摘要
Luteolin is an active ingredient found early from Fofium perillae and Flos Ionicerae, and has a specific inhibition on phosphodiesterase 4 （PDE4） activity in vitro. Researches show luteolin has pharmacological effects of anti-inflammation, anti-anaphylaxis, antitumor, antioxidant, protection of nervous system and so on, and has mainly been used for the treatment of respiratory inflammatory diseases, cancer and cardiovascular disease in clinic. PDE4, specific to hydrolyze cyclic AMP （cAMP）, is considered to be a new anti-inflammatory target due to the decisive role on cAMP signal in inflammatory cells such as neutrophils. In order to explore the anti-inflammatory mechanism, we further studied the effects of luteolin on the activity and expression of PDE4, the expression of lymphocyte function-associated antigen-1 （LFA-1） and macrophage-1 （MAC-l） in neutrophils, and the adhesion of neutrophils and endothelial cells. The results showed that luteolin had a dose-dependent inhibition on both bare PDE4 activity and PDE4 in cultured neutrophils, and had an obviously promotive effect on gene expressions of PDE4A, 4B and 4D in later period. Luteolin had a significant inhibitory effect on neutrophils adhesion and LFA-1 expression in early stage, and had no obvious effect on MAC-1 expression. Therefore, luteolin can inhibit LFA-1 expression of neutrophils, then inhibit the adhesion of neutrophils and endothelial cells, and the mechanism is at least related with the inhibition of PDE4 activity.
Luteolin is an active ingredient found early from Fofium perillae and Flos Ionicerae, and has a specific inhibition on phosphodiesterase 4 （PDE4） activity in vitro. Researches show luteolin has pharmacological effects of anti-inflammation, anti-anaphylaxis, antitumor, antioxidant, protection of nervous system and so on, and has mainly been used for the treatment of respiratory inflammatory diseases, cancer and cardiovascular disease in clinic. PDE4, specific to hydrolyze cyclic AMP （cAMP）, is considered to be a new anti-inflammatory target due to the decisive role on cAMP signal in inflammatory cells such as neutrophils. In order to explore the anti-inflammatory mechanism, we further studied the effects of luteolin on the activity and expression of PDE4, the expression of lymphocyte function-associated antigen-1 （LFA-1） and macrophage-1 （MAC-l） in neutrophils, and the adhesion of neutrophils and endothelial cells. The results showed that luteolin had a dose-dependent inhibition on both bare PDE4 activity and PDE4 in cultured neutrophils, and had an obviously promotive effect on gene expressions of PDE4A, 4B and 4D in later period. Luteolin had a significant inhibitory effect on neutrophils adhesion and LFA-1 expression in early stage, and had no obvious effect on MAC-1 expression. Therefore, luteolin can inhibit LFA-1 expression of neutrophils, then inhibit the adhesion of neutrophils and endothelial cells, and the mechanism is at least related with the inhibition of PDE4 activity.
基金
financial support of the Beijing Natural Science Foundation, China (6112007)
the National Natural Science Foundation of China (31101851)
the Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality, China (PHR201107134)
the Comprehensive Reforming Project to promote talents training of Beijing University of Agriculture, China (BNRC&GG201404)
