A nutritional composition and its use in assisting memory improvement

Abstract

This invention belongs to the field of functional substance research, specifically relating to a nutritional composition and its use in assisting memory improvement. The nutritional composition provided by this invention comprises the essential active ingredients shown in (I) and (II) below: (I) lysophosphatidylethanolamine; (II) L-α-GPC; wherein the essential active ingredient shown in (I) comprises at least lysophosphatidylethanolamine with a fatty acid chain length of 12-22 carbon atoms, and in the nutritional composition, the mass ratio of the essential active ingredient shown in (I) to the essential active ingredient shown in (II) is 1:(1-1000). The combination of lysophosphatidylethanolamine and L-α-GPC can synergistically assist in improving memory, repairing the cholinergic system in the body, and thereby improving cognitive and behavioral abilities.

Description

Technical Field

[0001] This invention belongs to the field of functional substance research, specifically relating to a nutritional composition and its use in assisting in improving memory. Background Technology

[0002] Memory decline or impairment refers to a decrease in the function of acquiring, storing, retrieving, or reproducing memories. It mainly manifests as forgetfulness, weak memory, difficulty in information retrieval, and short-term memory decline, and in severe cases, can affect daily life, work, and study efficiency. The causes of memory decline or impairment are complex and varied, including natural brain function decline due to aging, insufficient sleep, excessive fatigue, excessive mental stress, or certain medical conditions. Nutritional imbalance is one of the important controllable factors leading to memory impairment.

[0003] With the increasingly prominent problems of fast-paced modern life, unbalanced diet, and irregular work and rest, the population experiencing memory decline or impairment is showing a trend of becoming younger and more widespread. Not only are middle-aged and elderly people significantly affected, but teenagers and working professionals also often experience varying degrees of memory decline due to long-term sleep deprivation, mental stress, and insufficient nutrient intake, which has an adverse impact on personal quality of life and social productivity.

[0004] Currently, interventions for memory decline or impairment mainly include behavioral interventions, pharmacological interventions, and nutritional interventions. Among these, pharmacological interventions often have side effects and can only provide symptomatic relief, failing to fundamentally improve brain memory function. For example, the FDA-approved monoclonal antibody drug Donanemab, which targets Aβ plaque clearance, reported an adverse reaction rate of ≥5% in subjects receiving donepemab treatment, which was ≥2% higher than in the placebo group. Notably, it may cause side effects such as edema and bleeding. Behavioral interventions (such as memory training) are slow to take effect and require long-term adherence, resulting in poor compliance.

[0005] In recent years, nutritional intervention has become a research hotspot for improving impaired memory due to its advantages such as safety, convenience, lack of obvious adverse reactions, and long-term implementation. Studies have confirmed that the normal physiological functions of the brain and the processes of memory formation and storage depend on the synergistic support of various nutrients. Among these, dairy nutrients, rich in various bioactive substances and easily absorbed and utilized by the body, have become a core nutritional source for improving impaired memory. These include whey protein, casein, milk fat globule membrane, lactoferrin, milk-derived polypeptides, lactose, and milk-derived vitamins and minerals. These dairy nutrients can improve cerebral blood circulation, promote neuronal development, repair synaptic damage, inhibit oxidative stress, and regulate neurotransmitter secretion, thereby enhancing memory levels and delaying the decline or decay of memory function. For example, reference 1 (CN113455551B) uses phospholipid-rich milk fat globule membrane to prepare formula milk powder to promote brain development, improve learning ability, and alleviate cognitive decline; reference 2 (CN105435214B) uses lactoferrin to prevent impaired learning ability, mental and behavioral impairment, memory impairment, or reduced attention span.

[0006] The normal maintenance of memory function is closely related to brain energy metabolism, neurotransmitter balance, oxidative stress levels, and gut microbiota homeostasis. Milk-derived nutrients can participate in the regulation of these processes through multiple pathways: As a high-energy-consuming organ, the brain requires a continuous energy supply to maintain memory-related physiological activities. Lactose in milk can be broken down into glucose for direct use by the brain, while milk fat can be metabolized to produce ketone bodies, providing additional energy support for the brain. The synthesis and release of neurotransmitters (such as acetylcholine and dopamine) directly affect memory formation and retrieval. Tryptophan, tyrosine, and other amino acids contained in whey protein and casein are important precursors for neurotransmitter synthesis, promoting neurotransmitter secretion and maintaining memory function. Maintaining neurotransmitter balance; Oxidative stress can damage neurons and synaptic structures, leading to a decline in memory function. Lactoferrin, whey protein hydrolysate peptides, and milk-derived vitamins (such as vitamin E and vitamin C) in milk have significant antioxidant activity, which can protect brain memory-related tissues by scavenging free radicals and reducing oxidative damage. At the same time, the bidirectional regulatory effect of the brain-gut axis also participates in the regulation of memory function. Milk-derived probiotics, whey protein, and other components can regulate the composition of intestinal flora and promote intestinal health, thereby indirectly improving memory through the brain-gut axis. In addition, milk-derived nutrients can also enhance the body's immunity and reduce the damage of inflammatory responses to brain memory function, further enhancing memory improvement.

[0007] Milk-derived nutrients, as a natural and high-quality source of nutrition, are rich in various bioactive nutrients and have advantages such as easy absorption, high safety, wide availability, and easy accessibility. Furthermore, some of its nutrients can work synergistically to improve memory impairment through multiple pathways, making it suitable as a core nutritional intervention ingredient for improving memory impairment. Based on this, developing a nutritional composition with milk-derived nutrients as the core, combined with other functional nutrients, for multi-pathway and synergistic improvement of memory impairment, meets market demand and has significant practical value and promising prospects for promotion.

[0008] Phospholipids are key bioactive components of breast milk lipids, playing a crucial role in the development of the nervous system and metabolic regulation in infants and young children. Phospholipids can be broadly classified into two categories: glycerophospholipids (PL) and sphingomyelins (SM). PL can be further subdivided into lysophospholipids (LPL) and phosphatidylacetylphospholipids. Lysophospholipids are produced by hydrolyzing one fatty acid in the PL molecule, and the two main types found in breast milk are lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE).

