Blood fat reducing active peptide and application thereof

Abstract

The invention relates to a blood fat reducing active peptide and application thereof. The sequence of the blood fat reducing active peptide is NAIIGPRW, and the blood fat reducing active peptide not only can reduce the level of total cholesterol, triglyceride and low-density lipoprotein cholesterol, but also can improve the level of high-density lipoprotein cholesterol. An oil red O staining experiment shows that the blood fat reducing active peptide can effectively inhibit preadipocyte differentiation and has the capacity of inhibiting pancreatic lipase activity. Toxicity experiments show that the blood fat reducing active peptide also has the characteristic of high safety.

Description

Technical Field

[0001] The present invention relates to the field of small molecule peptides, and more specifically, to a lipid-lowering active peptide and application thereof. Background Art

[0002] Obese patients often have dyslipidemia, among which the increase in triglyceride levels is particularly prominent and positively correlated with the degree of obesity. In addition, it is also common for them to have increased levels of low-density lipoprotein cholesterol and total cholesterol and decreased levels of high-density lipoprotein cholesterol. Among obese patients who underwent weight loss and metabolic surgery in my country, 46% had dyslipidemia with elevated TG as the main manifestation before surgery.

[0003] Bioactive peptides are released from proteins. Their functional activity depends on the composition and arrangement of amino acids. They can meet different needs of human health and have the advantages of no side effects and easy absorption by the human body. Plants are a valuable source of bioactive peptides. Compared with animals, plant resources are richer, highly renewable and lower in cost. Obtaining bioactive peptides from plants will become a development trend.

[0004] Tartary buckwheat belongs to the genus Fagopyrum of the dicotyledonous Polygonaceae family. It is rich in protein, bioflavonoids, multiple amino acids and other ingredients, which are important nutritional components. Studies have shown that tartary buckwheat has the effects of lowering blood sugar and blood lipids, enhancing the body's immunity, anti-oxidation, and anti-tumor. Its related products have been used as auxiliary treatments for patients with cardiovascular diseases, obesity and diabetes, and are becoming more and more popular. For example, Koyama et al. (DOI: 10.1021 / jf305157y) found that the six peptides isolated from common buckwheat sprouts fermented with lactic acid all had a strong blood pressure lowering effect.

[0005] The development of more bioactive peptides with lipid-lowering activity has positive significance for obese patients. Summary of the invention

[0006] The primary purpose of the present invention is to overcome the problem that the above-mentioned existing bioactive peptides with lipid-lowering activity are still relatively scarce, and to provide a lipid-lowering active peptide. The lipid-lowering active peptide can not only reduce the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol, but also increase the level of high-density lipoprotein cholesterol. It can be seen from the Oil Red O staining experiment that the lipid-lowering active peptide of the present invention can effectively inhibit the differentiation of preadipocytes and has the ability to inhibit the activity of pancreatic lipase.

[0007] A further object of the present invention is to provide the use of the above lipid-lowering active peptide in the preparation of health products that assist in lowering blood lipids.

[0008] Another object of the present invention is to provide the use of the above lipid-lowering active peptide in the preparation of drugs for preventing and / or treating diseases related to hyperlipidemia.

[0009] Another object of the present invention is to provide a composition.

[0010] The above-mentioned object of the present invention is achieved by the following technical solutions:

[0011] A lipid-lowering active peptide, the lipid-lowering active peptide is the sequence shown in SEQ ID NO: 1.

[0012] The lipid-lowering active peptide of the present invention is extracted from tartary buckwheat, and the sequence of the lipid-lowering active peptide is as follows: NAIIGPRW (asn-ala-ile-ile-gly-pro-arg-trp).

[0013] The inventors of the present invention have found through research that the lipid-lowering active peptide of the present invention can not only reduce the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol, but also increase the level of high-density lipoprotein cholesterol. It can be seen from the Oil Red O staining experiment that the lipid-lowering active peptide of the present invention can effectively inhibit the differentiation of preadipocytes and has the ability to inhibit the activity of pancreatic lipase. It can be seen from the toxicity experiment that the lipid-lowering active peptide of the present invention also has the characteristics of high safety.

