Use of water-soluble tomato extract in the preparation of a hypolipidemic composition

Abstract

The application discloses application of a water-soluble tomato extract in preparation of a blood lipid-lowering composition, and belongs to the technical field of functional food, and comprises the following components in mass parts: water-soluble tomato extract 50-100 parts, morchella esculenta extract 30-50 parts, catalpa seed extract 20-30 parts, ampelopsis grossedentata extract 5-10 parts, bitter gourd extract 5-10 parts, green tea extract 5-10 parts, rye ferment 20-30 parts and white kidney bean extract 10-20 parts. The application takes the water-soluble tomato extract as a main raw material, and is compounded with various plant extracts which are edible and medicinal, and each component plays a synergistic role in three levels of intestinal tract, cells and organs to reduce blood lipid level. The application solves the problem that in the prior art, due to single action target point of blood lipid-lowering products and side effect risk, it is difficult to realize multi-target point synergistic regulation of blood lipid and the safety is limited, and has application potential in preparation of blood lipid-lowering functional food.

Description

Technical Field

[0001] This invention relates to the field of functional food technology, specifically to the application of water-soluble tomato extract in the preparation of lipid-lowering compositions. Background Technology

[0002] Hyperlipidemia is a group of diseases characterized by elevated lipid levels in the body due to genetic or acquired factors, and it is very common worldwide. Blood lipids mainly include cholesterol, lipoproteins, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), apolipoproteins, and high-density lipoprotein (HDL). Studies have shown that excessively high levels of LDL cholesterol significantly increase the risk of atherosclerotic plaque formation, leading to vascular disease. In contrast, HDL cholesterol helps regulate cholesterol balance, prevents lipid metabolism disorders, and thus reduces the risk of atherosclerotic vascular disease.

[0003] Tomatoes are a common vegetable containing a large amount of water-soluble saponins. Tomato saponins have the ability to maintain lipid metabolism balance, scavenge free radicals, and prevent lipid peroxidation in the liver. Tomato saponins can be divided into tomato saponin A and tomato saponin B. Tomato saponin A is the main saponin component in tomatoes. Pharmacological activity studies have shown that tomato saponin A and its aglycone are good inhibitors of acyl-CoA-cholesterol acyltransferase, and can inhibit the formation of foam cells in vitro. Existing technology CN101804122A discloses a tomato water-soluble saponin extract. Results showed that after high-dose administration of tomato total saponins to rats for 30, 45, and 60 days, the serum TC, TG, and LDL-C levels in rats were significantly lower than those in the high-lipidemia model group, indicating that tomato total saponins have a good lipid-regulating effect. Therefore, tomato saponins in water-soluble tomato extracts are promising lipid-lowering compounds with the potential for preparing lipid-lowering functional foods. Summary of the Invention

[0004] Therefore, this invention provides the application of water-soluble tomato extract in the preparation of lipid-lowering compositions to solve the problem in the prior art that it is difficult to achieve multi-target synergistic regulation of blood lipids and the safety is limited due to the single target of lipid-lowering products and the risk of side effects.

[0005] To achieve the above objectives, the present invention provides the following technical solution: According to a first aspect of the present invention, a water-soluble tomato extract lipid-lowering composition is provided, comprising the following components in parts by weight: 50-100 parts of water-soluble tomato extract, 30-50 parts of *Polygonum multiflorum* extract, 20-30 parts of *Citrus aurantium* extract, 5-10 parts of *Tea japonica* extract, 5-10 parts of bitter melon extract, 5-10 parts of green tea extract, 20-30 parts of rye ferment, and 10-20 parts of white kidney bean extract.

[0006] Furthermore, the method for preparing the composition includes the following steps: Weigh each component separately according to the proportion and mix them to obtain a mixture. Add 20-30% of the mass of the mixture to deionized water and put it into a mixer. Mix at 15-20 rpm at 20-30℃ for 30-45 minutes until the mixture is uniform and then pass it through a 200-mesh sieve.

[0007] Furthermore, the preparation method of the water-soluble tomato extract includes the following steps: S1. After washing the tomatoes with clean water, crush them, separate the skin and seeds, press and centrifuge to obtain tomato juice; S2. The tomato juice in S1 is enzymatically hydrolyzed and the enzymes are then inactivated to obtain tomato hydrolysate; S3. Pass the tomato enzymatic hydrolysate through a microfiltration membrane with a pore size of 0.1-1μm to remove suspended particles and obtain microfiltered tomato juice. S4. Microfiltration of tomato juice through an ultrafiltration membrane with a pore size of 0.001-0.1μm removes macromolecular substances, resulting in ultrafiltration tomato juice. S5. Nanofiltration is performed on the ultrafiltration tomato juice using a 1-3 nm nanofiltration membrane to separate and remove components smaller than 500 Da, resulting in a retentate direct flow solution. S6. Concentrate and spray-dry the retained liquid to obtain a water-soluble tomato extract.

[0008] Furthermore, step S2 specifically includes the following steps: S201, Enzymatic hydrolysis: Add 0.04-0.1% of hydrolytic enzyme by weight of tomato juice to the tomato juice, gradually raise the temperature to 45-55℃, and hydrolyze for 1-1.5 hours to obtain the hydrolysate. S202, enzyme inactivation: The resulting enzyme hydrolysate was heated to 90-95℃ and kept at that temperature for 15-20 minutes to inactivate the enzyme.

[0009] Further, the hydrolytic enzyme mentioned in step S201 is one or more of phytase, cellulase, pectinase, xylanase and β-glucosidase.