[0009] Glycophosphocholine (GPC) is a water-soluble choline phospholipid derivative found in animal-based foods such as dairy products, meat, and eggs, as well as plant-based foods such as soybeans, whole grains, and some fruits and vegetables. The naturally occurring type of GPC is L-α-glycophosphocholine (L-α-GPC). Diet is the primary route of GPC acquisition for the human body. GPC is easily absorbed and utilized. Studies have found that L-α-GPC can improve cognitive function, regulate mood, and enhance motor skills. Multiple clinical studies suggest that L-α-GPC has a positive effect on improving cognitive function. Meta-analysis showed that L-α-GPC can effectively improve cognitive function in patients with acute stroke. Its use alone or in combination with cholinesterase inhibitors can effectively improve cognition in patients with neurological diseases related to cerebrovascular injury (Reference 3: Chinese Institute of Food Science and Technology. Scientific consensus on L-α-glycine choline [J]. Chinese Journal of Food Science, 2025, 25(11):440-447.DOI:10.16429 / j.1009-7848.2025.11.036.). Summary of the Invention

[0010] The problem the invention aims to solve

[0011] In the past, memory decline or impairment primarily affected middle-aged and elderly people, often accompanied by various diseases such as mild cognitive impairment, neurodegenerative diseases (Alzheimer's, Parkinson's, etc.), and memory loss caused by some cerebrovascular diseases. However, currently available treatments for these diseases are not only expensive but also ineffective, and some even have strong side effects. Furthermore, memory decline or impairment is increasingly affecting younger people. Due to work pressure, changes in lifestyle and dietary habits, many young and middle-aged adults are experiencing memory decline or impairment, even if it hasn't reached the clinical treatment standard. These individuals may not pay much attention to memory decline or impairment, or even if they notice mild problems, they may not actively intervene. However, as they age, they are more likely to experience higher risks of memory decline or impairment, and may even develop diseases such as Alzheimer's or Parkinson's.

[0012] Given the poor efficacy and side effects of existing nutritional compositions or drugs in treating memory loss and related diseases in the elderly, and the tendency for young and middle-aged people to overlook memory decline or premature damage, nutritional interventions to help improve memory are of great significance to human health and well-being.

[0013] In this regard, the present invention aims to develop a phospholipid nutritional composition derived from natural milk, mainly comprising lysophosphatidylethanolamine and L-α-glycine choline, which work synergistically to help improve memory without any side effects and can be consumed long-term as a nutritional supplement.

[0014] Solution for solving the problem

[0015] [1]. A nutritional composition comprising the essential active ingredients shown in (I) and (II) below:

[0016] (I) Lysophosphatidylethanolamine;

[0017] (II) L-α-GPC;

[0018] Wherein, the essential active ingredient shown in (I) contains at least lysophosphatidylethanolamine with a fatty acid chain length of 12-22 carbon atoms, and in the nutritional composition, the mass ratio of the essential active ingredient shown in (I) to the essential active ingredient shown in (II) is 1:(1-1000).

[0019] [2]. According to the nutritional composition described in [1], wherein the fatty acid chain in the lysophosphatidylethanolamine is located at the sn-1 position.

[0020] [3]. The nutritional composition according to [1] or [2], wherein the fatty acid chain in the lysophosphatidylethanolamine is unsaturated.

[0021] [4]. The nutritional composition according to any one of [1]-[3], wherein the lysophosphatidylethanolamine is a dairy product containing it and / or enzymatically hydrolyzed soybean lecithin.

[0022] [5]. The nutritional composition according to any one of [1]-[4], wherein the L-α-GPC is provided in the form of a natural source and / or a synthetic source.

[0023] [6]. Use of the nutritional composition according to any one of [1]-[5] in the preparation of a product that helps improve memory.

[0024] [7]. According to the use described in [6], wherein the aid to improve memory includes improving the function of the cholinergic system.

[0025] [8]. According to the use described in [6] or [7], wherein the product helps improve memory and thus helps improve cognition and / or helps improve behavioral abilities.

[0026] [9]. Use of the nutritional composition according to any one of [1]-[5] in the preparation of products that help improve cognition.

[0027]

[10] . Use of the nutritional composition according to any one of [1]-[5] in the preparation of a product that helps improve behavioral abilities.

[0028]

[11] . Use according to any one of [6]-

[10] , wherein the product is in the form of a powder solid or a liquid.

[0029]

[12] . Use according to any one of [6]-

[11] , wherein the product contains any one or more of the following ingredients: plant-based ingredients, animal dairy ingredients, animal meat ingredients, functional additives and any acceptable excipients.

[0030] The effects of the invention

[0031] This invention is the first to propose that the combination of lysophosphatidylethanolamine and L-α-GPC in a dosage ratio of 1:1-1000 can synergistically improve memory, repair the cholinergic system in the body, and thus improve cognition and behavioral abilities.

[0032] The nutrients mentioned in this invention, lysophosphatidylethanolamine and L-α-GPC, are both natural nutrients found in breast milk or cow's milk, suitable for long-term use, and readily accepted by people throughout their entire life cycle. The nutritional composition can be added to various types of products, including food, nutritional supplements, health foods, and pharmaceuticals. Detailed Implementation

[0033] The following describes embodiments of the present invention, but the present invention is not limited thereto. The present invention is not limited to the various configurations described below, and various modifications can be made within the scope of the claims. Embodiments and examples obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of the present invention.

[0034] <Terminology Definition>

[0035] In this invention, "comprising," "having," "including," or "containing" can mean included or open-ended, and does not exclude additional, uncited elements or method steps. At the same time, "comprising," "having," "including," or "containing" can also mean closed-ended, excluding additional, uncited elements or method steps.

[0036] In this invention, the meaning of "may" includes both performing a certain process and not performing a certain process.

[0037] In this invention, "optional" or "optionally" means that certain substances, components, execution steps, application conditions, etc., are used or not used.

[0038] In this invention, the numerical ranges represented by "value A ~ value B", "value A - value B", and "value A above / below" refer to the ranges including the endpoint values ​​A and B.

[0039] In this invention, the term "about" is used to define that the numerical ranges and parameters of this invention are approximate values, and the relevant values ​​in the specific embodiments have been presented as precisely as possible. Unless otherwise explicitly stated, it should be understood that all ranges, quantities, values, and percentages used in this invention are modified by the term "about". Here, "about" generally means that the actual value is within ±5%, ±3%, ±1%, or ±0.5% of a specific value or range. Furthermore, the values ​​and ranges appearing in this invention should be understood to include systematic errors that are unavoidable in industrial production.

[0040] In this invention, terms such as "some specific / preferred embodiments," "other specific / preferred embodiments," and "implementation" refer to specific elements (e.g., features, structures, properties, and / or characteristics) related to a particular embodiment that are included in at least one of the embodiments described herein, and may or may not be present in other embodiments. Furthermore, it should be understood that these elements may be combined in any suitable manner in various embodiments.

[0041] In this invention, all unit names used are international standard unit names, and unless otherwise stated, the "%" used refers to weight or mass percentage content.

[0042] In this invention, "teenagers" refers to the human group aged 7-18.

[0043] In this invention, "young adult" refers to the human group aged 19-40.

[0044] In this invention, "middle-aged and elderly" refers to the human group aged 41 and above, including middle-aged people aged 41-65 and elderly people aged 65 and above.

