Regulation of Cholesterol Metabolism by Bioactive Components of Soy Proteins: Novel Translational Evidence

Caponio, Giusy Rita; Wang, David Q.–H.; Ciaula, Agostino Di; Angelis, Maria De; Portincasa, Piero

doi:10.3390/ijms22010227

Cited by 34 publications

(23 citation statements)

References 103 publications

(43 reference statements)

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“…Peptides from vegetable sources have been described as potentially responsible for a a cholesterol-lowering activity by statin-like mechanisms [ 21 , 22 ], as in the case of soy β-conglycinin peptides that lower the activity of HMGCoAR by roughly 50% [ 23 ]. Based on phage display technology, pepsin and trypsin hydrolyses, molecular docking studies and enzyme assays, the mechanism of the HMGCoAR inhibition has been postulated for some peptides, as a consequence of 3-dimensional similarity to statins [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells

et al. 2021

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Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmacological approaches, a nutritional strategy for CVD prevention has gained increasing attention. Among functional foods, the hypocholesterolemic properties of soy are driven by a stimulation of LDL-receptor (LDL-R) activity. Aim: To characterize the effect of two soy peptides, namely, β-conglycinin-derived YVVNPDNDEN and YVVNPDNNEN on the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key-regulators of the LDL-R. Methods: PCSK9 promoter activity (luciferase assay), PCSK9 protein expression (WB) and secretion (ELISA), PCSK9 interaction with LDL-R (binding assay) and human HepG2 cells were the objects of this investigation. Results: Treatment with YVVNPDNNEN peptide has led to a rise in PCSK9 gene expression (90.8%) and transcriptional activity (86.4%), and to a decrement in PCSK9 intracellular and secreted protein (−42.9%) levels. YVVNPDNNEN peptide reduced the protein expression of transcriptional factor HNF1α. Most changes driven by YVVNPDNDEN peptide were not statistically significant. Neither peptide inhibited the PCSK9–LDLR interaction. Conclusions: Although sharing a common effect on LDL-R levels through the inhibition of 3-hydroxy-3-methylglutaryl CoA reductase activity, only the YVVNPDNNEN peptide has an additional mechanism via the downregulation of PCSK9 protein levels.

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Section: Discussionmentioning

confidence: 99%

Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells

et al. 2021

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“…Moreover, SPs have strong gel-forming properties that, in turn, reinforce its foaming and emulsifying activities [4]. By regulating bile acids reabsorption within digestive systems or organs SPs can effectively lower blood cholesterol levels and decrease low-density lipoprotein (LDL) and fat accumulation, which supports their use for the prevention and treatment of arteriosclerosis [39,40]. Angiotensin-I converting enzyme (ACE) inhibitory peptides in soy proteins lower blood pressure, and antithrombotic peptides, which inhibit platelet aggregation [41].…”

Section: Functionality Of Soy Peptidesmentioning

confidence: 99%

Beneficial Effects of Soybean-Derived Bioactive Peptides

Kim

Yang²,

Kim

2021

IJMS

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Peptides present in foods are involved in nutritional functions by supplying amino acids; sensory functions related to taste or solubility, emulsification, etc.; and bioregulatory functions in various physiological activities. In particular, peptides have a wide range of physiological functions, including as anticancer agents and in lowering blood pressure and serum cholesterol levels, enhancing immunity, and promoting calcium absorption. Soy protein can be partially hydrolyzed enzymatically to physiologically active soy (or soybean) peptides (SPs), which not only exert physiological functions but also help amino acid absorption in the body and reduce bitterness by hydrolyzing hydrophobic amino acids from the C- or N-terminus of soy proteins. They also possess significant gel-forming, emulsifying, and foaming abilities. SPs are expected to be able to prevent and treat atherosclerosis by inhibiting the reabsorption of bile acids in the digestive system, thereby reducing blood cholesterol, low-density lipoprotein, and fat levels. In addition, soy contains blood pressure-lowering peptides that inhibit angiotensin-I converting enzyme activity and antithrombotic peptides that inhibit platelet aggregation, as well as anticancer, antioxidative, antimicrobial, immunoregulatory, opiate-like, hypocholesterolemic, and antihypertensive activities. In animal models, neuroprotective and cognitive capacity as well as cardiovascular activity have been reported. SPs also inhibit chronic kidney disease and tumor cell growth by regulating the expression of genes associated with apoptosis, inflammation, cell cycle arrest, invasion, and metastasis. Recently, various functions of soybeans, including their physiologically active functions, have been applied to health-oriented foods, functional foods, pharmaceuticals, and cosmetics. This review introduces some current results on the role of bioactive peptides found in soybeans related to health functions.

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“…As a result, the traditional lipid parameters cannot reflect the metabolic characteristics of cholesterol in the body. Cholesterol observed in the human serum is originated via either the cholesterol synthesis that occurs in the liver (endogenous cholesterol) or derived from the nourishments consumed that are absorbed in the small intestines (exogenous cholesterol), both of which contributes to cholesterol homeostasis [ 8 , 13 , 14 ]. Precursors of cholesterol synthesis in serum (desmosterol, lathosterol, and squalene) can be utilized as markers of cholesterol synthesis.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol Metabolic Markers for Differential Evaluation of Patients with Hyperlipidemia and Familial Hypercholesterolemia

Huang

Yang

et al. 2022

Disease Markers

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The cholesterol metabolism in humans can be indirectly reflected by measuring cholesterol metabolism marker levels. We aimed to investigate the association of cholesterol homeostasis markers on standard lipid profiling components in familial hypercholesteremia and hyperlipidemia patients. A total of 69 hyperlipidemia patients, 25 familial hypercholesteremia (FHC) patients, and 64 healthy controls were enrolled in this study. We performed routine testing of blood lipid water. Gas chromatography was used to determine the changes in the concentration of cholesterol synthesis (squalene, desmosterol, and lathosterol) and absorption markers (campesterol, sitosterol, and stigmasterol) in the blood. Baseline hyperlipidemia patients displayed significantly higher total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels in comparison to the control group, which was reflected in the increased levels of squalene, desmosterol, campesterol, and sitosterol observed ( P < 0.05 ) in the hyperlipidemia patients. The desmosterol, lathosterol, campesterol, stigmasterol, and sitosterol were statistically different in the FHC group than the hyperlipidemic group ( P < 0.05 ). The proportions of squalene/cholesterol, lathosterol/cholesterol, stigmasterol/cholesterol, and sitosterol/cholesterol in the FHC group were lower than those in the hyperlipidemic group; only desmosterol/cholesterol was higher than that in the hyperlipidemic group. Correlation studies between lipid metabolic factors showed that the proportion of moderate and strong correlations was much higher in the FHC group than in the other two groups (76.92% vs. 32.50% and 31.25%). Logistic regression analysis showed that the concentrations of glucose, LDL-C, lactosterol, and sitosterol were all independent risk factors for developing hyperlipidemia. This result was further confirmed by the ROC curve. These results indicated that the study of cholesterol synthesis and decomposition markers can serve as a reference index for related diseases caused by changes in its concentration.

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Regulation of Cholesterol Metabolism by Bioactive Components of Soy Proteins: Novel Translational Evidence

Cited by 34 publications

References 103 publications

Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells

Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells

Beneficial Effects of Soybean-Derived Bioactive Peptides

Cholesterol Metabolic Markers for Differential Evaluation of Patients with Hyperlipidemia and Familial Hypercholesterolemia

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