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Current Vascular Pharmacology

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ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

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Research Article

A Nutraceutical Compound Containing a Low Dose of Monacolin K, Polymethoxyflavones, Phenolic Acids, Flavonoids, and Hydroxytyrosol Improves HDL Functionality

Author(s): Carlo Cervellati, Alessandro Trentini, Valentina Rosta, Giovanni Zuliani, Francesco Vieceli Dalla Sega*, Francesca Fortini, Paola Rizzo, Paolo Cimaglia and Gianluca Campo

Volume 21, Issue 6, 2023

Published on: 26 October, 2023

Page: [433 - 442] Pages: 10

DOI: 10.2174/1570161121666230221142131

Price: $65

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Abstract

Background: In earlier studies, it has been observed that 8-week treatment with a novel nutraceutical compound (NC) containing low monacolin K dose, polymethoxyflavones, phenolic acids, flavonoids, and hydroxytyrosol improves lipid profile and endothelial function and reduces the level of oxidized low-density lipoprotein (oxLDL). We hypothesize that this effect might be, at least in part, explained by positive modulation exerted by the NC on the atheroprotective function of high-density lipoprotein (HDL).

Aim: This study aimed to evaluate whether the NC could influence determinants of HDL function.

Methods: Forty-five subjects with low-moderate dyslipidaemia were enrolled and treated for 8 weeks with the NC, followed by 4 weeks of washout. Blood samples were collected at every time point to evaluate changes in lipid profile, endothelial function, oxLDL, and markers of HDL function, such as the anti-oxidant activities of paraoxonase-1, glutathione peroxidase-3 (Gpx3), lipoprotein-phospholipase A2 (Lp-PLA2), and pro-oxidant activity of myeloperoxidase (MPO).

Results: Although the concentration of HDL-C did not change, the activity of Lp-PLA2 significantly decreased upon treatment (-11.6%, p<0.001) and returned to baseline level 4 weeks after the end of treatment. In contrast, Gpx3 increased after treatment (+5%, p<0.01) and remained unvaried after 4 weeks. Both MPO activity and concentration significantly decreased after the washout period (-33 and 32%, p<0.001).

Conclusion: For the first time, it was found that the administration of an NC with beneficial effects on lipid homeostasis also positively impacts HDL function by improving the balance between protective and damaging determinants. Further investigation is required to corroborate our findings.

Keywords: Nutraceutical compound, high-density lipoprotein, glutathione peroxidase-3, lipoprotein-phospholipase A2, myeloperoxidase, monacolin K dose, polymethoxyflavones, phenolic acids, flavonoids, hydroxytyrosol.