[0045] In this invention, "animal milk" refers to the liquid obtained from the mammary glands of a mammal in the process of lactation.

[0046] In this invention, "lysophosphatidylethanolamine (LysoPE, LPE)" is a glycerophospholipid composed of a glycerol backbone, a fatty acid chain, a phosphate group, and an ethanolamine head group. Compared to phosphatidylethanolamine, it lacks a fatty acid chain at the sn-1 or sn-2 position of its glycerol backbone.

[0047] In this invention, for ease of description of glycerophospholipids, the following characters are used to refer to different types of fatty acids: straight-chain fatty acids with a chain length of 18 carbon atoms and no carbon-carbon double bonds (18:0), such as stearic acid; straight-chain fatty acids with a chain length of 18 carbon atoms and one carbon-carbon double bond (18:1), such as oleic acid; straight-chain fatty acids with a chain length of 18 carbon atoms and two carbon-carbon double bonds (18:2), such as linoleic acid; and other fatty acid chain lengths are treated similarly. In this invention, for specific lysophosphatidylethanolamines, the format "LPE + the above characters" is used to indicate the type of lysophosphatidylethanolamine with different fatty acid chains, such as LPE 18:0, LPE 18:1, LPE 18:2, etc.

[0048] In this invention, L-α-glycine choline (L-α-GPC) can be abbreviated as glycine choline or GPC, with the molecular formula C8H. 20 NO6P.

[0049] Unless otherwise defined, other technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0050] <Nutritional Combinations>

[0051] The nutritional composition provided by this invention comprises the essential active ingredients shown in (I) and (II) below:

[0052] (I) Lysophosphatidylethanolamine;

[0053] (II) L-α-GPC;

[0054] Furthermore, in the nutritional composition, the mass ratio of the essential active ingredient shown in (I) to the essential active ingredient shown in (II) is 1:(1-1000).

[0055] This invention does not impose any special requirements on the source of lysophosphatidylethanolamine, as long as its source or form of use meets the requirements of local laws and regulations.

[0056] For example, it can be prepared through physical separation and extraction, chemical synthesis, enzymatic hydrolysis, and biosynthesis. It can be isolated and extracted from phospholipid-rich milk sources, or its natural phosphatidylethanolamine or natural phospholipids containing phosphatidylethanolamine can be enzymatically hydrolyzed using phospholipases. For example, deacetylation using phospholipase A2 can yield sn-1-acyl-LPE. Furthermore, lysophosphatidylethanolamine with a specific acyl group composition can be obtained using a combination of methods, such as the chemical-enzyme hybridization method.

[0057] In some embodiments, the lysophosphatidylethanolamine of the present invention can be separated and extracted from a phospholipid-rich milk source, wherein the phospholipid-rich milk source can be a milk fat globule membrane, and the separation and extraction method can be membrane separation.

[0058] In some embodiments, the lysophosphatidylethanolamine of the present invention is provided in the form of dairy products containing it (such as buttermilk products, phospholipid-containing milk proteins, milk phospholipid products, whole milk, whole milk powder, and / or phospholipid-containing cream products, etc.) and / or enzymatically hydrolyzed soybean lecithin. The content of lysophosphatidylethanolamine varies in each source form. For example, in the buttermilk products, the content of lysophosphatidylethanolamine, on a dry weight basis, can be 1-3000 mg / 100g, preferably 1-1000 mg / 100g; wherein the content of LPE (18:2(9Z,12Z) / 0:0) can be 1-1000 mg / 100g, preferably 10-500 mg / 100g; in the phospholipid-containing milk proteins, the content of lysophosphatidylethanolamine, on a dry weight basis, can be 0.1-1000 mg / 100g, preferably 0.5-500 mg / 100g. 0g; wherein the content of LPE (18:2(9Z,12Z) / 0:0) can be 0.1-300mg / 100g, preferably 0.5-200mg / 100g; in the phospholipid-containing cream product, on a dry weight basis, the content of lysophosphatidylethanolamine can be 0.0001-100mg / 100g liquid, preferably 0.001-50mg / 100g liquid; wherein the content of LPE (18:2(9Z,12Z) / 0:0) can be 0.0001-1mg / 100g liquid, preferably 0.0005-0.5mg / 100g liquid.

[0059] In other embodiments, the lysophosphatidylethanolamine of the present invention is provided in pure form with a purity of 99% or higher.

[0060] This invention does not impose any particular limitation on the source of L-α-GPC, as long as its source or form of use meets the requirements of local laws and regulations.

[0061] For example, it can be obtained by conventional chemical synthesis methods in the field, such as using polyphosphoric acid, choline chloride, R-3-chloro-1,2-propanediol, sodium hydroxide and water as raw materials, followed by condensation and esterification reactions, and then decolorization, impurity removal, concentration, purification and drying processes.

[0062] In some embodiments, the L-α-GPC of this invention is provided in the form of natural and / or synthetic sources, such as animal milk, soybean, commercially available raw materials, etc. The L-α-GPC content in each source form is typically 1%-99% by mass.

[0063] In some embodiments, the essential active ingredient shown in (I) comprises at least lysophosphatidylethanolamine with a fatty acid chain length of 12-22 carbon atoms, such as LPE 14:1, LPE 16:0, LPE 17:1, LPE 17:2, LPE 18:0, LPE 18:1, LPE 18:2, LPE 22:1, LPE 22:2 and / or LPE 22:6, which are present in milk sources; preferably, the essential active ingredient shown in (I) comprises at least lysophosphatidylethanolamine with a fatty acid chain length of 18 carbon atoms; preferably, the fatty acid chain in the lysophosphatidylethanolamine is unsaturated.

[0064] In some preferred embodiments, the fatty acid chain in the lysophosphatidylethanolamine with a fatty acid chain length of 12-22 carbon atoms is located at the sn-1 position.

[0065] In some preferred embodiments, the essential active ingredient shown in (I) comprises at least LPE (18:2(9Z,12Z) / 0:0). The present invention has found that the combination of LPE (18:2(9Z,12Z) / 0:0) and L-α-GPC can exert a synergistic effect in aiding memory improvement.

[0066] In some embodiments, lysophosphatidylethanolamine and L-α-GPC, with fatty acid chain lengths of 12-22 carbon atoms, are the main active ingredients of the nutritional composition. That is, the nutritional composition of the present invention mainly relies on the lysophosphatidylethanolamine and L-α-GPC, with fatty acid chain lengths of 12-22 carbon atoms, to exert specific physiological activities, such as aiding in memory improvement. In other words, in some embodiments, the active ingredients of the nutritional composition (the ingredients that exert specific physiological functions, i.e., the ingredients that aid in memory improvement) consist of lysophosphatidylethanolamine and L-α-GPC, with fatty acid chain lengths of 12-22 carbon atoms.