[0010] Furthermore, the preparation method of the *Porcini mushroom* extract includes the following steps: S1. Take dried pig stomach mushrooms, crush them, and pass them through a 40-mesh sieve to obtain pig stomach mushroom powder; S2. Mix the *Polygonum multiflorum* powder with deionized water at a mass-to-volume ratio of 1g:20mL, and stir at 90-100℃ and 200-300rpm for 2-3 hours to obtain *Polygonum multiflorum* aqueous extract. S3. Let the water extract of *Stachys edulis* cool naturally to room temperature, adjust the pH to 4.5-5.0, add 0.5-1% acidic protease (by weight of the water extract of *Stachys edulis*), and enzymatically hydrolyze at 50℃ for 2-3 hours. After the enzymatic hydrolysis is completed, raise the temperature to 90℃ and continue the reaction for 10 minutes to inactivate the enzyme, thus obtaining the enzymatic hydrolysate of *Stachys edulis*. S4. Centrifuge the pig stomach mushroom enzymatic hydrolysate at 12000 rpm for 20 min at 4℃, take the supernatant, and ultrafilter it with a 100 kDa ultrafiltration membrane to remove small molecule impurities. S5. Add ethanol to the ultrafiltered *Stachys amurensis* enzymatic hydrolysate from S4, and let it stand at 4°C for 12-24 hours. The volume ratio of the ultrafiltered *Stachys amurensis* enzymatic hydrolysate to ethanol is 1:4. After standing, centrifuge at 10,000 rpm, collect the precipitate, wash it three times with deionized water, concentrate and spray dry to obtain *Stachys amurensis* extract.

[0011] Furthermore, the method for preparing the rye ferment includes the following steps: S1. After cleaning the rye grains, dry them at 60-70℃ for 2-4 hours, then grind them through a 40-mesh sieve using a hammer mill to obtain coarse rye flour. S2. Mix rye coarse flour with deionized water at a mass-volume ratio of 1g:(8-10)mL, stir evenly to form a slurry, and obtain rye slurry. S3. Adjust the pH of the rye slurry to 6.0, heat it in a 95℃ water bath for 30 minutes for gelatinization and pasteurization, and then quickly cool it to below 30℃ to obtain rye gelatinized liquid. S4. Inoculate with a compound fermentation strain obtained by mixing *Lactobacillus plantarum* and *Saccharomyces cerevisiae* at a 1:1 ratio, with a total inoculum size of 1×10⁻⁶. 6 CFU / mL rye gelatinized liquid; after inoculation, place in a constant temperature fermentation tank and let it ferment at 30℃ for 60-72 hours. S5. After fermentation, the fermentation broth is heated to 80℃ and held for 15 minutes to terminate microbial activity and sterilize. After sterilization, the fermentation broth is centrifuged at 8000-10000 rpm for 20 minutes at 4℃. The supernatant is collected, concentrated under reduced pressure at 40-50℃, and spray-dried to obtain rye fermentation product.

[0012] Furthermore, the extraction method of the bitter melon extract includes the following steps: S1. Remove the seeds and pith from the fresh bitter melon and break it into small pieces of 1-2cm. After rinsing with water, press and filter to obtain bitter melon juice. S2. Mix bitter melon juice with deionized water at a volume ratio of 1:(5-8), adjust the pH to 5.0-8.0, add 0.1-0.3% of bitter melon hydrolytic enzyme by weight of the mixture, and hydrolyze at 40-50℃ for 1-2 hours. After the hydrolysis is completed, raise the temperature to 90-95℃ to inactivate the enzyme and obtain bitter melon hydrolysate. S3. Microfilter the bitter gourd enzymatic hydrolysate with a filter membrane with a pore size of 0.1-0.2 μm to remove macromolecular fibers and collect the permeate; S4. Ultrafiltration of the permeate to retain components with a molecular weight of 1000-5000 Da, and collection of bitter gourd retaining permeate; S5. After concentrating the bitter melon intercepted direct flow liquid, spray dry to obtain bitter melon extract.

[0013] Furthermore, in step S2 of the bitter melon extract extraction method, the bitter melon hydrolytic enzyme is one or more of pectinase, cellulase, and xylanase.

[0014] According to a second aspect of the present invention, the application of a water-soluble tomato extract lipid-lowering composition in the preparation of lipid-lowering functional foods is provided.

[0015] The present invention has the following advantages: 1. Water-soluble tomato extract: The main component is tomato saponins, which contain a large number of phenolic hydroxyl groups. These saponins can scavenge free radicals, reduce systemic chronic low-grade inflammation, improve the pathological basis of insulin resistance, and affect cholesterol metabolism and transport, thereby improving the cellular microenvironment. Simultaneously, tomato saponins can effectively reduce the synthesis of total cholesterol and triglycerides by activating the AMPK signaling pathway and upregulate LDL receptor expression in hepatocytes, promoting the metabolism of low-density cholesterol.

[0016] 2. Pig stomach mushroom extract: It is rich in β-glucan, which regulates immune balance, can also scavenge free radicals, reduce oxidative stress, and has a clear liver-protecting effect, ensuring the balance of lipid synthesis, decomposition and transport.

[0017] 3. Catalpa fruit extract: The main component is catalpa alcohol, which can regulate the NF-κB signaling pathway by inhibiting the activation of nuclear transcription factor-κB, downregulating the expression of its downstream inflammatory factors such as macrophage chemokine-1, and reducing the inflammatory response of the vascular wall; and activating Nrf2 and its downstream heme oxygenase 1, enhancing the body's antioxidant capacity, reducing the levels of reactive oxygen species and malondialdehyde in the blood, while increasing the activity of superoxide dismutase (SOD) and reducing the level of oxidized low-density lipoprotein, thus reducing its damage to the vascular endothelium.

[0018] 4. The components work synergistically at the gut, cellular, and organ levels, achieving comprehensive regulation of glucose and lipid metabolism disorders through a three-dimensional network of source blocking, environmental repair, and organ support. Detailed Implementation

[0019] The following specific embodiments illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] According to a first aspect of the present invention, a water-soluble tomato extract lipid-lowering composition is provided, comprising the following components in parts by weight: 50-100 parts of water-soluble tomato extract, 30-50 parts of *Polygonum multiflorum* extract, 20-30 parts of *Citrus aurantium* extract, 5-10 parts of *Tea japonica* extract, 5-10 parts of bitter melon extract, 5-10 parts of green tea extract, 20-30 parts of rye ferment, and 10-20 parts of white kidney bean extract.