[0014] The lipid-lowering active peptide of the present invention can also be synthesized by solid phase synthesis, which can not only realize large-scale production but also ensure that the synthesized lipid-lowering active peptide has the characteristics of high purity and stable quality.

[0015] The present invention also protects the use of the above-mentioned lipid-lowering active peptide in the preparation of health products for assisting in lowering blood lipids.

[0016] The use of the above-mentioned lipid-lowering activity in the preparation of drugs for preventing and / or treating diseases related to hyperlipidemia is also within the protection scope of the present invention.

[0017] Optionally, the drug is a drug that inhibits preadipocyte differentiation.

[0018] Optionally, the drug is a drug that inhibits pancreatic lipase activity.

[0019] Optionally, the drug is a triglyceride-lowering drug.

[0020] Optionally, the drug is a drug for lowering high-density lipoprotein cholesterol.

[0021] Optionally, the drug is a drug that increases high-density lipoprotein cholesterol.

[0022] Optionally, the drug is a drug for lowering total cholesterol.

[0023] Optionally, the hyperlipidemia-related disease is obesity and / or hyperlipidemia.

[0024] Optionally, the dosage form of the drug is at least one of an injection, a tablet, an oral solution, a granule or a capsule.

[0025] A composition comprises the above-mentioned lipid-lowering active peptide.

[0026] Optionally, the content of lipid-lowering active peptide in the composition is 1-800 μg / mL.

[0027] Optionally, the composition further comprises a pharmaceutically acceptable carrier or excipient.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The lipid-lowering active peptide of the present invention can not only reduce the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol, but also improve the level of high-density lipoprotein cholesterol. It can be seen from the Oil Red O staining experiment that the lipid-lowering active peptide of the present invention can effectively inhibit the differentiation of preadipocytes and has the ability to inhibit the activity of pancreatic lipase. It can be seen from the toxicity experiment that the lipid-lowering active peptide of the present invention also has the characteristics of high safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 The pancreatic lipase inhibition ability diagram of two ultrafiltration fractions MW < 3kDa, MW > 3kDa and enzymatic hydrolysate; Figure 1 A is the PL inhibition rate of each component at different concentrations; Figure 1 B is the PL inhibition rate IC of each component 50 .

[0031] Figure 2 It is the elution peak diagram of the MW < 3kDa component separated by RP-HPLC and the pancreatic lipase inhibition ability diagram of the P1 to P9 components; wherein, Figure 2 A is the elution peak diagram of the component with MW < 3 kDa separated by RP-HPLC; Figure 2 B is a graph showing the pancreatic lipase inhibitory ability of fractions P1 to P9.

[0032] Figure 3 It is the binding site and interaction force between lipid-lowering active peptide and pancreatic lipase (PDB: 1LPB).

[0033] Figure 4 It is the binding site and interaction force between lipid-lowering active peptide and cholesterol esterase (PDB: 1F6W).

[0034] Figure 5 This is a graph showing the pancreatic lipase inhibitory ability of lipid-lowering active peptides.

[0035] Figure 6 This is a graph showing the toxicity test results of lipid-lowering active peptides and orlistat.

[0036] Figure 7 The results of Oil Red O staining of lipid-lowering active peptide and orlistat are shown.

[0037] Figure 8 This is the absorbance value at 520nm of lipid droplets stained with Oil Red O and orlistat after being dissolved in isopropanol.

[0038] Fig. 9 This is a graph showing the lipid-lowering activity of lipid-lowering active peptides in 3T3-L1 preadipocytes; Fig. 9 A is the effect diagram on TG content; Fig. 9 B is the effect diagram on TC content; Fig. 9 C is the effect diagram on HDL-C content; Fig. 9 D is the effect diagram on LDL-C content. DETAILED DESCRIPTION

[0039] In order to more clearly and completely describe the technical solution of the present invention, the present invention is further described in detail through specific embodiments below. It should be understood that the specific embodiments described herein are only used to explain the present invention, and are not used to limit the present invention. Various changes can be made within the scope of the rights of the present invention.

