Compositions for improving cognition and uses thereof

Abstract

The invention provides a composition for improving cognition and application thereof, the composition at least contains gamma-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid in physiologically acceptable media, and the three substances in the composition are compounded and have a synergistic effect to achieve the effects of benefiting brain health and improving cognition.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of oral products, in particular to a composition for improving cognition and use thereof. BACKGROUND

[0002] There is a close relationship between aging and cognitive impairment, which involves multiple levels of physiological and pathological mechanisms. With age, the brain undergoes a series of structural degenerative changes, including a decrease in the number of neurons, a decrease in synaptic plasticity, a decrease in hippocampal volume, and a decrease in prefrontal cortex thickness, which directly affects high-level cognitive abilities such as learning, memory, and executive function, perceptual-motor function, language, complex attention, and social cognition, often causing learning and memory impairment, and accompanied by aphasia, apraxia, agnosia, and akinesia.

[0003] With the intensification of global population aging, the incidence of cognitive impairment and related neurodegenerative diseases (such as Alzheimer's disease and Parkinson's disease) has increased significantly, which seriously threatens the quality of life of the elderly and the social medical burden.

[0004] Currently, drugs for improving cognitive function in clinical use (such as cholinesterase inhibitors and NMDA receptor antagonists) have certain efficacy, but have problems such as large side effects, limited long-term effect, and high price. Therefore, it is of great practical significance to develop safe, effective, and easy-to-take natural or composite oral cognitive improvement preparations.

[0005] Existing research shows that the maintenance of cognitive function is related to a variety of mechanisms, including: Neuroprotection and antioxidant — oxidative stress and mitochondrial dysfunction can accelerate neuronal damage, while natural antioxidants (such as curcumin and resveratrol) can reduce free radical damage and protect neural cells.

[0006] Synaptic plasticity and neurogenesis — a decrease in neurotrophic factors (such as BDNF) is associated with cognitive decline, and certain plant extracts (such as ginkgo biloba leaves and ginsenosides) can promote neuroregeneration and synaptic plasticity.

[0007] Anti-neuroinflammation — chronic low-grade inflammation is an important inducer of cognitive impairment, and Omega-3 fatty acids and flavonoids can inhibit the release of pro-inflammatory factors and improve the brain microenvironment.

[0008] Cerebral blood flow and metabolic optimization — decreased cerebral vascular function leads to insufficient blood supply to the brain, and certain active ingredients (such as tanshinone and huperzine A) can improve microcirculation and enhance brain energy metabolism.

[0009] The cognitive health products on the market at present mostly use single active ingredient or simple combination, and have problems of low bioavailability, insufficient synergistic effect, etc. Therefore, there is an urgent need for a composite oral composition based on multi-target and multi-mechanism synergistic effect, which can improve the absorption rate, enhance the efficacy and reduce adverse reactions, so as to more effectively delay cognitive decline and improve brain function.

[0010] Zebrafish shows high conservation in neuroanatomical organization and neurotransmitter signaling pathways, and its dorsal, medial and lateral sides correspond to the isocortex, amygdala and hippocampus of mammals, respectively. The neural behaviors related to learning and memory of zebrafish have been reported for a long time, and the behavior performance comparable to human beings such as motor activity, anxiety-like behavior, learning, memory retention, spatial and object recognition, fear response, social preference and interaction can be embodied on zebrafish. SUMMARY

[0011] In view of the technical problems in the prior art, the present application provides a composition for improving cognition, which contains at least γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid in a physiologically acceptable medium. The three substances can synergistically enhance brain health and improve cognition.

[0012] The specific technical solutions of the present application are as follows: 1. A composition containing at least γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid in a physiologically acceptable medium, wherein the mass ratio of the γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-8):(0.2-5):1.

[0013] 2. The composition according to item 1, wherein the mass ratio of the γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-5):(0.2-3):1.

[0014] 3. The composition according to item 1, wherein the mass ratio of the γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-4):(0.25-2):1.

[0015] 4. The composition according to any one of items 1-3, wherein the composition further comprises an auxiliary material.

[0016] 5. The composition according to item 4, wherein the dosage form of the composition is a tablet, a powder, a granule, a capsule or an aqueous agent.

[0017] 6. An article comprising the composition according to any one of items 1-5.

[0018] 7. Use of the composition according to any one of items 1-5 or the article according to item 6 in the preparation of a product for improving cognition.

