Bergamot (Citrus bergamia) peel extract as new hypocholesterolemic agent modulating PCSK9 expression

Citrus bergamia extracts have been studied for the management of hypercholesterolemia disorders. Up to now limited information is available concerning the activity of its main phytoconstituents towards the main targets of the cholesterol homeostasis. In the present study, the effects of bergamot peel extract and isolated constituents, namely glycosidic and non-glycosidic flavonoids, one coumarin and one limonoid on the low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) were evaluated by using cultured HuH7 cell line. Furthermore, for the first time the effects of bergamot peel extract were studied to describe a potential hypolipidemic action. Significant differences were observed due to glycosylation and different substitution on flavanone moiety (O-methylation). Considering the thirteen isolated compounds, both naringenin-7-O-rutinoside (NA-rut) and apigenin-6,8-C-glicoside induced the expression of the LDLR while no effect was observed o...