A lipid-lowering small molecule peptide and its application

Abstract

The present invention relates to a lipid-lowering small-molecule peptide and its use. The lipid-lowering small-molecule peptide has the sequence LPSYSNAPYI and effectively inhibits pancreatic lipase activity and preadipocyte differentiation. This lipid-lowering small-molecule peptide can reduce levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, while promoting an increase in high-density lipoprotein cholesterol. Furthermore, this lipid-lowering small-molecule peptide has been shown to be highly safe through cytotoxicity testing.

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 applications thereof. Background Art

[0002] Obesity is often accompanied by complications such as hyperlipidemia. Hyperlipidemia generally refers to elevated total cholesterol (TC) and / or triglycerides (TG) in the blood, elevated low-density lipoprotein cholesterol (LDL-C), and may also be accompanied by decreased 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 ingredients that lower blood lipids. 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 shown to contain many substances that are beneficial to human health. Current studies have shown that it has excellent 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 enzymatically hydrolyzed components is still unclear. Summary of the Invention

[0004] The primary objective of the present invention is to overcome the aforementioned problem of a relative lack of existing bioactive peptides with lipid-lowering activity and to provide a lipid-lowering small-molecule peptide. This lipid-lowering small-molecule peptide effectively inhibits pancreatic lipase activity and preadipocyte differentiation. This lipid-lowering small-molecule peptide can lower levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, while promoting an increase in 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 a drug 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 products that assist in lowering blood lipids.

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

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

[0009] A lipid-lowering small molecule peptide, wherein the lipid-lowering small molecule peptide has 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] Through research, the inventors of the present invention have discovered that the lipid-lowering small-molecule peptide of the present invention effectively inhibits pancreatic lipase activity and can effectively inhibit preadipocyte differentiation. This lipid-lowering small-molecule peptide can reduce levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, while promoting an increase in high-density lipoprotein cholesterol. Furthermore, this lipid-lowering small-molecule peptide has been shown to be highly safe through cytotoxicity testing.

[0012] The lipid-lowering small-molecule peptides described in this invention can be prepared through two approaches: extraction via enzymatic hydrolysis of tartary buckwheat followed by isolation and purification; and synthesis via solid-phase synthesis. The solid-phase synthesis method not only enables large-scale production but also ensures high purity and stable product quality of the synthesized lipid-lowering small-molecule peptides, thus providing a significant competitive advantage 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 scope of protection of the present invention.

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

[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 an 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 that assist in lowering blood lipids.

[0021] A composition comprising 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] Typically, 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 peptide of the present invention effectively inhibits pancreatic lipase activity and can effectively inhibit preadipocyte differentiation. It can reduce levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, while promoting an increase in high-density lipoprotein cholesterol. Furthermore, the lipid-lowering peptide has been shown to be highly safe through cytotoxicity testing. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Figure 2 shows the pancreatic lipase inhibitory ability of two ultrafiltration fractions with MW < 3 kDa, MW > 3 kDa and the hydrolyzate.

[0027] Figure 2 This is a graph showing the pancreatic lipase inhibitory ability of fractions 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 diagram showing the toxicity test results of lipid-lowering small molecule peptides and orlistat.

[0032] Figure 7 The results of Oil Red O staining of lipid-lowering small molecule peptides and orlistat are shown.

[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] Figure 9 The figure shows the lipid-lowering activity assay of lipid-lowering small molecule 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

[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 determination method of pancreatic lipase (PL) inhibition rate of the present invention is as follows:

[0037] 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 as follows: 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 methods of various embodiments of the present invention are as follows:

[0040] 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.

[0041] Example 1 Extraction and enzymatic hydrolysis of tartary buckwheat protein, and separation and purification of the enzymatic hydrolysate

[0042] 1. Extraction and enzymatic hydrolysis of 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% tartary buckwheat crude protein solution was prepared, and the optimal enzymatic hydrolysis process of the prior art "Enzymatic Preparation, Amino Acid Composition and Activity of Tartary 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 centrifuged (8000 r / min, 20 min). The supernatant was the enzymatic hydrolyzate containing the lipid-lowering small molecule peptide, 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 rates and IC values ​​were determined. 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 hydrolysate is as follows Figure 1 As shown. Figure 1 It can be seen that the IC of the component with MW < 3kDa 50 The lowest concentration was only 0.019 mg / mL. Therefore, the fraction with MW < 3 kDa was selected for further purification.

[0048] The ultrafiltration fraction with a MW <3 kDa was purified by reversed-phase high-performance liquid chromatography (RP-HPLC). The ultrafiltration fraction was filtered through a 0.22 μm membrane and separated using a C18 reversed-phase column (20 mm × 450 mm, 10 μm). Nine fractions were isolated and designated P1 to P9. 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 1 mg / mL concentration to determine their pancreatic lipase inhibitory ability and screen out the component 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 As can be seen, fraction P9 has the highest pancreatic lipase inhibitory activity. At a concentration of 1 mg / mL, its pancreatic lipase inhibition rate reached 68.23% ± 0.98%, significantly higher than that of other fractions. Therefore, fraction P9 was selected for subsequent peptide composition identification.

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

[0051] 1. Identification of P9 components by high performance liquid chromatography-tandem mass spectrometry

[0052] 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.

[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 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.

[0055] A total of 2,662 peptide sequences were identified for the P9 component using the above method, including 40 small molecule peptide sequences with a peptide 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. 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.

[0058] The 40 peptides were ranked based on their molecular docking binding energy, with lower binding energies indicating better binding efficacy. A single lipid-lowering peptide, LPSYSNAPYI, was identified and subsequently named LI-10, using the initials and final letters of the peptide sequence and its length. The identification results and peptide characteristics of this lipid-lowering peptide 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 bond 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-cationic 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, VAL391, and ILE353, respectively.

[0064] The above results show that lipid-lowering small molecule peptides bind to receptors through hydrogen bonds, π-π bonds, hydrophobic, electrostatic and other interactions. These interactions will 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 test sample solutions of different concentrations (50, 100, 200, 400, and 800 μg / mL). 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.

[0067] from Figure 5It can be seen that when the concentration of the lipid-lowering small molecule 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 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 the white star flower beetle, and the inhibition rate of this peptide on pancreatic lipase IC 50 The above results indicate that the lipid-lowering small molecule peptide of the present invention has excellent pancreatic lipase inhibitory 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 Cells were inoculated into 96-well plates at 100 μL / mL, and blank and experimental groups were set up, where the experimental 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 experimental group. After 24 hours of continuous culture, 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 the toxicity test results of lipid-lowering small molecule 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 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 Inhibition of Preadipocyte Differentiation

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

[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, then wash with PBS for 20 seconds, and discard PBS. Cover the cells evenly with PBS again, observe under a microscope and take pictures. 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 the figure. 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 higher 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, the lipid-lowering small molecule peptide 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] 3T3-L1 preadipocytes were differentiated according to the high-fat model differentiation induction steps of Example 4. After differentiation, the old culture medium was discarded and the cells were washed once with PBS. The cells were collected according to the procedures 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). The cells were disrupted with lysis buffer and the TG, TC, HDL-C, and LDL-C levels in the cells were measured. The results are shown in FIG. Figure 9 shown.

[0078] from Figure 9 A. Figure 9 B and Figure 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 Figure 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 increased by 321.60%±43.29% compared with 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 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 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 a drug for preventing and / or treating hyperlipidemia-related diseases, characterized in that: The hyperlipidemia-related disease is obesity and / or hyperlipidemia.

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

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 that inhibits 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. 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.

9. A composition, characterized in that The invention comprises the lipid-lowering small molecule peptide according to claim 1.

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