[0019] 8. Use of gamma-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid in the preparation of a cognitive improvement product.

[0020] 9. The use according to item 8, wherein the mass ratio of the gamma-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-8):(0.2-5):1.

[0021] 10. The use according to item 9, wherein the mass ratio of the gamma-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-5):(0.2-3):1.

[0022] 11. The use according to item 9, wherein the mass ratio of the gamma-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-4):(0.25-2):1.

[0023] Beneficial effects (1) The cognitive improvement composition described in the present application comprises gamma-aminobutyric acid (GABA), L-ergothioneine and N-acetylneuraminic acid, which are compounded together and synergistically enhance the effect of helping brain health and improving cognition.

[0024] (2) The raw materials used in the present application are of fermentation origin, which are highly safe.

[0025] (3) The production cost of the present application is low, the process cycle is short, the pollution is small, the energy consumption is low, and the industrialization is easy to realize. DETAILED DESCRIPTION

[0026] The present application will be described in detail below with reference to the described embodiments. Although specific embodiments of the present application are shown, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments described herein. On the contrary, these embodiments are provided to enable a more thorough understanding of the present application and to fully convey the scope of the present application to those skilled in the art.

[0027] It should be noted that certain terms are used in the specification and claims to refer to particular components. It will be understood by those skilled in the art that different names can be used to refer to the same component. The present specification and claims do not distinguish components based on the difference in names, but rather on the difference in function. As mentioned throughout the specification and claims, "comprising" or "including" is an open term, which should be interpreted as "including but not limited to". The subsequent description in the specification is a preferred embodiment for implementing the present application, but the description is for the purpose of illustrating the general principles of the specification, and is not intended to limit the scope of the present application. The scope of protection of the present application is defined by the appended claims.

[0028] This application provides a composition containing at least γ-aminobutyric acid, L-ergothioneine, and N-acetylneuraminic acid in a physiologically acceptable medium; wherein the mass ratio of γ-aminobutyric acid, L-ergothioneine, and N-acetylneuraminic acid is (0.1-8):(0.2-5):1.

[0029] In this application, the physiologically acceptable medium has the meaning commonly understood by those skilled in the art. For example, a physiologically acceptable medium refers to a liquid or material basis that can be safely used in a biological body or experimental environment and is compatible with physiological conditions. It is designed to simulate or maintain the natural environment of a biological system and avoid causing toxicity, immune response or significant interference with normal function.

[0030] The N-acetylneuraminic acid mentioned refers to a representative compound of the sialic acid family, which has antibacterial, detoxifying, anti-adhesion, and anti-cancer properties.

[0031] For example, the mass ratio (m) of γ-aminobutyric acid, L-ergothioneine, and N-acetylneuraminic acid. γ-氨基丁酸 :M L-麦角硫因 :m N-乙酰神经酰胺The possible values ​​are 0.1:0.2:1, 0.1:0.25:1, 0.1:0.3:1, 0.1:0.4:1, 0.1:0.5:1, 0.1:0.5:1, 0.1:0.6:1, 0.1:0.7:1, 0.1:0.8:1, 0.1:0.9:1, 0.1:1.0:1, 0.1:1.1:1, 0.1:1.2:1, 0.1:1.3:1, 0. 1:1.4:1, 0.1:1.5:1, 0.1:1.6:1, 0.1:1.7:1, 0.1:1.8:1, 0.1:1.9:1, 0.1:2:1, 0.1:3:1, 0.1:4:1, 0.1:5:1, 0.2:1:1, 0.3:1:1, 0.4:1:1, 0.5:1:1, 0.6:1:1, 0.7:1:1, 0.8:1:1, 0. 9:1:1, 1:1:1, 1.1:1:1, 1.2:1:1, 1.3:1:1, 1.4:1:1, 1.5:1:1, 1.6:1:1, 1.7:1:1, 1.8:1:1, 1.9:1:1, 2:1:1, 2.1:1:1, 2.2:1:1, 2.3:1:1, 2.4:1:1, 2.5:1:1, 2.6:1:1, 2.7:1:1, 2 8:1:1, 2.9:1:1, 3:1:1, 3.1:1:1, 3.2:1:1, 3.3:1:1, 3.4:1:1, 3.5:1:1, 3.6:1:1, 3.7:1:1, 3.8:1:1, 3.9:1:1, 4:1:1, 5:1:1, 6:1:1, 7:1:1, 8:1:1, 1:2:1, 1:3:1, 1:4:1, 1:5:1, etc.