[0021] The preparation method of the composition includes the following steps: Weigh each component separately according to the proportion and mix them to obtain a mixture. Add 20-30% of the mass of the mixture to deionized water and put it into a mixer. Mix at 15-20 rpm at 20-30℃ for 30-45 minutes until the mixture is uniform and then pass it through a 200-mesh sieve.

[0022] The preparation method of water-soluble tomato extract includes the following steps: S1. After washing the tomatoes with clean water, crush them, separate the skin and seeds, press and centrifuge to obtain tomato juice; S2. The tomato juice in S1 is enzymatically hydrolyzed and the enzymes are then inactivated to obtain tomato hydrolysate; S3. Pass the tomato enzymatic hydrolysate through a microfiltration membrane with a pore size of 0.1-1μm to remove suspended particles and obtain microfiltered tomato juice. S4. Microfiltration of tomato juice through an ultrafiltration membrane with a pore size of 0.001-0.1μm removes macromolecular substances, resulting in ultrafiltration tomato juice. S5. Nanofiltration is performed on the ultrafiltration tomato juice using a 1-3 nm nanofiltration membrane to separate and remove components smaller than 500 Da, resulting in a retentate direct flow solution. S6. Concentrate and spray-dry the retained liquid to obtain a water-soluble tomato extract.

[0023] Step S2 specifically includes the following steps: S201, Enzymatic hydrolysis: Add 0.04-0.1% of hydrolytic enzyme by weight of tomato juice to the tomato juice, gradually raise the temperature to 45-55℃, and hydrolyze for 1-1.5 hours to obtain the hydrolysate. S202, enzyme inactivation: The resulting enzyme hydrolysate was heated to 90-95℃ and kept at that temperature for 15-20 minutes to inactivate the enzyme.

[0024] In step S201, the hydrolytic enzyme is one or more of phytase, cellulase, pectinase, xylanase, and β-glucosidase.

[0025] The preparation method of *Porcini mushroom* extract includes the following steps: S1. Take dried pig stomach mushrooms, crush them, and pass them through a 40-mesh sieve to obtain pig stomach mushroom powder; S2. Mix the *Polygonum multiflorum* powder with deionized water at a mass-to-volume ratio of 1g:20mL, and stir at 90-100℃ and 200-300rpm for 2-3 hours to obtain *Polygonum multiflorum* aqueous extract. S3. Let the water extract of *Stachys edulis* cool naturally to room temperature, adjust the pH to 4.5-5.0, add 0.5-1% acidic protease (by weight of the water extract of *Stachys edulis*), and enzymatically hydrolyze at 50℃ for 2-3 hours. After the enzymatic hydrolysis is completed, raise the temperature to 90℃ and continue the reaction for 10 minutes to inactivate the enzyme, thus obtaining the enzymatic hydrolysate of *Stachys edulis*. S4. Centrifuge the pig stomach mushroom enzymatic hydrolysate at 12000 rpm for 20 min at 4℃, take the supernatant, and ultrafilter it with a 100 kDa ultrafiltration membrane to remove small molecule impurities. S5. Add ethanol to the ultrafiltered *Stachys amurensis* enzymatic hydrolysate from S4, and let it stand at 4°C for 12-24 hours. The volume ratio of the ultrafiltered *Stachys amurensis* enzymatic hydrolysate to ethanol is 1:4. After standing, centrifuge at 10,000 rpm, collect the precipitate, wash it three times with deionized water, concentrate and spray dry to obtain *Stachys amurensis* extract.

[0026] The preparation method of rye fermentation product includes the following steps: S1. After cleaning the rye grains, dry them at 60-70℃ for 2-4 hours, then grind them through a 40-mesh sieve using a hammer mill to obtain coarse rye flour. S2. Mix rye coarse flour with deionized water at a mass-volume ratio of 1g:(8-10)mL, stir evenly to form a slurry, and obtain rye slurry. S3. Adjust the pH of the rye slurry to 6.0, heat it in a 95℃ water bath for 30 minutes for gelatinization and pasteurization, and then quickly cool it to below 30℃ to obtain rye gelatinized liquid. S4. Inoculate with a compound fermentation strain obtained by mixing *Lactobacillus plantarum* and *Saccharomyces cerevisiae* at a 1:1 ratio, with a total inoculum size of 1×10⁻⁶. 6 CFU / mL rye gelatinized liquid; after inoculation, place in a constant temperature fermentation tank and let it ferment at 30℃ for 60-72 hours. S5. After fermentation, the fermentation broth is heated to 80℃ and held for 15 minutes to terminate microbial activity and sterilize. After sterilization, the fermentation broth is centrifuged at 8000-10000 rpm for 20 minutes at 4℃. The supernatant is collected, concentrated under reduced pressure at 40-50℃, and spray-dried to obtain rye fermentation product.

[0027] The extraction method for bitter melon extract includes the following steps: S1. Remove the seeds and pith from the fresh bitter melon and break it into small pieces of 1-2cm. After rinsing with water, press and filter to obtain bitter melon juice. S2. Mix bitter melon juice with deionized water at a volume ratio of 1:(5-8), adjust the pH to 5.0-8.0, add 0.1-0.3% of bitter melon hydrolytic enzyme by weight of the mixture, and hydrolyze at 40-50℃ for 1-2 hours. After the hydrolysis is completed, raise the temperature to 90-95℃ to inactivate the enzyme and obtain bitter melon hydrolysate. S3. Microfilter the bitter gourd enzymatic hydrolysate with a filter membrane with a pore size of 0.1-0.2 μm to remove macromolecular fibers and collect the permeate; S4. Ultrafiltration of the permeate to retain components with a molecular weight of 1000-5000 Da, and collection of bitter gourd retaining permeate; S5. After concentrating the bitter melon intercepted direct flow liquid, spray dry to obtain bitter melon extract.

[0028] In step S2 of the bitter melon extract extraction method, the bitter melon hydrolytic enzyme is one or more of pectinase, cellulase, and xylanase.

