Flax polyphenol composition for regulating and controlling absorption and metabolic transformation of alpha-linolenic acid and application

Abstract

The invention discloses a flax polyphenol composition for regulating and controlling absorption and metabolic transformation of alpha-linolenic acid and application, and relates to the technical field of nutrition metabolism. Comprising the following components: any one or more of flax lignan macromolecules FLM, ring-opening isolariciresinol diglucoside SDG or ring-opening isolariciresinol SECO. The invention discloses a unique synergistic effect (for example, low-dose lignan optimizes interfacial properties, moderately inhibits digestive enzyme to improve absorption and differentially regulates expression of a liver invertase system) of polyphenols (FLM, SDG and SECO) of different structural units and a nano delivery system, and establishes a new mode of regulating ALA metabolic transformation based on multiple targets of intestine-liver-flora.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of nutritional metabolism, and more particularly to a technology system for realizing efficient delivery, stable absorption and efficient metabolic conversion of n-3 long-chain polyunsaturated fatty acids (n-3LCPUFAs, including EPA and DHA) in the body by using natural polyphenol active ingredients such as flax lignan to synergistically regulate stable flaxseed oil nanoemulsion of sunflower phospholipid, which has the functions of delivery carrier design, nutritional metabolism mechanism analysis and multi-dimensional health application expansion. BACKGROUND

[0002] n-3LCPUFAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important physiological active lipid components of the human body, and have been proven to play a key role in the development of the nervous system, visual protection, cognitive function improvement, cardiovascular health maintenance, and inflammation inhibition. However, the human body has very limited ability to synthesize n-3LCPUFAs, and must rely on exogenous intake. The global recommended daily intake of EPA+DHA is 200-500 mg, but the average actual intake of Chinese residents is only about 20% of the recommended amount, resulting in potential health risks. At present, the main sources of n-3LCPUFAs are marine fish and fish oil products. However, with the global shortage of marine resources, environmental pollution, and the popularity of vegetarian diets, the intake of n-3LCPUFAs is facing multiple challenges such as shortage of raw material sources, safety risks, and insufficient applicability to the population.

[0003] Alpha-linolenic acid (ALA) is the main dietary precursor of n-3LCPUFAs, which can be converted to EPA and DHA in human liver and other tissues through a series of metabolic processes such as enzymatic chain extension and desaturation. Therefore, improving the in vivo bioavailability and conversion efficiency of ALA has important scientific and application value for realizing sustainable n-3LCPUFAs supply and promoting national health. China has abundant flaxseed resources, with ALA content as high as more than 50%, which is a high-quality source of ALA. However, research data shows that the digestion and absorption rate of ALA in the intestine is low, and the conversion rate to EPA and DHA in the liver is only 0.2%-1% and 0.05%-0.2%, which is far below the ideal level, making it difficult to realize its potential health value.

[0004] Recent studies have shown that the key bottlenecks affecting the metabolic conversion efficiency of ALA in vivo mainly include three aspects: (1) ALA is easily oxidized in the gastrointestinal tract, insufficiently absorbed by micelles, and then affects the assembly and lymphatic transport process of chylomicrons, and limits its available amount as a substrate: ALA is a polyunsaturated fatty acid, which is easily oxidized and inactivated under the action of gastric acid and bile salts, forming harmful products such as fatty acid peroxides and carbonyl groups, resulting in loss of metabolic activity; ALA needs to be assembled into chylomicrons after being absorbed in the intestine and enter the lymphatic system, but when the oil droplets are large in size and poor in dispersibility, the chylomicron generation rate is low, and ALA cannot be efficiently transported to the blood.(2) The expression of related desaturation enzymes, chain elongation enzymes and other key metabolic enzymes in the liver is limited, and the chain elongation / desaturation and beta-oxidation pathways compete for distribution, which aggravates the loss of ALA conversion: The key enzymes Elovl2 / 5, Fads1 / 2 in the liver have poor regulation ability and conversion pathway competition, resulting in most of ALA being consumed by beta-oxidation, and the proportion of real chain elongation converted to EPA and DHA is extremely low. In addition, intestinal flora imbalance affects substrate supply and conversion environment: when the flora composition is unbalanced, harmful bacteria will decompose / consume ALA substrate, and the product distribution efficiency will decrease, further limiting effective conversion.

[0005] Nanoemulsion delivery system has great potential in improving the bioavailability of fat-soluble active ingredients due to its small particle size, large specific surface area and strong stability. Nanoemulsion with phospholipid as emulsifier not only improves the solubility and gastrointestinal absorption efficiency of ALA, but also improves the assembly of chylomicrons and blood transport by regulating lipid metabolism-related protein expression. However, a single delivery system still cannot completely break through the technical bottleneck of ALA conversion limitation in multiple links in vivo.

[0006] Natural polyphenols such as flax lignans have antioxidant, interface regulation, digestive enzyme inhibition and metabolic pathway regulation effects. Different structural units of flax lignans (natural macromolecule FLM, secoisolaricic acid resinol diglucoside SDG and secoisolaricic acid resinol SECO) have differences in interface affinity, distribution stability and targeted regulation ability, providing a theoretical basis for efficient delivery and in vivo conversion of ALA. However, there is still a lack of systematic and mechanism-based overall technical system for flax lignan and ALA delivery synergistic regulation.

[0007] Therefore, it is a major demand and research frontier in the field of food health and functional lipid delivery to develop a new method for flax lignan as an active ingredient to synergistically regulate the delivery efficiency of ALA in nanoemulsion, to target multiple links such as digestion and absorption, blood transport, liver enzyme expression and microecological structure, and to systematically improve the in vivo conversion of ALA. SUMMARY

[0008] Therefore, the present application provides a flax polyphenol composition for regulating the absorption and metabolic conversion of alpha-linolenic acid and its application.

[0009] To achieve the above object, the present application adopts the following technical solutions:

[0010] A flax polyphenol composition for regulating absorption and metabolic conversion of α-linolenic acid, comprising the following components:

[0011] Any one or more of flax lignan macromolecule FLM, secoisolaricic acid resinol diglucoside SDG or secoisolaricic acid resinol SECO.

[0012] FLM is in the form of an oligomer, and SDG and SECO are two main structural units thereof.

[0013] Further, the flax polyphenol composition further comprises flaxseed oil and PBS buffer;

[0014] The flaxseed oil in the composition is 20 wt%, and ALA in the flaxseed oil is ≥50%;

[0015] The PBS buffer contains 3 wt% sunflower phospholipid, and has a pH of 7.0;

[0016] The final concentration of the flax polyphenol in the composition is 300-1500 μmol / L.

