A nutritional composition to promote brain development and uses thereof

Abstract

The present application belongs to the technical field of nutrient research, and particularly relates to a nutrient composition for promoting brain development and use thereof. The nutrient composition provided by the present application comprises two necessary components: i) lysophosphatidyl ethanolamine; and ii) docosahexaenoic acid; and the mass ratio of the lysophosphatidyl ethanolamine to the docosahexaenoic acid in the nutrient composition is 1:(10-2100). The combination of lysophosphatidyl ethanolamine and docosahexaenoic acid can effectively promote the overall growth and development of the body, especially the brain development, increase the expression levels of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor in brain tissue, and effectively assist the improvement of cognitive ability.

Description

Technical Field

[0001] This invention belongs to the field of nutrient research technology and relates to a nutrient composition that promotes brain development and its uses. Background Technology

[0002] Brain development is a complex and multi-factor-regulated dynamic process that spans the entire period from fetal development to adolescence. The period from 0 to 6 years of age is a critical window for the rapid proliferation of synapses and the construction of neural networks in the brain. The quality of development during this stage directly determines an individual's lifelong cognitive abilities, learning abilities, emotional regulation abilities, and the integrity of their nervous system function. Cognitive function, as the core of higher neural activity in the brain, refers to a series of complex abilities for an individual to acquire, process, store, and utilize information, encompassing key psychological processes such as learning, memory, attention, decision-making, and problem-solving. For children and adolescents, healthy cognitive development directly affects their learning efficiency (such as attention and memory), emotional and behavioral performance, social skills, and future ability to live independently.

[0003] If nutritional supplements can be developed that are suitable for long-term use by individuals in early life, as well as children and adolescents, and that effectively promote brain development and enhance cognitive abilities, it will be of great significance in improving the health of people throughout their entire life cycle.

[0004] Phospholipids are key bioactive components in 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 phosphatidylacetals. Lysophospholipids are produced through the hydrolysis of one fatty acid in the PL molecule, and the main components in breast milk are lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE).

[0005] Docosahexaenoic acid (DHA) is an essential omega-3 fatty acid for the human body. As an important component of the cell membranes in the cerebral cortex and hippocampus, DHA participates in the proliferation, differentiation, and regulation of synaptic plasticity of nerve cells. Studies have shown that DHA exerts neuroprotective effects through multiple pathways: on the one hand, it can promote the activity of acetylcholinesterase on the presynaptic membrane, increase the synthesis of the neurotransmitter acetylcholine, and thus improve the function of the central cholinergic system; on the other hand, DHA can inhibit the release of pro-inflammatory factors (such as interleukin-6 and tumor necrosis factor-α), enhance the activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, and reduce the accumulation of malondialdehyde, a lipid peroxidation product, thereby alleviating neuroinflammation and oxidative stress damage.

[0006] Currently, there is a wealth of research on the role of DHA in promoting brain and cognitive development (see citations 1 and 2). Studies have shown that newborns fed formula containing 0.64% DHA in their total fatty acids during the first year of life, compared to infants not supplemented with long-chain polyunsaturated fatty acids, exhibited stronger functional connectivity between the prefrontal and parietal lobes at age 9. However, the KUDSO study indicated that while DHA supplementation significantly reduced the incidence of preterm birth and improved attention performance in the first year of life, it had little impact on neurodevelopmental outcomes in children aged 10 months to 6 years.

[0007] References:

[0008] Reference 1: CN120836753B;

[0009] Reference 2: CN121926369A. Summary of the Invention

[0010] The problem the invention aims to solve

[0011] In order to enable effective interventions at an early stage of life, thereby providing a good foundation for brain and cognitive health throughout the entire life cycle, this invention has conducted extensive research and provides a naturally sourced nutritional composition, mainly comprising lysophosphatidylethanolamine and docosahexaenoic acid (DHA) with a fatty acid chain of a specific length linked at the sn-1 position. The two work synergistically to promote brain development and cognitive enhancement in early-life groups such as infants and children, without any side effects, and can be consumed long-term as a nutritional supplement.

[0012] Solution for solving the problem

[0013] To address the aforementioned technical problems, the present invention provides the following technical solution:

[0014] [1]. A nutritional composition, wherein the nutritional composition is a nutritional composition having functions that promote growth and / or brain development, and the nutritional composition comprises the following two essential components:

[0015] i) LPE(18:2(9Z,12Z) / 0:0);

[0016] ii) docosahexaenoic acid;

[0017] Furthermore, in the nutritional composition, the mass ratio of LPE (18:2(9Z,12Z) / 0:0) to docosahexaenoic acid is 1:(10-2100).

[0018] [2]. The nutritional composition according to [1], wherein the LPE (18:2(9Z,12Z) / 0:0) is provided in the form of dairy products and / or enzymatically hydrolyzed soybean lecithin containing it.

[0019] [3]. The nutritional composition according to [1] or [2], wherein the docosahexaenoic acid is provided in the form of natural and / or synthetic and / or biofermentation sources.

[0020] [4]. The nutritional composition according to any one of [1]-[3], wherein the nutritional composition further comprises ω-3 fatty acids other than docosahexaenoic acid.

[0021] [5]. The nutritional composition according to [4], wherein the ω-3 fatty acid other than docosahexaenoic acid includes at least one of α-linolenic acid and eicosapentaenoic acid.

[0022] [6]. Use of the nutritional composition according to any one of [1]-[5] in the preparation of products for non-therapeutic purposes that promote growth and / or brain development.

[0023] [7]. According to the use described in [6], the contribution to brain development includes the contribution to cognitive ability enhancement.

