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

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.

Browning Effects of a Chronic Pterostilbene Supplementation in Mice Fed a High-Fat Diet.

Obesity and related comorbidities are a major health concern. The drugs used to treat these conditions are largely inadequate or dangerous, and a well-researched approach based on nutraceuticals would be highly useful. Pterostilbene (Pt), i.e., 3,5-dimethylresveratrol, has been reported to be effective in animal models of obesity, acting on different metabolic pathways. We investigate here its ability to induce browning of white adipose tissue. Pt (5 µM) was first tested on 3T3-L1 mature adipocytes, and then it was administered (352 µmol/kg/day) to mice fed an obesogenic high-fat diet (HFD) for 30 weeks, starting at weaning. In the cultured adipocytes, the treatment elicited a significant increase of the levels of Uncoupling Protein 1 (UCP1) protein-a key component of thermogenic, energy-dissipating beige/brown adipocytes. In vivo administration antagonized weight increase, more so in males than in females. Analysis of inguinal White Adipose Tissue (WAT) revealed a trend towards browning, with significantly increased transcription of several marker genes (Cidea, Ebf2, Pgc1α, PPARγ, Sirt1, and Tbx1) and an increase in UCP1 protein levels, which, however, did not achieve significance. Given the lack of known side effects of Pt, this study strengthens the candidacy of this natural phenol as an anti-obesity nutraceutical.