[0017] The flax polyphenol composition for regulating absorption and metabolic conversion of α-linolenic acid is applied to the preparation of health food, and is characterized in that the composition can be developed into high-end functional oil food, n-3 fatty acid nutritional supplement, brain health / cardiovascular health / vision protection health food, and the endogenous generation capacity of EPA and DHA in the human body is improved to improve the current situation of insufficient intake of n-3 LCPUFAs.

[0018] The flax polyphenol composition for regulating absorption and metabolic conversion of α-linolenic acid is applied to the preparation of special medical purpose food, and is characterized in that it is suitable for special nutritional needs of pregnant and infant, children, adolescents, the elderly, sub-health and patients with chronic diseases.

[0019] The chronic diseases include hyperlipidemia, diabetes, cardiovascular and cerebrovascular diseases, and cognitive impairment.

[0020] The population also includes n-3 fatty acid intake-restricted population such as people sensitive to marine products, people allergic to marine products, and vegetarians.

[0021] The flax polyphenol composition for regulating absorption and metabolic conversion of α-linolenic acid is applied to the promotion of intestinal health and intervention in intestinal microecology, and is characterized in that intestinal flora structure is optimized, abundance of beneficial flora is improved, and generation of pathogenic bacteria and harmful metabolites is reduced, and intestinal health products, microecological regulators and prebiotic functional foods are developed.

[0022] The application of the flax polyphenol composition for regulating the absorption and metabolic conversion of alpha-linolenic acid in the industrial high-value of bioactive oil, characterized in that, promoting the high-value deep processing and whole industry chain development of agricultural products rich in ALA such as flaxseed, improving the functional utilization of by-products, and promoting the sustainable circulation of oil resources; the by-products are flaxseed shells and meal.

[0023] The application of the flax polyphenol composition for regulating the absorption and metabolic conversion of alpha-linolenic acid in scientific research and health engineering, characterized in that, providing a theoretical basis and practical tool for basic and applied research of lipid metabolism mechanism, functional lipid delivery, and natural polyphenol synergistic nutritional intervention.

[0024] Through the above technical solutions, compared with the prior art, the beneficial effects of the present application are:

[0025] Full-process multi-target synergistic improvement of ALA utilization rate: from delivery protection (improving physical stability, potential interface antioxidant), absorption and transport (low dose 300 μmol / L FLM / SECO significantly improves lymphatic absorption of ALA by 31.4% / 39.6%; delays blood peak and improves AUC by 32.3% / 45.9%), metabolic conversion (long-term intervention significantly improves liver n-3 LCPUFAs conversion, FLM and SDG groups serum EPA+52.7%-55.9%, SDG group liver EPA and DHA content increased by 10%-13%; target up-regulation of Fads1 / 2, Elovl2 / 5, etc. Key enzyme expression) to optimization of flora (significantly increasing the abundance of Bacteroidota and beneficial bacteria, reducing pathogenic bacteria, and forming a "pro-conversion flora" network), each link has experimental data and molecular mechanism support, far beyond single delivery or supplementation scheme;

[0026] Low dose, strong effect, high safety: low dose flax lignan (300 μmol / L) can achieve maximum absorption and conversion effect, avoiding the inhibitory absorption effect caused by medium and high doses. 42-day long-term experiments have confirmed its safety and reliability, and no obvious adverse reactions have been observed;

[0027] Strong product stability and applicability: the nanoemulsion system has good physical / chemical stability (low TSI index and gentle change), small average particle size (226-263 nm) and uniform distribution, and is suitable for various dosage forms such as drinks, capsules, milk powder, etc., which is convenient for actual promotion and industrialized production;

[0028] Innovative synergistic mechanism and industrialization potential: The unique synergies of different structural units of polyphenols (FLM, SDG, SECO) with nanodelivery systems are revealed (such as low-dose lignan optimizing interface properties and moderate inhibition of digestive enzymes to enhance absorption), and a new model based on intestinal-liver-bacterial flora multi-target regulation of ALA metabolic transformation is established. This provides an innovative technical paradigm for the development of ALA high-value development (promoting the utilization of the whole flaxseed industry chain, and improving the value of by-products such as shells and meal), n-3 fatty acid health intervention (especially suitable for people with limited intake of marine products), and microecological regulation product development, and builds a solid patent barrier. BRIEF DESCRIPTION OF DRAWINGS

[0029] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or prior art description will be briefly introduced below. Obviously, the drawings in the following description are only embodiments of the present application, and those skilled in the art can also obtain other drawings according to the provided drawings without creative labor.

[0030] Figure 1 Physical stability characteristics of sunflower phospholipid-stabilized nanoemulsions containing different doses of flax lignans; Figure 1 a) appearance morphology diagram; Figure 1 b) emulsion particle size distribution diagram; Figure 1 c) TSI index of each emulsion;

[0031] Figure 2 Oil-water-interface distribution of lignans in sunflower phospholipid-stabilized nanoemulsions containing different doses of flax lignans;

[0032] Figure 3 Lymph-blood transport of ALA in mice after co-ingestion of sunflower phospholipid-stabilized nanoemulsions containing different doses of flax lignans for 4h; Figure 3 a) TG content in mouse serum after 4h under LPL inhibition; Figure 3 b) ALA content in mouse serum;

[0033] Figure 4 Blood lipid bioavailability of mice based on intestinal absorption and blood transport of ALA in nanoemulsions under low-dose flax lignan co-delivery; Figure 4 a) ALA content-time curve of mouse serum after ingestion of different emulsions; Figure 4 b) Area under the curve of ALA content-time curve in mouse serum;

[0034] Figure 5 Time cumulative effect of ALA absorption-transformation in mouse serum and liver after the last intragastric administration for 6h at the end of 14 days, 28 days and 42 days; Figure 5 a, Figure 5c) EPA content; Figure 5 b) DPA content; Figure 5 d) DHA content;

[0035] Figure 6 n-3 PUFAs content in serum and liver of mice after 6h post last gavage at day 42; Figure 6 a, Figure 6 c) EPA content; Figure 6 b, Figure 6 e) DHA content; Figure 6 d) DPA content;

[0036] Figure 7 n-3 PUFAs content in serum and liver of mice after 12h fasting after 35 days of nanoemulsion gavage; Figure 7 a, Figure 7 c) EPA content; Figure 7 b) ALA content; Figure 7 d) DHA content;

