Small molecule peptide for reducing blood fat and application thereof

Abstract

The invention relates to a blood fat reducing small molecule peptide and application thereof. The sequence of the blood fat reducing small molecule peptide is LPSYSNAPYI, and the blood fat reducing small molecule peptide has a good pancreatic lipase activity inhibition effect and can effectively inhibit preadipocyte differentiation. The blood fat-reducing small molecule peptide can reduce the level of total cholesterol, triglyceride and low-density lipoprotein cholesterol and promote the increase of high-density lipoprotein cholesterol at the same time. In addition, a cytotoxicity test proves that the blood fat reducing small molecule peptide has very high safety.

Description

Technical Field

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

[0002] Obesity is usually accompanied by complications such as hyperlipidemia. Hyperlipidemia generally refers to increased total cholesterol (TC) and / or triglycerides (TG) in the blood, increased low-density lipoprotein cholesterol (LDL-C), and may also be accompanied by a decrease in high-density lipoprotein cholesterol (HDL-C). Due to the increasing incidence of complications such as obesity or hyperlipidemia caused by unhealthy lifestyles and high-fat diets, society has an even more urgent need for health products and medicines containing lipid-lowering ingredients. Bioactive peptides are a class of protein fragments that can actively regulate body functions and play an important role in maintaining and promoting physical health. Bioactive peptides derived from a variety of animals and plants have shown significant lipid-lowering effects.

[0003] Buckwheat has been proven to contain many substances that are beneficial to human health. Current studies have shown that it has good auxiliary therapeutic effects such as lowering blood sugar, lowering blood pressure and anti-cancer. For example, Zhou et al. (DOI: 10.1016 / j.fct.2018.02.052) found that buckwheat protein can not only maintain healthy plasma cholesterol levels by increasing the binding and excretion of bile acids, but also improve intestinal microbiota imbalance, inhibit inflammation, and increase intestinal short-chain fatty acids, thereby preventing high-fat diet-induced hypercholesterolemia. However, there is still little research on buckwheat protein, and the lipid-lowering activity mechanism of its enzymatic components is still unclear. Summary of the invention

[0004] The primary purpose of the present invention is to overcome the problem that the existing bioactive peptides with lipid-lowering activity are still relatively scarce, and to provide a lipid-lowering small molecule peptide. The lipid-lowering small molecule peptide has a good effect of inhibiting pancreatic lipase activity and can effectively inhibit pre-adipocyte differentiation. The lipid-lowering small molecule peptide can reduce the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol, while promoting the increase of high-density lipoprotein cholesterol.

[0005] A further object of the present invention is to provide the use of the above-mentioned lipid-lowering small molecule peptide in the preparation of drugs for preventing and / or treating diseases related to hyperlipidemia.

[0006] Another object of the present invention is to provide the use of the above-mentioned lipid-lowering small molecule peptide in the preparation of health care products that assist in lowering blood lipids.

[0007] Another object of the present invention is to provide a composition.

[0008] The above-mentioned object of the present invention is achieved by the following technical solutions:

[0009] A lipid-lowering small molecule peptide, wherein the lipid-lowering small molecule peptide is the sequence shown in SEQ ID NO: 1.

[0010] The lipid-lowering small molecule peptide of the present invention is derived from tartary buckwheat, and the sequence of the lipid-lowering small molecule peptide is as follows: LPSYSNAPYI (leu-pro-ser-tyr-ser-asn-ala-pro-tyr-ile).

[0011] The inventors of the present invention have found through research that the lipid-lowering small molecule peptide of the present invention has a good effect of inhibiting pancreatic lipase activity and can effectively inhibit pre-adipocyte differentiation. The lipid-lowering small molecule peptide can reduce the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol, while promoting the increase of high-density lipoprotein cholesterol. In addition, the lipid-lowering small molecule peptide has been proven to have high safety through cytotoxicity tests.

