dos fármacos , Masculino , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Endothelial dysfunction is thought to be a major cause of vascular injury in smokers. Ghrelin is a recently discovered peptide that plays a modulatory role in atherosclerosis. However, it is unknown how ghrelin regulates nicotine-induced vascular cell adhesion molecule-1 (VCAM-1) expression. We examined nicotine-induced VCAM-1 expression in human umbilical vein endothelial cells pretreated with ghrelin and detected the activity of protein kinase C (PKC), p38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor (NF)-kappaB. Our study showed that ghrelin inhibited nicotine-induced VCAM-1 expression in human umbilical vein endothelial cells in a concentration-dependent and time-dependent way. We also found that ghrelin inhibited nicotine-induced PKC, p38 MAPK, and NF-kappaB activation. The results suggest that ghrelin inhibits nicotine-induced VCAM-1 expression, and PKC, p38 MAPK, and NF-kappaB play active roles in that process. Exogenous ghrelin may provide a possible approach for preventing or reversing atherosclerosis in smokers.