Antarctic Krill Oil Exhibited Synergistic Effects with Nobiletin and Theanine on Regulating Ligand‐Specific Receptor‐Mediated Transcytosis in Blood–Brain Barrier by Inhibiting Alkaline Phosphatase in SAMP8 Mice

Abstract

Blood−brain barrier (BBB) impairment is related to the development of Alzheimer's disease (AD), which is dependent not only on tight junction but also on transcytosis of brain endothelial cells (BECs) in the BBB. Aging induces the decrease of ligand-specific receptor-mediated transcytosis (RMT) and the increase of non-specific caveolar transcytosis in BECs, which lead to the entry into parenchyma of neurotoxic proteins and the smaller therapeutic index in central nervous system drug delivery, further provoking neurodegenerative disease. A previous study suggests that sea-derived Antarctic krill oil (AKO) exhibits synergistic effects with land-derived nobiletin (NOB) and theanine (THE) on ameliorating memory and cognitive deficiency in SAMP8 mice. However, it is still unclear whether BBB change is involved. Hence, the effects of AKO combined with NOB and THE on aging-induced BBB impairment, including tight junction between BECs, ligand-specific RMT, and non-specific caveolar transcytosis in BECs, are investigated. The results suggest that AKO exhibits synergistic effects with NOB and THE on regulating ligand-specific RMT in BBB by inhibiting alkaline phosphatase (ALPL). The study provides a potential strategy candidate or targeted dietary patterns to prevent and treat AD by improving the BBB function.

A review on recent advances on nobiletin in central and peripheral nervous system diseases

“…The major effects of nobiletin on the nervous system are inhibiting inflammatory cytokine expression [ 1 , 48 , 63 ], reducing neurotoxicity [ 20 , 21 , 25 ], promoting the survival of nerve cells and axon outgrowth [ 52 ], reducing blood‒brain barrier permeability and cerebral oedema [ 36 , 59 , 60 , 77 ], promoting mild depolarization of nerve cell mitochondria and increasing capacity against oxidative stress [ 3 , 53 ]. The biological roles of nobiletin are inseparable from its basic mechanism.…”

Influence of 1,3-diacylglycerol on physicochemical and digestion properties of nanoemulsions and its enhancement of encapsulation and bioaccessibility of hydrophobic nobiletin

“…Nobiletin (NOB) is one of the most prevalent PMFs in citrus peels with plenty of beneficial bioactivities, including metabolic syndrome, regulation of circadian rhythms and anti-Alzheimer's disease. 20,21 However, its highly hydrophobic crystals and poor oral bioavailability make it challenging for application in functional foods. 22 Recently, many formulations have been developed to encapsulate NOB into delivery systems and enhanced its aqueous solubility and bioaccessibility, such as nanoemulsions (load capacity of 5 mg g −1 ), nanoparticles (load capacity of 800 μg mL −1 ) and hydrogels (load capacity of 4.5 mg mL −1 ).…”