Effect of a novel nutraceutical combination on serum lipoprotein functional profile and circulating PCSK9

Abstract

Background: A beneficial effect on cardiovascular risk may be obtained by improving lipid-related serum lipoprotein functions such as high-density lipoproteins (HDLs) cholesterol efflux capacity (CEC) and serum cholesterol loading capacity (CLC) and by reducing proprotein convertase subtilisin kexin type 9 (PCSK9), independently of lipoprotein concentrations.

Aim: We aimed to evaluate the effect of an innovative nutraceutical (NUT) combination containing red yeast rice (monacolin K 3.3 mg), berberine 531.25 mg and leaf extract of Morus alba 200 mg (LopiGLIK^®), on HDL-CEC, serum CLC and on circulating PCSK9 levels.

Materials and methods: Twenty three dyslipidemic subjects were treated for 4 weeks with the above NUT combination. HDL-CEC was measured using specific cell-based radioisotopic assays; serum CLC and PCSK9 concentrations were measured fluorimetrically and by enzyme-linked immunosorbent assay, respectively.

Results: The NUT combination significantly reduced plasma level of the total cholesterol and low-density lipoprotein cholesterol (-9.8% and -12.6%, respectively). Despite no changes in HDL-cholesterol, the NUT combination improved total HDL-CEC in 83% of the patients, by an average of 16%, as a consequence of the increase mainly of the ATP-binding cassette A1-mediated CEC (+28.5%). The NUT combination significantly reduced serum CLC (-11.4%) while it did not change PCSK9 plasma levels (312.9±69.4 ng/mL vs 334.8±103.5 mg/L, before and after treatment, respectively).

Conclusion: The present NUT combination improves the serum lipoprotein functional profile providing complementary beneficial effects, without any detrimental increase of PCSK9 plasma levels.

Keywords: HDL; Morus alba; PCSK9; berberine; cholesterol efflux capacity; macrophage; monacolin K; nutraceutical.

Figure 1

Effect of NUT combination on serum HDL-CEC. Notes: Total serum HDL-CEC (A), serum HDL-CEC mediated by ABCA1 (B) and by AD (C) in subjects (n=23) at baseline (T1, empty circles) and after (T2, black circles) consumption of the NUT combination. Each point represents the mean of values obtained from evaluation in triplicate of each serum sample. Horizontal lines represent the mean (±SD) of values within each subject group. Statistical significance was calculated by the two-tailed Student’s paired t-test. *p<0.05; ***p<0.001. Abbreviations: CEC, cholesterol efflux capacity; HDL, high-density lipoproteins; ABCA1, ATP-binding cassette transporter A1; AD, aqueous diffusion; NUT, nutraceutical.

Figure 2

Effect of NUT combination on serum CLC. Notes: CLC of serum from subjects (n=23) at baseline (T1, empty circles) and after (T2, black circles) consumption of the NUT combination. Each point represents the mean of the values obtained from evaluation in triplicate of each serum sample. Horizontal lines represent the mean (±SD) of values within each subject group. Statistical significance was calculated by the two-tailed Student’s paired t-test. *p<0.05. Abbreviations: NUT, nutraceutical; CLC, cholesterol loading capacity.

Figure 3

Effect of NUT combination on plasma levels of PCSK9. Notes: PCSK9 levels of serum from subjects (n=23) at baseline (T1, empty circles) and after (T2, black circles) consumption of the NUT combination. Each point represents the mean of the values obtained from evaluation in triplicate of each serum sample. Horizontal lines represent the mean (±SD) of values within each subject group. Statistical significance was calculated by the two-tailed Student’s paired t-test. Abbreviations: NUT, nutraceutical; PCSK9, proprotein convertase subtilisin kexin type 9 (PCSK9); ns, not significant.