[0032] In the composition described in this application, γ-aminobutyric acid, L-ergothioneine, and N-acetylneuraminic acid can synergistically enhance brain health and thus improve cognition.

[0033] In some embodiments, the mass ratio of γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-5):(0.2-3):1, and preferably, the mass ratio of γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-4):(0.25-2):1.

[0034] In some embodiments, the composition further includes excipients.

[0035] In some embodiments, the dosage form of the composition is tablets, powders, granules, capsules, or liquids.

[0036] In this application, no restrictions are placed on the excipients used in the dosage form. Those skilled in the art can select conventional excipients to prepare the dosage form of this application according to actual needs, such as tablets, powders, granules, capsules or liquids.

[0037] In this application, no restrictions are placed on the method for preparing the dosage form. Those skilled in the art can use conventional methods in the field to prepare the dosage form, as long as they can meet the requirements of this application.

[0038] This application provides an article of manufacture comprising any of the compositions described above.

[0039] In this application, no restrictions are placed on the mass percentage of the composition in the article. Those skilled in the art can select the concentration of the composition in the article according to actual needs, as long as it meets the requirements of this application.

[0040] This application provides for the use of any of the compositions or articles described above in the preparation of cognitive-enhancing products.

[0041] As described above, the three substances in the composition can work synergistically to improve brain health, and thus can be used to prepare products that improve cognition.

[0042] Furthermore, the improvement of cognition includes at least the improvement of cognitive impairment; improvement of neurodegenerative and cerebrovascular diseases such as Alzheimer's disease, vascular dementia, Lewy body dementia, and frontotemporal dementia; improvement of acquired brain injury caused by traumatic brain injury, intracranial infection, or brain tumor; improvement of mental illnesses related to schizophrenia, major depressive disorder, etc.; improvement of other neurological diseases caused by multiple sclerosis, epilepsy, etc.; and improvement of metabolic and toxic factors (such as chronic alcohol dependence, thyroid disease), mild cognitive impairment, and attention deficit hyperactivity disorder.

[0043] This application provides the use of γ-aminobutyric acid, L-ergothioneine, and N-acetylneuraminic acid in the preparation of cognitive-enhancing products.

[0044] In some embodiments, the mass ratio of γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-8):(0.2-5):1, preferably, the mass ratio of γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-5):(0.2-3):1.

[0045] In some embodiments, the mass ratio of γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-4):(0.25-2):1.

[0046] For example, the mass ratio (m) of γ-aminobutyric acid, L-ergothioneine, and N-acetylneuraminic acid. γ-氨基丁酸 :M L-麦角硫因 :m N-乙酰神经酰胺 The possible values ​​are 0.1:0.2:1, 0.1:0.25:1, 0.1:0.3:1, 0.1:0.4:1, 0.1:0.5:1, 0.1:0.5:1, 0.1:0.6:1, 0.1:0.7:1, 0.1:0.8:1, 0.1:0.9:1, 0.1:1.0:1, 0.1:1.1:1, 0.1:1.2:1, 0.1:1.3:1, 0. 1:1.4:1, 0.1:1.5:1, 0.1:1.6:1, 0.1:1.7:1, 0.1:1.8:1, 0.1:1.9:1, 0.1:2:1, 0.1:3:1, 0.1:4:1, 0.1:5:1, 0.2:1:1, 0.3:1:1, 0.4:1:1, 0.5:1:1, 0.6:1:1, 0.7:1:1, 0.8:1:1, 0. 9:1:1, 1:1:1, 1.1:1:1, 1.2:1:1, 1.3:1:1, 1.4:1:1, 1.5:1:1, 1.6:1:1, 1.7:1:1, 1.8:1:1, 1.9:1:1, 2:1:1, 2.1:1:1, 2.2:1:1, 2.3:1:1, 2.4:1:1, 2.5:1:1, 2.6:1:1, 2.7:1:1, 2 8:1:1, 2.9:1:1, 3:1:1, 3.1:1:1, 3.2:1:1, 3.3:1:1, 3.4:1:1, 3.5:1:1, 3.6:1:1, 3.7:1:1, 3.8:1:1, 3.9:1:1, 4:1:1, 5:1:1, 6:1:1, 7:1:1, 8:1:1, 1:2:1, 1:3:1, 1:4:1, 1:5:1, etc.