[0012] The lipid-lowering small molecule peptides involved in the present invention can be prepared by two ways: one is to extract by enzymatic hydrolysis of tartary buckwheat and subsequent separation and purification steps; the other is to synthesize by solid phase synthesis. The solid phase synthesis method can not only achieve large-scale production, but also ensure that the synthesized lipid-lowering small molecule peptides have high purity and stable product quality, thereby having obvious competitive advantages in the market.

[0013] The use of the above-mentioned lipid-lowering small molecule peptide in the preparation of drugs for preventing and / or treating diseases related to hyperlipidemia is also within the protection scope of the present invention.

[0014] Generally, the drug is a drug that inhibits the activity of pancreatic lipase.

[0015] Generally, the drug is a drug that lowers at least one of total cholesterol, triglycerides or low-density lipoprotein cholesterol.

[0016] Typically, the drug is a drug that increases high-density lipoprotein cholesterol.

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

[0018] Generally, the dosage form of the drug is at least one of injection, tablet, oral solution, granule or capsule.

[0019] Generally, the hyperlipidemia-related disease is obesity and / or hyperlipidemia.

[0020] The present invention also protects the use of the above-mentioned lipid-lowering small molecule peptide in the preparation of health care products for assisting in lowering blood lipids.

[0021] A composition comprises the above-mentioned lipid-lowering small molecule peptide.

[0022] Generally, the content of the lipid-lowering small molecule peptide in the composition is 1 to 800 μg / mL.

[0023] Generally, the composition also includes a pharmaceutically acceptable carrier or excipient.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] The lipid-lowering small molecule peptide of the present invention has a good effect of inhibiting pancreatic lipase activity and can effectively inhibit pre-adipocyte differentiation. The lipid-lowering small molecule peptide can reduce the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol, while promoting the increase of high-density lipoprotein cholesterol. In addition, the lipid-lowering small molecule peptide has been proven to have high safety through cytotoxicity tests. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The pancreatic lipase inhibition ability graph of two ultrafiltration fractions MW < 3kDa, MW > 3kDa and the enzymatic hydrolysate.

[0027] Figure 2 This is a graph showing the pancreatic lipase inhibitory ability of components P1 to P9.

[0028] Figure 3 It is the binding site and interaction force between the lipid-lowering small molecule peptide and pancreatic lipase (PDB: 1LPB).

[0029] Figure 4 The binding site and interaction force between the lipid-lowering small molecule peptide and cholesterol esterase (PDB: 1F6W).

[0030] Figure 5 This is a graph showing the pancreatic lipase inhibitory ability of lipid-lowering small molecule peptides.

[0031] Figure 6 This is a graph showing the toxicity test results of lipid-lowering small molecule peptides and orlistat.

[0032] Figure 7 This is the Oil Red O staining result of lipid-lowering small molecule peptide and orlistat.

[0033] Figure 8 This is the absorbance value at 520nm of lipid droplets stained with Oil Red O and orlistat after being dissolved in isopropanol.

[0034] Fig. 9 This is a graph showing the lipid-lowering activity of lipid-lowering small molecule 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

[0035] 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.

[0036] The method for determining the pancreatic lipase (PL) inhibition rate of the present invention is as follows:

[0037] 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 constant temperature 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-(A-A1) / A0] × 100;

[0038] 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.

[0039] The test data processing method of each embodiment of the present invention is as follows:

[0040] 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.

[0041] Example 1 Extraction and enzymolysis of buckwheat protein, and separation and purification of the enzymolyzate

[0042] 1. Extraction and enzymatic hydrolysis of 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 of the prior art "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, cooled, and centrifuged (8000r / min, 20min). The supernatant was the enzymatic hydrolyzate containing the lipid-lowering small molecule peptides, which was freeze-dried to obtain the enzymatic hydrolyzate.

[0045] 2. Separation and purification of enzymatic hydrolysates

[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 their pancreatic lipase inhibition rate and IC 50 Value, the result is Figure 1 shown.

[0047] 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 the IC of MW < 3kDa components 50 The lowest was only 0.019 mg / mL. Therefore, the fraction with MW < 3 kDa was selected for further purification.

