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Open AccessArticle

Cholesterol-Lowering Action of a Novel Nutraceutical Combination in Uremic Rats: Insights into the Molecular Mechanism in a Hepatoma Cell Line

Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, 35131, Padova, Italy
PharmaNutra S.p.A., 56122, Pisa, Italy
Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, 43100, Parma, Italy
Laboratory of Physiopharmacology, Research Unit GENCOR, University of Antwerp, 2610, Antwerp, Belgium
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072, Tianjin, China
Dipartimento di Medicina, Università degli Studi di Padova, 35121, Padova, Italy
Medicina Generale I^-Ca' Foncello Hospital, 31100, Treviso, Italy
Author to whom correspondence should be addressed.
Nutrients 2020, 12(2), 436;
Received: 10 January 2020 / Revised: 5 February 2020 / Accepted: 6 February 2020 / Published: 9 February 2020
(This article belongs to the Section Nutrition and Metabolism)
Appropriate nutraceutical combinations may represent a valid approach to prevent vascular calcification associated with chronic kidney disease (CKD). In the present study, we tested the effect of a new nutraceutical combination named RenaTris®, containing MK-7, magnesium carbonate, and Sucrosomial® Iron, on vascular calcification in uremic rats. Rats were randomly divided into three groups, i.e. control (high-phosphate diet), uremic (high-phosphate diet containing 0.5% adenine), and supplemented uremic diet (0.5% adenine, MK-7, magnesium carbonate, and Sucrosomial® Iron). After six weeks, sera and vascular calcification were examined. The uremic diet increased creatinine and phosphate levels and induced extensive vascular calcification. The uremic condition also induced a mild hypercholesterolemic condition (+52% of total cholesterol; p < 0.05). The supplemented uremic diet did not reduce creatinine, phosphate levels, or vascular calcification, however, we observed a significant hypocholesterolemic effect (−18.9% in supplemental uremic vs. uremic diet; p < 0.05). Similar to simvastatin, incubation of cultured human hepatoma cells (Huh7) with MK-7 significantly reduced cholesterol biosynthesis (−38%) and induced 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and low-density lipoprotein receptor (LDLR) at both mRNA and protein levels. The effect of MK-7 on LDLR was counteracted by the co-incubation with squalene. Unlike simvastatin, MK-7 reduced PCSK9 in Huh7. These results indicated that the new nutraceutical combination significantly impacts cholesterol metabolism and its supplementation may help to control mild hypercholesterolemic conditions in CKD patients.
Keywords: MK-7; cholesterol; PCSK9; uremic; mevalonate pathway MK-7; cholesterol; PCSK9; uremic; mevalonate pathway
MDPI and ACS Style

Lupo, M.G.; Biancorosso, N.; Brilli, E.; Tarantino, G.; Adorni, M.P.; Vivian, G.; Salvalaio, M.; Dall’Acqua, S.; Sut, S.; Neutel, C.; Chen, H.; Bressan, A.; Faggin, E.; Rattazzi, M.; Ferri, N. Cholesterol-Lowering Action of a Novel Nutraceutical Combination in Uremic Rats: Insights into the Molecular Mechanism in a Hepatoma Cell Line. Nutrients 2020, 12, 436.

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