A lipid-lowering active peptide and its application

Abstract

The present invention relates to a lipid-lowering peptide and its use. The lipid-lowering peptide has the sequence: NAIIGPRW, and can reduce the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, while also increasing the level of high-density lipoprotein cholesterol. Oil Red O staining experiments have shown that the lipid-lowering peptide of the present invention can effectively inhibit preadipocyte differentiation and has the ability to inhibit pancreatic lipase activity. Toxicity experiments have shown that the lipid-lowering peptide of the present invention is also highly safe.

Description

Technical Field

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

[0002] Obese patients often have dyslipidemia, with elevated triglyceride levels being particularly prominent and positively correlated with the degree of obesity. Furthermore, elevated low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels, along with decreased high-density lipoprotein cholesterol (HDL-C), are also common. Among obese patients undergoing bariatric and metabolic surgery in my country, 46% had preoperative dyslipidemia, primarily manifested by elevated triglycerides.

[0003] Bioactive peptides are released from proteins. Their functional activity depends on the composition and arrangement of amino acids. They can meet the diverse needs of human health, have no side effects, and are easily absorbed by the body. Plants are a valuable source of bioactive peptides. Compared with animals, plant resources are more abundant, highly renewable, and less expensive. Obtaining bioactive peptides from plants will become a development trend.

[0004] Tartary buckwheat, a member of the dicotyledonous Polygonaceae family, is rich in protein, bioflavonoids, various amino acids, and other essential nutrients. Studies have shown that tartary buckwheat can lower blood sugar and lipids, enhance immunity, and provide antioxidant and anti-tumor benefits. Its products are increasingly popular as adjunctive treatments for patients with cardiovascular disease, obesity, and diabetes. For example, Koyama et al. (DOI: 10.1021 / jf305157y) found that six peptides isolated from lactic acid-fermented common buckwheat sprouts all exhibited potent blood pressure-lowering effects.

[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 of the lack of existing bioactive peptides with lipid-lowering activity and to provide a lipid-lowering peptide. This lipid-lowering peptide can not only lower the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, but also increase the level of high-density lipoprotein cholesterol. Oil Red O staining experiments show that the lipid-lowering peptide of the present invention can effectively inhibit preadipocyte differentiation and has the ability to inhibit pancreatic lipase activity.

[0007] A further object of the present invention is to provide the use of the above-mentioned 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-mentioned 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 purpose of the present invention is achieved through the following technical solutions:

[0011] A lipid-lowering active peptide, the lipid-lowering active peptide having 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 discovered through research that the lipid-lowering 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. Oil Red O staining experiments have shown that the lipid-lowering peptide of the present invention can effectively inhibit preadipocyte differentiation and has the ability to inhibit pancreatic lipase activity. Toxicity experiments have shown that the lipid-lowering peptide of the present invention is also highly safe.

[0014] The lipid-lowering active peptide of the present invention can also be synthesized by solid-phase synthesis, which not only enables large-scale production but also ensures 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-care products for assisting in lowering blood lipids.

[0016] The application 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 scope of protection 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 that lowers 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 comprising the above-mentioned lipid-lowering active peptide.

[0026] Optionally, the content of the lipid-lowering active peptide in the composition is 1 to 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 peptide of the present invention can reduce the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and can also increase the level of high-density lipoprotein cholesterol. Oil Red O staining experiments have shown that the lipid-lowering peptide of the present invention can effectively inhibit preadipocyte differentiation and has the ability to inhibit pancreatic lipase activity. Toxicity experiments have shown that the lipid-lowering peptide of the present invention is also highly safe. 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 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; Figure 2 A is the elution peak of the MW < 3 kDa component 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 The binding site and interaction force between the 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 peptides.

[0035] Figure 6 The figure shows the toxicity test results of lipid-lowering active peptide 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 520 nm of lipid droplets stained with Oil Red O and orlistat after being dissolved in isopropanol.

[0038] Figure 9 The figure shows the lipid-lowering activity assay of lipid-lowering peptides in 3T3-L1 preadipocytes; Figure 9 A is the effect diagram on TG content; Figure 9 B is the effect diagram on TC content; Figure 9 C is the effect diagram on HDL-C content; Figure 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 methods of various embodiments of the present invention are as follows:

[0041] The data were plotted using Prism 8.0.2 and Origin 2019, and statistically analyzed using SPSS 21.0 and Excel 2021. The results are expressed as mean ± standard deviation (SD). The ANOVA method was used to analyze the significance of differences between samples (P < 0.05). Each experiment was repeated three times.