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[1]
Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. Am J Med 1977; 62(5): 707-14.
[http://dx.doi.org/10.1016/0002-9343(77)90874-9] [PMID: 193398]
[2]
Assmann G, Schulte H, von Eckardstein A, Huang Y. High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis 1996; 124 (Suppl.): S11-20.
[http://dx.doi.org/10.1016/0021-9150(96)05852-2] [PMID: 8831911]
[3]
Wilkins JT, Ning H, Stone NJ, et al. Coronary heart disease risks associated with high levels of HDL cholesterol. J Am Heart Assoc 2014; 3(2): e000519.
[http://dx.doi.org/10.1161/JAHA.113.000519] [PMID: 24627418]
[4]
Tenkanen L, Mänttäri M, Kovanen PT, Virkkunen H, Manninen V. Gemfibrozil in the treatment of dyslipidemia: An 18-year mortality follow-up of the Helsinki heart study. Arch Intern Med 2006; 166(7): 743-8.
[5]
Behar S, Brunner D, Kaplinsky E, Mandelzweig L, Benderly M. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: The bezafibrate infarction prevention (BIP) study. Circulation 2000; 102(1): 21-7.
[6]
Rosenson RS, Brewer HB, Ansell BJ, et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol 2016; 13(1): 48-60.
[http://dx.doi.org/10.1038/nrcardio.2015.124]
[7]
Cervellati C, Vigna GB, Trentini A, et al. Paraoxonase-1 activities in individuals with different HDL circulating levels: Implication in reverse cholesterol transport and early vascular damage. Atherosclerosis 2019; 285: 64-70.
[http://dx.doi.org/10.1016/j.atherosclerosis.2019.04.218] [PMID: 31029939]
[8]
Soria-Florido MT, Castañer O, Lassale C, et al. Dysfunctional high-density lipoproteins are associated with a greater incidence of acute coro-nary syndrome in a population at high cardiovascular risk. Circulation 2020; 141(6): 444-53.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.041658] [PMID: 31941372]
[9]
Calabresi L, Gomaraschi M, Simonelli S, Bernini F, Franceschini G. HDL and atherosclerosis: Insights from inherited HDL disorders. Biochim Biophys Acta Mol Cell Biol Lipids 2015; 1851(1): 13-8.
[http://dx.doi.org/10.1016/j.bbalip.2014.07.015] [PMID: 25068410]
[10]
Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest 1998; 101(8): 1581-90.
[http://dx.doi.org/10.1172/JCI1649] [PMID: 9541487]
[11]
Fisher EA, Feig JE, Hewing B, Hazen SL, Smith JD. High-density lipoprotein function, dysfunction, and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 2012; 32(12): 2813-20.
[http://dx.doi.org/10.1161/ATVBAHA.112.300133] [PMID: 23152494]
[12]
Trentini A, Rosta V, Spadaro S, et al. Development, optimization and validation of an absolute specific assay for active myeloperoxidase (MPO) and its application in a clinical context: role of MPO specific activity in coronary artery disease. Clin Chem Laboratory Med (CCLM) 2020; 58(10): 1749-58.
[http://dx.doi.org/10.1515/cclm-2019-0817] [PMID: 32031967]
[13]
Passaro A, Vigna GB, Romani A, et al. Distribution of paraoxonase-1 (PON-1) and lipoprotein phospholipase A2 (Lp-PLA2) across lipoprotein subclasses in subjects with type 2 diabetes. Oxid Med Cell Longev 2018; 2018: 1752940.
[http://dx.doi.org/10.1155/2018/1752940] [PMID: 30524650]
[14]
Cai R, Huang R, Han J, et al. Lipoprotein-associated phospholipase A2 is associated with risk of mild cognitive impairment in chinese patients with type 2 diabetes. Sci Rep 2017; 7(1): 12311.
[http://dx.doi.org/10.1038/s41598-017-12515-z] [PMID: 28951620]
[15]
Chang C, Worley BL, Phaëton R, Hempel N. Extracellular glutathione peroxidase GPx3 and its role in cancer. Cancers (Basel) 2020; 12(8): 2197.
[http://dx.doi.org/10.3390/cancers12082197] [PMID: 32781581]
[16]
Furlong CE, Marsillach J, Jarvik GP, Costa LG. Paraoxonases-1, -2 and -3: What are their functions? Chem Biol Interact 2016; 259(Pt B): 51-62.
[http://dx.doi.org/10.1016/j.cbi.2016.05.036] [PMID: 27238723]
[17]
Costa LG, Vitalone A, Cole TB, Furlong CE. Modulation of paraoxonase (PON1) activity. Biochem Pharmacol 2005; 69(4): 541-50.
[http://dx.doi.org/10.1016/j.bcp.2004.08.027] [PMID: 15670573]
[18]
Camps J, Marsillach J, Joven J. Pharmacological and lifestyle factors modulating serum paraoxonase-1 activity. Mini Rev Med Chem 2009; 9(8): 911-20.
[http://dx.doi.org/10.2174/138955709788681591] [PMID: 19601886]
[19]
Pastori D, Carnevale R, Menichelli D, et al. Is there an interplay between adherence to mediterranean diet, antioxidant status, and vascular disease in atrial fibrillation patients? Antioxid Redox Signal 2016; 25(14): 751-5.
