| Abstract |
The global prevalence and burden of dementia continue to rise, driven not only by an aging population but also by obesity associated with unhealthy dietary habits. From a Quality of Life (QoL) perspective, identifying naturally derived compounds that enhance cognitive function is increasingly encouraged alongside pharmaceutical interventions. In this study, we investigated the anti-dementia effects of a peptide derived from bovine serum albumin using high-fat diet (HFD)-fed mice. We first found that the enzymatic digest of bovine serum albumin could orally alleviate cognitive decline induced by HFD. Then, we confirmed the oral pro-cognitive effects of the peptide derived from the digest and the underlying mechanisms. The peptide had an EC50 of 0.01 mg/kg BW/day. Therefore, we designated it bSAPP (bovine serum albumin-derived pro-cognitive peptide). The cognition-enhancing effects of bSAPP were blunted by an α7nAChR antagonist, suggesting that the pro-cognitive effect of bSAPP was mediated by acetylcholine signaling. Moreover, bSAPP became ineffective in the presence of a CCK1R antagonist as well as in CCK1R-/- mice, highlighting the involvement of CCK1R signaling. Furthermore, bSAPP increased the number of BrdU-positive cells in the dentate gyrus of the hippocampus and upregulated hippocampal expression of VEGF and NGF in a CCK1R-dependent manner. Additionally, the cognitive benefits of bSAPP were nullified by a capsaicin pre-treatment. In summary, we observed that bSAPP could orally enhance cognitive function in HFD-fed mice through CCK1R signaling via the gut-brain axis, accompanied by facilitated hippocampal cell proliferation and involvement of acetylcholine signaling.
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