Hempseed Peptides Exert Hypocholesterolemic Effects with a Statin-Like Mechanism

Journal of Agricultural and Food Chemistry

Volumn 65, Issue 40, 2017, Pages 8829-8838

  Zanoni, Chiara ^a   Aiello, Gilda ^a   Arnoldi, Anna ^a   Lammi, Carmen ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

bioactive peptides; Cannabis sativa; functional foods; hempseed; PCSK9; plant proteins

Indexed keywords

CATALYST ACTIVITY; ENZYME ACTIVITY; FUNCTIONAL FOOD; HEMP; PEPTIDES;

BIOACTIVE PEPTIDES; CANNABIS SATIVA; HEMPSEED; PCSK9; PLANT PROTEINS;

PROTEINS;

AMINO ACID; CANNABIS; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYPOCHOLESTEROLEMIC AGENT; LOW DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR; PEPTIDE; STATINE; STEROL REGULATORY ELEMENT BINDING PROTEIN 2;

CELL SURVIVAL; CHEMISTRY; ENZYMOLOGY; HEP-G2 CELL LINE; HUMAN; HYPERCHOLESTEROLEMIA; METABOLISM; PLANT SEED; TANDEM MASS SPECTROMETRY;

AMINO ACIDS; ANTICHOLESTEREMIC AGENTS; CANNABIS; CELL SURVIVAL; HEP G2 CELLS; HUMANS; HYDROXYMETHYLGLUTARYL COA REDUCTASES; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; LIPOPROTEINS, LDL; PEPTIDES; RECEPTORS, LDL; SEEDS; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; TANDEM MASS SPECTROMETRY;

EID: 85031001457     PISSN: 00218561     EISSN: 15205118     Source Type: Journal    
DOI: 10.1021/acs.jafc.7b02742     Document Type: Article

References (38)

