Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene

Abstract

The ability of the coumarin derivative cloricromene (8‐monochloro‐3‐β‐diethylaminoethyl‐4‐methyl‐7‐ethoxy‐carbonylmethoxycoumarin) to inhibit monocyte adhesion to human cultured umbilical vein endothelial cells (HUVEC) was investigated. Cloricromene (10–200 μm) inhibited, in a concentration‐dependent manner, the adhesion of both resting and activated monocytes to HUVEC. Significant inhibition was reached with drug concentrations ranging between 15 to 30 μm. The inhibitory activity was, at least in large part, directed to monocytes since no inhibition was observed after selective preincubation of HUVEC with cloricromene and the drug maintained its effect also on monocyte adhesion to paraformaldehyde‐treated HUVEC. Inhibition was maximal after 1 min of exposure of monocytes to cloricromene and persisted even in the absence of the drug. Both basal and chemoattractant‐mediated monocyte adhesion was inhibited by cloricromene as it was by TS1/18, a monoclonal antibody (mAb) directed to β2 integrins; however, cytofluorimetric analysis showed that cloricromene was unable to modulate the expression of β2 integrins on the monocyte surface. When monocyte adhesion was mediated by a large set of adhesive receptors, as obtained after treatment of HUVEC with either interleukin 1β (IL‐1; 50 ng ml−1) or tumour necrosis factor‐α (TNF; 100 u ml−1), the inhibitory effect of cloricromene was considerably reduced. The results of this study show that cloricromene may regulate monocyte adhesion to HUVEC, an event relevant in vivo in the pathogenesis of inflammatory and atherosclerotic processes.

Inhibition of PAF synthesis by stimulated human polymorphonuclear leucocytes with cloricromene, an inhibitor of phospholipase A2 activation

“…It is conceivable that a drug simultaneously inhibiting the synthesis of both leukotrienes and PAF may be advantageous in a series of conditions where the interaction between activated leucocytes and the vessel wall plays a pathogenic role. PAF appears to modulate leucocyte adhesion to, or migration through, the endothelium (Zimmerman et al, 1986) and it is tempting to speculate that the inhibitory activity of cloricromene on PAF-synthesis may in part contribute to the ability of this drug to inhibit some leucocyte functions, especially adhesion to the endothelium (Bertocchi et al, 1989;Tranchina et al, 1994).…”

“…Cloricromene is a coumarine derivative which possesses vasodilator, antithrombotic and antiischaemic activity in animals (Aporti et al, 1987;Prosdocimi et al, 1985;Cirillo et al, 1992;Lidbury et al, 1993) and which reduces several leucocyte functions, including chemotaxis, adhesion, superoxide anion generation, and tumour necrosis factor a (TNF-cx) release (Bertocchi et al, 1989;Squadrito et al, 1991;Tranchina et al, 1994).…”

Anti-Inflammatory Activity of Ferula assafoetida Oleo-Gum-Resin (Asafoetida) against TNF-α-Stimulated Human Umbilical Vein Endothelial Cells (HUVECs)

“…The LC-MS analysis revealed the existence of 33 different compounds in this plant, including foetisulfide A, foetisulfide C, fetidone B, assafoetidin, umbelliprenin, and others, which may have a role in the inflammation-induced action. In this context, some studies demonstrated that luteolin and coumarin, as important constituents of the asafoetida, suppress ROS formation and reduce monocyte adhesion to TNF- α -stimulated HUVECs [ 35 , 36 ]. Khaghanzadeh and colleagues revealed that umbelliprenin, a sesquiterpene coumarin, induces anti-inflammatory responses via an increase in the secretion of anti-inflammatory cytokines in the sera and splenocytes of mice [ 37 ].…”