[0037] Figure 8 Expression of fatty acid desaturation, elongation and beta-oxidation related proteins in liver of mice; Figure 8 a) Relative expression level of FADS1 and FADS2 proteins; Figure 8 b) Relative expression level of ELOVL2 and ELOVL5 proteins; Figure 8 c) Relative expression level of CPT1a and CPT2 proteins;

[0038] Figure 9 Intestinal microbiota species distribution; Figure 9 a) Phylum level; Figure 9 b) Family level;

[0039] Figure 10 GO functional annotation analysis of intestinal microbiota species distribution;

[0040] Figure 11 Correlation network analysis of intestinal microbiota and ALA metabolic conversion regulation;

[0041] Figure 12 Quantitative analysis of characteristic metabolites of secoisolaricirecinols in mice based on nanoemulsion delivery system; Figure 12 a) FLM-containing emulsion group; Figure 12 b) SDG-containing emulsion group; Figure 12 c) SECO-containing emulsion group;

[0042] Figure 13 Quantitative analysis of intracellular fatty acids after co-incubation of secoisolaricirecinols characteristic metabolite-ALA in HepG2 cells in vitro; Figure 13a) Intracellular ALA (18:3n-3) quantification; Figure 13 b) Intracellular 20:3n-3 quantification; Figure 13 c) Intracellular 20:4n-3 (ETA) quantification. DETAILED DESCRIPTION

[0043] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by a person of ordinary skill in the art without creative work are within the protection scope of the present application.

[0044] Example 1: Construction of flax lignan-nanoemulsion delivery system and regulation of physical properties

[0045] The present embodiment provides a preparation method of sunflower phospholipid-stabilized flaxseed oil nanoemulsion in cooperation with flax lignans. Flaxseed oil (ALA≥50%) is used as an oil phase (20wt%) and mixed with PBS buffer (pH 7.0) containing sunflower phospholipid (3wt%), and FLM, SDG or SECO (final concentrations are 300μmol / L, 750μmol / L and 1500μmol / L, respectively) pre-dissolved in 70% ethanol is added. Nanoemulsion is prepared by high-speed shearing and high-pressure microjet. Characterization shows that the average particle size of the emulsion is 226-263nm (monomodal distribution); SECO is enriched at the oil-water interface due to its hydrophobicity, reaching 49-59%; FLM and SDG are mainly distributed in the aqueous phase (accounting for 56-82%). Backscattering spectrum shows that the Turbiscan stability index (TSI) of the nanoemulsion is <2, which is significantly better than that of the coarse emulsion (TSI linearly increases). The present system realizes interface antioxidant strengthening through differential phase distribution of lignans, and provides physical stability guarantee for efficient delivery of ALA (see the accompanying drawings Figures 1-2 ).

[0046] Preparation of nanoemulsion and physical properties

[0047] (see the accompanying drawings Figure 1 : Appearance, particle size distribution and TSI stability index of co-delivery nanoemulsion, showing the uniformity and stability of the nanoemulsion)

[0048] The sunflower phospholipids were dispersed in 5mM PBS (pH 7.0) at 3% mass fraction to obtain the water phase. The FLM, SDG and SECO were pre-dissolved in a small amount of 70% ethanol (v / v), mixed with the water phase (80%, w / w) and flaxseed oil (oil phase, 20%, w / w). The low, medium and high dose concentrations of SDG and SECO in the final emulsion were 300 μmol / L, 750 μmol / L and 1500 μmol / L, respectively, and the amount of FLM added was determined according to the equivalent mass of SDG. A high-speed shearing machine was used to shear the mixture at 10000 r / min for 2 min to obtain a coarse emulsion, which was then subjected to four cycles of high-pressure microfluidization at a pressure of 10000 psi to obtain a nanoemulsion.

[0049] Results analysis: In addition to the slightly yellowish color of the coarse emulsion (Coa-E), the nanoemulsions with or without flax lignans all exhibited a white and uniform appearance. The particle size distribution showed that all nanoemulsions exhibited a unimodal distribution, while Coa-E exhibited a relatively wide and multimodal distribution. The average particle size (D3,2) showed that the addition of flax lignans did not significantly change the D3,2 value of the nanoemulsion, ranging from 226 to 263 nm. The Turbiscan stability index (TSI) showed that Coa-E had a linear increase in TSI within 30 min of monitoring, while the TSI of the nanoemulsions increased more slowly and gradually leveled off. For the nanoemulsions, the addition of flax lignans slightly increased the TSI, but all the emulsions exhibited good physical stability.

[0050] Phase distribution of flax lignans in emulsion system

[0051] (Attachment Figure 2 : High-speed centrifugation combined with UPLC to determine the three-phase distribution of flax lignans, showing the content ratio of FLM, SDG and SECO in water phase / interface / oil phase)

[0052] A low-temperature high-speed centrifuge was used at 4°C at 20000 r / min for 1 h. A syringe was used to aspirate the upper oil phase and the lower water phase, respectively. After discarding the upper liquid, a precipitate was obtained. The content of flax lignans in the whole emulsion, oil phase, water phase and precipitate was determined by ultra-high performance liquid chromatography (UPLC), and the standard curve was established by a series of concentration lignan ethanol solutions (70%, v / v).

[0053] Results analysis: FLMs were mainly distributed in the water phase, and with the increase of the additive dose, the water phase content increased, but the percentage decreased (82%→62%). The absolute content of FLM on the interface gradually increased, but the percentage decreased (18%→12%). These results showed that the higher concentration of FLM in the water phase may limit its distribution in the water phase or on the interface due to intermolecular interactions. Different doses of SDG were also mainly present in the water phase, and with the increase of the additive dose, the content increased, but the percentage did not change significantly (56%→62%). At the same time, the absolute content of SDG on the interface increased, and the percentage gradually increased but was not significant (38%→44%). Therefore, within the dose range of the current study, the interface adsorption of SDG was dose-dependent. In addition, the proportion of SECO in the water phase was low (44%-50%), which may be due to its interaction with phospholipids in the water phase or its presence in the micellar structure formed by phospholipids. These results showed that low-dose lignan could effectively adsorb on the interface of the emulsion, which may enhance the oxidative stability of the emulsion. At medium and high doses, FLM and SECO may aggregate in the water phase or interact with phospholipids to form unstable complexes, which may to some extent hinder their antioxidant efficacy on the interface.