[0040] The test data processing method of each embodiment of the present invention is as follows:

[0041] The obtained data were plotted using Prism 8.0.2 software and Origin 2019, and statistically processed using SPSS21.0 and Excel2021 software. The results were expressed as mean ± standard deviation (SD), and the ANOVA method was used to analyze the significance of the differences between samples (P<0.05). Each experiment was repeated 3 times.

[0042] Example 1 Extraction and enzymolysis of tartary buckwheat protein

[0043] The bitter buckwheat (Xiqiao No. 8, provided by Xichang University) was crushed, passed through a 100-mesh sieve, and degreased for 2 hours with petroleum ether at a solid-liquid ratio of 1:5 (g / mL). After repeated degreasing twice, the bitter buckwheat defatted powder was dried in a fume hood. Based on the principle of alkali dissolution and acid precipitation, water was added to the bitter buckwheat defatted powder at a solid-liquid ratio of 1:10 (g / mL), and the pH was adjusted to 9.0 with NaOH solution (0.1 mol / L). The mixture was stirred and extracted for 2 hours in a constant temperature water bath at 45°C, and the supernatant was taken after centrifugation (4000 r / min, 20 min). The pH of the supernatant was adjusted to 4.4 with HCl solution (0.1 mol / L), and the protein was precipitated at 4°C for 2 hours. The precipitate was freeze-dried for later use.

[0044] A 3% crude buckwheat protein solution was prepared, and the optimal enzymatic hydrolysis process was referred to the literature "Enzymatic preparation, amino acid composition and activity of buckwheat protein lipid-lowering peptides" (DOI: 10.13386 / j.issn1002-0306.2023110029), and bromelain was used for enzymatic hydrolysis. The enzyme was inactivated at 95°C, cooled, and centrifuged (8000r / min, 20min). The supernatant was the enzymatic hydrolyzate containing lipid-lowering active peptides, which was freeze-dried to obtain the enzymatic hydrolyzate.

[0045] Example 2 Separation and purification of enzymolysate

[0046] The hydrolysate was separated by an ultrafiltration membrane with a molecular weight cutoff (MW) of 3 kDa, and two ultrafiltration fractions were obtained: MW>3 kDa and MW<3 kDa. The two ultrafiltration fractions and the hydrolysate were freeze-dried and prepared into test sample solutions of different concentrations (0.1, 0.25, 0.5, 1, 2, 4 mg / mL) to determine their pancreatic lipase inhibition rate and IC 50 Value, the result is Figure 1 As shown, the fraction with the highest pancreatic lipase inhibition rate was selected for the following purification.

[0047] The components screened by the above steps were filtered through a filter membrane (0.22 μm) and separated using a C18 reverse phase chromatographic column (20 mm×450 mm, 10 μm), and a total of 9 components were separated, named P1 to P9. The chromatographic conditions were: mobile phase A: double distilled water containing 0.1% trifluoroacetic acid (TFA); mobile phase B: methanol containing 0.1% TFA; elution gradient: 0-40 min, 8% to 50% mobile phase B; 40 to 80 min, 50% to 75% mobile phase B; 80 to 85 min, 75% to 90% mobile phase B; 85 to 95 min, 90% to 90% mobile phase B, injection volume 5 mL, flow rate 10 mL / min, detection wavelengths 214 nm and 280 nm. The eluted peaks were collected, concentrated, freeze-dried and prepared at a concentration of 1 mg / mL to determine their pancreatic lipase inhibitory abilities, and the components with the highest pancreatic lipase inhibitory rates were screened for subsequent experiments.

