Physicochemical properties of selenized quinoa protein hydrolysate and its regulatory effects on neuroinflammation and gut microbiota in hypoxic mice

• SeMet is the dominant Se species in SQPP. • SQPP was different from QPP in physicochemical property and structure. • SQPP with excellent antioxidation was prepared by germination selenium rich. • SQPP better counteracts oxidative stress and neuroinflammation responses than QPP. • Gut microbiota and synapse modulation mediated SQPP's neuroprotection in HH mice. Selenopeptides are bioactive compounds with demonstrated potential to support brain health, and selenium-enriched protein hydrolysates represent a promising source of these compounds. In this study, selenium-enriched quinoa protein hydrolysate (SQPP) was prepared using a germination-based selenium biofortification method. The physicochemical characteristics and neuroprotective effects of SQPP were investigated in mice subjected to hypobaric hypoxia (HH). The content of organic selenium (4.762 ± 0.029 mg/kg) accounted for the majority of total selenium, with selenomethionine (SeMet) identified as the predominant form. Structural analysis showed shifts in the O–H, N–H, and amide I (C=O) peaks of SQPP relative to quinoa protein hydrolysate (QPP), suggesting that selenium incorporation stabilizes the α-helix by modifying polar group microenvironments and hydrogen bonding, leading to alterations in physicochemical structure. In vitro assays showed that SQPP exhibited markedly greater antioxidant activity than QPP. In vivo, SQPP significantly attenuated HH-induced cognitive deficits, enhanced levels of neurotrophic factors and neurotransmitters, and restored synaptic function and neuronal integrity in mice. Both QPP and SQPP supplementation mitigated neuroinflammation, oxidative stress, and gut microbiota imbalance in HH-exposed mice, with SQPP exerting a more pronounced protective effect against oxidative damage and neuroinflammatory responses. These results highlight SQPP as a potential dietary supplement for preventing and treating hypoxia-related brain injury.