[0054] Example 2: Low-dose lignan improves ALA intestinal absorption and blood bioavailability

[0055] The dose effect of flax lignans on ALA intestinal absorption was verified by lipoprotein lipase (LPL) inhibition mouse model. After a single gavage of nanoemulsion containing low (300 μmol / L), medium (750 μmol / L), and high (1500 μmol / L) doses of FLM / SDG / SECO, serum ALA detection under LPL inhibition showed that the serum ALA content of the low-dose FLM group and the SECO group was increased by 31.4% and 39.6% (p<0.05) respectively compared with the nanoemulsion control group (Nano-E), while the medium and high dose groups significantly inhibited ALA absorption. Further analysis based on the serum "concentration-time" curve of normal metabolism mice, low-dose lignan delayed the peak of ALA in blood to 3h after gavage, and increased the area under the curve (AUC) in a "slow and efficient" manner: FLM group +32.3%, SECO group +45.9% (p<0.05). This example demonstrates that low-dose lignan optimizes chylomicron assembly and blood transport efficiency by moderately inhibiting digestive enzyme activity (corresponding to Figure 2). Figures 3-4 ).

[0056] Intestinal absorption of ALA under different doses of lignan-nanoemulsion co-delivery

[0057] (appendix Figure 3Serum triglyceride (TG) and ALA content in animal experiments showed the effect of different doses of lignan on the lymph-blood transport of ALA in mice 4h after the intake of nanoemulsion;

[0058] Experimental protocol: In addition to the Coa-E and Nano-E control groups, the remaining mice were randomly divided into 9 groups, corresponding to the low (L), medium (M), and high (H) dose of FLM, SDG, and SECO nanoemulsion. After one week of environmental adaptation and feeding of standard feed, the mice were fasted for 12h (free water). First, the mice were given intraperitoneal injection of 100μL Tyloxapol solution (125mg / mL, dissolved in physiological saline), and 30min later, 300μL emulsion was given by gavage. Four hours after gavage, the mice were anesthetized with ether, blood samples were collected, and the mice were sacrificed by cervical dislocation, followed by collection of intestinal and liver samples. After standing for 30min, the blood samples were centrifuged at 4℃, 4000r / min for 10min to obtain serum. The tissue samples were immediately frozen in liquid nitrogen after collection, and then stored at -80℃ for further determination and analysis.

[0059] Results analysis: Compared with the Coa-E group, the intake of Nano-E significantly increased the serum TG (+11.3%) and ALA (+40.4%) levels, indicating that nanoization enhanced the absorption of lipids and the assembly of chylomicrons. Compared with Nano-E alone, the co-intake of low-dose lignan did not change the serum TG level, but as the lignan dose increased, the serum TG content decreased in a dose-dependent manner, and lignans of different structures showed similar effects. In addition, low-dose lignan intake significantly increased serum ALA levels, and FLM-L (+31.4%) and SECO-L (+39.6%) groups showed more significant effects than Nano-E (p<0.05). However, medium and high doses of lignan significantly reduced serum ALA levels, and lignans of different structures showed similar effects, possibly due to lignan's inhibition of lipase activity, which inhibited intestinal lipid hydrolysis and absorption.

[0060] Lymph-blood transport of ALA under low-dose lignan-emulsion co-delivery

[0061] (Attachment Figure 4 Serum ALA concentration-time curve and area under the curve (AUC) graph in animal experiments showing the effect of low-dose lignan on the bioavailability of blood lipids in mice after the intake of nanoemulsion)

[0062] Experimental protocol: In addition to the baseline group, mice were randomly divided into 5 groups, corresponding to the Coa-E, Nano-E, and Nano-E containing FLM (FLM-N), SDG (SDG-N) or SECO (SECO-N) groups, respectively. After one week of environmental adaptation and feeding of standard feed, the mice were fasted for 12 h (free water). The mice were anesthetized with ether and blood samples were collected 1 h, 3 h, 6 h and 12 h after gavage of 300 μL of emulsion, respectively. Subsequently, the mice were sacrificed by cervical dislocation, and tissue samples such as small intestine and liver were collected. After 30 min of blood sample standing, serum was obtained by centrifugation at 4°C, 4000 r / min for 10 min. The tissue samples were immediately frozen in liquid nitrogen after collection, and then stored at -80°C for further determination and analysis.

[0063] Results analysis: The quantitative analysis of serum ALA showed that compared with Coa-E, the serum ALA level of mice after ingesting Nano-E was significantly increased, especially at 1 h and 3 h after ingestion, indicating that nano-treatment improved the intestinal lipid hydrolysis and absorption efficiency of ALA, and the concentration peak of ALA was observed at 1 h. Compared with Nano-E, the serum ALA level of mice decreased (-7.8% to -29.6%) after ingesting low-dose lignan, which may be due to the preliminary inhibitory effect of lignan on hydrolytic enzymes during the digestion of emulsion in the intestine. Low-dose lignan significantly increased the serum ALA level at 3 h (+38.5% to +71.6%), indicating that lignan delayed the absorption of ALA, showing a peak delay phenomenon. According to the area analysis of the serum ALA cumulative curve, the co-ingestion of lignan increased the real-time accumulation of ALA in serum, especially in the FLM (+32.3%) and SECO (+45.9%) groups. The current results showed that the lignan from flaxseed enhanced the bioavailability of serum lipids in the form of "slow-release synergistic effect".

[0064] Example 3: Long-term intervention of lignan from flaxseed enhances the metabolic conversion of ALA in the liver

[0065] The cumulative effect of lignan on the conversion of ALA to n-3 LCPUFAs was investigated by 42-day gavage experiment. C57BL / 6J mice were daily administered with nanoemulsion containing low-dose FLM / SDG / SECO (300 μL per mouse). After the last gavage for 6 h, the metabolites in non-fasted state were detected. In FLM group, the serum EPA and DHA increased by 31.9% and 20.2%, respectively, and the liver EPA increased by 35.1%; in SDG group, the serum and liver EPA increased by 38.0% and 47.4%, respectively; in SECO group, the liver EPA (57.9%), DPA (19.7%) and DHA (17.7%) were simultaneously increased. In the fasting state (35-day intervention), the metabolic distribution difference was further revealed. In SDG group, the liver EPA and DHA increased by 10-13%, in FLM group, the serum EPA increased by 52.7-55.9%, and in SECO group, the liver ALA, EPA and DPA were significantly reduced (by 19.3-45.5%) due to the activation of β-oxidation. The results showed that FLM / SDG significantly improved the conversion efficiency of n-3 LCPUFAs by optimizing the liver metabolic pathway distribution (corresponding to Figures 5-7 ).