[0024] [8]. According to the use described in [6] or [7], wherein the product contains any one or more of the following ingredients: plant-based ingredients, animal dairy ingredients, animal meat ingredients, and functional additives.

[0025] The effects of the invention

[0026] This invention proposes for the first time that the combination of lysophosphatidylethanolamine and docosahexaenoic acid, with a fatty acid chain of a specific length linked at the sn-1 position, has a synergistic effect in promoting brain development. In particular, when the two are combined in a certain proportion, they can synergistically promote the overall growth and development of the body, as well as increase the expression levels of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor in brain tissue, effectively assisting in the improvement of cognitive abilities. Detailed Implementation

[0027] 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.

[0028] <Terminology Definition>

[0029] 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.

[0030] In this invention, the meaning of "may" includes both performing a certain process and not performing a certain process.

[0031] In this invention, "optional" or "optionally" means that certain substances, components, execution steps, application conditions, etc., are used or not used.

[0032] 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.

[0033] 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.

[0034] 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.

[0035] 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.

[0036] In this invention, "infants and toddlers" refers to the human group under the age of 3 years, including infants aged 0-6 months, older infants aged 6-12 months, and toddlers aged 12-36 months.

[0037] In this invention, "children" refers to the human group aged 3-6 years.

[0038] In this invention, "teenagers" refers to the human group aged 7-18.

[0039] In this invention, "young adult" refers to the human group aged 19-40.

[0040] In this invention, "pregnant women" includes women who are pregnant and women who are breastfeeding.

[0041] 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.

[0042] In this invention, "animal milk" refers to the liquid obtained from the mammary glands of a mammal in the process of lactation.

[0043] In this invention, "lysophosphatidyl ethanolamine (LysoPE, LPE)" is a glycerophospholipid composed of a glycerol backbone, a fatty acid chain, a phosphate group, and an ethanolamine head group. Compared to phosphatidyl ethanolamine, it lacks a fatty acid chain at the sn-1 or sn-2 position of its glycerol backbone.

[0044] 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.

[0045] In this invention, "LPE(18:2(9Z,12Z) / 0:0)" refers to a lysophosphatidylethanolamine molecule characterized by the following structural features: linoleic acid (18:2(9Z,12Z)) is attached to the sn-1 position of glycerol, while a hydroxyl group (-OH) is present at the sn-2 position, indicating that this position does not contain a fatty acid chain (represented as 0:0). Here, 18:2(9Z,12Z) represents a fatty acid chain consisting of 18 carbon atoms and containing two cis double bonds (located at the 9th and 12th carbon atoms, respectively), i.e., linoleic acid; 0:0 indicates that the corresponding position lacks a fatty acid chain and is replaced by a hydroxyl group.

[0046] In this invention, docosahexaenoic acid (DHA) can be abbreviated as DHA, and its molecular formula is C6H2O. 22 H 32 O2.

[0047] 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.

[0048] (Nutritional composition)

[0049] The nutritional composition of the present invention comprises the following two essential components: i) lysophosphatidylethanolamine and ii) docosahexaenoic acid;

[0050] Furthermore, in the nutritional composition, the mass ratio of the lysophosphatidylethanolamine to the docosahexaenoic acid is 1:(10-2100).

[0051] This invention does not impose special requirements on the source of lysophosphatidylethanolamine, as long as its source or form of use meets the requirements of local laws and regulations. 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 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 a chemical-enzyme hybrid method.

[0052] 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.

[0053] In some embodiments, the lysophosphatidylethanolamine of the present invention is provided in the form of dairy products containing it (e.g., 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.

[0054] In other embodiments, the lysophosphatidylethanolamine of the present invention is provided in pure form (commercially available product) with a purity of 99% or higher.

[0055] The docosahexaenoic acid (DHA) described in this invention is all-cis-4,7,10,13,16,19-docosahexaenoic acid. This invention does not impose any particular limitation on the source of DHA, as long as its source or form of use meets the requirements of local laws and regulations. For example, it can be derived from docosahexaenoic acid oil obtained through bio-fermentation using *Schizochytrium sp.*, *Ulkenia amoeboida*, or *Crypthecodinium cohnii* strains. Alternatively, it can be derived from tuna oil rich in docosahexaenoic acid, produced through processes such as heating, separation, refining, and purification using tuna as raw material.

[0056] In some embodiments, the docosahexaenoic acid (DHA) of this invention is provided in the form of natural and / or synthetic and / or bio-fermentation sources. Examples include DHA products isolated from animal milk or animal feed, chemically synthesized DHA products, and fermentation products of DHA-producing microorganisms. For DHA, the DHA content in each source form is typically 35-99% by mass.

[0057] In some embodiments, the docosahexaenoic acid (DHA) of the present invention may exist in the form of phospholipid DHA, triglyceride DHA, ethyl ester DHA, and / or free fatty acid DHA; preferably, the docosahexaenoic acid of the present invention exists in the form of triglyceride DHA; more preferably, the docosahexaenoic acid of the present invention exists in the form of sn-2 DHA (i.e., DHA is attached to the sn-2 position of the triglyceride).

[0058] In some embodiments, the lysophosphatidylethanolamine comprises at least a lysophosphatidylethanolamine with a fatty acid chain of 12-22 carbon atoms attached to the sn-1 position, such as LPE14:1, LPE16:0, LPE17:1, LPE17:2, LPE18:0, LPE18:1, LPE18:2, LPE22:1, LPE22:2 and / or LPE22:6 present in milk sources; preferably, the lysophosphatidylethanolamine comprises at least a lysophosphatidylethanolamine with a fatty acid chain of 18 carbon atoms attached to the sn-1 position; preferably, the fatty acid chain in the lysophosphatidylethanolamine is unsaturated.

