Abstract

Redox signaling regulates different gastrointestinal (G.I.) epithelium functions. At the intestinal level, the loss of redox homeostasis in intestinal epithelial cells (IECs) is responsible for the pathogenesis and development of a wide diversity of G.I. disorders. Thus, the manipulation of oxidative stress in IECs could represent an important pharmacological target for different diseases. In this study, peptides released from in vitro gastro intestinal digestion of different buffalo-milk commercial dairy products were identified and evaluated for their bioactive properties. In particular, six G.I. digests of dairy products were tested in a model of oxidative stress for IECs. Among them, buffalo ricotta cheese was the most active and the presence of an abundant β-lactoglobulin peptide (YVEELKPTPEGDL, f:60-72) was also revealed. The antioxidant potential of the identified peptide was also evaluated in a model of hydrogen peroxide (H2O2)-induced oxidative stress in the IEC-6 cell line. The peptide was able to reduce ROS release, while, on the other hand, it increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation and the expression of antioxidant cytoprotective factors, such as heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), and superoxide dismutase (SOD). These results indicate that buffalo ricotta cheese-isolated peptide could have potential in the treatment of some gastrointestinal disorders.

Highlights

  • Reactive oxygen species (ROS) are byproducts of normal cellular metabolism

  • The digestion by gastrointestinal enzymes is a natural process for the release of antioxidant peptides, differing from oral administration of commercially available bioactive peptides which are subjected to degradation and, inactivation, after oral intake

  • An important aspect is the low bioavailability of food-derived antioxidant peptides, which determine their accumulation in the gastrointestinal tract, suggesting that the major physiological effects could be locally explicated [9]

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Summary

Introduction

Reactive oxygen species (ROS) are byproducts of normal cellular metabolism. Low and moderate amounts of ROS have beneficial effects on several physiological processes, including killing of invading pathogens, wound healing, and tissue repair processes. The use of pharmaceutical drugs is sometimes associated with side effects For this reason, the search for natural alternatives originating from foods/dietary compounds has gained increasing attention [5]. Different studies have suggested that bioactive peptides, released from dietary proteins during digestion, could exert metabolic and physiologic actions by acting on specific targets at the digestive level or after absorption [6,7,8]. Many food proteins possess antioxidant peptide sequences which are released during the gastrointestinal digestion process. An important aspect is the low bioavailability of food-derived antioxidant peptides, which determine their accumulation in the gastrointestinal tract, suggesting that the major physiological effects could be locally explicated [9]. During gastrointestinal digestion of parent proteins there is a slow and continuous release of antioxidant peptides and amino acids, which protect the gastrointestinal tract itself and prevent the onset of oxidative stress [9]

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