[0047] The composition described in this application can significantly increase the proportion of blue area activity in zebrafish models, indicating that the composition has a superior effect on improving cognition.

[0048] Example This application provides a general and / or specific description of the materials and test methods used in the experiments. In the following examples, unless otherwise specified, % represents wt%, i.e., weight percentage. Reagents or instruments used, unless otherwise specified, are all commercially available conventional reagent products.

[0049] Example 1: Preparation of tablets (1) Mixing: GABA, L-ergothioneine and N-acetylneuraminic acid are mixed evenly with the excipients; wherein, the mass ratio of GABA, L-ergothioneine and N-acetylneuraminic acid is 4:2:1, the total mass of GABA, L-ergothioneine and N-acetylneuraminic acid is 42g, and the excipients consist of 29g of starch and 29g of sodium carboxymethyl cellulose; (2) Wet granulation: After mixing evenly, add 10ml of purified water by spraying to perform wet granulation; (3) Drying: Place the wet granulated material into an oven and dry at a constant temperature of 50°C for 4 hours. After drying, sterilize with ultraviolet light for 15 minutes to obtain whole granules. (4) Tableting: The dried whole grains are compressed to obtain 80 tablets, each weighing 1.0g.

[0050] Example 2 Preparation of Granules (1) Mixing: GABA, L-ergothioneine and N-acetylneuraminic acid are mixed evenly in a mass ratio of 4:0.5:1; wherein the total mass of GABA, L-ergothioneine and N-acetylneuraminic acid is 1 kg. (2) One-step granulation: After mixing evenly, add it to an FBM-3 type fluidized bed granulator (equipment capacity is 3L). Use purified water as a binder and spray it from the top of the fluidized bed granulator. The atomization pressure of the fluidized bed granulator is 0.1MPa and the air inlet temperature is 55℃. After processing for 80 minutes, use 20 mesh and 60 mesh sieves to screen and obtain particles between 60 mesh and 80 mesh. (3) Sterilization: The material obtained in step (2) is sterilized by ultraviolet light for 30 minutes; (4) Packaging: The sterilized material is packaged to obtain 180 bags of granules, each bag containing 5g.

[0051] Example 3: Preparation of Powder Seven different powders were prepared, and the specific formulations are shown in Table 1. These are the samples required for subsequent efficacy tests.

[0052] (1) Mixing: GABA, L-ergothioneine and N-acetylneuraminic acid were mixed together. The total mass of each group of active ingredients was 100g. The proportion of each group of active ingredients is shown in Table 1. (2) Sieving: The mixed material is sieved through a 60-mesh Taylor standard sieve to obtain a uniform powder. (3) Sterilization: The material obtained in step (2) is sterilized by ultraviolet light for 30 minutes; (4) Packaging: The sterilized material is packaged to obtain 32 bags of powder, each bag containing 2.5g.

[0053] Comparative Examples 1-3 Comparative Examples 1-3 were all single-function powders, containing 100g of γ-aminobutyric acid (GABA), 100g of L-ergothioneine, and 100g of N-acetylneuraminic acid, respectively. They were sterilized by ultraviolet light for 30 minutes and then packaged, with each package containing 2.5g.

[0054] Comparative Example 4 (1) Mixing: GABA and L-ergothionein are mixed together. The total mass of the active ingredients is 100g. The proportion of active ingredients added is shown in Table 1. (2) Sieving: Pass the evenly mixed material through a 60-mesh Taylor standard sieve to obtain a uniform powder. (3) Sterilization: The material obtained in step (2) is sterilized by ultraviolet light for 30 minutes; (4) Packaging: The sterilized material is packaged to obtain 32 bags of powder, each bag containing 2.5g.

[0055] Comparative Example 5 (1) Mixing: GABA and N-acetylneuraminic acid are mixed together. The total mass of the active ingredients is 100g. The proportion of active ingredients added is shown in Table 1. (2) Sieving: Pass the evenly mixed material through a 60-mesh Taylor standard sieve to obtain a uniform powder. (3) Sterilization: The material obtained in step (2) is sterilized by ultraviolet light for 30 minutes; (4) Packaging: The sterilized material is packaged to obtain 32 bags of powder, each bag containing 2.5g.