[0029] To better illustrate the inventiveness of this invention, the following embodiments and comparative examples are provided.

[0030] Example 1 S1. Preparation of water-soluble tomato extract: a. After washing the tomatoes with clean water, crush them, separate the skin and seeds, press them, and centrifuge them at 3000 rpm for 10 minutes to obtain tomato juice; b. After enzymatic hydrolysis of the tomato juice, the enzymes are inactivated to obtain tomato enzymatic hydrolysate. This process includes the following steps: b01, Enzymatic hydrolysis: Add 2.0g of pectinase to 2000mL of tomato juice, gradually raise the temperature to 50℃, and hydrolyze for 1.5h to obtain tomato hydrolysate; b02, enzyme inactivation: The obtained enzyme hydrolysate was heated to 90℃ and kept at that temperature for 15 minutes to inactivate the enzyme. c. Pass the enzyme-inactivated tomato hydrolysate through a microfiltration membrane with a pore size of 0.1 μm to remove suspended particles and obtain microfiltered tomato juice; d. Microfiltration of tomato juice is performed by passing it through an ultrafiltration membrane with a pore size of 0.01 μm to remove macromolecular substances, resulting in ultrafiltration tomato juice; e. Nanofiltration of ultrafiltration tomato juice was performed using a 0.001 μm nanofiltration membrane to separate and remove components smaller than 500 Da, resulting in a retentate stream. f. Concentrate and spray-dry the retained liquid to obtain a water-soluble tomato extract; S2. Preparation of *Polygonum multiflorum* extract: a. Take 100g of dried pig stomach mushrooms, crush them, and pass them through a 40-mesh sieve to obtain pig stomach mushroom powder; b. Mix 80g of *Polygonum multiflorum* powder with 1600mL of deionized water and stir at 250rpm for 3 hours at 95℃ to obtain *Polygonum multiflorum* water extract. c. Let 1500mL of *Stachys edulis* aqueous extract cool to room temperature, adjust the pH to 5.0, add 15g of acidic protease, and hydrolyze at 50℃ for 3h. After hydrolysis, raise the temperature to 90℃ and continue the reaction for 10min to inactivate the enzyme, and obtain *Stachys edulis* hydrolysate. d. Centrifuge the *Porcini* enzymatic hydrolysate at 12000 rpm for 20 min at 4℃, collect the supernatant, and ultrafilter it using a 100 kDa ultrafiltration membrane to remove small molecule impurities; e. Add ethanol to the ultrafiltered *Scutellaria baicalensis* hydrolysate in S4, let stand at 4°C for 12 h, the volume ratio of the ultrafiltered *Scutellaria baicalensis* hydrolysate to ethanol is 1:4; after standing, centrifuge at 10000 rpm, collect the precipitate, wash with deionized water 3 times, concentrate and spray dry to obtain *Scutellaria baicalensis* extract. S3. Preparation of rye fermentation product: a. After cleaning the rye grains, dry them at 65℃ for 3 hours, then grind them through a 40-mesh sieve using a hammer mill to obtain coarse rye flour; b. Mix 50g of coarse rye flour with 500mL of deionized water and stir until a paste is formed to obtain rye slurry; c. Adjust the pH of the rye slurry to 6.0, heat it in a 95℃ water bath for 30 minutes for gelatinization and pasteurization, and then quickly cool it to below 30℃ to obtain rye gelatinized liquid. d. Inoculate with 1 mL of a compound fermentation culture obtained by mixing *Lactobacillus plantarum* and *Saccharomyces cerevisiae* at a 1:1 ratio, with a total inoculum of 1 × 10⁻⁶. 6 CFU / mL rye gelatinized liquid; after inoculation, it was placed in a constant temperature fermentation tank and allowed to ferment at 30℃ for 72 hours. e. After fermentation, the fermentation broth is heated to 80℃ and held for 15 minutes to terminate microbial activity and sterilize; after sterilization, the fermentation broth is centrifuged at 10,000 rpm for 20 minutes at 4℃, the supernatant is collected, concentrated under reduced pressure at 45℃, and spray-dried to obtain rye fermentation product. S4. The extraction method of bitter melon extract includes the following steps: a. Remove the seeds and pith from the fresh bitter melon, break it into 2cm pieces, wash it with water, squeeze it, and filter it to obtain bitter melon juice; b. Mix 50 mL of bitter melon juice with 300 mL of deionized water, adjust the pH to 7.0, add 0.7 g of pectinase, and enzymatically hydrolyze at 45 °C for 2 h. After the enzymatic hydrolysis is completed, raise the temperature to 95 °C to inactivate the enzyme and obtain bitter melon enzymatic hydrolysate. c. Microfilter the enzyme-inactivated bitter melon hydrolysate with a 0.2 μm pore size filter membrane to remove macromolecular fibers and collect the permeate; d. Ultrafiltration of the permeate to retain components with a molecular weight of 3000 Da, and collection of bitter gourd retaining permeate; e. After concentrating the bitter melon intercepted direct flow solution, spray dry to obtain bitter melon extract; S5. Weigh out 100g of water-soluble tomato extract, 50g of *Polygonum multiflorum* extract, 30g of *Zanthoxylum bungeanum* extract (purchased from Shaanxi Xintianyu Biotechnology Co., Ltd.), 5g of *Zanthoxylum bungeanum* extract (purchased from Xi'an Tianfeng Biotechnology Co., Ltd.), 5g of bitter melon extract, 5g of green tea extract (purchased from Shanyang Lianfeng Biotechnology Co., Ltd.), 20g of rye fermentation product, and 15g of white kidney bean extract (purchased from Lanzhou Waterles Biotechnology Co., Ltd.), mix them separately, add 57.5mL of deionized water, put them into a mixer, mix at 25℃ and 20rpm for 30min until the mixture is uniform, and pass through a 200-mesh sieve.