[0048] The ultrafiltration fraction with MW < 3 kDa was purified by reverse phase high performance liquid chromatography (RP-HPLC). The ultrafiltration fraction with MW < 3 kDa was passed through a filter membrane (0.22 μm) and separated using a C18 reverse phase column (20 mm × 450 mm, 10 μm). A total of 9 fractions were separated 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% 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 1 mg / mL concentrations to determine their pancreatic lipase inhibitory ability and screen out the components with the strongest pancreatic lipase inhibitory rate. The results are as follows Figure 2 shown.

[0049] Figure 2 The figure shows the pancreatic lipase inhibitory ability of components P1 to P9. Figure 2 It can be seen that the P9 component has the highest pancreatic lipase inhibitory activity. At a concentration of 1 mg / mL, its pancreatic lipase inhibition rate reached 68.23% ± 0.98%, which is significantly higher than other components. Therefore, the P9 component was selected for the subsequent identification of peptide components.

[0050] Example 2 Identification of peptide composition, molecular docking and determination of pancreatic lipase inhibition rate

[0051] 1. Identification of P9 components by HPLC-MS / MS

[0052] 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.

[0053] 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.

[0054] 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.

[0055] A total of 2662 peptide sequences were identified for the P9 component using the above method, of which 40 were small molecule peptides with a length of no more than 10 amino acids and no modification groups.

[0056] 2. Molecular docking

[0057] 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.

[0058] 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 small molecule peptide was screened out, LPSYSNAPYI, which will be named LI-10 using the first and last letters of the peptide sequence and the length of the peptide. The identification results of the lipid-lowering small molecule peptide and its peptide characteristics are shown in Table 1.

[0059] Table 1 Identification results and peptide characteristics of lipid-lowering small molecule peptides

[0060]

[0061]

[0062] Figure 3 The binding site and interaction force between the lipid-lowering small molecule peptide and pancreatic lipase (PDB: 1LPB). Figure 3It can be seen that LI-10 forms a salt bridge with 1LPB at GLU64, hydrogen bonds with GLU13, CYS39, ASP331, LYS367 and GLN368, carbon-hydrogen bonds with THR29, and π-alkyl and alkyl hydrophobic interactions with ALA40, CYS61, LEU41, ALA332, ARG38, ILE248 and LYS42.

[0063] Figure 4 The binding site and interaction force between the lipid-lowering small molecule peptide and cholesterol esterase (PDB: 1F6W). Figure 4 It can be seen that LI-10 forms hydrogen bonds with 1F6W at LEU527, PHE351, LYS231, ASN2332, TRP236, HIS283, PRO226, and ILE229, carbon-hydrogen bonds with PHE235, LYS231, HIS238, and VAL391, π-cation electrostatic interactions with amino acid residue HIS283, π-donor hydrogen bonds with TRP522, π-πT-shape hydrophobic interactions with PHE235, and π-alkyl and alkyl interactions with VAL395, PRO396, PRO226, and ILE229, respectively.

[0064] The above results indicate that lipid-lowering small molecule peptides bind to receptors through hydrogen bonds, π-π bonds, hydrophobic, electrostatic and other interactions. These interactions enhance the binding of lipid-lowering small molecule peptides and receptor proteins or change the spatial conformation of the enzyme, thereby affecting its normal physiological function and showing a lipid-lowering effect.

[0065] 3. Determination of pancreatic lipase inhibition rate

[0066] Pancreatic lipase (PL) is a key enzyme in fat metabolism. The LI-10 lipid-lowering small molecule 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.

[0067] from Figure 5It can be seen that when the concentration of lipid-lowering small molecule peptides 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 inhibition rate of LI-10 on pancreatic lipase is 73.92%±1.24%. The inhibition rate of lipid-lowering small molecule peptides on pancreatic lipase is higher than that of existing bioactive peptides on pancreatic lipase. For example, Zhang et al. (DOI: 10.1016 / j.foodres.2023.113813) extracted the peptide YPGFGK from the larvae of white-spotted flower beetles, and the inhibition rate of this peptide on pancreatic lipase IC 50 The above indicates that the lipid-lowering small molecule peptide of the present invention has excellent pancreatic lipase inhibition ability.

