Abstract
Bergamot, a Mediterranean citrus fruit native to southern Italy, has been reported to have cholesterol-lowering properties; however, the mechanism of action is not well understood. Due to structural similarities with 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors, it has been proposed that the phenolic compounds in bergamot may also inhibit HMGCR. Statins are widely used for their cholesterol-lowering properties; however, they are not universally well tolerated, suggesting there is a need to identify novel cholesterol-lowering strategies. In the present study, we investigated bergamot fruit extract (BFE) and its principal components (neoeriocitrin, naringin, neohesperidin, melitidin, and brutieridin) for their ability to regulate cholesterol levels in HepG2 and Caco-2 cells. BFE at increasing concentrations decreased the levels of total and free cholesterol in HepG2 cells. BFE and its constituents did not directly inhibit HMGCR activity. However, BFE and neohesperidin decreased HMGCR levels in HepG2 cells, suggesting that neohesperidin and BFE may downregulate HMGCR expression. An increase in AMP-kinase phosphorylation was observed in BFE and neohesperidin-treated cells. In Caco-2 cells, brutieridin exhibited a significant reduction in cholesterol uptake and decreased the level of Niemann-Pick C1 Like 1, an important cholesterol transporter. Taken together, our data suggest that the cholesterol-lowering activity of bergamot is distinct from statins. We hypothesize that BFE and its principal constituents lower cholesterol by inhibiting cholesterol synthesis and absorption.
Highlights
It has been widely recognized that lowering cholesterol reduces atherosclerotic cardiovascular disease (ASCVD) risk [1,2]
bergamot fruit extract (BFE) and its principal constituents reduce cholesterol in a mechanism that is distinct from direct inhibition of hydroxy-3-methylglutaryl coenzyme A (HMG-certificate of analysis (CoA)) reductase, as has been suggested previous laboratory and clinical studies
This is significant as there is evidence that bergamot fruit extract does not share the same pharmacological mechanism as the cholesterol-lowering drugs known as statins
Summary
It has been widely recognized that lowering cholesterol reduces atherosclerotic cardiovascular disease (ASCVD) risk [1,2]. Many patients do not attain their risk-based target LDL-C level with a statin therapy set for either a high risk (LDL-C target
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