[0031] Example 2 This embodiment is based on Example 1, except that the mass of each component added is as follows: 50g of water-soluble tomato extract, 50g of *Polygonum multiflorum* extract, 30g of *Citrus aurantium* extract, 10g of *Tea japonica* extract, 10g of bitter melon extract, 10g of green tea extract, 20g of rye ferment, and 15g of white kidney bean extract. These components are weighed and mixed, and 48.75mL of deionized water is added. All other specific parameters are the same as in Example 1.

[0032] Example 3 This embodiment is based on Example 1, except that the mass of each component added is as follows: 50g of water-soluble tomato extract, 50g of *Polygonum multiflorum* extract, 30g of *Citrus aurantium* extract, 5g of *Tea japonica* extract, 5g of bitter melon extract, 5g of green tea extract, 30g of rye ferment, and 20g of white kidney bean extract. After weighing, they are mixed and 48.75mL of deionized water is added. The other specific parameters are the same as in Example 1.

[0033] Comparative Example 1 This comparative example is based on Example 1, except that the mass of each component added is as follows: 50g of *Stachys aurea* extract, 30g of *Citrus aurantium* extract, 5g of *Tea japonica* extract, 5g of bitter melon extract, 5g of green tea extract, 20g of rye ferment, and 15g of white kidney bean extract. After weighing, they are mixed and 32.5mL of deionized water is added. That is, tomato extract is not added. The other specific parameters are the same as in Example 1.

[0034] Comparative Example 2 This comparative example is based on Example 1, except that the mass of each component added is as follows: 100g of water-soluble tomato extract, 50g of *Polygonum multiflorum* extract, 30g of *Citrus aurantium* extract, 5g of bitter melon extract, 20g of rye ferment, and 15g of white kidney bean extract. These components were weighed separately, mixed, and 55mL of deionized water was added. That is, vine tea extract and green tea extract were not added. All other specific parameters are the same as in Example 1.

[0035] Comparative Example 3 This comparative example is based on Example 1, except that the mass of each component added is as follows: 100g of water-soluble tomato extract, 5g of vine tea extract, 5g of bitter melon extract, 5g of green tea extract, 20g of rye ferment, and 15g of white kidney bean extract. These components were weighed separately, mixed, and 37.5mL of deionized water was added. That is, no *Stachys aurea* extract or *Zanthoxylum bungeanum* extract was added. All other specific parameters are the same as in Example 1.

[0036] Comparative Example 4 This comparative example is based on Example 1, except that the mass of each component added is as follows: 100g of water-soluble tomato extract, 50g of *Polygonum multiflorum* extract, 30g of *Citrus aurantium* extract, 5g of *Tea japonica* extract, 5g of bitter melon extract, and 5g of green tea extract. These components were weighed separately, mixed, and 48.75mL of deionized water was added. That is, no rye fermentation product or white kidney bean extract was added. All other specific parameters are the same as in Example 1.

[0037] Test Example 1 After thawing, passage, and plating, HepG-2 cells (purchased from Shanghai Yongchuan Biotechnology Co., Ltd.) were incubated at 37°C for 30 min with 100 mM recombinant human insulin (purchased from Beijing Zhihe Xinchuang Biotechnology Co., Ltd.). Then, the concentration of the compound was increased to 400 μg / mL, and the cells were incubated at 37°C for 1 h. Finally, 50 μM 2-NbdG (purchased from Shanghai Maokang Biotechnology Co., Ltd.) was added, and the cells were incubated at 37°C for 1 h. After incubation, the culture medium was removed, and the cells were washed twice with PBS buffer. After digestion with 1 mL of trypsin-EDTA solution, culture medium was added to obtain a single-cell suspension, which was transferred to a centrifuge tube and centrifuged at 1000 rpm for 5 min. The supernatant was discarded, and the cells were centrifuged again, repeated three times. HepG-2 cells were collected in flow cytometry tubes, and fluorescence intensity was measured by flow cytometry. The fluorescence intensity comparison value was calculated using the formula: The higher the contrast value of fluorescence intensity, the stronger the cell's glucose uptake capacity and the better the hypoglycemic effect. HepG-2 cells without the added composition were used as a control group. The contrast values ​​of fluorescence intensity for each group are shown in Table 1.

[0038] Table 1 Comparison of fluorescence intensity values ​​for each group

[0039] As can be seen, the fluorescence intensity contrast values ​​of the example groups were significantly higher than those of the comparative groups. Among them, the composition prepared in Example 1 exhibited the highest fluorescence intensity contrast value of 0.89, indicating that HepG-2 cells had the strongest glucose uptake capacity. Compared with Example 1, the fluorescence intensity contrast values ​​of Comparative Examples 1-4 decreased by 0.58, 0.44, 0.37 and 0.28, respectively, indicating that the water-soluble tomato extract is the core component of the composition prepared in this invention that promotes glucose uptake by cells, while the other components play a synergistic role.

[0040] Test Example 2 The high-fat cell culture medium consisted of DMEM medium supplemented with 500 μmol / L sodium oleate and 250 μmol / L sodium palmitate. HepG-2 cells were treated with 0.25% trypsin and then transferred to culture dishes. The blank control group and the model group were cultured in basal DMEM medium and high-fat medium, respectively, at 37°C and 5% CO2 for 24 h. The sample groups were first cultured in high-fat medium at 37°C and 5% CO2 for 24 h, and then 100 μg / mL of the composition was added, followed by another 24 h of culture.

[0041] After HepG-2 cell culture, the culture medium was discarded. Cells were washed three times with phosphate-buffered saline (PBS) at 4°C. RIPA lysis buffer was added to each culture dish, and cells were placed on ice for 30 min. The lysis buffer was collected and centrifuged at 10,000 rpm for 10 min at 4°C. The supernatant was collected, and the TC and TG levels were measured using a total cholesterol (TC) and triglyceride (TG) assay kit (purchased from Nanjing Jiancheng Biotechnology Research Institute Co., Ltd.). The results are recorded in Table 2.

