Fermented Soy-Derived Bioactive Peptides Selected by a Molecular Docking Approach Show Antioxidant Properties Involving the Keap1/Nrf2 Pathway

Abstract

Bioactive peptides are a group of molecules with health beneficial properties, deriving from food matrices. They are protein fragments consisting of 2–20 amino acids that can be released by microbial fermentation, food processing and gastrointestinal digestion. Once hydrolyzed from their native proteins, they can have different functions including antioxidant activity, which is important for cell protection by oxidant agents. In this work, fermented soy products were digested in vitro in order to improve the release of bioactive peptides. These were extracted, purified and analyzed in vitro and in a cellular model to assess their antioxidant activity. Peptide sequences were identified by LC-MS/MS analysis and a molecular docking approach was used to predict their ability to interact with Keap1, one of the key proteins of the Keap1/Nrf2 pathway, the major system involved in redox regulation. Peptides showing a high score of interaction were selected and tested for their antioxidant properties in a cellular environment using the Caco-2 cell line and examined for their capability to defend cells against oxidative stress. Our results indicate that several of the selected peptides were indeed able to activate the Keap1/Nrf2 pathway with the consequent overexpression of antioxidant and phase II enzymes.

Production and Characterization of Medium-Sized and Short Antioxidant Peptides from Soy Flour-Simulated Gastrointestinal Hydrolysate

“…In the gut, endogenous proteases, such as pepsin, trypsin, and chymotrypsin, hydrolyze proteins into peptides, which will be further processed by peptidases in the intestinal tract [ 29 ]. Therefore, to reproduce gastrointestinal digestion, a sequence of different enzymes is generally used, mainly pepsin, trypsin, chymotrypsin, and papain [ 17 ].…”

“…Soy proteins contain all the essential amino acids, and therefore they represent a valid alternative to food of animal origin; furthermore, several biological functions and bioactivities have been attributed to their derived peptides [ 13 ], such as cancer and cardiovascular disease prevention, antihypertensive activity [ 14 ], hypocholesterolemic effect, and antioxidant properties [ 1 , 4 , 7 , 15 , 16 ]. In particular, the antioxidant activity, i.e., the defense against the free radical damage [ 17 ], could be useful in contrasting several pathologies, as well as in nutraceutical and cosmetics applications.…”

Purification, Identification and Characterization of Antioxidant Peptides from Corn Silk Tryptic Hydrolysate: An Integrated In Vitro-In Silico Approach

“…Antioxidant peptides could alleviate cellular oxidative damage by scavenging free radicals and/or by regulating the cellular production of antioxidants or oxidants. The Keap1/Nrf2 pathway is a major pathway that modulates cellular antioxidant responses, which can be activated by antioxidant peptides [6]. Under oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) bound to Kelch-like ECH-associated protein 1 (Keap1) will detach and migrate to the nucleus, where it activates the expression of antioxidant genes [7].…”

Assessment of Intestinal Immunity and Permeability of Broilers on Partial Replacement Diets of Two-Stage Fermented Soybean Meal by Bacillus velezensis and Lactobacillus brevis ATCC 367

“…The influence of FSBM on the host are divided into two categories: (I) Reduction in the antigen from glycinin (11S globulin, 40% of total protein) and β-conglycinin (7S globulin, 30% of total protein) after enzyme hydrolysis leads to better absorption of FSBM, down-regulation of the NF-κB pro-inflammatory pathway [ 6 ], and then restoration of the intestinal tight junction proteins [ 7 ]; (II) soy isoflavone release and deglycosylase after the hydrolysis of cellulose, hemicellulose modified by β-glucosidase [ 8 ], and soy peptides produced by the hydrolysis of glycinin and β-conglycinin [ 9 ]. While these compounds provide FSBMs bioactivity, soy peptides are considered to have more potential for FSBM development.…”