Major Peptides from Amaranth (Amaranthus cruentus) Protein Inhibit HMG-CoA Reductase Activity

Abstract

The objective of this study was to identify the major peptides generated by the in vitro hydrolysis of Amaranthus cruentus protein and to verify the effect of these peptides on the activity of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), a key enzyme in cholesterol biosynthesis. A protein isolate was prepared, and an enzymatic hydrolysis that simulated the in vivo digestion of the protein was performed. After hydrolysis, the peptide mixture was filtered through a 3 kDa membrane. The peptide profile of this mixture was determined by reversed phase high performance chromatography (RP-HPLC), and the peptide identification was performed by LC-ESI MS/MS. Three major peptides under 3 kDa were detected, corresponding to more than 90% of the peptides of similar size produced by enzymatic hydrolysis. The sequences identified were GGV, IVG or LVG and VGVI or VGVL. These peptides had not yet been described for amaranth protein nor are they present in known sequences of amaranth grain protein, except LVG, which can be found in amaranth α‑amylase. Their ability to inhibit the activity of HMG-CoA reductase was determined, and we found that the sequences GGV, IVG, and VGVL, significantly inhibited this enzyme, suggesting a possible hypocholesterolemic effect.

Rediscovering the therapeutic potential of Amaranthus species: A review

“…Leaf extracts of A. spinosus singularly and in combination with vitamin C reversed unfavorable alterations (increased MDA but reduced GSH, CAT and SOD of heart) in adult rats on high fat diet [78]. Soares et al [79] cited in their work, three novel peptides from grain of A. cruentus, that significantly inhibited HMG-CoA reductase, a key enzyme in cholesterol biosynthesis; suggesting a possible hypocholesterolemic effect. Unprocessed and extruded amaranth hydrolysates (EAH) from A. hypochondriacus showed a reduction in the expression of interleukins involved in atherosclerosis in THP-1 lipopolysaccharide (LPS)-induced human macrophages.…”

The Vicilin protein (Vigna radiata L.) of mung bean as a functional food

“…Tachibana et al attributed that the hypolipidemic effect to the amino acid composition and sequence of the protein isolate, consistent with previous studies of legumes (Moriyama et al, 2004;Lovati et al, 2008). Inhibitory effects of natural (Pak et al, 2005: Soares et al, 2015 and synthetic (Lin et al, 2015;Pak et al, 2008aPak et al, , 2008bPak et al, , 2012 peptides on HMG-CoAr have been reported, but the underlying mechanism remained unclear. Marques et al (2015) and Lammi et al (2015) suggested that legume peptide inhibit HMG-CoAr via the interaction of these peptides with either the active site or NADH-binding site of the enzyme, thus preventing substrate binding to the enzyme and promoting endogenous cholesterol synthesis.…”

Inhibitory effects on the HMG-CoA Reductase in the chemical constituents of the Cassia mimosoides Linn

“…The change of HMG-CoA Reductase Activity [17] 1, 5, 25 or 125 μg/mL of β-Sitosterol, Oleanolic Acid, Emodin, Carotene, Resorcinol, Luteolin, α-L-Rhamnose, Pravastatin respectively were mixed into the reaction mixture for the HMGCoA activity detection. The reaction without HMG-CoA reaction substrate was incubated at 37°C, and absorbance was measured at 340 nm after 1 min and recorded as ΔA 1 Δt 1 .…”