[0042] Table 2. TC and TG content in HepG-2 cells

[0043] The TC and TG contents of HepG-2 cells after treatment with the composition prepared in this invention are shown in Table 2. The results indicate that the composition with complete components significantly reduces TC and TG contents in HepG-2 cells by more than 50%, which is significantly better than the comparative groups with missing components. Among them, Example 1 group showed the best lipid-lowering effect, with TC content reduced by 54.7% and TG content reduced by 56.3% compared to the model group, indicating that the water-soluble tomato extract composition with complete components prepared in this invention has a significant lipid-lowering effect. In contrast, the TC contents of Comparative Examples 1-4 were only reduced by 12.3%, 25.1%, 21.2%, and 33.5% respectively, and the TG contents were reduced by 14.1%, 25.5%, 21.4%, and 33.3% respectively, significantly lower than the Example groups, indicating that the components in the composition have a synergistic effect in inhibiting cellular lipid accumulation, with the water-soluble tomato extract playing a core role.

[0044] Test Example 3 To verify the lipid-lowering effect of the water-soluble tomato extract prepared in this invention, rats were selected as animal models for the experiment.

[0045] Male adult SD rats weighing 180-220g were randomly divided into 10 groups of 10 rats each. They were fed a diet (purchased from Beijing Animal Experiment Center) containing 64% carbohydrates, 21% protein, 4% fat, and 5% fiber. The rearing environment was 55±5% relative humidity and 23±2℃. After 7 days of acclimatization, the rats were randomly divided into 10 groups of 10 rats each. The control group was administered 7% Tween 80 by gavage, while the model group was administered fat emulsion by gavage, with fructose water as the sole water source, for 10 weeks. Rats were weighed every 3 days, and the gavage volume was adjusted according to weight changes. The fat emulsion was prepared by mixing 50g lard, 1.5g cholesterol, 0.3g pig bile salts, and 7mL Tween 80, then bringing the volume to 100mL with deionized water. The daily gavage volume of the fat emulsion was calculated using the formula: Calculations. Before gavage, the fat emulsion was diluted to 0.2 mL / 10 g rat body weight to accommodate the gavage volume in rats.

[0046] Meanwhile, rats that were administered simvastatin at a dose of 0.5 mg / kg body weight daily by gavage, and were given fat emulsions and fructose water as the sole water source, served as the positive control group; rats that were administered the compositions prepared in each example and comparative example by gavage at a dose of 0.7 g / kg body weight daily by gavage, and were given fat emulsions and fructose water as the sole water source, served as the experimental group.

[0047] After the modeling was completed, the rats were fasted for 12 hours, weighed, and their eyeballs were enucleated to collect blood. After separating the serum, the levels of total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the rats were detected using a kit.

[0048] After 10 weeks of feeding, the body weight of rats in each group is shown in Table 3, and the blood lipid indicators are shown in Table 4.

[0049] Table 3. Body weight of rats in each group after 10 weeks of feeding.

[0050] Table 4. Blood lipid levels in rats of different groups after 10 weeks of feeding

[0051] As shown in Tables 3 and 4, the rats gained 89.0% more body weight after the model was established. The levels of TC, TG and LDL-C increased to 2.57 mM, 2.36 mM and 2.29 mM, respectively, while HDL-C decreased to 0.64 mM, which is consistent with the physiological characteristics of hyperlipidemic rats, indicating that the model was successfully established.

[0052] Meanwhile, the example groups showed better weight control and lipid stabilization in hyperlipidemic rats compared to the control group. The weight gain rate of rats in Example 1-Example 3 groups was less than 55%, and the LDL-C growth rates compared to the blank group were 61.8%, 68.2%, and 74.5%, respectively, while the total cholesterol growth rates were 66.3%, 73.7%, and 81.1%, respectively, which were close to the positive control group's LDL-C growth rate of 56.4% and total cholesterol growth rate of 61.1%. Among them, Example 1 showed the best weight and lipid control effect, indicating that the composition prepared in this invention can effectively control rat weight and significantly reduce blood lipid levels, and that the appropriate component ratio can effectively regulate rat weight gain and blood lipid elevation.

[0053] Compared with Example 1, the weight gain rates of rats in Comparative Examples 1-4 increased by 40.3%, 27.1%, 25.3%, and 18.8%, respectively. Among them, Comparative Example 1, lacking water-soluble tomato extract, showed the lowest weight control effect and also the lowest lipid control ability among the experimental groups. Compared with the blank group, the levels of TC, TG, and LDL-C in Comparative Example 1 increased by 131.5%, 103.9%, and 104.5%, respectively, while HDL-C decreased by 38.9%. This indicates that water-soluble tomato extract is the key substance for the weight loss effect of the composition prepared in this invention.

[0054] Compared with Example 1, the TC content of Comparative Examples 2-4 increased by 21.5%, 26.6%, and 13.9%, respectively; the TG content increased by 61.8%, 68.2%, and 45.5%, respectively; the LDL-C content increased by 19.1%, 15.2%, and 9.6%, respectively; and the HDL-C content decreased by 21.5%, 24.7%, and 13.98%, respectively. Combined with the rat weight change data, it shows that the water-soluble tomato extract and the other components in this composition have a synergistic effect on the fat reduction and weight loss of rats.

[0055] Among them, Comparative Group 2 showed the highest LDL-C increase rate. LDL-C, also known as bad cholesterol, is a major pathogenic target of atherosclerosis. Excessive LDL-C in the blood deposits under the vascular endothelium, and its oxidation triggers inflammation. Vine tea extract and green tea extract contain a large amount of phenolic substances, which can effectively reduce inflammation and scavenge free radicals to achieve antioxidant function. Comparative Group 3, which lacks *Citrus aurantium* and *Stachys aureus* extracts, showed a 79.6% increase in TG content compared to the control group, indicating that β-glucan in *Stachys aureus* and catalpol in *Citrus aurantium* play an important role in regulating triglyceride metabolism and improving fatty liver. Comparative Group 4, which lacks rye ferment and white kidney bean extracts, showed the lowest blood lipid growth rate among the comparative groups, indicating that the intestinal regulatory effects of these two on gut microbiota and blocking starch absorption are only synergistic components in the composition to enhance the lipid-lowering and weight-loss effects.

