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

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    Micaela Gliozzi
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    Research Centre for Food Safety & Health (IRC-FSH), University “Magna Graecia”, Catanzaro, Italy
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    Ross Walker
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    Research Centre for Food Safety & Health (IRC-FSH), University “Magna Graecia”, Catanzaro, Italy
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    Saverio Muscoli
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    Department of Medicine, Chair of Cardiology, University of Rome Tor Vergata, Rome, Italy
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    Cristiana Vitale
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    IRCCS San Raffaele, Rome, Italy
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    Santo Gratteri
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    Research Centre for Food Safety & Health (IRC-FSH), University “Magna Graecia”, Catanzaro, Italy
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    Cristina Carresi
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    Research Centre for Food Safety & Health (IRC-FSH), University “Magna Graecia”, Catanzaro, Italy
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    Vincenzo Musolino
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    Research Centre for Food Safety & Health (IRC-FSH), University “Magna Graecia”, Catanzaro, Italy
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    Vanessa Russo
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    Research Centre for Food Safety & Health (IRC-FSH), University “Magna Graecia”, Catanzaro, Italy
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    Elzbieta Janda
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    Salvatore Ragusa
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    Research Centre for Food Safety & Health (IRC-FSH), University “Magna Graecia”, Catanzaro, Italy
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    Antonio Aloe
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    Ernesto Palma
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    Carolina Muscoli
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    Franco Romeo
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    Department of Medicine, Chair of Cardiology, University of Rome Tor Vergata, Rome, Italy
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    Vincenzo Mollace
    Correspondence
    Corresponding author at: Faculty of Pharmacy, Department of Health Sciences, University “Magna Graecia”, Complesso Ninì Barbieri, Roccelletta di Borgia, 88100 Catanzaro, Italy. Tel.: +39 0961 369 4128, +39 0961 369 5732; fax: +39 0961 369 4237.
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    1 Each author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
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    Research Centre for Food Safety & Health (IRC-FSH), University “Magna Graecia”, Catanzaro, Italy

    IRCCS San Raffaele, Rome, Italy
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Published:November 14, 2013DOI:https://doi.org/10.1016/j.ijcard.2013.08.125

      Abstract

      Background

      Statins are the most commonly prescribed drugs to reduce cardiometabolic risk. Besides the well-known efficacy of such compounds in both preventing and treating cardiometabolic disorders, some patients experience 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 of the present study is to investigate the occurrence of an enhanced effect of bergamot-derived polyphenolic fraction (BPF) on rosuvastatin-induced hypolipidemic and vasoprotective response in patients with mixed hyperlipidemia.

      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 = 16 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 = 15).

      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 accompanied 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.

      Keywords

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