Defining the cholesterol lowering mechanism of bergamot (Citrus bergamia) extract in HepG2 and Caco-2 cells

Huang, Y., Tocmo, R. ORCID: https://orcid.org/0009-0007-4850-977X, Nauman, M. C. ORCID: https://orcid.org/0000-0002-1339-4745, Haughan, M. A. and Johnson, J. J. ORCID: https://orcid.org/0000-0001-5489-2372 (2021) Defining the cholesterol lowering mechanism of bergamot (Citrus bergamia) extract in HepG2 and Caco-2 cells. Nutrients, 13 (9). 3156. ISSN 2072-6643 doi: 10.3390/nu13093156

Abstract/Summary

<jats:p>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.</jats:p>

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/117260
Identification Number/DOI	10.3390/nu13093156
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Food Microbial Sciences Research Group
Publisher	MDPI
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