[0048] The method for determining the pancreatic lipase (PL) inhibition rate is as follows:

[0049] 1mg / mL lauric acid-4-nitrophenyl ester solution was used as the reaction substrate, and the reaction substrate contained 0.05mol / L sodium acetate solution and 1% Triton X-100 solution. The reaction substrate was heated to dissolve, mixed thoroughly, and cooled to room temperature for use. In a 2mL test tube, the reaction substrate, the sample solution to be tested, and the reaction buffer (pH8.2, 0.1mol / L Tris-HCl buffer) were added in sequence, and finally the pancreatic lipase solution (5mg / mL) was added to start the reaction. The volume ratio of the sample was 5:2:4:3. After incubation at 37°C for 2h, the absorbance was measured at a wavelength of 420nm. At the same time, a sample group without enzyme and a blank group without sample were set up. The pancreatic lipase inhibition rate (PL) was calculated according to the following formula: PL (%) = [1-(AA 1 ) / A 0 ]×100;

[0050] Where A is the absorbance value of the sample group to be tested; A 1 is the absorbance value of the sample group without enzyme; A 0 is the absorbance value of the blank group without sample.

[0051] The pancreatic lipase inhibition ability of the two ultrafiltration fractions MW < 3 kDa, MW > 3 kDa and the enzymatic hydrolysate is as follows Figure 1 As shown. Figure 1 It can be seen that at a concentration of 4 mg / mL, the inhibition rate of the MW < 3 KDa component on pancreatic lipase was the highest, at 68.65% ± 0.34%, and the IC 50 The lowest was 0.019 mg / mL, so the fraction with MW < 3 kDa was selected for further purification.

[0052] Figure 2 The figure shows the elution peak of the MW < 3 kDa component separated by RP-HPLC and the pancreatic lipase inhibition ability of the P1 to P9 components. Figure 2 It can be seen that the P9 fraction has the highest pancreatic lipase inhibitory activity, so the P9 fraction was selected for the subsequent identification of peptide composition.

[0053] Example 3 Identification of peptide composition and molecular docking

[0054] 1. High performance liquid chromatography-tandem mass spectrometry identification

[0055] The P9 fraction was analyzed by LC-MS / MS equipped with an online nanospray ion source. The entire system was an Orbitrap Q-Exactive Plus mass spectrometer (ThermoFisherScientific, MA, USA) connected in series with an EASY-nanoLC1200. A total of 1 μL of sample was loaded (analytical column: Acclaim PepMap C18, 75 μm x 25 cm), and the sample was separated by a gradient of 60 min. The column flow was controlled at 300 nL / min, the column temperature was 40 °C, the electrospray voltage was 2 kV, and the gradient started from 2% of phase B, increased to 35% in 47 min with a nonlinear gradient, increased to 100% in 1 min, and maintained for 12 min.

[0056] The mass spectrometer was operated in data-dependent acquisition mode, automatically switching between MS and MS / MS acquisition. The mass spectrometry parameters were set as follows: (1) MS: scan range (m / z): 200-1800; resolution: 70,000; AGC target: 3e6; maximum injection time: 50 ms; (2) HCD-MS / MS: resolution: 17,500; AGC target: 1e5; maximum injection time: 45 ms; collision energy: 28%; dynamic exclusion time: 30 s.

[0057] Tandem mass spectra were analyzed by PEAKSStudio version 10.6 (Bioinformatics Solutions Inc., Waterloo, Canada). PEAKSDB searched the uniprot-Fagopyrum tataricum (version 2023, 382 entries) database and set None digestion. The search parameters were fragment ion mass tolerance: 0.02 Da, parent ion mass tolerance: 10 ppm, variable modification: Oxidation (M) 15.99, Deamination (NQ) 0.98, protein card value was at least 1 unique peptide; peptide card value was -10lgP ≥ 20.

