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• KRQKYD can ameliorate alcohol-induced HHL-5 hepatocytes damage.
• KRQKYD has strong stability at temperature (20–80 ℃), pH (2–9) and NaCl concentrations (1%–7%).
• KRQKYD is unstable at high temperature and alkaline conditions because of self-assembly aggregation and diacylation.
• KRQKYD is highly resistant to pepsin but can be degraded by trypsin into smaller peptide fragments.
• The trans-epithelial transport mechanism of KRQKYD is paracellular pathways.
The study evaluated the stability of an oligopeptide (Lys-Arg-Gln-Lys-Tyr-Asp, KRQKYD) and its transport mechanism by simulating gastrointestinal digestion and a model of human intestinal Caco-2 monolayer cells in vitro. In this study, the effects of environmental factors (temperature, pH and NaCl concentration) and simulated gastrointestinal digestion on the stability of KRQKYD were evaluated by indicators of the levels of alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) in an alcoholinduced hepatocyte injury model. The results showed that KRQKYD still maintained satisfactory hepatocyte-protective activity after treatment with different temperatures (20−80 ℃), pH (3.0−9.0), NaCl concentration(1%−7%) and simulated gastrointestinal digestion, which indicated that KRQKYD showed good stability to environmental factors and simulated gastrointestinal digestion. Furthermore, the intact KRQKYD could be absorbed in a model of Caco-2 monolayer cells with a Papp value of (9.70 ± 0.53) × 10−7 cm/s. Pretreatment with an energy inhibitor (sodium azide), a competitive peptide transporter inhibitor (Gly-Pro) and a transcytosis inhibitor wortmannin did not decrease the level of transepithelial KRQKYD transport, indicating that the transport mechanism of KRQKYD was not associated with energy dependent, vector mediated and endocytosis. The tight junction disruptor cytochalasin D signif icantly increased the level of transepithelial KRQKYD transport (P＜0.05), suggesting that intact KRQKYD was absorbed by paracellular transport.
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