[0056] Test Example 4 Compared with the positive control group, the lipid-lowering and weight-loss effects of each example and comparative group were slightly reduced. However, simvastatin, as a potent lipid-lowering drug, carries a risk of liver damage. Therefore, the level of liver damage in rats was measured, specifically including the following steps: After completing the experiment in Test Example 3, blood was collected by enucleation. After separating the serum, the serum transaminase content of rats was determined using an ELISA kit according to the instructions.

[0057] The serum transaminase levels of rats in each group are shown in Table 5.

[0058] Table 5. Serum transaminase levels in rats

[0059] Serum transaminases are important markers of liver injury. As shown in Table 5, the model group exhibited the highest serum transaminase levels, reaching 610.9 pg / mg protein, indicating that hyperlipidemia can lead to hepatocellular damage. The positive control group and Example 1 group showed the highest and lowest serum transaminase levels, respectively, outside the model group, at 574.2 pg / mg protein and 299.2 pg / mg protein, indicating that simvastatin carries a certain risk of liver damage while exerting its lipid-lowering effect. The tomato extract lipid-lowering composition prepared in this invention contains *Porcine strychnos nucifera* extract, which has certain hepatoprotective effects and is safer than simvastatin.

[0060] Test Example 5 Human efficacy evaluation specifically includes the following steps: Seventy participants aged 35-70 years with mild to moderate hyperlipidemia were recruited and randomly and double-blindly assigned to seven groups. The experimental group received 700 mg of the composition prepared in this invention orally once daily for 12 weeks. The levels of total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured before oral administration of the composition and at weeks 4 and 12. The results are recorded in Tables 6, 7, and 8.

[0061] Table 6. Levels of TC, TG, HDL-C, and LDL-C in subjects before taking the composition.

[0062] Table 7. Levels of TC, TG, HDL-C, and LDL-C in subjects after 4 weeks of taking the composition.

[0063] Table 8. Levels of TC, TG, HDL-C, and LDL-C in subjects after 12 weeks of taking the composition.

[0064] The differences in blood lipid levels before and after taking the composition in each group are shown in Tables 6-8. It can be seen that after 4 and 12 weeks of administration, the levels of total cholesterol, total triglycerides, and low-density lipoprotein cholesterol in each group significantly decreased, while the level of high-density lipoprotein cholesterol increased. This indicates that the composition prepared in this invention can significantly improve the blood lipid levels of the subjects, and the subjects taking the composition showed a significant reduction in blood lipid levels after 4 weeks, indicating that the composition can rapidly exert its lipid-lowering effect in the human body. Among them, the blood lipid level improvement ability of the example group was significantly better than that of the comparative group with missing components. Example 1 demonstrated the best ability to improve blood lipid levels. After 4 weeks of administration, the total cholesterol, total triglycerides, and low-density lipoprotein cholesterol levels in the Example 1 group decreased to 4.86 mM, 0.66 mM, and 2.57 mM, respectively, while the high-density lipoprotein cholesterol level increased to 1.79 mM. After 12 weeks of administration, the total cholesterol, total triglycerides, and low-density lipoprotein cholesterol levels further decreased to 4.43 mM, 0.54 mM, and 2.23 mM, respectively, while the high-density lipoprotein cholesterol level further increased to 2.09 mM, which is within the normal blood lipid range. The effects of Examples 2 and 3 were slightly lower than those of Example 1, but still significantly better than the comparative examples, indicating that the complete composition can effectively lower blood lipids, and that the components in the composition have synergistic effects.

[0065] After 12 weeks of administration, in Comparative Example 1, total cholesterol, total triglycerides, and LDL cholesterol decreased by only 29.2%, 30.0%, and 36.5%, respectively, while HDL cholesterol increased by 25.4%, exhibiting the worst lipid-lowering ability. This indicates that water-soluble tomato extract is the core component responsible for the lipid-lowering effect of the composition prepared in this invention. Comparative Examples 2 and 3, lacking phenolic substances (vine tea extract and green tea extract) and β-glucan and catalpol (stomach mushroom extract and catalpol fruit extract), respectively, showed higher LDL-C and total triglyceride increases. Comparative Example 4, lacking rye ferment and white kidney bean extract, showed the lowest lipid growth rate among the comparative examples, indicating that these two components only act as synergistic components in the composition to enhance the lipid-lowering effect.

[0066] The above results confirm that the composition of the present invention has a clear lipid-lowering effect in the human body. The complete formula has the best effect, and the absence of each component leads to a decrease in efficacy, which reflects the synergistic effect of multiple targets.

[0067] Although the present invention has been described in detail above with general descriptions and specific embodiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A water-soluble tomato extract composition for lowering blood lipids, characterized in that, The product contains the following components in parts by weight: 50-100 parts water-soluble tomato extract, 30-50 parts *Polygonum multiflorum* extract, 20-30 parts *Citrus aurantium* extract, 5-10 parts *Tea vine* extract, 5-10 parts bitter melon extract, 5-10 parts green tea extract, 20-30 parts rye ferment, and 10-20 parts white kidney bean extract.

2. The lipid-lowering composition of water-soluble tomato extract as described in claim 1, characterized in that, The method for preparing the composition includes the following steps: Weigh each component separately according to the proportion and mix them to obtain a mixture. Add 20-30% of the mass of the mixture to deionized water and put it into a mixer. Mix at 15-20 rpm at 20-30℃ for 30-45 minutes until the mixture is uniform and then pass it through a 200-mesh sieve.

