Background/Objectives: Hippocampal neuroinflammation (HNF) is a key pathological feature in neurodegenerative disorders. Milk-derived exosomes, as bioactive extracellular vesicles, have underexplored potential in regulating brain neuroinflammatory responses. This study aimed to characterize desert milk exosomes (D-Exo) and investigate their neuroprotective and anti-neuroinflammatory effects in LPS-induced HNF mice model and an LPS-stimulated BV2 microglia. Methods: Exosomes were isolated from desert and non-desert milk (ND-Exo) for proteomic analysis. After pretreating BV2 cells with exosomes and stimulating with LPS, their inflammatory responses and polarization were assessed by RT-PCR. Balb/c mice were orally gavaged with D-Exo or 0.9% NaCl for 28 days before LPS injection. Cognitive function was assessed via behavioral tests, with microglial/astrocyte activation analyzed by immunofluorescence. Results: D-Exo exhibited superior stability and a unique proteomic profile enriched with proteins linked to neuroinflammation and blood-brain barrier (BBB) integrity, notably within the AMPK signaling pathway. In vitro, D-Exo shifted LPS-stimulated microglia from the M1 to the M2 phenotype. In vivo, it alleviated HNF and cognitive decline, reduced Aβ_1-42 and Tau deposition, elevated BDNF and MAP2, and suppressed neuroinflammation and glial activation. Conclusions: D-Exo is enriched with specific proteins, attenuates neuroinflammation and cognitive decline by regulating microglial M1/M2 polarization and AMPK pathway, highlighting its preventive potential.

This study aimed to characterize the nutritional and sensory profiles of commercial liquid milk available in China (CN) from three different major global regions. Sixteen milk samples [six from CN, five from Western Europe (WEU), and five from Australia/New Zealand (ANZ)] were analyzed for macronutrients, minerals, vitamins, fatty acids (FAs), and sensory properties. CN milk had higher levels of fat, zinc, iodine, vitamin E, and vitamin B3, whereas imported milk contained more vitamin B2. Distinct FA profiles were observed: CN milk was richer in n-6 FAs, whereas imported milk had higher n-3 FAs and a more favorable n-3/n-6 ratio. Sensory analysis showed that imported milk exhibited stronger ‘cowy’ and ‘tea’ flavors. These variations were mainly caused by different feeding systems (total mixed rations-based confined production in CN vs. pasture-based grazing in WEU and ANZ), along with milk processing and supply chain factors. The results provide evidence for dairy product differentiation and help Chinese consumers make informed purchasing decisions.