[0042] Example 1 Extraction and enzymatic hydrolysis of tartary buckwheat protein

[0043] Buckwheat (Xiqiao No. 8, provided by Xichang University) was ground, passed through a 100-mesh sieve, and defatted for 2 h with petroleum ether at a solid-liquid ratio of 1:5 (g / mL). Degreasing was repeated twice and the powder was air-dried in a fume hood to obtain defatted buckwheat powder. Based on the principle of alkali dissolution and acid precipitation, water was added to the defatted buckwheat powder at a solid-liquid ratio of 1:10 (g / mL). The pH was adjusted to 9.0 with NaOH solution (0.1 mol / L). Extraction was carried out in a 45°C water bath with stirring for 2 h. The supernatant was centrifuged (4000 rpm, 20 min) and the pH of the supernatant was adjusted to 4.4 with HCl solution (0.1 mol / L). The protein was allowed to precipitate at 4°C for 2 h. The resulting precipitate was freeze-dried for later use.

[0044] A 3% crude buckwheat protein solution was prepared, and the optimal enzymatic hydrolysis process of the document "Enzymatic Preparation, Amino Acid Composition and Activity of Buckwheat Protein Lipid-lowering Peptides" (DOI: 10.13386 / j.issn1002-0306.2023110029) was referred to. Bromelain was used for enzymatic hydrolysis, the enzyme was inactivated at 95°C, the solution was cooled, and the solution was centrifuged (8000 r / min, 20 min). 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 enzymatic hydrolysate

[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, and 4 mg / mL), and their pancreatic lipase inhibition rates and IC values ​​were determined. 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 in the above steps were filtered through a 0.22 μm filter membrane and separated using a C18 reverse phase column (20 mm × 450 mm, 10 μm). A total of 9 components were isolated and named P1 to P9. The chromatographic conditions were as follows: 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%-50% mobile phase B; 40-80 min, 50%-75% mobile phase B; 80-85 min, 75%-90% mobile phase B; 85-95 min, 90%-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 ability, and the fraction with the highest pancreatic lipase inhibition rate was screened for subsequent experiments.

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

[0049] A 1 mg / mL solution of 4-nitrophenyl laurate was used as the reaction substrate, which contained 0.05 mol / 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 later use. The reaction substrate, the sample solution to be tested, and the reaction buffer (pH 8.2, 0.1 mol / L Tris-HCl buffer) were added to a 2 mL test tube in sequence. Finally, a pancreatic lipase solution (5 mg / mL) was added to initiate the reaction. The volume ratio of the added samples was 5:2:4:3. After incubation at 37°C for 2 hours, the absorbance was measured at a wavelength of 420 nm. A sample group without enzyme and a blank group without sample were also set up. The pancreatic lipase inhibition rate (PL) was calculated according to the following formula: PL (%) = [1-(A-A1) / A0] × 100;

[0050] Wherein, A is the absorbance value of the sample group to be tested; A1 is the absorbance value of the sample group without enzyme; A0 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 hydrolysate is as follows Figure 1 As shown. Figure 1 It can be seen that at a concentration of 4 mg / mL, the MW < 3 KDa component had the highest inhibition rate on pancreatic lipase, which was 68.65% ± 0.34%, and the IC 50 The lowest concentration 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 < 3kDa fraction separated by RP-HPLC and the pancreatic lipase inhibitory ability of the P1 to P9 fractions. 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. Identification by high performance liquid chromatography-tandem mass spectrometry