1. Chen, Z.-Y.; Ma, K. Y.; Liang, Y.; Peng, C.; Zuo, Y. Role and classification of cholesterol-lowering functional foods J. Funct. Foods 2011, 3 (2) 61-69 10.1016/j.jff.2011.02.003
2. Scicchitano, P.; Cameli, M.; Maiello, M.; Modesti, P. A.; Muiesan, M. L.; Novo, S.; Palmiero, P.; Saba, P. S.; Pedrinelli, R.; Ciccone, M. M. Nutraceuticals and dyslipidaemia: Beyond the common therapeutics J. Funct. Foods 2014, 6, 11-32 10.1016/j.jff.2013.12.006
3. Braithwaite, M. C.; Tyagi, C.; Tomar, L. K.; Kumar, P.; Choonara, Y. E.; Pillay, V. Nutraceutical-based therapeutics and formulation strategies augmenting their efficiency to complement modern medicine: An overview J. Funct. Foods 2014, 6, 82-99 10.1016/j.jff.2013.09.022
4. Callaway, J. C. Hempseed as a nutritional resource: An overview Euphytica 2004, 140 (1-2) 65-72 10.1007/s10681-004-4811-6
5. Russo, R.; Reggiani, R. Evaluation of protein concentration, amino acid profile and antinutritional compounds in hempseed meal from dioecious and monoecious varieties Am. J. Plant Sci. 2015, 6 (1) 14-22 10.4236/ajps.2015.61003
6. Park, S. K.; Seo, J. B.; Lee, M. Y. Proteomic profiling of hempseed proteins from Cheungsam Biochim. Biophys. Acta, Proteins Proteomics 2012, 1824 (2) 374-82 10.1016/j.bbapap.2011.10.005
7. House, J. D.; Neufeld, J.; Leson, G. Evaluating the quality of protein from hemp seed (Cannabis sativa L.) products through the use of the Protein Digestibility-Corrected Amino Acid Score method J. Agric. Food Chem. 2010, 58 (22) 11801-11807 10.1021/jf102636b
8. Aiello, G.; Fasoli, E.; Boschin, G.; Lammi, C.; Zanoni, C.; Citterio, A.; Arnoldi, A. Proteomic characterization of hempseed (Cannabis sativa L.) J. Proteomics 2016, 147, 187 10.1016/j.jprot.2016.05.033
9. Girgih, A. T.; Alashi, A. M.; He, R.; Malomo, S. A.; Raj, P.; Netticadan, T.; Aluko, R. E. A novel hemp seed meal protein hydrolysate reduces oxidative stress factors in spontaneously hypertensive rats Nutrients 2014, 6 (12) 5652-5666 10.3390/nu6125652
10. Girgih, A. T.; He, R.; Aluko, R. E. Kinetics and molecular docking studies of the inhibitions of angiotensin converting enzyme and renin activities by hemp seed (Cannabis sativa L.) peptides J. Agric. Food Chem. 2014, 62 (18) 4135-4144 10.1021/jf5002606
11. Girgih, A. T.; Udenigwe, C. C.; Aluko, R. E. In vitro antioxidant properties of hemp seed (Cannabis sativa L.) protein hydrolysate fractions J. Am. Oil Chem. Soc. 2011, 88 (3) 381-389 10.1007/s11746-010-1686-7
12. Girgih, A. T.; Udenigwe, C. C.; Aluko, R. E. Reverse-phase HPLC separation of hemp seed (Cannabis sativa L.) protein hydrolysate produced peptide fractions with enhanced antioxidant capacity Plant Foods Hum. Nutr. 2013, 68 (1) 39-46 10.1007/s11130-013-0340-6
13. Gavel, N. T.; Edel, A. L.; Bassett, C. M. C.; Weber, A. M.; Merchant, M.; Rodriguez-Leyva, D.; Pierce, G. N. The effect of dietary hempseed on atherogenesis and contractile function in aortae from hypercholesterolemic rabbits Acta Physiol. Hung. 2011, 98 (3) 273-283 10.1556/APhysiol.98.2011.3.4
14. Prociuk, M. A.; Edel, A. L.; Gavel, N. T.; Lukas, A.; Pierce, G. N. Influence of dietary hempseed on arrhythmia generation by ischemia/reperfusion J. Mol. Cell Cardiol 2004, 37 (1) 275-275
15. Prociuk, M. A.; Edel, A. L.; Richard, M. N.; Gavel, N. T.; Ander, B. P.; Dupasquier, C. M. C.; Pierce, G. N. Cholesterol-induced stimulation of platelet aggregation is prevented by a hempseed-enriched diet Can. J. Physiol. Pharmacol. 2008, 86 (4) 153-159 10.1139/Y08-011
16. Castoreno, A. B.; Wang, Y.; Stockinger, W.; Jarzylo, L. A.; Du, H.; Pagnon, J. C.; Shieh, E. C.; Nohturfft, A. Transcriptional regulation of phagocytosis-induced membrane biogenesis by sterol regulatory element binding proteins Proc. Natl. Acad. Sci. U. S. A. 2005, 102 (37) 13129-13134 10.1073/pnas.0506716102
17. Horton, J. D.; Shimomura, I.; Brown, M. S.; Hammer, R. E.; Goldstein, J. L.; Shimano, H. Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2 J. Clin. Invest. 1998, 101 (11) 2331-9 10.1172/JCI2961
18. Brugger, D.; Schuster, H.; Zollner, N. Familial hypercholesterolemia and familial defective apolipoprotein B-100: comparison of the phenotypic expression In 116 cases Eur. J. Med. Res. 1996, 1 (8) 383-6
19. Ishibashi, S.; Brown, M. S.; Goldstein, J. L.; Gerard, R. D.; Hammer, R. E.; Herz, J. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery J. Clin. Invest. 1993, 92 (2) 883-93 10.1172/JCI116663