[0066] Regulatory effect of flax lignan on the conversion of ALA to n-3 LCPUFAs

[0067] Time-cumulative effect of ALA absorption-conversion after the last gavage in non-fasted state

[0068] (appendix Figure 5 : n-3 PUFA content in serum and liver of mice at different time stages during long-term gavage, revealing the time-cumulative effect of ALA absorption-conversion in serum and liver)

[0069] Experimental scheme: mice were divided into 5 groups (18 mice per group), and after one week of adaptation, they were respectively gavaged with control (normal saline), nanoemulsion (Nano-E), FLM-N, SDG-N and SECO-N, with a dose of 300 μL per mouse per day, for 42 days. On the 14th, 28th and 42nd day, the mice were killed in batches, and blood samples, liver, fat, brain and small intestine were collected 6 h after the last gavage. After centrifugation, serum was obtained, and liver and other tissues were quickly frozen in liquid nitrogen and stored at -80°C.

[0070] Results analysis: Compared with Control, the intake of flaxseed oil nanoemulsion can significantly increase the content of ALA in serum of mice at each time point, and further increase the content of EPA, DPA and DHA converted from ALA. For Nano-E, the dynamic change of serum content is caused by intestinal absorption-liver uptake and secretion of ALA. The content of ALA is higher at 14 days, slightly decreased at 28 days, and then slightly increased at 42 days. The decrease of serum content may be related to the real-time accumulation and metabolic increase of liver. Compared with Nano-E, the co-intake of flax lignan causes the fluctuation of ALA content over time, but there is no significant change. For EPA, the content in serum also has limited cumulative effect over time, and the overall change is small. The increase of EPA content in Nano-E group at 28 days may be related to the real-time conversion increase, which corresponds to the decrease of serum ALA content. At the same time, the content of DPA in serum has obvious cumulative effect over time, especially for FLM-N and SDG-N groups, which shows a steady increase. In contrast, the content of DHA in serum remains relatively stable over the experimental period, only FLM-N group shows a small increase trend, indicating that the regulation of FLM on the conversion of ALA to DHA has a time cumulative effect. The decrease of EPA content in Nano-E group at 42 days may be the inhibition effect of the conversion product, and the co-intake of flax lignan may slow down the absorption-transport rate of ALA, and reduce the adverse effects of product inhibition by reducing the real-time metabolic rate of liver.

[0071] At the same time, for the NanoE group, the ALA uptake of mouse liver shows a small increase trend. The co-intake of SDG or SECO causes the decrease of liver ALA content at 28 days, which may be related to the real-time secretion and metabolic increase of serum. For liver EPA, FLM-N, SDG-N and SECO-N groups all show an upward trend, showing a time cumulative increase effect on the metabolic conversion of ALA. The decrease of EPA content in Nano-E group at 42 days may be the decrease of liver ALA uptake and the increase of synchronous DPA and DHA conversion. At the same time, the slow absorption in the intestine and liver transport caused by the co-intake of flax lignan may reduce the negative feedback inhibition effect caused by the conversion product of liver. In contrast, the fluctuation of DPA content in liver over time is relatively small, and for FLM-N and SECO-N groups, it shows a steady increase. Similarly, the content of DHA in liver has no significant fluctuation at 14 days and 28 days, and it has a small increase at 42 days, especially for SDG-N and SECO-N groups. The current results show that FLM, SDG or SECO all have a certain time cumulative regulation effect on the metabolic conversion of ALA to n-3 LCPUFAs, and may contain the material basis composition that promotes the metabolic conversion of ALA.

[0072] Apparent accumulation of ALA absorption-metabolic conversion under non-fasting gavage at the last time

[0073] (Attach Figure 6 : The content of ALA, EPA, DHA and other in serum and liver of mice after long-term gavage in non-fasting state, showing the differential regulation effect of different structure of flax lignan on the metabolic transformation of ALA)

[0074] Results analysis: After gavage of nanolipid emulsion, the n-3PUFAs level in the serum of each group of mice was significantly improved, among which the content of ALA, EPA and DPA in NanoE group was increased to 0.21 mg / mL, 0.025 mg / mL and 0.025 mg / mL, and the content of DHA was further increased to 0.19 mg / mL. At the same time, compared with the NanoE group, the content of EPA (+31.9%) and DHA (+20.2%) in the serum of FLMN group of mice was significantly improved (p<0.05), indicating that the co-consumption of FLM has certain advantages in promoting the liver transformation and lipoprotein secretion of ALA. In contrast, after co-consumption of SDG or SECO, the content of EPA in the serum was increased by 30.0%-38.0%, which did not cause significant changes in the content of DPA and DHA. At the same time, the content of n-3PUFAs in the liver of each group of mice gavaged with nanolipid emulsion was significantly improved, among which the content of ALA, EPA and DPA in NanoE group was increased to 6.26 mg / mL, 0.57 mg / mL and 0.71 mg / mL, and the content of DHA was further increased to 5.19 mg / mL. At the same time, compared with the NanoE group, the co-consumption of FLM and SDG further increased the content of EPA (+35.1%-47.4%) in the liver; while the co-consumption of SECO simultaneously increased the content of EPA (+57.9%), DPA (+19.7%) and DHA (+17.7%), showing the regulation effect of improving the metabolic transformation of ALA to n-3LCPUFAs.

[0075] Metabolic distribution and apparent accumulation of ALA after the last gavage and fasting

[0076] (Attach Figure 7 : The content of ALA, EPA, DHA and other in serum and liver of mice after long-term gavage and fasting, showing the differential regulation effect of different structure of flax lignan on the differential metabolic distribution of ALA after transformation)

[0077] Experimental scheme: Mice were divided into 5 groups (10 per group), after one week of adaptation, gavage control, Nano-E, FLM-N, SDG-N, SECO-N, 300 μL per mouse per day, 35 days. After the last gavage, fasting for 12 h, blood and liver tissues were taken, serum was obtained by centrifugation of blood, and tissue fluid was frozen in liquid nitrogen and stored at -80℃.