[0059] In some preferred embodiments, the lysophosphatidylethanolamine contains at least LPE (18:2(9Z,12Z) / 0:0). This invention has found that the combination of LPE (18:2(9Z,12Z) / 0:0) and docosahexaenoic acid can exert a synergistic effect that promotes growth and development and brain development.

[0060] In some embodiments, lysophosphatidylethanolamine and docosahexaenoic acid (DHA), comprising a fatty acid chain with a length of 12-22 carbon atoms linked at the sn-1 position, are the main active ingredients of the nutritional composition. That is, the nutritional composition of the present invention primarily relies on the lysophosphatidylethanolamine and DHA, comprising a fatty acid chain with a length of 12-22 carbon atoms linked at the sn-1 position, to exert specific physiological activities, such as promoting growth and development and brain development. In other words, in some embodiments, the active ingredients of the nutritional composition (the ingredients that exert specific physiological activities, i.e., those that promote growth and development and brain development) consist of lysophosphatidylethanolamine and DHA, comprising a fatty acid chain with a length of 12-22 carbon atoms linked at the sn-1 position.

[0061] In some specific embodiments, the active ingredient of the nutritional composition comprises, or is composed of, lysophosphatidylethanolamine and docosahexaenoic acid, a fatty acid chain of 18 carbon atoms linked at the sn-1 position.

[0062] In some preferred embodiments, the active ingredient of the nutritional composition comprises, or is composed of, lysophosphatidylethanolamine and docosahexaenoic acid, an unsaturated fatty acid chain of 18 carbon atoms linked at the sn-1 position.

[0063] In some preferred embodiments, the active ingredients of the nutritional composition comprise, or consist of, LPE (18:2(9Z,12Z) / 0:0) and docosahexaenoic acid (DHA).

[0064] In some embodiments, the nutritional composition comprises an active ingredient (a component that performs a specific physiological function, i.e., a component that contributes to growth and development and brain development) and an inactive ingredient (a substance that does not contribute to growth and development and brain development, or at least does not synergize with LPE (18:2(9Z,12Z) / 0:0) or docosahexaenoic acid). 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.

[0065] In some embodiments, the nutritional composition further comprises ω-3 fatty acids other than docosahexaenoic acid (DHA); preferably, the ω-3 fatty acids other than DHA include at least one of alpha-linolenic acid (ALA) and eicosapentaenoic acid (EPA). All of the above substances may be present in the nutritional composition as inactive ingredients.

[0066] In some embodiments, in the nutritional composition, the mass ratio of the essential component shown in i) to the essential component shown in ii) is 1:(10-2100), for example, it can be 1:10, 1:15, 1:16, 1:18, 1:20, 1:22, 1:25, 1:28, 1:30, 1:32, 1:34, 1:36, 1:38, 1:40, 1:42, 1:44, 1:46, 1: 48, 1:50, 1:55, 1:60, 1:64, 1:70, 1:75, 1:80, 1:85, 1:90, 1:95, 1:100, 1:110, 1:120, 1:128, 1:130, 1:140, 1:150, 1:160, 1:170, 1:180, 1:190, 1:200, 1:210, 1:220, 1:230, 1:240 1:250, 1:260, 1:270, 1:280, 1:290, 1:300, 1:400, 1:500, 1:512, 1:550, 1:600, 1:700, 1:800, 1:900, 1:1000, 1:1100, 1:1200, 1:1300, 1:1400, 1:1500, 1:1600, 1:1700, 1:1800 The ratios are 1:1900, 1:2000, 1:2050, 1:2051, 1:2100, etc.; preferably, the mass ratio of the two is 1:(15-600); more preferably, the mass ratio of the two is 1:(15-200); even more preferably, the mass ratio of the two is 1:(30-100); preferably, the above ratio is the mass ratio of LPE (18:2(9Z,12Z) / 0:0) to docosahexaenoic acid. Within the above mass ratio range, the essential components shown in i) (especially LPE (18:2(9Z,12Z) / 0:0)) and the essential components shown in ii) synergistically play a role in promoting growth and / or brain development.

[0067] 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.

[0068] (Uses of the nutritional composition)

[0069] The present invention provides the use of the above-described nutritional composition to aid in growth and / or brain development.

[0070] In some embodiments, the effects of promoting growth and development and brain development are not intended for disease prevention or treatment, but can be further exerted on the basis of a healthy organism. That is, the present invention provides the non-therapeutic use of the above-mentioned nutritional composition to promote growth and / or brain development. Based on this, the present invention also provides the use of the above-mentioned nutritional composition in the preparation of products that promote growth and / or brain development for non-therapeutic purposes, such products being food or health products, wherein the lysophosphatidylethanolamine in the nutritional composition is provided in the form of dairy products containing it and / or enzymatically hydrolyzed soybean lecithin.

[0071] In some implementations, the contribution to brain development includes the contribution to cognitive ability enhancement; preferably, the contribution to cognitive ability enhancement includes the contribution to spatial cognitive ability enhancement.

[0072] Furthermore, the present invention also provides the use of the above-described nutritional composition in the preparation of products that promote growth and / or brain development, wherein the products are non-food or non-health products, such as pharmaceuticals. In some embodiments, the promotion of brain development includes promoting the expression levels of neurotrophic factors in the brain; preferably, the neurotrophic factors include brain-derived neurotrophic factor and / or glial cell-derived neurotrophic factor.

[0073] In some more specific embodiments, the aid to brain development includes helping to increase the expression levels of brain-derived neurotrophic factor (BDNF) and / or glial cell-derived neurotrophic factor (GNF) in brain tissue; preferably, the aid to brain development includes helping to increase the expression levels of BDNF and GNF in brain tissue; more preferably, the aid to brain development includes helping to increase the gene expression levels of BDNF and GNF in brain tissue; and even more preferably, the aid to brain development includes helping to increase the mRNA levels of BDNF and GNF genes in brain tissue.