[0058] 2. Molecular docking

[0059] The docking software used was Autodock vina 1.1.2. Pancreatic lipase (PDB ID: 1LPB) and cholesterol esterase (PDB ID: 1F6W) were selected as docking receptors, and their three-dimensional structures were downloaded from the Protein Data Bank (PDB). The selected peptide sequences were mapped using Discovery Studio 2019, and the original ligands methoxyundecylphosphonic acid (MUP) and metal ions of the receptor protein 1LPB were separated and docked. The receptor protein 1F6W does not contain the original ligand and can be docked directly. The protein receptor was dehydrated and hydrogenated, and then the ligand energy was minimized and their rotation centers and rotation bonds were detected. After the receptor and ligand were imported into the docking software, the parameters of the docking box were set. The docking parameters of the peptide segment with the active site of 1LPB were set as follows: center coordinates: x = -6.05, y = 28.03, z = 38.479; docking box size: x = 79.2, y = 66.0, z = 77.73, energy_range = 3, exhaustion = 8, number modes = 10. The docking parameters of the peptide segment with the active site of 1F6W were set as follows: center coordinates: x = 3.189, y = 4.989, z = 17.976; docking box size: x = 74.894, y = 60.161, z = 69.983, energy_range = 3, exhaustion = 8, number modes = 10. The docking conformation with the lowest binding energy was selected as the optimal conformation. The three-dimensional structure diagram of the interaction between the peptide segment and the enzyme was drawn using PYMOL, and the visualization was performed using DiscoveryStudio2019. A two-dimensional interaction diagram was drawn to analyze the interaction type after docking.

[0060] A total of 2662 peptide sequences were identified in the P9 component using high performance liquid chromatography-tandem mass spectrometry, including 40 small molecule peptides with a peptide length of no more than 10 amino acids and no modification groups.

[0061] The 40 peptides were ranked according to the molecular docking binding energy. The smaller the binding energy, the better the binding effect. A lipid-lowering active peptide was screened out, NAIIGPRW, which will be named NW-8 using the first and last letters of the peptide sequence and the length of the peptide. The identification results of the lipid-lowering active peptide and its peptide characteristics are shown in Table 1.

[0062] Table 1 Identification results of lipid-lowering active peptides and their peptide characteristics

[0063]

[0064] Figure 3 The binding site and interaction force between lipid-lowering active peptide and pancreatic lipase (PDB: 1LPB). Figure 3It can be seen that NW-8 and 1LPB generate electrostatic interactions at amino acid residues PHE215 and GLU233, form hydrogen bonds at amino acid residues ASN212, LEU213, LYS238, ARG256, and ALA259, form carbon-hydrogen bonds at amino acid residues PHE77, HIS151, and HIS263, form π-cation electrostatic interactions at amino acid residue ARG256, form π-donor hydrogen bonds with amino acid residue PHE215, generate π-πT-shape hydrophobic interactions with amino acid residue TRP252, and form π-alkyl interactions and alkyl interactions with amino acid residues ILE78, ALA259, ARG256, PHE258, LEU213, LYS238, and CYS237.

[0065] Figure 4 The binding site and interaction force between lipid-lowering peptide and cholesterol esterase (PDB: 1F6W). Figure 4 It can be seen that NW-8 forms hydrogen bonds with 1F6W at amino acid residues VAL285, LEU282, LYS231, ILE229, ILE353, VAL391, and THR354, and forms a carbon-hydrogen bond with amino acid residue ASP299. It also generates π-alkyl and alkyl hydrophobic interactions with amino acid residues TRP522, TYR526, LEU282, ILE353, VAL391, ILE229, and LEU527.

[0066] The above results indicate that the lipid-lowering active peptide of the present invention binds to the receptor through multiple interactions, which may be one of the reasons why it exerts the effect of lowering blood lipids.

[0067] Example 4 Determination of pancreatic lipase inhibition rate

[0068] The NW-8 lipid-lowering active peptide obtained after molecular docking was prepared into sample solutions of different concentrations (50, 100, 200, 400, 800 μg / mL), and Orlistat, a key drug for the treatment of obesity, was selected as a positive control to determine the inhibition rate of pancreatic lipase. The results are as follows: Figure 5 shown.