[0078] Results analysis: After the intake of flaxseed oil nanoemulsion, the serum levels of ALA (+6.2-10.9-fold), EPA (+3.56-fold) and DHA (+1.3-1.5-fold) were significantly increased. Compared with the Nano-E group, the co-intake of flaxseed lignans reduced the serum ALA level (-8.4%-39.6%), with the most significant in the SECO-N group (p<0.05). At the same time, the serum EPA level increased (+52.7%-55.9%) after the intake of FLM-N and SDG-N. However, the co-intake of lignans did not significantly affect the serum DHA level in the fasting state. But it can be inferred that the liver metabolism of ALA to n-3 LCPUFAs was enhanced in the FLM-N and SDG-N groups. After the intake of flaxseed oil nanoemulsion, the levels of ALA (+2.49-6.24-fold), EPA (0→12.95-20.5 μg / g), DPA (0→10.41-12.9 μg / g) and DHA (+1.27-1.57-fold) in the liver of mice were significantly increased. Compared with the Nano-E group, the contents of ALA (+13%), EPA (+11%) and DHA (+10%) in the liver further increased after the intake of SDG-N, indicating that the co-intake of SDG promoted the transport of ALA to the liver and enhanced the metabolic process of its conversion to n-3 LCPUFAs. However, the co-intake of FLM did not significantly affect the levels of ALA and n-3 LCPUFAs in the liver, which may be related to the increase in VLDL secretion from the liver. In addition, the intake of SECO-N significantly reduced the levels of ALA (-45.5%), EPA (-30%) and DPA (-19.3%) in the liver. Combined with the results of serum n-3 PUFAs, the co-intake of SECO may trigger the increased consumption of β-oxidation metabolism in tissues such as liver.

[0079] Example 4: Targeted regulation of liver metabolic enzyme expression by lignans and synergistic mechanism with gut microbiota

[0080] By analyzing the liver transcriptome, Western blot and RT-qPCR, the molecular mechanism of flax lignans regulating ALA conversion was analyzed. FLM significantly up-regulated the expression of Fads2 (+44.7%), Elovl2 / 5 (+15.7% / +24.2%) protein and Elovl5 gene (+23.3%) in the liver, promoting the ALA desaturation and chain elongation metabolic pathways; SDG enhanced the expression of Fads1 / 2 protein (+30.4% / +45.6%) and gene (+34.0% / +43.9%), strengthening the desaturation-driven n-3 LCPUFAs synthesis; SECO simultaneously enhanced the expression of Fads1 / 2 (+37.9% / +24.1%) and Elovl2 / 5 (+30.7% / +11.7%) protein, but significantly up-regulated the β-oxidation rate-limiting enzyme Cpt1a (+45.1%), resulting in a "pro-conversion-increase-consumption" two-way effect (seeFigure 8 ) and intestinal microbiota 16S rDNA sequencing showed that FLM / SDG group significantly increased the abundance of Bacteroidota phylum and beneficial bacteria genera (such as Alloprevotella), reduced Desulfobacterota phylum and hydrogen sulfide-producing bacteria, and globally optimized the ALA conversion environment through the "microbiota-metabolic enzyme" synergistic network (corresponding to Fig. 4). Figures 8-10 ) and intestinal microbiota 16S rDNA sequencing showed that FLM / SDG group significantly increased the abundance of Bacteroidota phylum and beneficial bacteria genera (such as Alloprevotella), reduced Desulfobacterota phylum and hydrogen sulfide-producing bacteria, and globally optimized the ALA conversion environment through the "microbiota-metabolic enzyme" synergistic network (corresponding to Fig. 4).

[0081] Regulation of flax lignans on the expression of ALA metabolic conversion enzyme system to n-3 LCPUFAs

[0082] (Attached Figure 8 : Western Blot results of key enzyme protein expression in mouse liver Fads1 / 2, Elovl2 / 5, etc., showing the differential regulation mechanism of different structural flax lignans on ALA metabolic conversion)

[0083] Results analysis: After ingesting SDG-N or SECO-N, the Fads1 protein expression in mouse liver was up-regulated by 30.4% and 37.9%, respectively. Ingesting FLM-N, SDG-N or SECO-N significantly promoted the expression of Fads2 protein (24.1%-45.6%), indicating that flax lignans could enhance the ALA desaturation process in mouse liver. In addition, after ingesting FLM-N or SECO-N, the expression levels of Elovl2 (+15.7% and +30.7%) and Elovl5 (+24.2% and +11.7%) proteins in mouse liver were significantly increased (p<0.05), indicating that FLM and SECO could positively regulate the ALA chain elongation pathway in mouse liver. Compared with Nano-E group, the expression of Cpt1a protein was significantly increased after ingesting SECO-N, which would exacerbate the fatty acid β-oxidation metabolic process in mouse liver. Therefore, while promoting ALA chain elongation and desaturation, SECO up-regulated β-oxidation to accelerate fatty acid decomposition, which may be the key mechanism leading to the decrease of ALA, EPA and DHA levels in serum and liver of mice in SECO-N group.

[0084] Synergistic regulation of flax lignans on intestinal microbiota optimization and metabolic function improvement

[0085] (Attached Figures 9-10 : 16S rDNA sequencing intestinal microbiota species abundance accumulation chart, functional annotation analysis chart after long-term gavage, showing the synergistic regulation effect of flax lignans on intestinal microenvironment)

[0086] Results analysis: Microbial community analysis showed that the composition of microbial community was significantly different among groups, and the main phyla included Bacteroidota, Firmicutes, Desulfobacterota, Campilobacterota, etc. Compared with the Control group, the abundance of Firmicutes and Desulfobacterota phyla increased, and the abundance of Bacteroidota and Campilobacterota decreased in the NanoE group, indicating that NanoE might interfere with the balance of the intestinal flora by changing the intestinal microenvironment. Compared with the NanoE group, the abundance of Bacteroidota and Campilobacterota phyla increased, and the abundance of Firmicutes and Desulfobacterota decreased in the FLMnanoE group, indicating that FLMnanoE might promote the proliferation of flora related to metabolic balance and reduce the abundance of hydrogen sulfide generating related phyla, which helps to improve the intestinal microecological environment. In addition, the abundance of Bacteroidota phylum increased, and the abundance of Desulfobacterota decreased in the SDGnanoE group and the SECOnanoE group, indicating that these two groups also reduced the generation of harmful metabolites, improved the intestinal metabolic function and immune environment, and showed potential positive health effects.

[0087] At the genus level, compared with the NanoE group, the abundance of Lachnospiraceae and Prevotellaceae increased, and the abundance of Desulfovibrionaceae decreased in the FLMnanoE group, indicating that FLMnanoE reduced the abundance of hydrogen sulfide generating bacteria while enhancing the activity of short-chain fatty acid and fiber metabolism related bacteria, which would be more conducive to improving the intestinal barrier function, reducing the risk of inflammation and promoting intestinal health. At the same time, the abundance of Prevotellacea increased, and the abundance of Desulfovibrionaceae decreased in the SDGnanoE group and the SECOnanoE group, which promoted the intestinal microbial community to change to a more healthy and low inflammation potential ecological state.

