RESUMO
Berberine, which is a wellknown drug used in traditional medicine, has been demonstrated to exert diverse pharmacological effects, including antiinflammatory effects. However, whether berberine can affect the production of inflammatory molecules in vascular endothelial cells remains to be elucidated. Therefore, the present study aimed to determine the effects of berberine, and the underlying molecular mechanisms of these effects. The effect of berberine on tumor necrosis factor (TNF)αinduced inflammatory molecule expression was examined in cultured human aortic endothelial cells (HAECs). The HAECs were stimulated with TNFα and incubated with or without berberine. The activation of nuclear factor (NF)κB and adenosine monophosphateactivated protein kinase (AMPK) were analyzed using western blotting, and the protein secretion of intercellular adhesion molecule (ICAM)1 and monocyte chemoattractant protein (MCP)1 was measured using ELISA kits. The mRNA expression levels of ICAM1 and MCP1 were analyzed using reverse transcriptionquantitative polymerase chain reaction. The results of the present study demonstrated that berberine significantly inhibited the TNFαinduced expression of ICAM1 and MCP1, as well as the activation of NFκB in the HAECs. These effects were attenuated following cotreatment with AMPK inhibitor compound C, or specific small interfering RNAs. In conclusion, the results of the present study indicated that berberine inhibits the TNFαinduced expression of ICAM1 and MCP1, and the activation of NFκB in HAECs in vitro, possibly through the AMPKdependent pathway.
Assuntos
Proteínas Quinases Ativadas por AMP/genética , Anti-Inflamatórios não Esteroides/farmacologia , Berberina/farmacologia , Células Endoteliais/efeitos dos fármacos , NF-kappa B/genética , Fator de Necrose Tumoral alfa/farmacologia , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular , Quimiocina CCL2/agonistas , Quimiocina CCL2/antagonistas & inibidores , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Humanos , Inflamação , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , NF-kappa B/agonistas , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/agonistas , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Berberine, a type of isoquinoline alkaloid isolated from Chinese medicinal herbs, has been reported to have various pharmacological activities. Studies have demonstrated that berberine has beneficial effects on vascular remodeling and alleviates restenosis after vascular injury. However, its mechanism of action on vascular smooth muscle cell migration is not fully understood. We therefore investigated the effect of berberine on human aortic smooth muscle cell (HASMC) migration. Boyden chamber assay was performed to show that berberine inhibited HASMC migration dosedependently. Real-time PCR and Western blotting analyses showed that levels of matrix metalloproteinase (MMP)-2, MMP-9, and urokinase-type plasminogen activator (u-PA) were reduced by berberine at both the mRNA and protein levels. Western blotting assay further confirmed that activities of c-Fos, c-Jun, and NF-κB were significantly attenuated. These results suggest that berberine effectively inhibited HASMC migration, possibly by down-regulating MMP-2, MMP-9, and u-PA; and interrupting AP-1 and NF-κB mediated signaling pathways.