20. Hussain, M. M. Structural, biochemical and signaling properties of the low-density lipoprotein receptor gene family Front. Biosci., Landmark Ed. 2001, 6, D417-D428 10.2741/Hussain1
21. Boschin, G.; Scigliuolo, G. M.; Resta, D.; Arnoldi, A. ACE-inhibitory activity of enzymatic protein hydrolysates from lupin and other legumes Food Chem. 2014, 145, 34-40 10.1016/j.foodchem.2013.07.076
22. Levashov, P. A.; Sutherland, D. S.; Besenbacher, F.; Shipovskov, S. A robust method of determination of high concentrations of peptides and proteins Anal. Biochem. 2009, 395 (1) 111-2 10.1016/j.ab.2009.08.017
23. Endo, A. The discovery and development of HMG-CoA reductase inhibitors J. Lipid Res. 1992, 33 (11) 1569-82
24. Gencer, B.; Lambert, G.; Mach, F. PCSK9 inhibitors Swiss Med. Wkly. 2015, 145, w14094 10.4414/smw.2015.14094
25. Zhang, D. W.; Lagace, T. A.; Garuti, R.; Zhao, Z.; McDonald, M.; Horton, J. D.; Cohen, J. C.; Hobbs, H. H. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation J. Biol. Chem. 2007, 282 (25) 18602-12 10.1074/jbc.M702027200
26. Horton, J. D.; Goldstein, J. L.; Brown, M. S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver J. Clin. Invest. 2002, 109 (9) 1125-1131 10.1172/JCI0215593
27. Edwards, P. A.; Tabor, D.; Kast, H. R.; Venkateswaran, A. Regulation of gene expression by SREBP and SCAP Biochim. Biophys. Acta, Mol. Cell Biol. Lipids 2000, 1529 (1-3) 103-13 10.1016/S1388-1981(00)00140-2
28. Ching, Y. P.; Davies, S. P.; Hardie, D. G. Analysis of the specificity of the AMP-activated protein kinase by site-directed mutagenesis of bacterially expressed 3-hydroxy 3-methylglutaryl-CoA reductase, using a single primer variant of the unique-site-elimination method Eur. J. Biochem. 1996, 237 (3) 800-8 10.1111/j.1432-1033.1996.0800p.x
29. Pallottini, V.; Martini, C.; Pascolini, A.; Cavallini, G.; Gori, Z.; Bergamini, E.; Incerpi, S.; Trentalance, A. 3-Hydroxy-3-methylglutaryl coenzyme A reductase deregulation and age-related hypercholesterolemia: a new role for ROS Mech. Ageing Dev. 2005, 126 (8) 845-51 10.1016/j.mad.2005.02.009
30. Lammi, C.; Zanoni, C.; Arnoldi, A. Molecular characterization of the hypocholesterolemic mechanism of action of IAVPGEVA, IAVPTGVA, and LPYP, three peptides from soy glycinin, in HepG2 cells J. Funct. Foods 2015, 14, 469-478 10.1016/j.jff.2015.02.021
31. Lammi, C.; Zanoni, C.; Scigliuolo, G. M.; D'Amato, A.; Arnoldi, A. Lupin peptides lower low-density lipoprotein (LDL) cholesterol through an up-regulation of the LDL receptor/sterol regulatory element binding protein 2 (SREBP2) pathway at HepG2 cell line J. Agric. Food Chem. 2014, 62 (29) 7151-9 10.1021/jf500795b
32. Oliaro-Bosso, S.; Calcio Gaudino, E.; Mantegna, S.; Giraudo, E.; Meda, C.; Viola, F.; Cravotto, G. Regulation of HMGCoA reductase activity by Policosanol and octacosadienol, a new synthetic analogue of octacosanol Lipids 2009, 44 (10) 907-16 10.1007/s11745-009-3338-y
33. Sun, W.; Lee, T. S.; Zhu, M.; Gu, C.; Wang, Y.; Zhu, Y.; Shyy, J. Y. Statins activate AMP-activated protein kinase in vitro and in vivo Circulation 2006, 114 (24) 2655-62 10.1161/CIRCULATIONAHA.106.630194
34. Lammi, C.; Zanoni, C.; Arnoldi, A.; Vistoli, G. Two peptides from soy beta-conglycinin induce a hypocholesterolemic effect in HepG2 cells by a statin-like mechanism: comparative in vitro and in silico modeling studies J. Agric. Food Chem. 2015, 63 (36) 7945-7951 10.1021/acs.jafc.5b03497
35. Dubuc, G.; Chamberland, A.; Wassef, H.; Davignon, J.; Seidah, N. G.; Bernier, L.; Prat, A. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia Arterioscler., Thromb., Vasc. Biol. 2004, 24 (8) 1454-1459 10.1161/01.ATV.0000134621.14315.43
36. Lammi, C.; Zanoni, C.; Calabresi, L.; Arnoldi, A. Lupin protein exerts cholesterol-lowering effects targeting PCSK9: from clinical evidences to elucidation of the in vitro molecular mechanism using HepG2 cells J. Funct. Foods 2016, 23, 230-240 10.1016/j.jff.2016.02.042
37. Lammi, C.; Aiello, G.; Vistoli, G.; Zanoni, C.; Arnoldi, A.; Sambuy, Y.; Ferruzza, S.; Ranaldi, G. A multidisciplinary investigation on the bioavailability and activity of peptides from lupin protein J. Funct. Foods 2016, 24, 297-306 10.1016/j.jff.2016.04.017
38. Girgih, A. T.; He, R.; Malomo, S.; Offengenden, M.; Wu, J.; Aluko, R. E. Structural and functional characterization of hemp seed (Cannabis sativa L.) protein-derived antioxidant and antihypertensive peptides J. Funct. Foods 2014, 6, 384-394 10.1016/j.jff.2013.11.005