[0088] The GO database-based analysis of intestinal flora functional differences showed that the NanoE group up-regulated intracellular transport, lipid transport and metabolism, etc.; the FLMnanoE group up-regulated signal transduction mechanisms and amino acid metabolism, and down-regulated lipid metabolism, etc., thereby enhancing metabolic capacity and response mechanisms; the SDGnanoE group up-regulated cytoskeleton and signal transduction, and down-regulated lipid and nucleotide metabolism, thereby improving structural stability and adaptability; the SECOnanoE group up-regulated energy production and amino acid metabolism, etc., and up-regulated energy and metabolic adaptability. In summary, compared with NanoE, the nanoemulsions added with different structural secoisolariciricinol derivatives can promote or inhibit specific metabolic pathways by regulating the metabolic functions and cellular response capacity of intestinal flora, thereby having beneficial effects on the metabolic health of the host, and the positive regulation effects of FLM and SDG are more significant.

[0089] Multi-level interaction network analysis of secoisolariciricinol derivatives based on the regulation of ALA metabolic conversion along the intestinal-liver axis

[0090] (Attachment Figure 11 : Correlation network analysis diagram of intestinal flora and regulation of ALA metabolic conversion, further analyzing the synergistic regulation of secoisolariciricinol derivatives on the conversion of ALA to n-3 LCPUFAs based on differential intestinal absorption, targeted regulation of liver enzyme expression and optimization of intestinal flora structure)

[0091] Result analysis: The serum ALA content was positively correlated with the serum DHA, liver ALA, EPA, DPA, DHA levels, and flora diversity index (Chao, Sobs), indicating that serum ALA was closely related to changes in its metabolic products in the liver and was also closely related to intestinal flora diversity; at the same time, serum ALA was negatively correlated with Cpt1a protein and Muribaculaceae family, suggesting that it may be negatively regulated by these factors. Further analysis found that serum EPA was positively correlated with serum DHA, liver EPA, DHA, Fads2 protein, Cpt2 protein, Rikenellaceae family, etc., and was negatively correlated with Cpt1a protein and Verrucomicrobiota phylum. Serum DHA was positively correlated with serum ALA, EPA, and liver fatty acid content, Deinococcota phylum, and was negatively correlated with Muribaculaceae and Verrucomicrobiota, indicating that flora diversity and specific flora have a regulatory effect on n-3 PUFA conversion.

[0092] The liver ALA, EPA, DPA, DHA content was positively correlated with serum ALA, DHA levels and bacterial diversity, and negatively correlated with Cpt1a protein and Muribaculaceae. The fatty acid conversion products were negatively correlated with Cpt1a protein and Muribaculaceae, indicating that the two had inhibitory effects in metabolism. Fads2 protein was positively correlated with serum EPA, liver DPA, Prevotellaceae and Bdellovibrionota phylum, Cpt1a was negatively correlated with fatty acid levels and diversity, and Cpt2 protein was positively correlated with serum EPA, Rikenellaceae and Elovl5 gene expression, and negatively correlated with Cpt1a protein expression, indicating that it had alternative regulatory effects in fatty acid transport or oxidation.

[0093] At the level of the bacterial community, Oscillospiraceae family, Rikenellaceae family, Bdellovibrionota phylum, and Deinococcota phylum were positively correlated with fatty acid metabolic conversion products and key conversion proteins, and were potential "pro-conversion bacterial communities"; while Muribaculaceae family, Verrucomicrobiota phylum, and Fusobacteriota phylum were mostly negatively correlated with fatty acid metabolic products and Fads1 / Fads2 expression, suggesting that they might have metabolic antagonistic functions. Microbial diversity indices (Shannon, Chao, Sobs) were positively correlated with fatty acid content, metabolic factors and dominant bacterial community, suggesting that the ecological stability of the bacterial community was an important supporting factor for the efficient conversion of ALA. Therefore, the current results suggest that lignan may regulate the metabolic conversion of ALA by affecting host gene expression and regulating the composition of the bacterial community.

[0094] Example 5: Analysis of lignan characteristic metabolic products and verification of ALA co-incubation cell level

[0095] To analyze the metabolic pathway of flax lignans in the intestine-liver axis of mice by in vivo metabolic study, and to elucidate the material basis of ALA metabolic transformation regulated by flax lignans by combining in vitro co-incubation experiments of ALA-lignan characteristic metabolites in HepG2 cells. The results showed that FLM only underwent a small amount of depolymerization and simultaneous deglycosylation in the gastrointestinal tract, and the product mainly reached the liver as ENL(64.7%-93.8%). SDG(52.9%-57.5%-16.1%) and SECO(57.1%-70.3%-23.5%) can be directly absorbed and further metabolized to mainly END and ENL. HepG2 cell co-incubation experiments showed that after co-incubation of SDG(100 μM) and ALA for 48 h, the conversion efficiency of ALA to ETA(20:4n-3) was increased by 48.1%(p<0.05), and the intracellular ALA uptake was not affected. ENL(100 μM) increased the intracellular ALA content by 23.1% and the accumulation of 20:3n-3 by 48.6%, but inhibited the generation of ETA. SECO increased the intracellular transport of ALA but did not significantly promote the conversion. The results showed that SDG may be the core substance for directly regulating the conversion of ALA, and ENL may indirectly participate in metabolic regulation by affecting substrate accumulation or liver metabolism. Figures 12-12 )。

[0096] Metabolic analysis of flax lignans in the liver of mice based on nanoemulsion delivery system

[0097] (appendix Figure 13 : Quantitative analysis of characteristic metabolites of flax lignans in mice under nanoemulsion delivery system, revealing the characteristic metabolites of flax lignans in the liver)

[0098] Experimental design: Mice were randomly divided into 4 groups, 20 in each group, and 5 as baseline group. After one week of adaptive feeding, the mice were fasted for 12 h and then administered ① nanoemulsion(NanoE); ② FLM nanoemulsion(FLM-N); ③ SDG nanoemulsion(SDG-N); ④ SECO nanoemulsion(SECO-N), dose 300 μL per mouse. Blood samples and tissues were collected at 1, 3, 6, 12, and 24 h. Serum samples were centrifuged, and tissue samples were frozen in liquid nitrogen and stored at -80℃ for analysis.

