Targeting of LOX-1 by willow bark, its etoh-fraction and by the antidepressant imipramine

The NESDA-study showed a higher likelihood of atherosclerosis in depressive disorders¹, extending indications for anti-inflammatory drugs. The oxidized LDL receptor-1 (LOX-1) represents a key mo-lecule in atherosclerosis and a promising drug target, but appears different from “druggable” targets like G protein-coupled receptors². We examined whether willow bark (WB), its salicin rich ethanol fraction and the tricyclic antidepressant imipramine modulate gene-expressions of LOX-1, MCP-1 and CRP in peripheral blood of rats in a model of depression. Male Sprague Dawley rats (n=12 per group), treated for 14 days p.o. with WB extract STW 33-I (group A), its salicin rich fraction (group B) or imipramine (group C), showed a reduction of immobility time in the Porsolt Swimming Test³. Gene expressions of all groups (n=4 per group) were analysed by Agilent whole genome microarray, validated by reverse transcriptase-PCR and compared to those of untreated controls (n=4)³. Trans-cripts of LOX-1 were down regulated (-6.1 to -9.3 fold, p<0.01) in all groups (Microarray, RT-PCR). CRP-transcripts were down regulated (-3.9 to -2.9, p<0.05) whereas MCP-1 was not regulated (Microarray). Thus, the gene expression of LOX-1 is targeted by WB and imipramine. Transcript down regulation of LOX-1 may be easier than a receptor blockage. Further studies should elucidate WB's mode of action for a co-medication in indications with low grade inflammation.

1)J Psychosom Res. 2010 Aug;69(2):203–10. 2) Cardiovasc Drug Ther 2011; 25:379–391. 3) Phytomedicine 2012, 19(3–4):322–9.