GPETAFLR, a biopeptide from Lupinus angustifolius L., protects against oxidative and inflammatory damage in retinal pigment epithelium cells

Abstract

GPETAFLR, an octapeptide released from the enzymatic hydrolysis of lupine (Lupinus angustifolius L.) protein, has demonstrated anti‐inflammatory effect in myeloid lineage. This work aims to evaluate in retinal pigment epithelium (RPE) cells the protective role of GPETAFLR on both oxidative and inflammatory markers known to be involved in age‐related macular degeneration (AMD). In comparison with stimulated control cells, GPETAFLR increased glutathione production and diminished the secretion and gene expression of VEFG, IL‐1β, IL‐6, IFNγ, and TNF‐α, as well as reactive oxygen species, and nitrite output. Our findings reveal that GPETAFLR, a novel plant peptide, is able to protect against RPE oxidative stress and inflammation. Taken together, these results strongly support innovative nutritional strategies considering Lupinus angustifolius L. as source of proteins to prevent the onset and progression of AMD. Practical applications We reveal a novel nutraceutical impact of GPETAFLR peptide in human RPE cells to prevent oxidative and inflammatory mediators. Our results support that the intake of Lupine angustifolius L., proposed to be a reservoir of GPETAFLR, could lessen the functional decay of RPE cells, leading therefore to a slowdown of the progress of AMD during age. Not only this work, but also future simple clinical studies should raise new nutritional strategies focused on understanding the etiological role of the foods, nutrition, and metabolism in the pathogenesis of ocular disorders.

Lupin-Derived Bioactive Peptides: Intestinal Transport, Bioavailability and Health Benefits

“…In another model of inhibition of oxidative stress, GPETAFLR, a lupin-originated octapeptide, was demonstrated to increase cell viability and improve GSH synthesis, while suppressing ROS generation in retinal pigment epithelium cells [ 28 ]. This finding suggests that consumption of lupin-rich diet will provide health benefits such as delaying the onset of AMD, a condition that has been shown to be associated with free radical attack on ocular tissues, compromising the blood-retinal barrier that results in initiation and progression of ADM [ 82 , 83 , 84 ].…”

“…Additionally, the peptide suppressed NO production, probably by suppressing the gene expression of iNOS [ 31 ]. In LPS-generated inflammation of retinal pigment epithelium cells (ARPE-19 cells), a lupin-derived octapeptide, GPETAFLR downregulated gene expression profile and protein levels of VEFG, IL-1β, IL-6, IFNγ, and TNF-α [ 28 ], indicating that it has anti-inflammatory properties. Taken together, the above findings show that lupin-derived peptides modulate immune response by restoring inflammatory and redox balance.…”

“…Due to the high protein content of lupin seeds (31–52%) [ 23 , 24 , 25 , 26 ], proteins derived from lupin seeds are gaining attention as source of bioactive peptides. Several lines of evidence highlight the biological activities of lupin protein hydrolysates (LPHs) and peptides (LDPs) including hypocholesterolemic, hypoglycemic, antimicrobial, anti-inflammatory and immunomodulatory effects [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. The health-promoting effects of lupin proteins and hydrolysates consumptions have been tested in human clinical trials.…”

A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways

“…In fact, several pieces of evidence highlight the biological activities of lupin protein hydrolysates and peptides, including hypocholesterolemic, hypoglycemic, antimicrobial, anti-inflammatory, and immunomodulatory effects. [2][3][4][5][6][7][8][9][10] The health-promoting effects of lupin peptides have been tested in different animal models and clinical trials. Briefly, diets containing protein from L. albus 11,12 or L. angustifolius [13][14][15] significantly reduced both total cholesterol and low-density lipoprotein (LDL) cholesterol (LDL-C) levels compared to control diets containing casein in a rat model of hypercholesterolemia.…”

Osteo‐modulatory dietary proteins and peptides: A concise review

“…Classic examples of DP with potential effects in inhibiting different pathways involved in the pathogenesis of bone diseases are proteins from soybean, lupin, milk, and other animal products as demonstrated in cell culture, animal and human studies (Arjmandi et al, 2005; Cruz‐Chamorro et al, 2019; del Carmen Millán‐Linares et al, 2015; Dirkes et al, 2018; Hinton et al, 2018; Lemus‐Conejo et al, 2020; Mada, Abaya, et al, 2020; Montserrat‐de la Paz et al, 2019). Notably, an octapeptide from lupin (GPETAFLR) inhibited inflammation in human monocyte‐derived osteoclasts challenged with lipopolysaccharide (an agent that induces clonal expansion of osteoclasts) (Millan‐Linares et al, 2019). This review discusses the potential of DP and peptides in modulating bone remodeling and bone diseases as demonstrated by in vitro and in vivo studies reported in the last decade.…”