Abstract 406: Flavocoxid a Dual Cox/Lox Inhibitor Reduces Atherosclerosis Development in ApoE KO Mice Fed With a Western High Fat Diet

Abstract

Flavocoxid is composed by two flavonoids, baicalin and catechin and it exerts anti-inflammatory effect blocking the peroxidase activity of COX1/2 and 5-LOX. This balanced inhibition prevents the development of adverse effects as demonstrated in clinical trials. The antinflammatory effect of flavocoxid was tested in ApoE knock out mice fed with a high fat western diet. Mice (of both sex) were 5 weeks old at the beginning of the experiment and were fed with a high fat diet for 8 weeks. Mice were randomized to receive: vehicle, or simvastatin (40mg/kg/day by oral suspension), or flavocoxid by oral suspension at the human equivalent dose of 500 mg/day (20mg/kg/day) that was previously reported effective in other inflammatory conditions. The body weight, food intake, cholesterol, and triglyceride levels were recorded every week and at the time of sacrifice the thoracic aorta, liver, and blood samples were taken. Flavocoxid supplementation reduced blood levels of triglycerides and cholesterol and the extent of atherosclerotic plaques. In liver samples the mRNA expression of PPAR-alpha and SREBP-1 was significantly affected by flavocoxid supplementation (p less than 0.05 vs untreated ApoE mice), and the western blot analysis demonstrated an increased expression of the AMPK-alpha kinase demonstrating increased cellular metabolism in treated animals (p less than 0.05 vs untreated ApoE mice). The positive results obtained in this pre-clinical model further support the use of flavocoxid to reduce the atherosclerotic burden.