[0067] In some preferred embodiments, the active ingredient of the nutritional composition comprises, or consists of, lysophosphatidylethanolamine and L-α-GPC, a fatty acid chain of 18 carbon atoms linked at the sn-1 position.

[0068] In some preferred embodiments, the active ingredient of the nutritional composition comprises, or consists of, lysophosphatidylethanolamine and L-α-GPC, an unsaturated fatty acid chain of 18 carbon atoms linked at the sn-1 position.

[0069] In some further preferred embodiments, the active ingredient of the nutritional composition (the ingredient that performs a specific physiological function, i.e., the ingredient that helps improve memory) comprises LPE (18:2(9Z,12Z) / 0:0) and L-α-GPC, or is composed of therewith.

[0070] In some embodiments, the nutritional composition comprises an active ingredient (a component that performs a specific physiological function, i.e., a component that helps improve memory) and an inactive ingredient (a substance that does not help improve memory, or at least does not have a synergistic effect with LPE (18:2(9Z,12Z) / 0:0) or L-α-GPC). Exemplarily, the inactive ingredient may be other nutrients, any food-acceptable excipient, and / or substances that are generated during the production or acquisition of the active ingredient and cannot be effectively separated from the active ingredient or do not require separation. In some embodiments, the nutritional composition consists of the active ingredient and the inactive ingredient.

[0071] In some embodiments, in the nutritional composition, the mass ratio of the essential active ingredient shown in (I) to the essential active ingredient shown in (II) is 1:(1-1000), for example, it can be 1:1, 1:5, 1:10, 1:15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, 1:50, 1:55, 1:60, 1:65, 1:70, 1:75, 1:80, 1:85, 1:90, 1:95, 1:100, 1:150, 1:200, 1:250, 1:300, 1... The ratios are 1:350, 1:400, 1:450, 1:500, 1:550, 1:600, 1:650, 1:700, 1:750, 1:800, 1:850, 1:900, 1:950, 1:1000, etc.; preferably, the mass ratio of the two is 1:(2-250); more preferably, the mass ratio of the two is 1:(2-170); even more preferably, the mass ratio of the two is 1:(2-100); preferably, the above ratio is the mass ratio of LPE (18:2(9Z,12Z) / 0:0) to L-α-GPC.

[0072] The present invention does not impose any particular limitation on the form of the nutritional composition; typically, it can be a liquid or a solid. From the perspective of ease of production, transportation, storage, and use, the nutritional composition of the present invention is preferably a powdered solid.

[0073] <Uses of Nutritional Combinations>

[0074] This invention provides the use of the above-described nutritional composition to assist in improving memory. In some embodiments, the improvement of memory is not intended to prevent or treat diseases; therefore, this invention provides the use of the above-described nutritional composition for non-therapeutic purposes in assisting in improving memory. Based on this, this invention also provides the use of the above-described nutritional composition in the preparation of products that assist in improving memory.

[0075] In some implementations, the aid to improve memory includes improving the function of the cholinergic system.

[0076] In some specific implementations, the improvement of cholinergic system function includes inhibiting acetylcholinesterase activity.

[0077] Based on this, the present invention also provides the use of the above-mentioned nutritional composition in the preparation of products for improving the function of the cholinergic system.

[0078] Furthermore, the product can also improve cognition and / or behavioral abilities by assisting in memory improvement; preferably, the behavioral abilities include motor abilities.

[0079] Based on this, the present invention also provides the use of the above-mentioned nutritional composition in the preparation of products for assisting in the improvement of cognition and / or assisting in the improvement of behavioral abilities.

[0080] The present invention does not specifically limit the products containing the above-mentioned nutritional composition or products that can be prepared using the above-mentioned nutritional composition; for example, they can be food products.

[0081] In some implementation schemes, the food is designated as food for teenagers, young adults, or middle-aged and elderly people.

[0082] In some embodiments, the food described in this invention is a confectionery, such as hard candy, gel candy, shortbread candy, compressed candy, and aerated candy.

[0083] In some embodiments, the food described in this invention is a beverage, such as carbonated beverages, tea beverages, coffee beverages, fruit and vegetable juice beverages, and lactic acid bacteria beverages. In some embodiments, the food described in this invention is a dairy product, such as milk powder, cheese, yogurt, and liquid milk. In some embodiments, the food described in this invention is a baked product, such as bread, cakes, and biscuits. In some embodiments, the food described in this invention is a dietary supplement, such as hard capsules, soft capsules, tablets, oral liquids, pills, granules, and powders.

[0084] In some embodiments, the food described in this invention is in the form of a liquid or a solid under normal temperature conditions.

[0085] In some embodiments, in the food product of the present invention, the mass ratio of the essential active ingredient shown in (I) to the essential active ingredient shown in (II) is 1:(1-1000), for example, it can be 1:1, 1:5, 1:10, 1:15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, 1:50, 1:55, 1:60, 1:65, 1:70, 1:75, 1:80, 1:85, 1:90, 1:95, 1:100, 1:150, 1:200, 1:250, 1:300, etc. The ratios are 1:350, 1:400, 1:450, 1:500, 1:550, 1:600, 1:650, 1:700, 1:750, 1:800, 1:850, 1:900, 1:950, 1:1000, etc.; preferably, the mass ratio of the two is 1:(2-250); more preferably, the mass ratio of the two is 1:(2-170); even more preferably, the mass ratio of the two is 1:(2-100); preferably, the above ratio is the mass ratio of LPE (18:2(9Z,12Z) / 0:0) to L-α-GPC.

[0086] This invention does not impose any specific absolute limits on the content of lysophosphatidylethanolamine, LPE (18:2(9Z,12Z) / 0:0), and L-α-GPC in food, as long as the requirements of local food-related laws and regulations are met.

[0087] In some embodiments, the content of LPE (18:2(9Z,12Z) / 0:0) in the food may be 1 mg / 100g-100 mg / 100g, and the content of L-α-GPC may be 100 mg / 100g-1000 mg / 100g.

[0088] In addition to the components described above in the nutritional composition, the food may also contain other ingredients, such as common food ingredients like proteins / amino acids, carbohydrates, fats, vitamins, and minerals.

[0089] Furthermore, depending on the type of food and the end needs of the target audience, in some embodiments, the food contains any one or more of the following ingredients: plant-based ingredients, animal dairy ingredients, animal meat ingredients, functional additives, and any acceptable excipients.