[0099] Results analysis: FLM is a macromolecular structure, only a small amount of depolymerization in the gastrointestinal tract, and the released SDG can be simultaneously deglycosylated to generate SECO. The early stage enters the liver, and the remaining part is metabolized by intestinal microorganisms. No SDG was detected in the liver, and the main metabolite was ENL (64.7%-93.8%). SDG and SECO have a fast absorption, metabolism, and transport rate, and can be absorbed into the liver in small amounts at the initial stage. SDG exists as a parent substrate in the liver at 1-6h (52.9%-57.5%-16.1%), and is enzymatically generated as SECO. The liver accounts for 6.8%-43.3%-23.0% at 3-12h, and the rest reaches the liver after generating END and ENL in the intestine. ENL accounts for 32.0%-45.2%. SECO can reach the liver within 1h, and the parent substrate (57.1%-70.3%-23.5%) is generated as END and ENL in the liver at 1-24h. The liver accounts for 23.4%-59.1%. Different structural lignans have different metabolic pathways in mice. SDG, SECO, END, and ENL are the main characteristic metabolites.

[0100] Analysis of the results of in vitro HepG2 cell co-incubation of lignan characteristic metabolite ALA

[0101] (Attachment ​ : Fatty acid quantitative analysis after in vitro HepG2 cell co-incubation of lignan characteristic metabolite ALA, to determine the lignan material basis for regulating ALA metabolic transformation)

[0102] Experimental scheme: HepG2 cells were cultured in DMEM medium containing 10% FBS at 37°C in a 5% CO2 environment, and the experiment was performed after the cells were fused to 80%. The preparation method of the ALA-BSA complex used was as follows: ALA was dissolved in 1M NaOH to prepare a stock solution; FFA-free BSA was dissolved in serum-free DMEM, and the ALA stock solution was added dropwise, vortexed, and then nitrogen was added. After incubation at 37°C for 2h, the ALA-BSA complex with a molar ratio of 3:1 (ALA 1mM, BSA 0.33mM) was prepared by filtering through a 0.22μm filter membrane. The lignan stock solution was dissolved in DMSO. The cells were cultured in DMEM medium containing ALA (100μM) and lignan (100μM) for 48h, and the samples were collected for lipid extraction and fatty acid determination.

[0103] Results analysis: Intracellular fatty acid determination showed that ALA and its conversion products (20:3n-3 and 20:4n-3) were monitored in the ALA supplemented group. Co-incubation with SDG, SECO and END did not significantly change the intracellular ALA content compared to the ALA control group, while co-incubation with ENL increased the intracellular ALA content by 23.1% (p<0.05). Co-incubation with SDG decreased the 20:3n-3 content by 11.8% compared to the ALA control group, co-incubation with END increased the 20:3n-3 content by 11.2% (not significant), and co-incubation with ENL increased the 20:3n-3 content by 48.6% (p<0.05). 20:4n-3 (ETA) quantification showed that co-incubation with SDG increased the ETA content by 48.1% (p<0.05) compared to the ALA control group, co-incubation with SECO increased the ETA content by 9.2% (not significant), and no ETA was detected in the ENL co-incubation group. ALA quantification in the culture medium showed that co-incubation with SDG and END did not significantly change the ALA content compared to the ALA control group. Co-incubation with SECO and ENL significantly decreased the ALA content in the culture medium (p<0.05), by 10.2% in the SECO group and by 40.1% in the ENL group.

[0104] Combining the culture medium and intracellular content analysis: SDG did not affect ALA uptake, but promoted the simultaneous conversion of ALA to 20:3n-3 and ETA; SECO promoted ALA cellular uptake, but had limited effect on the conversion of ALA to ETA; END did not affect ALA intracellular transport and metabolic conversion; ENL significantly increased ALA cellular uptake, promoted the conversion and accumulation of ALA to 20:3n-3, but limited the conversion of 20:3n-3 to ETA. The results showed that the characteristic metabolites of flax lignan played different roles in regulating the conversion process of ALA. SDG might be an effective material basis for regulating the metabolic conversion of ALA, and SECO and ENL might mediate the regulation through multiple pathways.

[0105] The above description of disclosed embodiments allows a person skilled in the art to implement or use the present application. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to these embodiments shown herein, but will accord with the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A flax polyphenol composition for regulating the absorption and metabolic conversion of α-linolenic acid, characterized in that, Comprise the following components: Any one or more of the following components: flax lignan macromolecule FLM, secoisolaricic acid resinol diglucoside SDG, or secoisolaricic acid resinol SECO.

2. The flax polyphenol composition of claim 1, characterized in that, The flax polyphenol composition further comprises flaxseed oil and PBS buffer; The flaxseed oil in the composition is 20wt%, and the ALA in the flaxseed oil is ≥50%; The PBS buffer contains 3wt% sunflower phospholipid, and the pH is 7.0; The final concentration of flax polyphenols in the composition is 300-1500μmol / L.

3. Use of the flax polyphenol composition according to claim 1 for the manufacture of a health food, characterized in that, The composition can be developed into high-end functional oil food, n-3 fatty acid nutritional supplement, brain health / cardiovascular health / vision protection health food, which can improve the endogenous generation capacity of EPA and DHA in human body and improve the current situation of insufficient intake of n-3 LCPUFAs.

4. Use of the flax polyphenol composition according to claim 1 for the manufacture of a food for special medical purposes, characterized in that, It is suitable for the special nutritional needs of pregnant and infant, children, adolescents, the elderly, sub-health and patients with chronic diseases. The chronic diseases include hyperlipidemia, diabetes, cardiovascular and cerebrovascular diseases, cognitive impairment, etc. The population also includes people with limited n-3 fatty acid intake, such as people sensitive to seafood, people allergic to seafood, and vegetarians.

5. Use of the flax polyphenol composition according to claim 1 for promoting intestinal health and intervening in the intestinal microflora, characterized in that, By optimizing the structure of intestinal flora, increasing the abundance of beneficial flora, and reducing the generation of pathogenic bacteria and harmful metabolites, intestinal health products, microecological regulators, and functional foods containing prebiotics can be developed.

6. Use of flax polyphenol composition according to claim 1 in the industrial valorization of bioactive oils, characterized in that, Promote the high-value deep processing and whole industry chain development of flaxseed and other agricultural products rich in ALA, improve the functional utilization of by-products such as flaxseed hull and meal, and promote the sustainable circulation of oil resources.

7. Use of the flax polyphenol composition according to claim 1 in scientific research and health engineering, characterized in that, Provide theoretical basis and practical tools for basic and applied research on lipid metabolism mechanism, functional lipid delivery, and natural polyphenol synergistic nutritional intervention, etc.

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