3. The lipid-lowering composition of water-soluble tomato extract as described in claim 1, characterized in that, The method for preparing the water-soluble tomato extract includes the following steps: S1. After washing the tomatoes with clean water, crush them, separate the skin and seeds, press and centrifuge to obtain tomato juice; S2. The tomato juice in S1 is enzymatically hydrolyzed and the enzymes are then inactivated to obtain tomato hydrolysate; S3. Pass the tomato enzymatic hydrolysate through a microfiltration membrane with a pore size of 0.1-1μm to remove suspended particles and obtain microfiltered tomato juice. S4. Microfiltration of tomato juice through an ultrafiltration membrane with a pore size of 0.001-0.1μm removes macromolecular substances, resulting in ultrafiltration tomato juice. S5. Nanofiltration is performed on the ultrafiltration tomato juice using a 1-3 nm nanofiltration membrane to separate and remove components smaller than 500 Da, resulting in a retentate direct flow solution. S6. Concentrate and spray-dry the retained liquid to obtain a water-soluble tomato extract.

4. The lipid-lowering composition of water-soluble tomato extract as described in claim 3, characterized in that, Step S2 specifically includes the following steps: S201, Enzymatic hydrolysis: Add 0.04-0.1% of hydrolytic enzyme by weight of tomato juice to the tomato juice, gradually raise the temperature to 45-55℃, and hydrolyze for 1-1.5 hours to obtain the hydrolysate. S202, enzyme inactivation: The resulting enzyme hydrolysate was heated to 90-95℃ and kept at that temperature for 15-20 minutes to inactivate the enzyme.

5. The water-soluble tomato extract lipid-lowering composition as described in claim 4, characterized in that, The hydrolytic enzyme mentioned in step S201 is one or more of phytase, cellulase, pectinase, xylanase and β-glucosidase.

6. The lipid-lowering composition of water-soluble tomato extract as described in claim 1, characterized in that, The preparation method of the *Porcini mushroom* extract includes the following steps: S1. Take dried pig stomach mushrooms, crush them, and pass them through a 40-mesh sieve to obtain pig stomach mushroom powder; S2. Mix the *Polygonum multiflorum* powder with deionized water at a mass-to-volume ratio of 1g:20mL, and stir at 90-100℃ and 200-300rpm for 2-3 hours to obtain *Polygonum multiflorum* aqueous extract. S3. Let the water extract of *Stachys edulis* cool naturally to room temperature, adjust the pH to 4.5-5.0, add 0.5-1% acidic protease (by weight of the water extract of *Stachys edulis*), and enzymatically hydrolyze at 50℃ for 2-3 hours. After the enzymatic hydrolysis is completed, raise the temperature to 90℃ and continue the reaction for 10 minutes to inactivate the enzyme, thus obtaining the enzymatic hydrolysate of *Stachys edulis*. S4. Centrifuge the pig stomach mushroom enzymatic hydrolysate at 12000 rpm for 20 min at 4℃, take the supernatant, and ultrafilter it with a 100 kDa ultrafiltration membrane to remove small molecule impurities. S5. Add ethanol to the ultrafiltered *Stachys amurensis* enzymatic hydrolysate from S4, and let it stand at 4°C for 12-24 hours. The volume ratio of the ultrafiltered *Stachys amurensis* enzymatic hydrolysate to ethanol is 1:

4. After standing, centrifuge at 10,000 rpm, collect the precipitate, wash it three times with deionized water, concentrate and spray dry to obtain *Stachys amurensis* extract.

7. The lipid-lowering composition of water-soluble tomato extract as described in claim 1, characterized in that, The method for preparing the rye ferment includes the following steps: S1. After cleaning the rye grains, dry them at 60-70℃ for 2-4 hours, then grind them through a 40-mesh sieve using a hammer mill to obtain coarse rye flour. S2. Mix rye coarse flour with deionized water at a mass-volume ratio of 1g:(8-10)mL, stir evenly to form a slurry, and obtain rye slurry. S3. Adjust the pH of the rye slurry to 6.0, heat it in a 95℃ water bath for 30 minutes for gelatinization and pasteurization, and then quickly cool it to below 30℃ to obtain rye gelatinized liquid. S4. Inoculate with a compound fermentation strain obtained by mixing *Lactobacillus plantarum* and *Saccharomyces cerevisiae* at a 1:1 ratio, with a total inoculum size of 1×10⁻⁶. 6 CFU / mL rye gelatinized liquid; after inoculation, place in a constant temperature fermentation tank and let it ferment at 30℃ for 60-72 hours. S5. After fermentation, the fermentation broth is heated to 80℃ and held for 15 minutes to terminate microbial activity and sterilize. After sterilization, the fermentation broth is centrifuged at 8000-10000 rpm for 20 minutes at 4℃. The supernatant is collected, concentrated under reduced pressure at 40-50℃, and spray-dried to obtain rye fermentation product.

8. The lipid-lowering composition of water-soluble tomato extract as described in claim 1, characterized in that, The extraction method of the bitter melon extract includes the following steps: S1. Remove the seeds and pith from the fresh bitter melon and break it into small pieces of 1-2cm. After rinsing with water, press and filter to obtain bitter melon juice. S2. Mix bitter melon juice with deionized water at a volume ratio of 1:(5-8), adjust the pH to 5.0-8.0, add 0.1-0.3% of bitter melon hydrolytic enzyme by weight of the mixture, and hydrolyze at 40-50℃ for 1-2 hours. After the hydrolysis is completed, raise the temperature to 90-95℃ to inactivate the enzyme and obtain bitter melon hydrolysate. S3. Microfilter the bitter gourd enzymatic hydrolysate with a filter membrane with a pore size of 0.1-0.2 μm to remove macromolecular fibers and collect the permeate; S4. Ultrafiltration of the permeate to retain components with a molecular weight of 1000-5000 Da, and collection of bitter gourd retaining permeate; S5. After concentrating the bitter melon intercepted direct flow liquid, spray dry to obtain bitter melon extract.

9. The lipid-lowering composition of water-soluble tomato extract as described in claim 8, characterized in that, In step S2 of the extraction method for bitter melon extract, the bitter melon hydrolytic enzyme is one or more of pectinase, cellulase, and xylanase.

10. Application of water-soluble tomato extract lipid-lowering composition in the preparation of lipid-lowering functional foods.

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