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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

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† Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
§ HPF-Nutraceutics SRL, Milan, Italy
# Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Polytechnic of Milan, Milan, Italy
*(A.A.) Phone: +39 02 503 19372. Fax: +39 02 503 19343. E-mail: [email protected]
Cite this: J. Agric. Food Chem. 2014, 62, 29, 7151–7159
Publication Date (Web):June 27, 2014
https://doi.org/10.1021/jf500795b
Copyright © 2014 American Chemical Society
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Previous experiments in suitable animal models and in mild hypercholesterolemic individuals have shown that the consumption of lupin proteins may be useful for controlling total and low-density lipoprotein (LDL) cholesterol levels. With the objective of providing evidence that peptides deriving from the hydrolysis of lupin proteins may be responsible of the observed activities and for investigating the mechanism of action, HepG2 cells were treated with lupin peptides obtained by either pepsin (P) or trypsin (T) hydrolysis, and molecular and functional investigations were performed on the LDL receptor/SREBP2 pathway. For the first time, this paper provides experimental evidence that lupin peptides are able to interfere with the HMGCoAR activity, up-regulating the LDL receptor (136 and 84% vs the control for P and T peptides, respectively, at 1 mg/mL) and SREBP2 proteins (148 and 73% vs the control for P and T peptides, respectively, at 1 mg/mL) via the activation of PI3K/Akt/GSK3β pathways and increasing the LDL uptake at HepG2 cell line (40 and 50% vs the control for P and T peptides, respectively, at 1 mg/mL). These results may be useful in explaining the activities observed in vivo in animals and humans treated with lupin protein.

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  24. Ruth Boachie, Shixiang Yao, Chibuike C Udenigwe. Molecular mechanisms of cholesterol-lowering peptides derived from food proteins. Current Opinion in Food Science 2018, 20 , 58-63. https://doi.org/10.1016/j.cofs.2018.03.006
  25. Maria Hayes, Stephen Bleakley. Peptides from plants and their applications. 2018,,, 603-622. https://doi.org/10.1016/B978-0-08-100736-5.00025-9
  26. Shixiang Yao, Dominic Agyei, Chibuike C. Udenigwe. Structural Basis of Bioactivity of Food Peptides in Promoting Metabolic Health. 2018,,, 145-181. https://doi.org/10.1016/bs.afnr.2017.12.002
  27. Suwen Liu, Zhanyi Wu, Shuo Guo, Xianjun Meng, Xuedong Chang. Polyphenol-rich extract from wild Lonicera caerulea berry reduces cholesterol accumulation by mediating the expression of hepatic miR-33 and miR-122, HMGCR, and CYP7A1 in rats. Journal of Functional Foods 2018, 40 , 648-658. https://doi.org/10.1016/j.jff.2017.11.048
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  30. Arrigo F G Cicero, Federica Fogacci, Alessandro Colletti. Potential role of bioactive peptides in prevention and treatment of chronic diseases: a narrative review. British Journal of Pharmacology 2017, 174 (11) , 1378-1394. https://doi.org/10.1111/bph.13608
  31. Chiara Zanoni, Gilda Aiello, Anna Arnoldi, Carmen Lammi. Investigations on the hypocholesterolaemic activity of LILPKHSDAD and LTFPGSAED, two peptides from lupin β-conglutin: Focus on LDLR and PCSK9 pathways. Journal of Functional Foods 2017, 32 , 1-8. https://doi.org/10.1016/j.jff.2017.02.009
  32. Arrigo F. G. Cicero, Federica Fogacci, Alessandro Colletti. Food and plant bioactives for reducing cardiometabolic disease risk: an evidence based approach. Food & Function 2017, 8 (6) , 2076-2088. https://doi.org/10.1039/C7FO00178A
  33. Arrigo F.G. Cicero, Alessandro Colletti. Combinations of phytomedicines with different lipid lowering activity for dyslipidemia management: The available clinical data. Phytomedicine 2016, 23 (11) , 1113-1118. https://doi.org/10.1016/j.phymed.2015.10.011
  34. Arrigo F.G. Cicero, Alessandro Colletti. Role of phytochemicals in the management of metabolic syndrome. Phytomedicine 2016, 23 (11) , 1134-1144. https://doi.org/10.1016/j.phymed.2015.11.009
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  36. Carmen Lammi, Chiara Zanoni, Gilda Aiello, Anna Arnoldi, Giovanni Grazioso. Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells. Scientific Reports 2016, 6 (1) https://doi.org/10.1038/srep29931
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  40. Carmen Lammi, Chiara Zanoni, Laura Calabresi, Anna Arnoldi. Lupin protein exerts cholesterol-lowering effects targeting PCSK9: From clinical evidences to elucidation of the in vitro molecular mechanism using HepG2 cells. Journal of Functional Foods 2016, 23 , 230-240. https://doi.org/10.1016/j.jff.2016.02.042
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  42. Chibuike Udenigwe, Kirsti Rouvinen-Watt. The Role of Food Peptides in Lipid Metabolism during Dyslipidemia and Associated Health Conditions. International Journal of Molecular Sciences 2015, 16 (12) , 9303-9313. https://doi.org/10.3390/ijms16059303
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