[0068] Example 3 Toxicity determination of lipid-lowering small molecule peptides

[0069] LPSYSNAPYI was synthesized by Nanjing Jiepeptide Biotechnology Co., Ltd. (Nanjing, Jiangsu, China) with a purity of 98% and was used in the following experiments.

[0070] 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, where the test group included LI-10 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.

[0071] Figure 6 The following is a graph showing the toxicity test results of lipid-lowering small molecule 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 small molecule 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.

[0072] Example 4 Experiment on inhibiting differentiation of preadipocytes

[0073] Differentiation induction of high-fat model: 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.

[0074] After differentiation is complete, discard the old culture medium, wash the cells with PBS buffer, and 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 solution and cover the cells for 20 seconds. After removing the wash solution, add an appropriate amount of Oil Red O staining solution, stain for 30 minutes, remove the staining solution, wash with staining solution for 30 seconds, wash with PBS for 20 seconds, and discard PBS. Cover the cells evenly with PBS again, observe and take pictures under a microscope, and the results are as follows Figure 7 After taking the photo, discard the PBS, add 500 μL of isopropanol to the 24-well plate and shake for 5 minutes, and measure the absorbance at a wavelength of 520 nm. The results are shown in Figure 8 shown.

[0075] from 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 small molecule peptide of the present invention was added was reduced, and the greater the concentration, the fewer lipid droplets in the cells. Figure 8 It can be seen that when the concentration of the lipid-lowering small molecule peptide of the present invention is 40 μg / mL, it is reduced by 18.38%±1.38% compared with the model group, which indicates that the lipid-lowering small molecule peptide of the present invention can effectively inhibit the differentiation of 3T3-L preadipocytes.

[0076] Example 5 Determination of TC, TG, HDL-C and LDL-C Contents

[0077] The 3T3-L1 preadipocytes were differentiated according to the high-fat model differentiation induction steps of Example 4. After the 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 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 a lysis buffer, and the TG, TC, HDL-C and LDL-C contents in the cells were measured. The results are shown in FIG. Fig. 9 shown.

[0078] from Fig. 9 A. Fig. 9 B and Fig. 9 D It can be seen that at a concentration of 40 μg / mL, LI-10 lipid-lowering small molecule peptide can reduce the content of TG, TC and LDL-C in cells, which decreased by 61.37%±8.10%, 58.2%±6.09% and 69.75%±10.58% respectively compared with the model group.

[0079] from Fig. 9 C It can be seen that at a concentration of 40 μg / mL, LI-10 lipid-lowering small molecule peptide can increase the content of HDL-C in cells, which is 321.60%±43.29% higher than that in the model group.

[0080] The above experiments show that the lipid-lowering small molecule peptide of the present invention can reduce the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol, while promoting the increase of high-density lipoprotein cholesterol.

[0081] 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 small molecule peptide, characterized in that: The lipid-lowering small molecule peptide is the sequence shown in SEQ ID NO:

1.

2. Use of the lipid-lowering small molecule peptide according to claim 1 in the preparation of drugs for preventing and / or treating diseases related to hyperlipidemia.

3. The use according to claim 2, characterized in that: The drug is a drug that inhibits the activity of pancreatic lipase.

4. The use according to claim 2, characterized in that: The drug is a drug for lowering at least one of total cholesterol, triglycerides or low-density lipoprotein cholesterol.

5. The use according to claim 2, characterized in that: The drug is a drug for increasing high-density lipoprotein cholesterol.

6. The use according to claim 2, characterized in that: The drug is a drug for inhibiting the differentiation of preadipocytes.

7. The use according to claim 2, characterized in that: The dosage form of the drug is at least one of injection, tablet, oral solution, granule or capsule.

8. The use according to claim 2, characterized in that: The hyperlipidemia-related disease is obesity and / or hyperlipidemia.

9. Use of the lipid-lowering small molecule peptide according to claim 1 in the preparation of a health product for assisting in lowering blood lipids.

10. A composition, characterized in that It includes the lipid-lowering small molecule peptide according to claim 1.

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