Bergamot polyphenolic fraction potentiates rosuvastatin induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia

article i nfo Background: Statins are the most commonly prescribed drugs to reduce cardiometabolic risk. Besides the well- known efficacy of such compounds inboth preventing and treating cardiometabolicdisorders, some patients ex- perience statin-induced side effects. We hypothesize that the use of natural bergamot-derived polyphenols may allow patients undergoing statin treatment to reduce effective doses while achieving target lipid values. The aim ofthepresentstudyistoinvestigatetheoccurrenceofanenhancedeffectofbergamot-derivedpolyphenolicfrac- tion (BPF) on rosuvastatin-induced hypolipidemic and vasoprotective response in patients with mixed hyperlip- idemia. Methods: A prospective, open-label, parallel group, placebo-controlled study on 77 patients with elevated serum LDL-C and triglycerides was designed. Patients were randomly assigned to a control group receiving placebo (n = 15), two groups receiving orally administered rosuvastatin (10 and 20 mg/daily for 30 days; n =1 6 for each group), a group receiving BPF alone orally (1000 mg/daily for 30 days; n = 15) and a group receiving BPF (1000 mg/daily given orally) plus rosuvastatin (10 mg/daily for 30 days; n =1 5). Results: Both doses of rosuvastatin and BPF reduced total cholesterol, LDL-C, the LDL-C/HDL-C ratio and urinary mevalonate in hyperlipidemic patients, compared to control group. The cholesterol lowering effect was accom- panied by reductions of malondialdehyde, oxyLDL receptor LOX-1 and phosphoPKB, which are all biomarkers of oxidative vascular damage, in peripheral polymorphonuclear cells. Conclusions: Addition of BPF to rosuvastatin significantly enhanced rosuvastatin-induced effect on serum lipemic profile compared to rosuvastatin alone. This lipid-lowering effect was associated with significant reductions of biomarkers used for detecting oxidative vascular damage, suggesting a multi-action enhanced potential for BPF in patients on statin therapy. © 2013 Published by Elsevier Ireland Ltd.