[0056] Comparative Example 6 (1) Mixing: L-ergothioneine and N-acetylneuraminic acid are mixed together. The total mass of the active ingredients is 100g. The proportion of active ingredients added is shown in Table 1. (2) Sieving: Pass the evenly mixed material through a 60-mesh Taylor standard sieve to obtain a uniform powder. (3) Sterilization: The material obtained in step (2) is sterilized by ultraviolet light for 30 minutes; (4) Packaging: The sterilized material is packaged to obtain 32 bags of powder, each bag containing 2.5g.

[0057] Table 1

[0058] Experimental Example: Cognitive Improvement Test Zebrafish exhibit a high degree of conservation in their neuroanatomical structures and neurotransmitter signaling pathways. Their dorsal, medial, and lateral blunt structures correspond to the isocortex, amygdala, and hippocampus of mammals, respectively. Neurobehaviors related to learning and memory in zebrafish have long been reported, and behaviors comparable to those in humans, such as motor activity, anxiety-like behavior, learning, memory retention, spatial and object recognition, fear responses, social preferences, and interactions, are all observed in zebrafish.

[0059] Bisphenol compounds are one of the important raw materials for synthesizing polymer materials. They mainly include bisphenol A, bisphenol B, bisphenol F and bisphenol AF. Their structures are quite similar and they all have neurodevelopmental toxicity. They inhibit the movement behavior of zebrafish, damage glial cells, affect the formation of synapses and the release of neurotransmitters, and ultimately lead to a decline in learning and memory abilities.

[0060] Color preference tests can serve as an effective method for memory assessment, cognitive impairment assessment, neurodegenerative disease assessment, and toxic behavior assessment. Meanwhile, mazes are one of the important devices for assessing different phenomena (such as learning and memory, anxiety, and preferences) in zebrafish neurological disease models. Various cognitive tasks frequently utilize color cues in mazes to study zebrafish learning and memory.

[0061] I. Experimental Methods 1.1. Sample Preparation Information L-ergothioneine, γ-aminobutyric acid, and N-acetylneuraminic acid, in standard diluted water.

[0062] 1.2. Laboratory Animals Zebrafish were raised in aquarium water at 28℃ (water quality: 200 mg of readily soluble sea salt added per 1 L of reverse osmosis water; conductivity 450~550 μS / cm; pH 6.5~8.5; hardness 50~100 mg / L CaCO3), bred and provided by our company's aquarium. The laboratory animal use license number is: SYXK (Zhejiang) 2022-0004. The husbandry and management met the requirements of international AAALAC certification (certification number: 001458), and the IACUC ethics review number is: IACUC-2025-12568-01.

[0063] 1.3. Instruments, Consumables and Reagents Dissecting microscope (SZX7, OLYMPUS, Japan); CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd., China); Precision electronic balance (CP214, OHAUS, USA); Zebrafish behavior analysis system (Zebra Lab3.22.3.31, Viewpoint, France); 96-well plate (Nest Biotech, China).

[0064] Dimethyl sulfoxide (DMSO, batch number BCCD8942, Sigma, Switzerland), Bisphenol AF (batch number J1925142, Shanghai Aladdin Biochemical Technology Co., Ltd., China).

[0065] II. Detection Methods Evaluation of efficacy in improving cognitive impairment Wild-type AB strain zebrafish, 5 days post-fertilization (5 dpf), were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker. The experimental groups (example and comparative groups) received the sample in water, while a normal control group and a model control group were also included. Each beaker had a volume of 20 mL. Except for the normal control group, the other experimental groups and the model control group received bisphenol AF in water to establish a zebrafish cognitive impairment model. After treatment at 28℃ for 1 day, 5 zebrafish from each experimental group were randomly selected and placed in a cross-shaped module. The module was divided into four regions: yellow, blue, red, and green. Six modules were placed in each group. Data were collected using a behavior analyzer, and the percentage (%) of the total movement distance of the zebrafish within the blue region relative to the total movement distance of the entire region within 10 minutes was analyzed. The statistical analysis results of this indicator were used to evaluate the efficacy of the sample in improving cognitive impairment. Statistical results are expressed as mean ± SE, and p < 0.05 indicated statistical significance.