[0074] Based on this, the present invention also provides the use of the above-mentioned nutritional composition in the preparation of products that help improve cognitive abilities (preferably spatial cognitive abilities) and help increase the expression level of brain-derived neurotrophic factor or glial cell-derived neurotrophic factor in brain tissue.

[0075] In some embodiments, the present invention provides the use of the above-described nutritional composition in the preparation of a product that helps to increase the expression levels of brain-derived neurotrophic factor or glial cell-derived neurotrophic factor in brain tissue, said product being a pharmaceutical product.

[0076] In some embodiments, the present invention provides the use of the above-described nutritional composition in the preparation of products that contribute to cognitive enhancement (preferably spatial cognitive enhancement), said products being food or health products, wherein the lysophosphatidylethanolamine in the nutritional composition is provided in the form of dairy products containing it and / or enzymatically hydrolyzed soybean lecithin.

[0077] The present invention does not specifically limit the products containing or prepared from the above-mentioned nutritional composition, such as food or health products. When the product is a food, the components in the nutritional composition are used in a source or form that meets the requirements of local laws and regulations. Specifically, the lysophosphatidylethanolamine in the nutritional composition is provided in the form of dairy products containing it (e.g., 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, and is added to the food; docosahexaenoic acid (DHA) is provided in the form of DHA oil and / or tuna oil obtained by bio-fermentation of *Schizochytrium sp.*, *Ulkenia amoeboida*, or *Crypthecodinium cohnii* strains, and is added to the food.

[0078] In some implementation schemes, the food is infant food, children's food, adolescent food, pregnant and postpartum food, young and middle-aged food, or middle-aged and elderly food.

[0079] In some embodiments, the food product of this invention is a confectionery, such as hard candy, gel candy, shortbread candy, compressed candy, and aerated candy. In some embodiments, the food product of 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 product of this invention is a dairy product, such as milk powder, cheese, fermented milk, and liquid milk. In some embodiments, the food product of this invention is a baked product, such as bread, cakes, and biscuits. In some embodiments, the food product of this invention is a dietary supplement, such as hard capsules, soft capsules, tablets, oral liquids, pills, granules, and powders.

[0080] In some embodiments, the food described in this invention is in the form of a liquid or a solid under normal temperature conditions.

[0081] In some embodiments, in the food described in this invention, the mass ratio of the necessary component shown in i) to the necessary component shown in ii) can be 1:(10-2100); preferably, the mass ratio can be 1:(15-600); more preferably, the mass ratio can be 1:(15-200); even more preferably, the mass ratio can be 1:(30-100); preferably, the above ratio is the mass ratio of LPE (18:2(9Z,12Z) / 0:0) to docosahexaenoic acid.

[0082] This invention does not specifically limit the absolute content of lysophosphatidylethanolamine, LPE (18:2(9Z,12Z) / 0:0), and docosahexaenoic acid in food, as long as it meets the requirements of local food-related laws and regulations. The lysophosphatidylethanolamine and LPE (18:2(9Z,12Z) / 0:0) are provided in the form of dairy products containing them (e.g., 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, and are added to food.

[0083] In some embodiments, the content of LPE (18:2(9Z,12Z) / 0:0) in the food, based on the total dry matter content of the food, can be 0.1-1000 mg / 100g, preferably 0.5-500 mg / 100g, more preferably 1-100 mg / 100g; the content of docosahexaenoic acid can be 10-1000 mg / 100g, preferably 20-500 mg / 100g, more preferably 50-200 mg / 100g.

[0084] 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.

[0085] In addition, depending on the type of food and the end needs of the target audience, in some embodiments, the food may also contain one or more of the following ingredients: plant-based ingredients, animal dairy ingredients, animal meat ingredients, functional additives, and any acceptable excipients.

[0086] Examples of plant-based ingredients include fruits such as figs, pomegranates, kiwis, oranges, tangerines, pineapples, strawberries, apples, bananas, grapes, pears, cherries, blueberries, blackberries, blackcurrants, cranberries, raspberries, melons, amla, and bilberries, or their extracts; 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.

[0087] Animal dairy product ingredients can include fresh milk from mammals such as cows, sheep, and camels, 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.

[0088] Examples of animal meat product ingredients include pork, beef, mutton, seafood, and poultry.

[0089] 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, and vitamin B1). 12 Vitamin C, pantothenic acid, folic acid, niacin, biotin, etc.), mineral supplements (such as calcium, iron, copper, manganese, zinc, magnesium, fluorine, sodium, potassium, selenium, iodine, etc.), nucleotide supplements (such as disodium 5'-cytidine, disodium 5'-uridine, adenosine monophosphate, disodium 5'-guanylate, disodium 5'-inosine, etc.), dietary fiber (such as inulin, konjac flour, galactooligosaccharides, fructooligosaccharides, isomaltooligosaccharides, soybean polysaccharides, cyclodextrin, resistant dextrin, soybean fiber, etc.).

[0090] 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.