[http://dx.doi.org/10.1089/ars.2016.6839] [PMID: 27577528]
[20]
Cimaglia P, Vieceli Dalla Sega F, Vitali F, et al. Effectiveness of a novel nutraceutical compound containing red yeast rice, polymethoxyflavones and antioxidants in the modulation of cholesterol levels in subjects with hypercholesterolemia and low-moderate cardiovascular risk: The nirvana study. Front Physiol 2019; 10: 217.
[http://dx.doi.org/10.3389/fphys.2019.00217] [PMID: 30914970]
[21]
Guerrero-Bonmatty R, Gil-Fernández G, Rodríguez-Velasco FJ, Espadaler-Mazo J. A combination of Lactoplantibacillus plantarum Strains CECT7527, CECT7528, and CECT7529 plus monacolin K reduces blood cholesterol: Results from a randomized, double-blind, placebo-controlled study. Nutrients 2021; 13(4): 1206.
[http://dx.doi.org/10.3390/nu13041206] [PMID: 33917503]
[22]
Heinz T, Schuchardt JP, Möller K, Hadji P, Hahn A. Low daily dose of 3 mg monacolin K from RYR reduces the concentration of LDL-C in a randomized, placebo-controlled intervention. Nutr Res 2016; 36(10): 1162-70.
[http://dx.doi.org/10.1016/j.nutres.2016.07.005] [PMID: 27865358]
[23]
Piepoli MF, Hoes AW, Agewall S, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2016; 37(29): 2315-81.
[http://dx.doi.org/10.1093/eurheartj/ehw106] [PMID: 27222591]
[24]
Cervellati C, Bonaccorsi G, Trentini A, et al. Paraoxonase, arylesterase and lactonase activities of paraoxonase-1 (PON1) in obese and severely obese women. Scand J Clin Lab Invest 2018; 78(1-2): 18-24.
[http://dx.doi.org/10.1080/00365513.2017.1405274] [PMID: 29168398]
[25]
Hayek J, Cervellati C, Crivellari I, Pecorelli A, Valacchi G. Lactonase activity and lipoprotein-phospholipase A 2 as possible novel serum biomarkers for the differential diagnosis of autism spectrum disorders and rett syndrome: Results from a pilot study. Oxid Med Cell Longev 2017; 2017: 5694058.
[http://dx.doi.org/10.1155/2017/5694058] [PMID: 29317982]
[26]
Vieceli Dalla Sega F, Fortini F, Aquila G, et al. Ticagrelor improves endothelial function by decreasing circulating epidermal growth factor (EGF). Front Physiol 2018; 9: 337.
[http://dx.doi.org/10.3389/fphys.2018.00337] [PMID: 29686623]
[27]
Pannella M, Caliceti C, Fortini F, et al. Serum from advanced heart failure patients promotes angiogenic sprouting and affects the notch pathway in human endothelial cells. J Cell Physiol 2016; 231(12): 2700-10.
[http://dx.doi.org/10.1002/jcp.25373] [PMID: 26987674]
[28]
Cicero AFG, D’Addato S, Borghi C. A randomized, double-blinded, placebo-controlled, clinical study of the effects of a nutraceutical combi-nation (LEVELIP DUO®) on LDL cholesterol levels and lipid pattern in subjects with sub-optimal blood cholesterol levels (NATCOL Study). Nutrients 2020; 12(10): 3127.
[http://dx.doi.org/10.3390/nu12103127] [PMID: 33066334]
[29]
Mazza A, Schiavon L, Rigatelli G, Torin G, Montanaro F, Lenti S. The short-term supplementation of monacolin K improves the lipid and metabolic patterns of hypertensive and hypercholesterolemic subjects at low cardiovascular risk. Food Funct 2018; 9(7): 3845-52.
[http://dx.doi.org/10.1039/C8FO00415C] [PMID: 29951651]
[30]
Xiong Z, Cao X, Wen Q, et al. An overview of the bioactivity of monacolin K/lovastatin. Food Chem Toxicol 2019; 131: 110585.
[http://dx.doi.org/10.1016/j.fct.2019.110585] [PMID: 31207306]
[31]
Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005; 45(1): 89-118.
[http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.095748] [PMID: 15822172]
[32]
Lorenzon dos Santos J, Schaan de Quadros A, Weschenfelder C, Bueno Garofallo S, Marcadenti A. Oxidative stress biomarkers, nut-related antioxidants, and cardiovascular disease. Nutrients 2020; 12(3): 682.
[http://dx.doi.org/10.3390/nu12030682] [PMID: 32138220]
[33]
Lemmens KJA, van de Wier B, Koek GH, et al. The flavonoid monoHER promotes the adaption to oxidative stress during the onset of NAFLD. Biochem Biophys Res Commun 2015; 456(1): 179-82.
[http://dx.doi.org/10.1016/j.bbrc.2014.11.055] [PMID: 25462563]
[34]
Racherla S, Arora R. Utility of Lp-PLA2 in lipid-lowering therapy. Am J Ther 2012; 19(2): 115-20.
[http://dx.doi.org/10.1097/MJT.0b013e3181e70d32] [PMID: 20634673]
[35]
Albert MA, Glynn RJ, Wolfert RL, Ridker PM. The effect of statin therapy on lipoprotein associated phospholipase A2 levels. Atherosclerosis 2005; 182(1): 193-8.
