Polyphenols from Citrus Tacle® Extract Endowed with HMGCR Inhibitory Activity: An Antihypercholesterolemia Natural Remedy

Abstract

Tacle® is a citrus fruit obtained from the crossbreeding of Clementine and Tarocco cultivars. This fruit retains a promising nutraceutical potential most likely due to a high content in polyphenols, among which the main constituents are the two glycosides naringin and hesperidin. Herein, we evaluated, through an in vitro assay, the capability of Tacle extracts to inhibit the hydroxymethylglutaryl-CoA reductase enzyme, which plays a key role in cholesterol biosynthesis. The results obtained spurred us to investigate whether the anti-enzymatic activity observed may be due to a direct interaction of aglycones naringenin and hesperetin with the enzyme catalytic site. Molecular docking simulations indicated that these two compounds are able to anchor to the protein with binding modes and affinities similar to those found for statins, which represent mainstream medications against hypercholesterolemia. The overall results showed an interesting nutraceutical potential of Tacle, suggesting that its extract could be used for dietary supplementation in the treatment of moderate hypercholesterolemia.

Targeting of mitochondrial fission through natural flavanones elicits anti-myeloma activity

“…Data from our group and others have shown the lipid-lowering effects of citrus flavonoids [ 31 , 45 ]. Aberrant mitochondrial fission in cancer has been reported to rewire lipid metabolism by promoting the expression of master transcriptional activators of lipogenesis genes [ 46 ].…”

Mechanism Underlying Naringenin Hypocholesterolemic Effects: Involvement of Estrogen Receptor α Subtype

“…Moreover, docking analysis provided evidence that Nar can bind to the active site of HMGCR and compete with the ligand HMG-CoA, thus competitively inhibiting enzyme activity and reducing cholesterol intracellular synthesis [ 40 ]. More recently, another report highlights the direct inhibitory activity of Nar; notably, this compound anchors to HMGCR with modes and affinities like those observed for statins [ 13 ]. Despite this evidence, it has been postulated that the hypocholesterolemic activity of Nar may be exerted at multiple levels, but the exact molecular mechanisms are still unclear and deserve further investigation [ 36 , 41 ].…”

“…Interestingly, the Nar hypocholesterolemic effects may be determined by the direct HMGCR inhibition. Indeed, in vitro it has been shown that at millimolar doses, Nar directly interacts with HMGCR catalytic site with affinities similar to those observed for statins [ 13 ]. However, the precise molecular mechanisms underlying Nar effects are not fully elucidated.…”

Characterization and the cholesterol-lowering effect of dietary fiber from fermented black rice (Oryza sativa L.)

“…37 HMGCR is a rate-limiting enzyme in the production of cholesterol. [38][39][40] Compared with FG, the level of HMGCR in the FBL and FBH mice was significantly decreased ( p < 0.01), indicating that FB reduced the endogenous synthesis of cholesterol (Fig. 7C).…”