[0091] Example

[0092] 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 in the examples, conventional conditions or conditions recommended by the manufacturer are followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0093] The experimental equipment used in the experimental examples of this invention includes: a dissecting microscope (SZX7, OLYMPUS, Japan), a CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd.), a precision electronic balance (CP214, OHAUS, USA), a fully automated rapid sample grinder (JXFSTPRP-24L, Shanghai Jingxin Experimental Equipment Technology Department), a fully automated nucleic acid extractor (Auto-Pure32A, Hangzhou Aosheng Instrument Co., Ltd.), a conventional PCR amplification instrument (T100, BIO-RAD, Singapore), a real-time PCR instrument (CFX Connect, BIO-RAD, Singapore), and a high-speed refrigerated centrifuge (Heraeus). Fresco 17 (Thermo Fisher, Germany), UV-Vis spectrophotometer (Nanodrop 2000, Thermo, USA), microplate mini centrifuge (BE-6100, Haimen Qilin Bell Instrument Manufacturing Co., Ltd.), optical adhesive sealing film B (MSB1001, Bio-rad, USA), low-skirted 96-well plate (transparent) (HSP9601, Bio-rad, USA).

[0094] The experimental materials and reagents used in the experimental examples of this invention include: LPE18:2 (LPE(18:2(9Z,12Z) / 0:0)) provided by Heilongjiang Feihe Dairy Co., Ltd.; docosahexaenoic acid (DHA) provided by Roquette Corporation; positive control drug: Ginkgo biloba and Cistanche deserticola tablets; dimethyl sulfoxide (DMSO, batch number 20250624, Sinopharm Chemical Reagent Co., Ltd.); ChamQ Universal SYBR qPCR Master Mix (batch number 027E2201CD, Vazyme); Hifair III 1stStrand cDNA Synthesis SuperMix for qPCR (batch number H9305270, Yisheng Biotechnology (Shanghai) Co., Ltd.); and pre-loaded magnetic bead universal RNA extraction kit C (catalog number TL2402001643C, Foshan Aowei Biotechnology Co., Ltd.).

[0095] The experimental animals used in the experimental examples of this invention are wild-type AB strain zebrafish.

[0096] In the experimental examples of this invention, data processing was performed using SPSS 26.0 software for statistical analysis. Data were described by mean ± standard error (mean ± SE), and p < 0.05 was used as the significance level.

[0097] Experiment Example 1: Dose-response assessment of the effects of two nutrient interventions on the cognitive development of zebrafish

[0098] Zebrafish share high similarities with humans in brain physiology, anatomy, and neurochemistry. The zebrafish brain structure includes the telencephalon, diencephalon, midbrain, cerebellum, and medulla oblongata. Its cell types (such as astrocytes, microglia, and oligodendrocytes) and major neurotransmitter systems (such as GABA, acetylcholine, and serotonin) are similar to those in humans. Studies have shown that zebrafish possess an amygdala structure homologous to mammals and have functions similar to those in humans in regulating emotions, controlling learning, and memory. Mazes are important experimental tools for assessing various behavioral manifestations (such as learning and memory, anxiety, and preferences) in zebrafish neurological disease models. Various cognitive tasks are often conducted in mazes using color cues to study zebrafish learning and memory functions. Zebrafish prefer short-wavelength colors and show a strong preference for blue compared to other colors (such as red, green, and yellow). Therefore, this study uses the percentage (%) of the distance zebrafish travel within the blue area relative to the total distance traveled in the entire area as an indicator of the role of nutrients in promoting brain development.

[0099] 1. Determination of the maximum tolerated concentration (MTC) of two nutrients in zebrafish

[0100] This experiment first determined the maximum tolerable concentration (MTC) of two nutrients in zebrafish. The specific steps are as follows:

[0101] Zebrafish strain: Wild-type AB strain zebrafish, 30 fish in each experimental group, incubated in a 28℃ incubator.

[0102] Experimental groups: Two samples were set up (LPE18:2 and DHA), with 9 detection concentrations for the LPE18:2 sample and 5 detection concentrations for the DHA sample; at the same time, a normal control group (normal zebrafish without any treatment or intervention) was set up.

[0103] Experimental Methods: 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 (each experimental group). Samples were administered via water-soluble administration, and a normal control group was also included. Each beaker had a volume of 20 mL. After treatment at 28℃ for 1 day, the mean chromosomal conversion ratio (MTC) of each sample relative to normal zebrafish was measured.

[0104] Experimental Results: As shown in Table 1, when the concentration of LPE18:2 gradually increased from 0.0781 μg / mL to 1.25 μg / mL, the zebrafish condition was similar to that of the normal control group; when the concentration was further increased to 2.5 μg / mL, the zebrafish began to die; therefore, the MTC of LPE18:2 in the brain development promotion efficacy experiment was 1.25 μg / mL. For DHA, when the concentration increased from 125 μg / mL to 500 μg / mL, the zebrafish condition was similar to that of the normal control group; when the concentration was further increased to 1000 μg / mL, the zebrafish condition was significantly worse than that of the normal control group; therefore, the MTC of DHA in the brain development promotion efficacy experiment was 500 μg / mL.

[0105] Table 1. Results of the concentration exploration experiment on the brain development-promoting effects of the samples (n=30)

[0106]

[0107] 2. Dose-response assessment of the effect of nutrient intervention on cognitive development in zebrafish

[0108] Zebrafish strain: Wild-type AB strain zebrafish, 30 fish in each experimental group, incubated in a 28℃ incubator.

[0109] Experimental groups: Five concentrations of LPE18:2 and DHA were set up as intervention groups (MTC group, 1 / 2MTC, 1 / 4MTC, 1 / 8MTC, and 1 / 16MTC); one normal control group (normal zebrafish without any treatment or intervention) and one positive control group (zebrafish treated with 125μg / mL Ginkgo biloba and Cistanche deserticola tablets) were also set up, for a total of 12 groups.