[0090] Examples of plant-based ingredients include fruits such as figs, pomegranates, kiwis, oranges, pineapples, strawberries, apples, bananas, grapes, pears, cherries, blueberries, blackberries, blackcurrants, cranberries, raspberries, melons, amla, and bilberries, or their extracts; fruits and vegetables such as onions, cucumbers, tomatoes, cauliflower, carrots, spinach, kale, Brussels sprouts, garlic, basil, and oregano, or their extracts; grains such as rice (indica, japonica, glutinous rice), cereals (wheat, barley, oats, rye), corn, sorghum, millet, sorghum, yellow millet, buckwheat, soybeans, broad beans, peas, mung beans, red beans, and kidney beans, or their extracts; nuts such as walnuts, pistachios, cashews, hazelnuts, almonds, apricot kernels, pine nuts, peanuts, sunflower seeds, chestnuts, macadamia nuts, and ginkgo nuts, or their extracts; coffee or its extracts; and some medicinal and edible herbal medicines or their extracts.

[0091] Animal dairy product ingredients can include fresh milk from cows and sheep, as well as reprocessed dairy products such as whole milk powder, skim milk powder, whey protein concentrate, desalted whey powder, whey protein powder, hydrolyzed whey protein powder, and casein powder.

[0092] Examples of animal meat product ingredients include pork, beef, mutton, seafood, and poultry.

[0093] Examples of functional additives include vitamin supplements (such as vitamin A, beta-carotene, vitamin D3, vitamin E, vitamin K1, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, pantothenic acid, folic acid, niacin, biotin, etc.), mineral supplements (such as iron, copper, manganese, zinc, cobalt, molybdenum, chromium, nickel, vanadium, fluorine, selenium, iodine, silicon, tin, etc.), nucleotide supplements (e.g.), dietary fiber (e.g., inulin, konjac flour, galactooligosaccharides, fructooligosaccharides, isomaltooligosaccharides, soybean polysaccharides, cyclodextrin, resistant dextrin, soybean fiber, etc.), and functional polyunsaturated fatty acid supplements (e.g., arachidonic acid oil powder, docosahexaenoic acid oil powder, etc.).

[0094] Any acceptable excipients may include solvents, antioxidants, antibacterial agents, thickeners, diluents, cosolvents, stabilizers, emulsifiers, fillers, disintegrants, lubricants, coating materials, anti-caking agents, flavoring agents, sweeteners, food flavorings, and food colorings.

[0095] Example

[0096] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified, specific conditions in the examples are performed under conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, all materials and instruments used are commercially available conventional products.

[0097] Experimental Example 1: Determination of the Maximum Detectable Concentration of Nutrients

[0098] 1. Experimental materials and reagents

[0099] LPE 18:2 (LPE(18:2(9Z,12Z) / 0:0), a lysophosphatidylethanolamine with a linoleic acid chain attached at the sn-1 position and lacking a fatty acid chain at the sn-2 position) was provided by Heilongjiang Feihe Dairy Co., Ltd., and L-α-glycophosphocholine (GPC) was provided by Shenyang Jinjiuqi Technology Co., Ltd.

[0100] Dimethyl sulfoxide (DMSO, batch number I2229063, Shanghai Aladdin Biochemical Technology Co., Ltd., China); Aluminum chloride hexahydrate (batch number C1628001, Shanghai Aladdin Biochemical Technology Co., Ltd., China); BCA protein concentration assay kit (batch number AR1189, Boster Biological Engineering Co., Ltd., China); Acetylcholinesterase assay kit (batch number 3040802, AAT Bioquest, USA).

[0101] Positive drug: Donepezil hydrochloride.

[0102] 2. Experimental Equipment

[0103] Dissecting microscope (SZX7, OLYMPUS, Japan); CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd., China); Motorized focusing continuous zoom fluorescence microscope (AZ100, Nikon, Japan); Precision electronic balance (CP214, OHAUS, USA); Behavior analyzer (Zebra Lab 3.22.3.31, ViewPoint, France); Multifunctional microplate reader (SPARK, TECAN, Austria); High-speed refrigerated centrifuge (Heraeus) Fresco 17 (Thermo Fisher, Germany); UV-Vis spectrophotometer (Nanodrop 2000, Thermo, Austria); microplate mini centrifuge (BE-6100, Haimen Qilin Bell Instrument Manufacturing Co., Ltd., China); fully automated sample grinder (JXFSTPRP-24L, Shanghai Jingxin Laboratory Equipment Technology Department, China); 6-well plate (Berlanb Biotechnology Co., Ltd., China); 96-well plate (NestBiotech, China); black 96-well microplate (batch number 34519060, Costa, USA).

[0104] 3. Laboratory animals

[0105] Wild-type AB strain of zebrafish.

[0106] 4. Modeling and group intervention

[0107] 4.1 Model and Principle

[0108] A zebrafish model of memory impairment was induced using aluminum chloride. Excessive intake of aluminum chloride can lead to abnormal behavior in animals, damage cholinergic nerve function, and increase the production of amyloid protein, ultimately resulting in memory loss and reduced learning ability.

[0109] The specific procedure is as follows: zebrafish 4 days after fertilization are given 38.6 μg / mL aluminum chloride in water, and the sample is also given in water and treated at 28℃.

[0110] 4.2 Group Intervention Program

[0111] Zebrafish strain: Wild-type AB strain zebrafish, with 30 zebrafish in each experimental group, incubated in a 28℃ incubator.

[0112] Administration method: The zebrafish model was treated with water-soluble drug.

[0113] Experimental groups: There were 2 samples in total (LPE 18:2 and GPC). LPE 18:2 contained 8 detection concentrations, and GPC contained 5 detection concentrations. At the same time, 1 normal control group and 1 model control group were set up.

[0114] Experimental Methods: Wild-type AB strain zebrafish, 4 days post-fertilization (4 dpf), were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). The samples were administered in water solution, and a normal control group was also included. The volume per well was 3 mL. After treatment at 28℃ for 1 day, the minimum toxic concentration (MTC) of the sample for zebrafish was determined.

[0115] 5. Experimental Results

[0116] In this experiment, the maximum tolerance of two nutrients to zebrafish was first tested. The results are shown in Table 1. As can be seen from the table, as the concentration of LPE18:2 increased from 0.156 μg / mL to 10 μg / mL, the zebrafish were in a similar state to the model control group. However, when the concentration was further increased to 20 μg / mL, the zebrafish began to die. Therefore, the maximum detectable concentration (MTC) of LPE18:2 in the subsequent experiment on improving memory loss was 10 μg / mL. As for GPC, the zebrafish were in a similar state to the model control group from 125 μg / mL to 1000 μg / mL. When the concentration was further increased to 2000 μg / mL, the zebrafish were in a much worse state than the model control group. Therefore, the MTC of GPC in the subsequent experiment on improving memory was 1000 μg / mL.

[0117] Table 1 Results of the concentration exploration experiment for improving memory efficacy of samples (n = 30)

[0118]

[0119] Experiment Example 2: Measure-response evaluation of the effect of nutrient intervention on the improvement of total movement in zebrafish

[0120] 1. The experimental materials and reagents are the same as in Experiment 1.

