Walnut‐Derived Peptide PW5 Ameliorates Cognitive Impairments and Alters Gut Microbiota in APP/PS1 Transgenic Mice

Abstract

Scope: Decreasing β-amyloid (Aβ) accumulation is of significance in finding therapeutic candidates for cognitive impairments in Alzheimer's disease (AD). The aim of this study is to investigate the potency of the active components of walnut protein in decreasing Aβ aggregation and ameliorating cognitive impairments. Methods and results: Cell model of intracellular Aβ42 aggregation is used to explore the active ingredients in walnut protein hydrolysate (WPH). A bioactive peptide (Pro-Pro-Lys-Asn-Trp, PW5) with great anti-Aβ42 aggregation activity identified from the WPH is synthesized for in vitro and in vivo experiments. Using classic APP/PS1 mouse model, it is validated that PW5 exerts its effects on cognitive improvement through reducing Aβ plaques accumulation. Moreover, metabolomic analysis reveals that serum norepinephrine (NE) and isovalerate levels are significantly increased in response to PW5 intervention, with decreased serum levels of acetylcholine (AChe) and valerate, compared with the vehicle-treated APP/PS1 mice. PW5 feeding also improves gut dysbiosis in APP/PS1 transgenic mice by increasing the relative abundance of Firmicutes and decreasing Proteobacteria and Verrucomicrobia as displayed by 16s rRNA analyses. Conclusions: These promising results support the utilization of peptide PW5 as an active ingredient in functional foods or potential drug candidate for the prevention and/or treatment of AD.

Quercetin is protective against short‐term dietary advanced glycation end products intake induced cognitive dysfunction in aged ICR mice

“…AQ group had elevated Tenericutes and decreased Verrucomicrobia at the phylum level, while reduced genus Blautia and Anaerotruncus . The reduction in phylum Verrucomicrobia from AQ group was in consistent with the study by Wang et al (), suggesting that phylum Verrucomicrobia might play an important role for quercetin’s improvement on cognitive function post dAGEs intervention. While the roles of other bacteria, especially phylum Tenericutes , genus Blautia, and Anaerotruncus in cognitive function post AGE and/or quercetin intervention require further exploration.…”

“…Specifically, in regards to the altered gut microbiota associated with the present study, Zhuang et al () reported that in AD patients, at the family level, Ruminococcaceae was increased while Lachnospiraceae decreased. Wang et al () reported that in APP/PS1 mice, walnut‐derived bioactive peptide improved cognitive function and gut dysbiosis by decreasing Verrucomicrobia at the phylum level. Evidence also suggested that the genus Blautia was increased in APP/PS1 mice (Park et al, ).…”

“…reported that in AD patients, at the family level, Ruminococcaceae was increased while Lachnospiraceae decreased Wang et al (2019). reported that in APP/ The schematic diagram demonstrating the mechanisms of short-term quercetin intervention on dAGEsinduced cognitive dysfunction in aged ICR mice.…”

Honokiol Nanoscale Drug Delivery System Ameliorates the Cognitive Deficits in Tgcrnd8 Mice of Alzheimer’s Disease via Inhibiting Neuropathology and Modulating Gut Microbiota

“…The relative abundance of Actinobacteria had an 88% decrease in TgCRND8 mice, as compared with the WT mice, while the proportion of the Proteobacteria, Bacteroidetes and Cyanobacteria visibly increased by 235.3%, 99.7% and 125% respectively in TgCRND8 mice, as compared to the WT mice. Those alterations were in accordance with the previous reports [85,86]. Nano-HO inhibited the relative abundance of the Firmicutes, Proteobacteria, Bacteroidetes and Cyanobacteria in TgCRND8 mice as similar to that of regular HO.…”

Non-uinform gut microbiota alteration patterns associated with therapeutic outcomes in an Alzheimer's disease animal model

“…We then chose Metformin as a drug candidate because Metformin is a well-studied microbiota-manipulating chemical agent. Two peptides, PW5 (Pro-Pro-Lys-Asn-Trp), recently reported [19] by our lab to effectively reshaped the gut microbiota composition and reduced Aβ plaques in the same APP/PS1 mice model and WN5 (Try-Pro-Pro-Lys-Asn), were used as dietary nutrient candidates.…”