[0110] Experimental Methods: Wild-type AB strain zebrafish (5 dpf) were randomly selected and placed in beakers, with 30 zebrafish per beaker (each experimental group). Samples were administered via water-soluble administration. The positive control group received 125 μg / mL Ginkgo biloba and Cistanche deserticola tablets, and a normal control group was also included. Each beaker had a volume of 20 mL. After treatment at 28℃ for one day, 5 zebrafish from each experimental group were randomly selected and placed in 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 behavioral analyzer. 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 indicator were used to evaluate the dose-response relationship of the sample in promoting brain development.

[0111] Experimental results: As shown in Table 2, the proportion of the movement distance of zebrafish in the blue area in the normal control group was 43.61%; after intervention with Ginkgo biloba and Cistanche deserticola tablets, the proportion of the positive control group increased to 57.5%.

[0112] Under LPE18:2 intervention, five concentration gradients were set, with a maximum concentration of 1.25 μg / mL and each gradient halved sequentially. Results showed that the percentage of zebrafish movement distance within the blue region increased to varying degrees in all concentration groups, rising from 45.89% at the lowest concentration of 0.0781 μg / mL to 63.42% at 1.25 μg / mL, exhibiting a clear dose-dependent effect. Significance analysis showed that, except for the lowest concentration (0.0781 μg / mL), the percentage of movement distance within the blue region in all other concentration groups was significantly higher than that in the normal control group.

[0113] Under DHA intervention, five concentration gradients were set up, with a maximum concentration of 250 μg / mL and each gradient halved sequentially. Results showed that the proportion of zebrafish movement distance within the blue region increased to varying degrees in each concentration group, but the overall increase was slightly lower than that of LPE18:2. Significance analysis showed no significant difference between the DHA groups at doses of 15.6 μg / mL, 31.2 μg / mL, and 62.5 μg / mL and the normal control group. However, at a concentration of 125 μg / mL, the proportion of zebrafish movement distance within the blue region was significantly higher than that of the normal control group.

[0114] The results indicate that LPE18:2 can significantly improve the cognitive ability of zebrafish in the concentration range of 0.156-1.25 μg / mL; DHA can also significantly improve the cognitive ability of zebrafish in the concentration range of 125-250 μg / mL.

[0115] Table 2. Effects of different doses of the two nutrients on the percentage of distance traveled by zebrafish in the blue area.

[0116]

[0117] Experiment Example 2: Effects of different nutrients and their combinations on the body length of zebrafish

[0118] Body length is one of the important indicators for evaluating the growth and development of zebrafish. Generally, the longer the body length, the better the overall development level of the zebrafish, which also indirectly reflects a better state of brain development.

[0119] To verify that LPE18:2 and DHA have a synergistic effect on promoting brain development in zebrafish, this study set up different combinations of the two to analyze the effects of individual and combined nutrient interventions on zebrafish body length.

[0120] Experimental Groups: A normal control group, a positive control group, and sample treatment groups were set up (including Comparative Examples 1-5 and Examples 1-5). Zebrafish in the normal control group were cultured routinely without any treatment or intervention. The positive control group was treated with 125 μg / mL Ginkgo biloba and Cistanche deserticola tablets. Comparative Examples 1-2 were treated with 0.156 μg / mL and 1.25 μg / mL LPE18:2. Comparative Examples 3-5 were treated with 20 μg / mL, 80 μg / mL, and 320 μg / mL DHA. Examples 1-5 were intervention groups consisting of LPE18:2 and DHA mixed at different concentration ratios (1:16 to 1:2051). Specific experimental group settings are shown in Table 3.

[0121] Table 3. Design schemes for promoting brain development with different nutrient ratios

[0122]

[0123] Experimental Methods: 3dpf wild-type AB strain zebrafish were randomly selected and placed in beakers, 30 fish per beaker (each experimental group). The samples were administered in water-soluble form. The positive control group received 125 μg / mL Ginkgo biloba and Cistanche deserticola tablets. A normal control group was also included. Each beaker had a volume of 20 mL. After treatment at 28℃ for 3 days, 10 zebrafish were randomly selected from each experimental group, photographed under a dissecting microscope, and data were collected using NIS-Elements D 3.20 advanced image processing software. The body length of the zebrafish was analyzed, and the statistical analysis results of this index were used to evaluate the efficacy of the samples in promoting brain development. The experimental results are shown in Table 4.

[0124] Table 4 shows that the average body length of zebrafish in the normal control group was approximately 3.78 mm. After intervention with Ginkgo biloba and Cistanche deserticola tablets, the body length significantly increased to 3.95 mm. Intervention with LPE18:2 at low and high doses (Comparative Examples 1 and 2) further increased the body length of zebrafish compared to the normal control group. Significance analysis showed that the body length of the high-dose LPE18:2 group (Comparative Example 2) was significantly higher than that of the normal control group, but there was no significant difference compared to the positive control group. While intervention with DHA at low, medium, and high doses (Comparative Examples 3-5) increased the body length of zebrafish to varying degrees, the differences did not reach statistical significance (p>0.05), and all were significantly lower than those of the positive control group, indicating that its effect on promoting body length development did not reach the level of the positive control.

[0125] In contrast, Examples 1-5 used compositions formed by combining LPE18:2 and DHA in different proportions for combined intervention, and the results showed that the body length of zebrafish was further increased. Significant difference analysis showed that the body length of all five examples was significantly higher than that of the normal control group, and there was no significant difference compared with the positive control group. This indicates that the compositions formed by combining LPE18:2 and DHA are more effective than either alone in promoting the overall growth and development of zebrafish.

[0126] Table 4. Effects of interventions with individual and combined nutrients on the body length of zebrafish

[0127]

[0128] Experiment Example 3: Effects of different nutrients and combinations on the cognitive abilities of zebrafish

[0129] Zebrafish strain: Wild-type AB strain zebrafish, 30 fish in each experimental group, incubated in a 28℃ incubator.