[0055] The P9 fraction was analyzed by LC-MS / MS equipped with an online nanospray ionization source. The system consisted of an Orbitrap Q-Exactive Plus mass spectrometer (ThermoFisher Scientific, MA, USA) connected to an EASY-nanoLC1200. A total of 1 μL of sample was loaded onto an Acclaim PepMap C18 analytical column, 75 μm x 25 cm. The sample was separated using a 60-min gradient with a controlled column flow rate of 300 nL / min, a column temperature of 40°C, and an electrospray voltage of 2 kV. The gradient started with 2% phase B and was increased nonlinearly to 35% at 47 min, then to 100% over 1 min, where it was 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 using PEAKSStudio version 10.6 (Bioinformatics Solutions Inc., Waterloo, Canada). PEAKSDB was used to search the uniprot-Fagopyrum tataricum database (version 2023, 382 entries) with a "none" digestion setting. Search parameters included a fragment ion mass tolerance of 0.02 Da, a precursor mass tolerance of 10 ppm, variable modifications: oxidation (M) 15.99, destruction (NQ) 0.98, and a protein cardiology score of at least one unique peptide; a peptide cardiology score of -101 gP ≥ 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. The original ligand methoxyundecylphosphonic acid (MUP) and metal ion of the receptor protein 1LPB were isolated 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 the ligand energy was minimized, and their rotation centers and rotation bonds were detected. After importing the receptor and ligand into the docking software, the docking box parameters were set. The docking parameters for the peptide to 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, and number modes = 10. The docking parameters for the peptide to 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, and number modes = 10. The docked conformation with the lowest binding energy was selected as the optimal conformation. A three-dimensional structure diagram of the peptide-enzyme interaction was created using PYMOL and visualized using Discovery Studio 2019. A two-dimensional interaction map was generated to analyze the interaction types 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 peptide sequences with a peptide length of no more than 10 amino acids and no modification groups.

[0061] The 40 peptides were ranked based on their molecular docking binding energy, with lower binding energies indicating better binding efficacy. One lipid-lowering peptide, NAIIGPRW, was identified and subsequently named NW-8, using the initials and final letters of the peptide sequence and its length. The identification results and peptide characteristics of the lipid-lowering peptide 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 peptide and pancreatic lipase (PDB: 1LPB). Figure 3It can be seen that NW-8 generates electrostatic interactions with 1LPB at amino acid residues PHE215 and GLU233, forms hydrogen bonds at amino acid residues ASN212, LEU213, LYS238, ARG256, and ALA259, forms carbon-hydrogen bonds at amino acid residues PHE77, HIS151, and HIS263, forms π-cation electrostatic interactions at amino acid residue ARG256, forms π-donor hydrogen bonds with amino acid residue PHE215, generates π-πT-shape hydrophobic interactions with amino acid residue TRP252, and forms 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 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 lipid-lowering active peptide NW-8 obtained after molecular docking was prepared into test sample solutions of different concentrations (50, 100, 200, 400, 800 μg / mL), and Orlistat, a key drug for treating 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 As can be seen, when the concentration of the lipid-lowering peptide is between 50 and 800 μg / mL, it has a strong inhibitory effect on pancreatic lipase, and the effect is concentration-dependent. At a concentration of 800 μg / mL, NW-8 has a maximum inhibition rate of 74.68% ± 1.19% on pancreatic lipase. This demonstrates that the lipid-lowering peptide of the present invention has excellent pancreatic lipase inhibition ability.

[0070] Example 5 Determination of the lipid-lowering activity of lipid-lowering 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 cell culture incubator at 5% CO2 and 37°C. 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, wherein 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 in High-fat Model

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

[0076] 3. Oil Red O Staining

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

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

[0079] After differentiation was completed, the old culture medium was discarded and the cells were washed once with PBS. 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 disrupted with lysis buffer, and the TG, TC, HDL-C and LDL-C levels in the cells were determined.

[0080] Figure 6 The following is the toxicity test results of lipid-lowering peptide 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 peptide 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 higher the concentration, the fewer 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, the lipid-lowering peptide decreased by 36.21±1.22% compared with the model group, indicating that the lipid-lowering peptide of the present invention can effectively inhibit the differentiation of 3T3-L preadipocytes.

[0083] Figure 9 The figure shows the lipid-lowering activity of lipid-lowering peptides in 3T3-L1 preadipocytes. Figure 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. Figure 9 As shown in Figure B, 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. Figure 9 It can be seen from C 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 increased by 112.00%±48.08% compared with the model group. Figure 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 decreased 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 lower total cholesterol, triglycerides and high-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 the purpose of clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Those skilled in the art will appreciate that other variations or modifications can be made based on the above description. It is not necessary and impossible to enumerate all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection 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, characterized in that: The hyperlipidemia-related disease is obesity and / or hyperlipidemia.

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

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

6. The use according to claim 3, characterized in that The drug is a triglyceride-lowering drug.

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.

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