Comparative Effect of Bergamot Polyphenolic Fraction and Red Yeast Rice Extract in Rats Fed a Hyperlipidemic Diet: Role of Antioxidant Properties and PCSK9 Expression

Abstract

Elevated serum cholesterol levels, either associated or not with increased triglycerides, represent a risk of developing vascular injury, mostly leading to atherothrombosis-related diseases including myocardial infarction and stroke. Natural products have been investigated in the last few decades as they are seen to offer an alternative solution to counteract cardiometabolic risk, due to the occurrence of side effects with the use of statins, the leading drugs for treating hyperlipidemias. Red yeast rice (RYR), a monacolin K-rich natural extract, has been found to be effective in counteracting high cholesterol, being its use accompanied by consistent warnings by regulatory authorities based on the potential detrimental responses accompanying its statin-like chemical charcateristics. Here we compared the effects of RYR with those produced by bergamot polyphenolic fraction (BPF), a well-known natural extract proven to be effective in lowering both serum cholesterol and triglycerides in animals fed a hyperlipidemic diet. In particular, BPF at doses of 10 mg/Kg given orally for 30 consecutive days, counteracted the elevation of both serum LDL cholesterol (LDL-C) and triglycerides induced by the hyperlipidemic diet, an effect which was accompanied by significant reductions of malondialdehyde (MDA) and glutathione peroxidase serum levels, two biomarkers of oxidative stress. Furthermore, the activity of BPF was associated to increased HDL cholesterol (HDL-C) levels and to strong reduction of Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels which were found increased in hyperlipidemic rats. In contrast, RYR at doses of 1 and 3 mg/Kg, produced only significant reduction of LDL-C with very poor effects on triglycerides, HDL-C, glutathione peroxidase, MDA and PCSK9 expression. This indicates that while BPF and RYR both produce serum cholesterol-lowering benefits, BPF produces additional effects on triglycerides and HDL cholesterol compared to RYR at the doses used throughout the study. These additional effects of BPF appear to be related to the reduction of PCSK9 expression and to the antioxidant properties of this extract compared to RYR, thereby suggesting a more complete protection from cardiometabolic risk.

Keywords: bergamot polyphenolic fraction (BPF); hypercholesterolemia; malondialdehyde (MDA); oxidative stress; proprotein convertase subtilisin/kexin type 9 (PCSK9); red yeast rice (RYR).

Figure 1

The effect of BPF (Group 3) or RYR (Groups 4 and 5) in PCSK9 serum levels in rats fed a hyperlipidemic diet (Group 2) compared to control rats (Group 1).*: p < 0.05 Control (Group 1) vs. Hyperlipidemic rats (Group 2); ^§: p < 0.05 Hyperlipidemic (Group 2) vs. BPF or RYR (Groups 3–5). Abbreviations. BPF: Bergamot Poliphenolic Fraction; RYR: Red yeast rice; PCSK9: Proprotein convertase subtilisin/kexin type 9.

Figure 2

The effect of BPF (Group 3) or RYR (Groups 4 and 5) on MDA serum levels in rats fed a hyperlipidemic diet (Group 2) compared to control rats (Group 1). *: p < 0.05 Control (Group 1) vs. Hyperlipidemic rats (Group 2); ^§: p < 0.05 Hyperlipidemic (Group 2) vs. BPF or RYR (Groups 3–5), respectively. Abbreviations. BPF: Bergamot Poliphenolic Fraction; RYR: Red yeast rice; MDA: malondialdehyde.