[0130] Experimental grouping: As shown in Table 3, 10 groups were set up for intervention with LPE18:2 and DHA monomer and its different ratios. At the same time, one normal control group (normal zebrafish without any treatment or intervention) and one positive control group (zebrafish treated with 125 μg / mL Ginkgo biloba and Cistanche deserticola tablets) were set up.

[0131] Experimental Methods: Wild-type AB strain zebrafish, 5 days post-fertilization (5 dpf), were randomly selected and placed in beakers, with 30 zebrafish per beaker (each experimental group). Water-soluble samples were administered. The positive control group received 125 μg / mL Ginkgo biloba and Cistanche deserticola tablets, and a normal control group was also included. Each beaker had a volume of 20 mL. After treatment at 28℃ for 1 day, 5 zebrafish were randomly selected from each experimental group and placed in a cross-shaped module. This module was divided into four regions: yellow, blue, red, and green, with 6 modules per 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 promoting brain development and behavioral performance.

[0132] The experimental results are shown in Table 5, and the significance analysis of differences between groups is shown in Table 6.

[0133] As shown in Table 5, the average distance traveled by zebrafish in the blue area of ​​the cross maze in the normal control group was 43.74%. After intervention with Ginkgo biloba and Cistanche deserticola tablets, this percentage increased to 57.78% in the positive control group, indicating that the cognitive ability of the zebrafish was improved.

[0134] Comparative Examples 1 and 2 illustrate the percentage of movement distance in the blue area of ​​the cross maze in zebrafish after low and high doses of LPE18:2 intervention. The results showed that the percentage of movement distance in both dose groups was increased to varying degrees compared to the normal control group. Statistical analysis revealed no significant difference between the low-dose group (Comparative Example 1) and the normal control group (p>0.05); however, the high-dose group (Comparative Example 2) was significantly higher than the normal control group (p<0.05), but not significantly different from the positive control group (p>0.05), indicating that high-dose LPE18:2 can achieve an intervention effect comparable to the positive control.

[0135] Comparative Examples 3-5 illustrate the percentage of movement distance in the blue area of ​​the cross maze in zebrafish after intervention with low, medium, and high doses of DHA. The results showed that although the percentage of movement distance in each dose group was higher than that in the normal control group, the differences were not statistically significant (p>0.05). These results indicate that DHA intervention alone is less effective than LPE18:2 intervention alone.

[0136] Examples 1-5 demonstrate the effect of combining LPE18:2 and DHA in different proportions on the proportion of movement distance in the blue region of zebrafish. Table 5 shows that after intervention with the combination of the two nutrients, the proportion of movement distance in the blue region of zebrafish was significantly higher than that of either nutrient alone. Significant difference analysis showed that the proportion of movement distance in the blue region in all five examples was significantly higher than that in the normal control group (p<0.0001) and significantly higher than that in the five comparative examples (p values ​​are shown in Table 6). Specifically, Examples 1, 2, and 4 showed no significant difference compared to the positive control group (p>0.05), while Examples 3 and 5 were significantly higher than the positive control group (p values ​​are shown in Table 6). This indicates that the combined use of LPE18:2 and DHA has a synergistic effect on improving the cognitive ability of zebrafish.

[0137] Further analysis revealed that the effects of all five examples were greater than the sum of the effects of the two nutrients alone at the same concentration, confirming that the combination of LPE18:2 and DHA has a synergistic effect on increasing the proportion of zebrafish moving in the blue area.

[0138] Table 5. Effects of nutrient monomer and combination interventions on the proportion of movement in the blue area of ​​zebrafish in the cross maze.

[0139]

[0140] Table 6. Significant differences among zebrafish groups in the proportion of movement within the blue area of ​​the cross maze.

[0141]

[0142] Experiment Example 4: Effects of different nutrients and combinations on the expression of genes related to brain development in zebrafish

[0143] Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are two crucial neurotrophic factors in brain development. BDNF primarily exerts its biological effects by binding to the TrkB receptor, exhibiting sustained high expression from the embryonic stage to postnatal life, and is widely distributed in key brain regions such as the hippocampus, cortex, and cerebellum. Its functions include promoting neurogenesis, neuronal differentiation, synapse formation, and neural circuit construction, and it plays a specific regulatory role in specific brain regions such as the hippocampus, cerebral cortex, and cerebellum. GDNF, on the other hand, functions through the GFRα1 / RET receptor complex signaling pathway, exhibiting high specificity for dopaminergic neurons and motor neurons. It is a core regulator of the midbrain dopamine system development, ensuring not only the normal development of motor neurons and the peripheral nervous system but also participating in the regulation of functions such as the enteric nervous system. Therefore, this study measured the gene expression levels of BDNF and GDNF in the brains of zebrafish under normal control, positive control, and different nutrient intervention conditions.

[0144] Zebrafish strain: Wild-type AB strain zebrafish, 30 fish in each experimental group, incubated in a 28℃ incubator.

[0145] Experimental grouping: As shown in Table 3, 10 groups were set up for intervention with LPE18:2 and DHA monomer and its different ratios. At the same time, one normal control group (normal zebrafish without any treatment or intervention) and one positive control group (zebrafish treated with 125 μg / mL Ginkgo biloba and Cistanche deserticola tablets) were set up.