[0069] from Figure 5 It can be seen that when the concentration of the lipid-lowering active peptide is 50-800 μg / mL, it has a strong inhibitory effect on pancreatic lipase, and is concentration-dependent. When the concentration is 800 μg / mL, the highest inhibition rate of NW-8 on pancreatic lipase is 74.68%±1.19%. The above shows that the lipid-lowering active peptide of the present invention has excellent pancreatic lipase inhibition ability.

[0070] Example 5 Determination of the hypolipidemic activity of hypolipidemic active peptides

[0071] NAIIGPRW was synthesized by Nanjing Jiepeptide Biotechnology Co., Ltd. (Nanjing, Jiangsu, China) with a purity of 98% and was used in the following experiments.

[0072] 1. Toxicity Assay

[0073] 3T3-L1 preadipocytes were cultured in a high-glucose DMEM medium containing 10% FBS and 1% penicillin-streptomycin, i.e., complete medium, and placed in a 5% CO 2 , 37°C in a cell culture incubator. 100 μL of cell suspension (1×10 5 / mL) were inoculated in a 96-well plate, and a blank group and a test group were set up, where the test group included NW-8 and orlistat. After 24 hours of cell culture, the culture medium was discarded, 100 μL of culture medium was added to the blank group, and 100 μL of culture medium containing samples of different concentrations was added to the test group. After continuing to culture for 24 hours, the old culture medium was discarded, 100 μL of MTT (0.5 mg / mL) was added and incubated for 4 hours, 100 μL of DMSO was added to each well, and the absorbance was detected at 490 nm. Cell viability was calculated by the following formula: Cell viability (%) = (A t / A c )×100%; where A t is the absorbance value of the test group; A c is the absorbance value of the blank group.

[0074] 2. Differentiation Induction of High Fat Model

[0075] 3T3-L1 preadipocytes were seeded in 24-well plates (5 × 10 4 Cells / well), and cultured in DMEM medium until the cell density reached 100%, and the culture medium was replaced and continued for two days to allow the cells to exit the growth cycle by contact inhibition. Set up a blank control group, a positive control group, a model group and a test group. The model group was cultured with primary differentiation medium, that is, complete medium containing 0.5mM IBMX, 1μM DEX and 10μg / mL insulin for 3 days. The test group was cultured with primary differentiation medium containing samples of different concentrations. The positive control group was cultured with primary differentiation medium containing positive drugs, and the blank control group was cultured with normal complete medium. Then, the culture medium of the model group was replaced with secondary differentiation medium, and the test group and the positive control group were cultured with secondary differentiation medium containing samples of different concentrations and positive drugs, and the blank control group was still cultured with normal complete medium. The secondary differentiation medium is a complete medium containing 10μg / mL insulin. Each group of cells was cultured for 4 consecutive days, and the secondary differentiation medium was updated once a day, and then all were replaced with normal complete medium until 80% of the cells differentiated into mature adipocytes, that is, differentiation was completed.

[0076] 3. Oil Red O Staining

[0077] After differentiation is completed, discard the old culture medium, wash the cells with PBS buffer, fix the cells with 4% paraformaldehyde solution for 10 minutes at room temperature, and wash twice with PBS. Stain according to the instructions of the Oil Red O staining kit, add staining wash and cover the cells for 20 seconds. After removing the wash, add an appropriate amount of Oil Red O staining solution, stain for 30 minutes, remove the staining solution, wash with staining wash for 30 seconds, wash with PBS for 20 seconds, and discard PBS. Cover the cells evenly with PBS again, observe under a microscope and take pictures. After taking pictures, discard PBS, add 500μL of isopropanol to the 24-well plate and shake for 5 minutes, and measure the absorbance value at a wavelength of 520nm.

