Open Access Article
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Effects of ‘Mapo’ tangelo (Citrus x tangelo) extracts, essential oil, and isolated compounds on LDL receptor and PCSK9 expression in human hepatocarcinoma cell line Huh7

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Irene Ferrarese , Maria Giovanna Lupo , Ilaria Rossi , Giorgia Marodin , Haixia Chen , Stefania Sut , Nicola Ferri and Stefano Dall'Acqua

Received 17th April 2025 , Accepted 12th June 2025

First published on 1st August 2025


Abstract

Peel (MPLE), pulp extract (MPPE) and the essential oil (MPO) of Citrus x tangelo were studied for their chemical composition and for their ability to act on the expression of low-density lipoprotein (LDL) receptor and proprotein convertase subtilisin/kexin 9 (PCSK9), two key players of cholesterol metabolism, in human hepatocarcinoma cell line Huh7. MPPE shows ability to induce LDL-R and to reduce PCSK9 respectively. Chemical characterization of the extracts was obtained by LC-DAD-MS for the MPLE and MPPE while by GC-MS for MPO. The main compounds in MPLE and MPPE were isolated and were ferulic acid, narirutin, 3’-methoxy-narirutin, nobiletin, 3-methoxynobiletin and tangeretin. MPPE significantly induced the LDL receptor (+1.43±0.49-fold vs basal) and suppress PCSK9 levels (-64±24% vs basal). Among the different isolated compounds ferulic acid showed the most interesting modulation of both the LDL receptor (+1.26±0.14-fold vs basal) and PCSK9 (-59±14% vs basal), showing potential cholesterol-lowering properties.


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