[0121] 2. The experimental equipment is the same as in Experiment Example 1.

[0122] 3. The experimental animals are the same as in Experiment 1.

[0123] 4. Modeling and group intervention

[0124] 4.1 The model and principle are the same as in Experiment Example 1.

[0125] 4.2 Study on dose-effect relationship of samples

[0126] Zebrafish strain: Wild-type AB strain zebrafish, with 30 zebrafish in each experimental group, incubated in a 28℃ incubator.

[0127] Administration method: The zebrafish model was treated with water-soluble drug.

[0128] Experimental groups: LPE 18:2 and GPC were each set with 5 concentrations (MTC group, 1 / 2MTC, 1 / 4MTC, 1 / 8MTC, 1 / 16MTC), 1 normal control group, 1 model control group and 1 positive control group (donepezil hydrochloride), for a total of 13 groups.

[0129] Experimental Methods: Wild-type AB strain zebrafish (4 dpf) were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). The samples were administered water-soluble solutions, with donepezil hydrochloride at a concentration of 3.33 μg / mL as a positive control. A normal control group and a model control group were also included, with a volume of 3 mL per well. Except for the normal control group, the other experimental groups were administered aluminum chloride hexahydrate water-soluble solutions. After treatment at 28℃ for 1 day, 10 zebrafish were randomly selected from each experimental group, and the total distance traveled by the zebrafish over 1 hour was measured using a behavior analyzer. Statistical analysis of this indicator was used to evaluate the efficacy in improving the sample's locomotor ability.

[0130] 5. Experimental Results

[0131] Excessive intake of aluminum chloride can lead to abnormal behavior in animals, damage cholinergic nerve function, and increase amyloid protein production, ultimately resulting in memory loss and reduced learning ability. Therefore, this study used the behavioral ability of zebrafish, i.e., the total distance traveled, as an indicator to evaluate whether the two nutrients improved memory.

[0132] Table 2 shows the effects of two nutrients at different dosages on the total movement distance of zebrafish. The table shows that the average movement distance of zebrafish in the normal control group was 5512.83 mm, while after aluminum chloride induction, the total movement distance decreased to 2141.08 mm, significantly lower than the normal control group. In contrast, the total movement distance in the positive control group, after donepezil intervention, increased to 3532.42 mm. Statistical analysis of the differences between groups revealed that the positive control group was significantly higher than the model group, indicating that positive drug intervention can restore the behavioral ability of zebrafish. The movement distance of zebrafish treated with LPE18:2 and GPC both increased. As shown in the table, LPE 18:2 showed varying degrees of increase in total migration distance at the maximum concentration of 10 μg / mL and at five successively halved concentrations, exhibiting a dose-dependent effect. Furthermore, the inter-group significance analysis revealed that the total migration distance at all five concentrations was significantly higher than that of the model group. GPC also showed varying degrees of increase in total migration distance at the maximum concentration of 500 μg / mL and at five successively halved concentrations, exhibiting a dose-dependent effect. However, the overall increase was slightly lower than that of LPE 18:2. Inter-group significance analysis showed no significant difference from the model group at the two low-dose levels, but significantly higher than the model group at a concentration of 125 μg / mL.

[0133] The results above indicate that the total mobility of zebrafish induced by aluminum chloride was significantly improved under the intervention of LPE18:2 concentrations of 0.625-10 μg / mL, and the total mobility of zebrafish induced by aluminum chloride was also significantly improved under the intervention of GPC concentrations of 125-250 μg / mL.

[0134] Table 2. Effects of different doses of the two nutrients on the total distance traveled by zebrafish.

[0135]

[0136] Experiment Example 3: Effects of different nutrient formulations on the total distance traveled by zebrafish

[0137] 1. The experimental materials and reagents are the same as in Experiment 1.

[0138] 2. The experimental equipment is the same as in Experiment Example 1.

[0139] 3. The experimental animals are the same as in Experiment 1.

[0140] 4. Modeling and group intervention

[0141] 4.1 The model and principle are the same as in Experiment Example 1.

[0142] 4.2 Experimental Intervention Design

[0143] The experimental design is shown in Table 3. The control group consisted of normal zebrafish without any treatment or intervention; the model group consisted of zebrafish subjected to 38.6 μg / mL aluminum chloride to induce memory impairment without any intervention; the positive control group consisted of zebrafish induced by 38.6 μg / mL aluminum chloride and treated with 3.33 μg / mL donepezil hydrochloride as a positive control. Comparative Examples 1-3 involved 38.6 μg / mL aluminum chloride induction and different concentrations of LPE18:2 alone (0.2 μg / mL, 1 μg / mL, and 5 μg / mL); Comparative Examples 4-6 involved 38.6 μg / mL aluminum chloride induction and different concentrations of GPC alone (10 μg / mL, 40 μg / mL, and 160 μg / mL); Examples 1-9 involved 38.6 μg / mL aluminum chloride induction and combined intervention with complexes of LPE 18:2 and GPC in different ratios (1:2-800).

[0144] Table 3 Experimental Intervention Design

[0145]

[0146] 4.3 Evaluation of the impact of nutrient and composition interventions on athletic performance

[0147] Zebrafish strain: Wild-type AB strain zebrafish, with 30 zebrafish in each experimental group, incubated in a 28℃ incubator.

[0148] Administration method: The zebrafish model was treated with water-soluble drug.

[0149] Experimental groups: 15 groups of LPE 18:2 and GPC were intervened with monomers and different proportions of the combination. At the same time, one normal control group, one model control group and one positive control group (donepezil hydrochloride) were set up.

[0150] Experimental Methods: Wild-type AB strain zebrafish (4 dpf) were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). The samples were administered water-soluble solutions, with donepezil hydrochloride at a concentration of 3.33 μg / mL as a positive control. A normal control group and a model control group were also included, with a volume of 3 mL per well. Except for the normal control group, the other experimental groups were administered aluminum chloride hexahydrate water-soluble solutions. After treatment at 28℃ for 1 day, 10 zebrafish were randomly selected from each experimental group, and the total distance traveled by the zebrafish over 1 hour was measured using a behavior analyzer. Statistical analysis of this indicator was used to evaluate the efficacy in improving the sample's locomotor ability.

[0151] 5. Experimental Results

[0152] To verify the efficacy of LPE18:2 and GPC in synergistically improving the behavioral ability of zebrafish, different ratios of the two nutrients were set up as interventions in the form of prescriptions (as shown in Table 3). The effects of individual nutrient interventions and prescription interventions on the total movement distance were then analyzed. The experimental results are shown in Table 4, and the significance analysis of differences between groups is shown in Table 5.