[0078] 4. Determination of TC, TG, HDL-C and LDL-C content

[0079] After differentiation was completed, the old culture medium was discarded, the cells were washed once with PBS, and the cells were collected according to the steps in the instructions of the TG kit (A110-1-1, Nanjing Jiancheng Bioengineering Institute), TC kit (A111-1-1, Nanjing Jiancheng Bioengineering Institute), HDL-C kit (A112-1-1, Nanjing Jiancheng Bioengineering Institute) and LDL-C kit (A113-1-1, Nanjing Jiancheng Bioengineering Institute), and the cells were broken with lysis buffer, and the TG, TC, HDL-C and LDL-C contents in the cells were determined.

[0080] Figure 6 The following is a graph showing the toxicity test results of lipid-lowering active peptides and orlistat. Figure 6 It can be seen that when the concentration is 1-80 μg / mL, the cell survival rates of the lipid-lowering active peptide and orlistat groups are both above 90%, indicating that they are non-cytotoxic within this concentration range and are highly safe and can be used for subsequent experiments.

[0081] Figure 7 The results of Oil Red O staining of lipid-lowering active peptides and orlistat are shown. Figure 7 It can be seen that compared with the model group, the number of lipid droplets in the differentiated cells to which the lipid-lowering active peptide of the present invention is added is reduced, and the greater the concentration, the fewer the lipid droplets in the cells.

[0082] Figure 8 The absorbance value of lipid-lowering peptide and orlistat at 520nm after lipid droplets stained with Oil Red O were dissolved in isopropanol. Figure 8 It can be seen that when the lipid-lowering peptide concentration was 40 μg / mL, it was reduced by 36.21±1.22% compared with the model group, which indicates that the lipid-lowering peptide of the present invention can effectively inhibit the differentiation of 3T3-L preadipocytes.

[0083] Fig. 9 The figure shows the lipid-lowering activity of lipid-lowering peptides in 3T3-L1 preadipocytes. Fig. 9 A shows that at a concentration of 40 μg / mL, NW-8 lipid-lowering peptide can reduce the content of TG in cells, which is 64.70%±8.33% lower than that in the model group. Fig. 9 B shows that at a concentration of 40 μg / mL, NW-8 lipid-lowering peptide can reduce the content of TC in cells, which is 59.74%±13.73% lower than that in the model group. Fig. 9 C shows that at a concentration of 40 μg / mL, NW-8 lipid-lowering active peptide can increase the content of HDL-C in cells, which is 112.00%±48.08% higher than that in the model group. Fig. 9 D It can be seen that at a concentration of 40 μg / mL, NW-8 lipid-lowering active peptide can reduce the content of LDL-C in cells, which is reduced by 65.75%±12.76% compared with the model group.

[0084] The above results show that the lipid-lowering active peptide of the present invention can reduce total cholesterol, triglycerides and low-density lipoprotein cholesterol, and can increase high-density lipoprotein cholesterol, and has excellent lipid-lowering activity.

[0085] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A lipid-lowering active peptide, characterized in that: The lipid-lowering active peptide is the sequence shown in SEQ ID NO:

1.

2. Use of the lipid-lowering active peptide according to claim 1 in the preparation of health products for assisting in lowering blood lipids.

3. Use of the lipid-lowering active peptide according to claim 1 in the preparation of a medicament for preventing and / or treating diseases related to hyperlipidemia.

4. The use according to claim 3, characterized in that: The drug is a drug for inhibiting the differentiation of preadipocytes.

5. The use according to claim 3, characterized in that: The drug is a drug that inhibits the activity of pancreatic lipase.

6. The use according to claim 3, characterized in that: The drug is a drug for lowering triglycerides.

7. The use according to claim 3, characterized in that: The drug is a drug for lowering high-density lipoprotein cholesterol.

8. The use according to claim 3, characterized in that: The drug is a drug for increasing high-density lipoprotein cholesterol.

9. The use according to claim 3, characterized in that: The drug is a drug for lowering total cholesterol.

10. The use according to claim 3, characterized in that: The hyperlipidemia-related disease is obesity and / or hyperlipidemia.

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