[http://dx.doi.org/10.1016/j.atherosclerosis.2005.05.006] [PMID: 15982658]
[36]
Hermans N, Van der Auwera A, Breynaert A, et al. A red yeast rice-olive extract supplement reduces biomarkers of oxidative stress, Ox-LDL and Lp-PLA2, in subjects with metabolic syndrome: A randomised, double-blind, placebo-controlled trial. Trials 2017; 18(1): 302.
[http://dx.doi.org/10.1186/s13063-017-2058-5] [PMID: 28673363]
[37]
Zhou T, Zhou S, Qi S, Shen X, Zeng G, Zhou H. The effect of atorvastatin on serum myeloperoxidase and CRP levels in patients with acute coronary syndrome. Clin Chim Acta 2006; 368(1-2): 168-72.
[http://dx.doi.org/10.1016/j.cca.2005.12.040] [PMID: 16480969]
[38]
Stenvinkel P, Rodríguez-Ayala E, Massy ZA, et al. Statin treatment and diabetes affect myeloperoxidase activity in maintenance hemodialysis patients. Clin J Am Soc Nephrol 2006; 1(2): 281-7.
[http://dx.doi.org/10.2215/CJN.01281005] [PMID: 17699218]
[39]
Kumar AP, Reynolds WF. Statins downregulate myeloperoxidase gene expression in macrophages. Biochem Biophys Res Commun 2005; 331(2): 442-51.
[http://dx.doi.org/10.1016/j.bbrc.2005.03.204] [PMID: 15850779]
[40]
Zimetti F, Adorni MP, Marsillach J, et al. Connection between the altered HDL antioxidant and anti-inflammatory properties and the risk to develop Alzheimer’s disease: A narrative review. Oxid Med Cell Longev 2021; 2021: 6695796.
[http://dx.doi.org/10.1155/2021/6695796] [PMID: 33505588]
[41]
Tellis CC, Tselepis AD. The role of lipoprotein-associated phospholipase A2 in atherosclerosis may depend on its lipoprotein carrier in plasma. Biochim Biophys Acta Mol Cell Biol Lipids 2009; 1791(5): 327-38.
[http://dx.doi.org/10.1016/j.bbalip.2009.02.015] [PMID: 19272461]
[42]
Li D, Zhao L, Yu J, et al. Lipoprotein-associated phospholipase A2 in coronary heart disease: Review and meta-analysis. Clin Chim Acta 2017; 465: 22-9.
[http://dx.doi.org/10.1016/j.cca.2016.12.006] [PMID: 27956130]
[43]
Huang F, Wang K, Shen J. Lipoprotein‐associated phospholipase A2: The story continues. Med Res Rev 2020; 40(1): 79-134.
[http://dx.doi.org/10.1002/med.21597] [PMID: 31140638]
[44]
Lefkowitz DL, Mone J, Lefkowitz SS. Myeloperoxidase: The good, the bad, and the ugly. Curr Immunol Rev 2010; 6: 123-9.
[http://dx.doi.org/10.2174/157339510791111691]
[45]
Violi F, Loffredo L, Carnevale R, Pignatelli P, Pastori D. Atherothrombosis and oxidative stress: Mechanisms and management in elderly. Antioxidants Redox Signal 2017; 27(14): 1083-124.
[46]
Huang Y, Wu Z, Riwanto M, et al. Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex. J Clin Invest 2013; 123(9): 3815-28.
[http://dx.doi.org/10.1172/JCI67478] [PMID: 23908111]
[47]
Anatoliotakis N, Deftereos S, Bouras G, et al. Myeloperoxidase: Expressing inflammation and oxidative stress in cardiovascular disease. Curr Top Med Chem 2013; 13(2): 115-38.
[http://dx.doi.org/10.2174/1568026611313020004] [PMID: 23470074]
[48]
Trentini A, Bellini T, Bonaccorsi G, et al. Sex difference: An important issue to consider in epidemiological and clinical studies dealing with serum paraoxonase-1. J Clin Biochem Nutr 2019; 64(3): 250-6.
[http://dx.doi.org/10.3164/jcbn.18-73] [PMID: 31138960]
[49]
Hunjadi M, Lamina C, Kahler P, et al. HDL cholesterol efflux capacity is inversely associated with subclinical cardiovascular risk markers in young adults: The cardiovascular risk in Young Finns study. Sci Rep 2020; 10(1): 19223.
[http://dx.doi.org/10.1038/s41598-020-76146-7] [PMID: 33154477]
[50]
Protic O, Di Pillo R, Montesanto A, et al. Randomized, double-blind, placebo-controlled trial to test the effects of a nutraceutical combination monacolin K-free on the lipid and inflammatory profile of subjects with hypercholesterolemia. Nutrients 2022; 14(14): 2812.
[http://dx.doi.org/10.3390/nu14142812] [PMID: 35889769]
[51]
Madsen CM, Varbo A, Nordestgaard BG. Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies. Eur Heart J 2017; 38(32): 2478-86.
[http://dx.doi.org/10.1093/eurheartj/ehx163] [PMID: 28419274]
[52]
Trimarco V, Izzo R, Morisco C, et al. High HDL (High-Density Lipoprotein) cholesterol increases cardiovascular risk in hypertensive patients. Hypertension 2022; 79(10): 2355-63.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.122.19912] [PMID: 35968698]

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