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. 2022 Nov 18:5:2294-2308.
doi: 10.1016/j.crfs.2022.11.004. eCollection 2022.

Nutritional supplements formulated to prevent cognitive impairment in animals

Mengyu Cai  1 , Yicui Qu  1 , Zifu Ren  1 , Xin Xu  1 , Chuyang Ye  1 , Hongtao Lu  1 , Yinyin Zhang  1 , Wenlan Pan  1 , Hui Shen  1 , Hongxia Li  1
Affiliations

Nutritional supplements formulated to prevent cognitive impairment in animals

Mengyu Cai et al. Curr Res Food Sci. .

Abstract

Heat stress will cause a series of response in the living system and the most significant impact is on brain functions. The aim of this article is to develop nutritional supplements that can alleviate cognitive decline caused by heat stress. In this article, we screen functional food factors which can prevent or relieve effects on heat stress injury based on bioinformatics. 129 function factors related to the crossover targets were obtained, and a food database related to the prevention of high-temperature impairment was constructed. After a series of scoring standards combined with food classification, two formulas-nutrition fortifier formula (tyrosine and multivitamin B) and plant compound formula (quercetin, proanthocyanidin, and naringin) were investigated using animal experiments to determine their ability to prevent cognitive impairment of heat-stressed animals. Our results demonstrated that certain functional food factors and our two designed formulations significantly prevent cognitive impairment of heat-stressed animals. Further mechanism was carried out by cell viability assay, reactive oxygen species assay, real-time quantitative PCR and Western blot. The results showed that the plant compound formula diluted 4000 times had the best relieving effect on HT22 after heat stress, and this concentration formula can significantly alleviate the elevated levels of reactive oxygen species caused by heat stress. This formula also can significantly down-regulate IL-1β, IL-6, TNF-α, IL-10, iNOS and COX-2 expression. Likewise, Western blot results showed that the formula could activate the cAMP pathway and increase the expression of phosphorylated PKA and BDNF in hippocampal cells.

Keywords: Bioinformatics; Food functional factors; Heat stress; Nutritional supplements.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Bioinformatics of the target protein analysis (A) Intersection display of target interaction (B) PPI protein network construction (C) Barplot of target protein (D) Bubble chart of biological process entry for GO enrichment analysis (E) Cellular component (CC), molecular function (MF) and biological process (BP) of GO enrichment analysis (F) KEGG pathway enrichment histogram.
Fig. 2
Fig. 2
Effect of different nutrients on learning and memory in heat stress-exposed mice. (A) Latency time (B) The change of day 1 and 6 of the latency time (C) Platform quadrant time (D) Platform quadrant distance (E) Number of across the platform of water maze; Each bar represents the mean ± SD (n = 6). *P＜0.05,**P＜0.01,***P＜0.001vs. Heat Stress group; Statistical description: Uncorrected Fisher's LSD test was used in Fig. 2A,B,C,D, Uncorrected Dunn's test was used in Fig. 2E.
Fig. 3
Fig. 3
Effect of formula of plant compounds (Formula 1) on learning and memory in heat stress-exposed rats. (A) Latency time (B) The change of day 1 and 6 of the latency time (C) Platform quadrant time (D) Platform quadrant distance (E) Number of across the platform of water maze; (F)Number of active avoidances of shuttle experiment; Each bar represents the mean ± SD (n = 6). *P＜0.05,**P＜0.01,***P＜0.001 vs. Heat Stress group; Statistical description:.Dunnett's multiple comparisons was used in Fig. 3A,C,D,E,F, Uncorrected Fisher's LSD test was used in Fig. 3B.
Fig. 4
Fig. 4
Effect of Formula of Nutritional fortifier (F2) on learning and memory in heat stress-exposed rats. (A) Latency time (B) The change of day 1 and 6 of the latency time (C) Platform quadrant time (D) Platform quadrant distance (E) Number of across the platform of water maze; (F)Number of active avoidances of shuttle experiment; Each bar represents the mean ± SD (n = 6). *P＜0.05,**P＜0.01,***P＜0.001 vs. Heat Stress group; Statistical description:. Dunnett's multiple comparisons was used in Fig. 4A,C,D,E,F, Uncorrected Fisher's LSD test was used in Fig. 4B.
Fig. 5
Fig. 5
Effects of nutritional supplements on cell activity after heat stress, #P＜0.05,##P＜0.01,###P＜0.01vs. Control group; *P＜0.05,**P＜0.01,***P＜0.001 vs. Heat stress group; Statistical description: Uncorrected Fisher's LSD was used in Fig. 5.
Fig. 6
Fig. 6
ROS assessment of hippocampal cells after heat stress * P＜0.05, ***P＜0.001 vs. Heat Stress group; Statistical description: Uncorrected Fisher's LSD was used in Fig. 6.
Fig. 7
Fig. 7
The effect of formula 1 with hippocampal cells on iNOS, COX-2, IL-1β, IL-6, TNF-α and IL-10 mRNA expression by heat stress. Each bar represents the mean ± SD (n = 6). *P＜0.05,**P＜0.01,***P＜0.001 vs. Heat stress group; Statistical description: Dunnett's multiple comparisons test was used in Fig. 7.expression of heat stress (ΔΔct relative quantitative), *P＜0.05,**P＜0.01,***P＜0.001 vs heat stress group.
Fig. 8
Fig. 8
Influence of formula 1 on the cAMP pathway. (A–B) The effect of Formula 1 on the expression of phospho-PKA in HT22. (C–D) The effect of Formula 1 on the expression of BDNF in HT22. Values are expressed as means ± SD. *P < 0.05 as compared with the heat-stress group; Statistical description: Dunnett's multiple comparisons test was used in Fig. 8.
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