[0153] Table 4 shows that LPE18:2 intervention at low, medium, and high doses (Comparative Examples 1-3) improved the total movement distance of zebrafish to varying degrees compared to the model group. However, after significance analysis, it was found that the total movement distance after low-dose intervention was not significantly different from the model group (p>0.05), while the total movement distance after medium and high-dose intervention was significantly higher than the model group (p values ​​are shown in Table 5). Comparative Examples 4-6 show the changes in the total movement distance of zebrafish after intervention with GPC alone. It can be seen that although there was also a varying degree of improvement compared to the model group, significance analysis showed that only in Comparative Example 6, with high-dose intervention, was the total movement distance significantly higher than the model group (p=0.0064), while the total movement distance after low and medium-dose intervention (Comparative Examples 4 and 5) was not significantly different from the model group (p>0.05). These results indicate that intervention with either nutrient at a certain dose can improve the behavioral ability of zebrafish, but LPE 18:2 is more effective than GPC. Examples 1-9 demonstrate the effect of different ratios of LPE18:2 and GPC in combination on the total movement distance of zebrafish. The table shows that the total movement distance was significantly greater than that of the two nutrients alone. After significance analysis, all nine examples were significantly higher than the model group (p < 0.0001), and all nine examples were significantly higher than the six comparative examples (p values ​​are shown in Table 5). This indicates that the synergistic effect of the two nutrients on improving the total movement ability of zebrafish is better. Further analysis revealed that the effects of the nine examples were greater than the simple sum of the effects of the two nutrients at the same concentration. This suggests that the combination of LPE18:2 and GPC has a synergistic effect on improving the total movement distance of zebrafish.

[0154] Table 4. Effects of two nutrients and their combination on the total distance traveled by zebrafish.

[0155]

[0156] Table 5. Analysis of significant differences among groups in the effects of different nutrient interventions on the total distance traveled by zebrafish.

[0157]

[0158]

[0159] Experiment Example 4: The Effects of Different Nutrient Components on Cognitive Improvement in Zebrafish

[0160] 1. The experimental materials and reagents are the same as in Experiment 1.

[0161] 2. The experimental equipment is the same as in Experiment Example 1.

[0162] 3. The experimental animals are the same as in Experiment 1.

[0163] 4. Modeling and group intervention

[0164] 4.1 The model and principle are the same as in Experiment Example 1.

[0165] 4.2 The experimental intervention design is the same as in Experiment Example 3.

[0166] 4.3 Evaluation of the effects of nutritional interventions and their combinations on cognitive improvement

[0167] Zebrafish strain: Wild-type AB strain zebrafish, with 30 zebrafish in each experimental group, incubated in a 28℃ incubator.

[0168] Administration method: The zebrafish model was treated with water-soluble drug.

[0169] Experimental groups: 15 groups of LPE 18:2 and GPC were intervened with monomers and different proportions of the combination. At the same time, one normal control group, one model control group and one positive control group (donepezil hydrochloride) were set up.

[0170] Experimental Methods: Five dpf wild-type AB strain zebrafish were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker (experimental group). The samples were administered in water-soluble form. A positive control of donepezil hydrochloride at a concentration of 3.33 μg / mL was used, and a normal control group was also included. Each beaker had a volume of 20 mL. After treatment at 28℃ for one day, five zebrafish from each experimental group were randomly placed into a cross-shaped module. The module was divided into four areas: 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 area relative to the total movement distance of the entire area within 10 minutes was analyzed. The statistical analysis results of this index were used to evaluate the sample's effect on memory improvement.

[0171] Memory is the foundation of cognition and a component of cognition. Direct detection of the proportion of the total movement distance in the blue area to the total movement distance in the entire area reflects the zebrafish's own color cognition ability, which includes the scope of memory. Moreover, existing literature shows that the color-enhanced conditional position preference (CPP) test is a new type of learning and memory test, which is based on the zebrafish's natural preference for specific colors. This preference may lead to changes in visual discrimination learning, memory and decision-making abilities (Li X, Li X, Li YX, Zhang Y, Chen D, Sun MZ, Zhao X, Chen DY, Feng XZ. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish. PLoS One. 2015 Nov 11;10(11):e0141134.).

[0172] 5. Experimental Results

[0173] This invention investigates the effects of two nutrients, individually and in combination, on cognitive improvement in zebrafish using a cross-maze experiment. Data was collected using a behavior analyzer, and the percentage (%) of the total distance traveled by zebrafish within the blue area over 10 minutes was analyzed. Statistical analysis of this indicator was used to evaluate cognitive development. The experimental results are shown in Table 6, and the significance analysis of differences between groups is shown in Table 7.

[0174] As shown in Table 6, the average proportion of the blue area in the cross maze was about 56.30% in the normal control group of zebrafish. However, after induction with aluminum chloride, the proportion of movement in the blue area of ​​zebrafish decreased significantly to 27.62%, indicating that aluminum chloride induction caused severe cognitive impairment in zebrafish. However, after intervention with donepezil hydrochloride, the proportion of movement in the blue area rebounded to 53.43%, indicating that the cognition of zebrafish was improved. Comparative Examples 1-3 show the proportion of zebrafish moving within the blue area of ​​the cross maze induced by low, medium, and high doses of LPE18:2 with aluminum chloride. Table 6 shows that all three doses improved the proportion compared to the model group. However, after significance analysis, the low-dose intervention group (Comparative Example 1) showed no significant difference in the proportion of movement within the blue area compared to the model group (p > 0.05), while the total movement distance after medium and high dose interventions was significantly higher than the model group (p < 0.05). Comparative Examples 4-6 show the proportion of zebrafish moving within the blue area after intervention with GPC alone. While this also showed varying degrees of improvement compared to the model group, significance analysis revealed no significant difference between the low-dose intervention (Comparative Examples 4 and 5) and the model group (p > 0.05), while the high-dose intervention (Comparative Example 6) showed a significant improvement compared to the model group (p < 0.05). These results indicate that intervention with either nutrient at a certain dose can enhance the cognitive abilities of zebrafish. Examples 1-9 demonstrate the effect of different ratios of LPE18:2 and GPC combined to form a composition on the proportion of zebrafish moving in the blue region. Table 6 shows that the combined intervention of the two substances resulted in a greater distance the zebrafish moved in the blue region compared to interventions of the two nutrients alone. The proportion of zebrafish moving in the blue region was also higher. After significance analysis, all nine examples showed significantly higher results than the model group (p < 0.0001), and all nine examples showed significantly higher results than the six comparative examples (p values ​​are shown in Table 7). This indicates that the synergistic effect of the two nutrients on improving the overall cognition of zebrafish is better. Further analysis revealed that the effects of the nine examples were greater than the simple sum of the effects of interventions at the same concentration of the two nutrients. This suggests that the combination of LPE18:2 and GPC has a synergistic effect on increasing the proportion of zebrafish moving in the blue region.

