The Antioxidant And Antipsoriatic Activities Of Selenium-Rich Yeast Peptide Fraction And The Underlying Mechanism

Psoriasis is a common,chronic and incurable skin disease.Its pathogenesis is generally related to inflammation and oxidative stress.Food protein-derived bioactive peptides exert antioxidant,immunomodulatory,anti-aging and skin protection activities both in vivo and in vitro,thus it can be used to prevent inflammatory diseases.Selenium(Se),the essential trace for mammalian,has antioxidant and anti-inflammatory activities,and Se status is inversely associated with the severity of psoriasis.Based on the biological function of Se and bioactive peptide fractions,there should be a synergistic effect with more excellent antioxidant,anti-inflammatory and skin protection activities when they are combined.It might take an active role in treatment of psoriasis.Therefore,Se-rich yeast as natural raw material was used to obtain Se-rich yeast peptide fraction.In vivo and in vitro models were used to explore its multiple biological effects and investigate the underlying mechanisms.It not only provides a new clue for the treatment of psoriasis,but also contributes to broadening the application of Se-rich yeast bioactive peptide fraction in nutraceutical,pharmaceutical,and cosmeceutical industries.The main results in this study are as follows:1)Characterization and antioxidant activity of yeast peptide fractions.The 4 kinds of yeast peptide fractions were obtained by enzymatically hydrolyzing normal or Se-rich yeast proteins.In vitro assays showed that Se-rich peptide fraction with lower molecular weight(MW)of < 1 k Da(SeP)had the strongest ability to scavenge free radicals and to inhibit the lipid peroxidation.The analysis of amino acid compositions showed that the contents of methionine(1.66 ± 0.14 g/100 g),tyrosine(4.41 ± 0.02 g/100 g)and some hydrophobic amino acids such as leucine(9.05 ± 0.24 g/100 g),valine(5.84 ± 0.20 g/100 g),and alanine(5.26 ± 0.11 g/100 g)in SeP were higher compared with normal yeast peptide fraction with MW of < 1 k Da(NoP).The sequences of three peptides abundant in SeP,VLPVPF(ValLeu-Pro-Val-Pro-Phe),LLPF(Leu-Leu-Pro-Phe)and FFPM(Phe-Phe-Pro-Met),were identified by liquid chromatography-tandem mass spectrometry,and these peptides exhibited potential antioxidant amino acids.Oral administration of SeP significantly maintained the redox homeostasis of mice,thus exerting the antioxidant activity in vivo.When topically applied on the dorsal skin of mice,SeP effectively alleviated ultraviolet B radiation-induced skin damage and oxidative stress.2)The effect of SeP on psoriasis-like skin injuries and its antioxidant mechanism.In imiquimod(IMQ)-induced mouse model,high-dose(the peptide dose is 300 mg/kg/d)and low-dose(the peptide dose is 150 mg/kg/d)of SeP(the Se dose is 100 μg/kg/d)and NoP application alleviated psoriasis-like skin injuries,reduced the area of psoriasis and the severity index scores and improved the systemic adverse effects induced by IMQ including splenomegaly and weight loss in mice,and low-dose peptide fractions had better clinical outcomes compared with high-dose peptide fractions with the same Se dose respectively.In addition,the application of SeP more effectively increased the antioxidant enzymes activities and reduced the malondialdehyde content compared with NoP group with same peptide dose.Western blot results revealed that the antioxidant enzymes contents of mice in low-dose SeP group were extremely increased compared with low-dose NoP group.Mechanistically,the anti-psoriatic activity of SeP and NoP might be achieved by inhibiting the activation of mitogen-activated protein kinase(MAPK)pathway.In in vitro model,compared with NoP-treated group,SeP treatment more significantly activated the nuclear factor erythroid 2-related factor 2/Kelch like ECH associated protein 1(Nrf2/Keap1)pathway to protect human epidermal keratinocyte(Ha Ca T)cells from oxidative stress.3)SeP ameliorated IMQ-induced psoriasis-like dermatitis in model mice by regulating inflammatory response and its related mechanism.Results showed that SeP treatment significantly ameliorated the severity of skin lesion(including erythema,scaling,epidermal thickness,and inflammatory T cells infiltration)in IMQ-induced psoriasis-like mouse model.Moreover,the expression levels of key inflammatory cytokines including interleukin(IL)-17 A,IL-17 F and IL-23,were markedly decreased in the dorsal skin of SeP-treated mice.Mechanistically,SeP application inhibited not only the activation of c-Jun N-terminal kinase and p38 MAPK,but also the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)p65 into the nucleus in the dorsal skin.Furthermore,SeP treatment downregulated the levels of inflammatory cytokines and the activation of MAPK and NF-κB pathways induced by lipopolysaccharides in Ha Ca T cells and mouse macrophage cell line(RAW264.7).