[0146] Experimental Methods: Wild-type AB strain zebrafish (5 dpf) were randomly selected and placed in beakers, with 30 fish per beaker (each experimental group). Samples were administered via water-soluble solution. The positive control group received 125 μg / mL Ginkgo biloba and Cistanche deserticola tablets, and a normal control group was also included. Each beaker had a volume of 20 mL. After treatment at 28℃ for one day, total RNA was extracted from each group of zebrafish using a pre-loaded magnetic bead-based universal RNA extraction kit. The concentration and purity of total RNA were determined using a UV-Vis spectrophotometer. 2.00 μg of total RNA was used to synthesize 20.0 μL of cDNA according to the cDNA first-strand synthesis kit instructions. The expression of β-ACTIN, BDNF, and GDNF genes was detected by real-time quantitative PCR (q-PCR). Primer sequences are shown in Table 7. β-ACTIN was used as an internal reference gene, and the relative RNA expression levels of BDNF and GDNF genes were calculated.

[0147] Table 7. Primer sequence information

[0148]

[0149] The experimental results are shown in Table 8, and the significance analysis of differences between groups is shown in Table 9.

[0150] Table 8. Effects of nutrient monomers and combinations on the expression levels of neurotrophic factor genes in the zebrafish brain

[0151]

[0152] Table 9. Significant differences in the expression levels of neurotrophic factor genes in the brains of zebrafish among different groups.

[0153]

[0154] Table 8 shows that intervention with Ginkgo biloba and Cistanche deserticola tablets significantly increased the relative expression level of the BDNF gene in the brain tissue of normal zebrafish. Intervention with LPE18:2 and DHA also resulted in varying degrees of increase in BDNF gene expression compared to the normal control group. Statistical analysis revealed no significant difference between the low-dose LPE18:2 group (Comparative Example 1) and the low- and medium-dose DHA groups (Comparative Examples 3 and 4) and the normal control group (p>0.05); however, at relatively high doses (Comparative Examples 2 and 5), the relative expression level of the BDNF gene was significantly higher than that of the normal control group (p<0.05). This indicates that LPE18:2 and DHA only promote BDNF gene expression in zebrafish brain tissue at certain doses.

[0155] Examples 1-5 investigated the effects of combinations of LPE18:2 and DHA at different ratios on BDNF gene expression in normal zebrafish brain tissue. The results showed that the relative expression levels of BDNF in all five examples were significantly higher than those in the normal control group (p<0.0001), and there was no significant difference compared to the positive control group (p>0.05). Further analysis revealed that the BDNF expression levels in all five examples were significantly higher than those in the five comparative examples (p values ​​are shown in Table 9), and the effects of the five examples were significantly greater than the simple sum of the intervention effects of the two nutrients at equal concentrations, indicating a synergistic effect.

[0156] Meanwhile, this invention also found that after intervention with Ginkgo biloba and Cistanche deserticola tablets in normal zebrafish, the relative expression level of the GDNF gene in their brain tissue was significantly increased. Furthermore, intervention with LPE18:2 and DHA, respectively, also resulted in varying degrees of increase in GDNF gene expression compared to the normal control group. Statistical analysis showed that LPE18:2 significantly increased the relative expression level of GDNF in zebrafish brain tissue at both low and high doses (p values ​​are shown in Table 9); while the low and medium dose DHA groups (Comparative Examples 3 and 4) showed no significant difference compared to the normal control group (p>0.05), only the high dose group (Comparative Example 5) was significantly higher than the normal control group (p<0.05). This indicates that LPE18:2 is effective in promoting the increase of GDNF expression in brain tissue, while DHA requires a certain dose to promote the increase of GDNF gene expression in zebrafish brain tissue.

[0157] Examples 1-5 investigated the effects of combinations of LPE18:2 and DHA at different ratios on GDNF gene expression in normal zebrafish brain tissue. The results showed that the relative GDNF expression levels in all five examples were significantly higher than those in the normal control group (p<0.0001), and there was no significant difference compared to the positive control group (p>0.05). Further analysis revealed that the GDNF expression levels in all five examples were significantly higher than those in the five comparative examples (p values ​​are shown in Table 9), and the effects of the five examples were significantly greater than the simple sum of the intervention effects of the two nutrients at equal concentrations, further confirming the synergistic effect of the two.

[0158] In conclusion, combined intervention with LPE18:2 and DHA can significantly promote the mRNA expression of neurotrophic factors BDNF and GDNF in brain tissue, and the two have a synergistic effect.

Claims

1. A nutritional composition, characterized in that, The nutritional composition is a nutritional composition that has functions that promote growth and / or brain development, and the nutritional composition contains the following two essential components: i) LPE(18:2(9Z,12Z) / 0:0); ii) docosahexaenoic acid; Furthermore, in the nutritional composition, the mass ratio of LPE (18:2(9Z,12Z) / 0:0) to docosahexaenoic acid is 1:(10-2100).

2. The nutritional composition according to claim 1, characterized in that, The LPE (18:2(9Z,12Z) / 0:0) is provided in the form of dairy products containing it and / or enzymatically hydrolyzed soybean lecithin.

3. The nutritional composition according to claim 1, characterized in that, The docosahexaenoic acid is provided in the form of natural and / or synthetic and / or biofermentation sources.

4. The nutritional composition according to any one of claims 1-3, characterized in that, The nutritional composition also contains ω-3 fatty acids other than docosahexaenoic acid.

5. The nutritional composition according to claim 4, characterized in that, The ω-3 fatty acids other than docosahexaenoic acid include at least one of alpha-linolenic acid and eicosapentaenoic acid.

6. Use of the nutritional composition according to any one of claims 1-5 in the preparation of products for non-therapeutic purposes that promote growth and / or brain development.

7. The use according to claim 6, characterized in that, The benefits to brain development include improvements in cognitive abilities.

8. The use according to claim 6 or 7, characterized in that, The product contains any one or more of the following ingredients: plant-based ingredients, animal dairy ingredients, animal meat ingredients, and functional additives.

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