[0175] Table 6. Percentage of zebrafish movement within the blue area of ​​the cross maze after intervention with two nutrients and their combination (%)

[0176]

[0177] Table 7. Significant differences among groups in the effect of different nutrient interventions on the proportion of movement in the blue area of ​​the cross maze in zebrafish.

[0178]

[0179]

[0180] Experiment Example 5: Effects of nutrient and composition interventions on acetylcholinesterase activity in zebrafish

[0181] 1. The experimental materials and reagents are the same as in Experiment 1.

[0182] 2. The experimental equipment is the same as in Experiment Example 1.

[0183] 3. The experimental animals are the same as in Experiment 1.

[0184] 4. Modeling and group intervention

[0185] 4.1 The model and principle are the same as in Experiment Example 1.

[0186] 4.2 The experimental intervention design is the same as in Experiment Example 3.

[0187] 4.3 Effects of nutrient and compositional interventions on acetylcholinesterase activity

[0188] Zebrafish strain: Wild-type AB strain zebrafish, with 30 zebrafish in each experimental group, incubated in a 28℃ incubator.

[0189] Administration method: The zebrafish model was treated with water-soluble drug.

[0190] Experimental groups: 15 groups of LPE 18:2 and GPC were intervened with monomers and different proportions of the combination. At the same time, one normal control group, one model control group and one positive control group (donepezil hydrochloride) were set up.

[0191] Experimental Methods: Wild-type AB strain zebrafish (4 dpf) were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Samples were administered via water-soluble solution. A positive control was given donepezil hydrochloride at a concentration of 3.33 μg / mL. A normal control group and a model control group were also included, with a volume of 3 mL per well. Except for the normal control group, all other experimental groups were administered aluminum chloride hexahydrate via water-soluble solution. After treatment at 28℃ for 48 h, data were collected using an acetylcholinesterase assay kit and a multi-functional microplate reader. The fluorescence value of acetylcholinesterase in zebrafish was analyzed, and the statistical analysis results of this index were used to evaluate the inhibitory efficacy of the samples against acetylcholinesterase.

[0192] 5. Experimental Results

[0193] The cholinergic system (centered on acetylcholine ACh) is a key regulatory system for memory formation and consolidation; its damage directly leads to encoding difficulties, consolidation impairment, decreased hippocampal plasticity, and is highly correlated with memory impairments such as Alzheimer's disease (AD). Cholinergic damage is related to acetylcholinesterase activity; excessively high acetylcholinesterase activity rapidly degrades acetylcholine, directly causing functional impairment of the cholinergic system, thereby triggering memory and cognitive decline. Therefore, this study compared the degree of cholinergic damage and the improvement effect of nutrients in zebrafish after modeling and different nutrient interventions. The experimental results are shown in Table 8, and the significance analysis of differences between groups is shown in Table 9.

[0194] Table 8. Acetylcholinesterase levels in zebrafish after intervention with two nutrients and their combination.

[0195]

[0196] Table 9. Significant differences among groups in acetylcholinesterase activity in zebrafish treated with different nutrients.

[0197]

[0198]

[0199] As shown in Table 8, the average fluorescence value of acetylcholinesterase (AChE) in zebrafish in the normal control group was approximately 4890.4. However, after induction with aluminum chloride, the fluorescence value of acetylcholinesterase (AChE) in zebrafish increased significantly to 10040. This indicates that aluminum chloride induction caused severe damage to cholinergic function in zebrafish. However, after intervention with the positive control drug donepezil hydrochloride, the fluorescence value of acetylcholinesterase (AChE) in zebrafish decreased to 6669.4, indicating that cholinergic function in zebrafish was restored. Comparative Examples 1-3 involved different doses of LPE18:2 to intervene in the fluorescence levels of acetylcholinesterase (AChE) in zebrafish induced by aluminum chloride. Table 8 shows that all three doses reduced AChE levels to varying degrees compared to the model group, and after significance analysis, all three comparative examples were significantly lower than the model group (p values ​​are shown in Table 9). Comparative Examples 4-6 show the fluorescence levels of acetylcholinesterase (AChE) in zebrafish after intervention with GPC alone. It can be seen that all three comparative examples were also significantly lower than the model group (p values ​​are shown in Table 9). These results indicate that intervention with either nutrient alone can effectively repair cholinergic damage. Examples 1-9 demonstrate the effect of LPE18:2 and GPC in different proportions on the fluorescence level of acetylcholinesterase (AChE) in zebrafish. Table 8 shows that the combined intervention of the two substances resulted in a significantly lower AChE fluorescence level in zebrafish compared to intervention by either nutrient alone. Furthermore, after significance analysis, all nine examples showed significantly lower levels than the model group (p < 0.0001), and all nine examples were significantly lower than the six comparative examples (p values ​​are shown in Table 9). This indicates that the synergistic effect of the two nutrients on the repair of cholinergic damage in zebrafish is better. Further analysis revealed that the effects of the nine examples were greater than the simple sum of the effects of the two nutrients at the same concentration, suggesting that the combination of LPE18:2 and GPC has a synergistic effect in reducing the AChE fluorescence level in zebrafish.

Claims

1. The use of a nutritional composition in the preparation of a product that helps improve memory, characterized in that, The nutritional composition contains the essential active ingredients shown in (I) and (II) below: (I) Lysophosphatidylethanolamine; (II) L-α-GPC; Wherein, the essential active ingredient shown in (I) contains at least lysophosphatidylethanolamine with a fatty acid chain length of 12-22 carbon atoms and at least LPE (18:2(9Z,12Z) / 0:0), and in the nutritional composition, the mass ratio of the essential active ingredient shown in (I) to the essential active ingredient shown in (II) is 1:(1-1000).

2. The use according to claim 1, characterized in that, The fatty acid chain in the lysophosphatidylethanolamine is located at the sn-1 position.

3. The use according to claim 1, characterized in that, The fatty acid chains in the lysophosphatidylethanolamine are unsaturated.

4. The use according to claim 1, characterized in that, The lysophosphatidylethanolamine is provided in the form of dairy products containing it and / or enzymatically hydrolyzed soybean lecithin.

5. The use according to claim 1, characterized in that, The L-α-GPC is provided in the form of natural and / or synthetic sources.

6. The use according to claim 1, characterized in that, The aids to improve memory include improving the function of the cholinergic system.

7. The use according to claim 1, characterized in that, The product helps improve memory, thereby improving cognition and / or behavioral abilities.

8. The use according to any one of claims 1-7, characterized in that, The product is in the form of a powder, solid, or liquid.

9. The use according to any one of claims 1-7, characterized in that, The product contains any one or more of the following ingredients: plant-based ingredients, animal dairy ingredients, animal meat ingredients, functional additives, and any acceptable excipients.

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