[0066] III. Experimental Results and Analysis: The results are shown in Table 2. Table 2. Experimental Results of Sample Cognitive Improvement Efficacy Evaluation

[0067] Compared with the model control group (between the two groups), *p<0.05, **p<0.01, ***p<0.001 Color preference tests are commonly used in assessing cognitive impairment in zebrafish. Zebrafish prefer shorter wavelengths of color and show a strong preference for blue compared to other colors (such as red, yellow, and green). However, in zebrafish with cognitive impairment, changes in hormones and neurotransmitters in the brain cause them to lose their preference for blue. This study analyzed the percentage (%) of the total distance zebrafish traveled within the blue area over 10 minutes to evaluate the efficacy of the sample in improving cognitive impairment.

[0068] Under the experimental conditions, the single L-ergothioneine and γ-aminobutyric acid (GABA) groups and their combination groups showed no significant improvement in cognition, with no statistically significant difference compared to the model control group. The N-acetylneuraminic acid group and the combination of N-acetylneuraminic acid with L-ergothioneine and γ-aminobutyric acid respectively showed cognitive improvement effects, with a significant increase in the proportion of blue area activity in zebrafish compared to the model control group. However, when GABA, L-ergothioneine, and N-acetylneuraminic acid were combined, the percentage of blue area activity in zebrafish was significantly increased. As shown in Table 2 above, the proportion of blue area activity in zebrafish in each example group was higher than that in the model group and each comparative group, and the results were statistically significant.

[0069] Examples 3-1 were compared with Comparative Examples 1-6, and the results are shown in Table 3. The results show that the numerical differences between each pair of examples are significant. This indicates that the effect of the combination of γ-aminobutyric acid (GABA), L-ergothioneine, and N-acetylneuraminic acid in a 1:1:1 ratio is better than the effect of using γ-aminobutyric acid, ergothioneine, and N-acetylneuraminic acid alone or in pairs in the same ratio. As shown in Table 4, Examples 3-2 to 3-7 were compared with Comparative Examples 1-3. The results show that the numerical differences between each pair of examples 3-2 to 3-6 and Comparative Examples 1-3 are significant. However, there is no significant difference between Example 3-7 and Comparative Examples 2 and 3. Therefore, Examples 3-7 were compared with Examples 3-1 to 3-6, and the results are shown in Table 5. The results show that the numerical differences between each pair of examples are significant.

[0070] Table 3

[0071] Note: Compared with Example 3-1 (between two groups), *p<0.05, **p<0.01, ***p<0.001 Table 4

[0072] Note: Compare with Comparative Example 1 (between the two groups). * p<0.05, ** p<0.01, *** p<0.001 Compare with Comparative Example 2 (between the two groups). † p<0.05, †† p<0.01, ††† p<0.001 Compare with Comparative Example 3 (between the two groups). § p<0.05, §§ p<0.01, §§§ p<0.001 Table 5

[0073] Note: Comparison with Examples 3-7 (between two groups). * p<0.05, ** p<0.01, *** p<0.001 The experimental results show that in the composition described in this application, when the mass ratio of γ-aminobutyric acid (GABA), L-ergothioneine and N-acetylneuraminic acid is (0.1-4):(0.25-2):1, it can significantly increase the proportion of blue area activity in zebrafish and has a better cognitive improvement effect.

[0074] The above description is merely a preferred embodiment of this application and is not intended to limit the application in any other way. Any person skilled in the art may make changes or modifications to the disclosed technical content to create equivalent embodiments. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of this application without departing from the scope of the technical solution of this application shall still fall within the protection scope of this application.

Claims

1. A composition comprising at least γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid in a physiologically acceptable medium; wherein the mass ratio of said γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-8):(0.2-5):

1.

2. The composition according to claim 1, characterized in that, The mass ratio of γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-5):(0.2-3):

1.

3. The composition according to claim 1 or 2, wherein the composition further comprises excipients.

4. An article comprising the composition according to any one of claims 1-3.

5. Use of the composition of any one of claims 1-3 or the article of claim 4 in the preparation of cognitive-enhancing products.

6. Use of γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid in the preparation of cognitive-enhancing products.

7. The use according to claim 6, wherein the mass ratio of γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-8):(0.2-5):

1.

8. The use according to claim 6 or 7, wherein the mass ratio of γ-aminobutyric acid, L-ergothioneine and N-acetylneuraminic acid is (0.1-5):(0.2-3):1.

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