Oligopeptide and application thereof in preparation of products for improving vascular endothelial dysfunction

Abstract

The invention relates to oligopeptide and application thereof in preparation of products for improving vascular endothelial dysfunction, and belongs to the technical field of biology. The invention provides an oligopeptide, wherein the amino acid sequence of the oligopeptide is Ala-Ile-Pro-Tyr-Leu. The invention also provides a preparation method of the oligopeptide. The oligopeptide AIPYL provided by the invention has remarkable innovativeness and advantages in the aspect of improving vascular endothelial cell dysfunction. Through multi-target collaborative regulation and control, ACE activity is inhibited, NO generation is promoted, ET-1 generation is inhibited, an antioxidant defense system is enhanced, inflammatory factors are reduced, adhesion factor expression is reduced, and comprehensive and effective treatment potential is shown. Compared with the prior art, the AIPYL peptide fragment not only has higher activity and efficiency, but also has no toxic or side effect, and provides a new potential strategy for treatment of vascular endothelial dysfunction.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, in particular to an oligopeptide and application thereof in the preparation of a product for improving vascular endothelial dysfunction. Background Art

[0002] Endothelial cells, the single cell layer lining the blood vessels, play a crucial role in maintaining vascular homeostasis and health. They ensure the proper functioning of the vascular system by regulating vascular permeability, controlling vasoconstriction and relaxation, maintaining vascular integrity, and participating in blood anticoagulation and coagulation. When endothelial cells fail to function properly, endothelial dysfunction occurs. This dysfunction is the initial stage of cardiovascular disease development and can lead to a variety of conditions, including hypertension, diabetes, atherosclerosis, and heart failure.

[0003] Endothelial dysfunction is a key pathological basis for various cardiovascular diseases, and its mechanisms involve an imbalance in the interactions between oxidative stress and multiple signaling pathways. Under pathological conditions, angiotensin-converting enzyme (ACE) activity is abnormally elevated, catalyzing increased production of angiotensin II (Ang II). Ang II, through activation of the angiotensin II type 1 receptor (AT1R), triggers a burst of NADPH oxidase (NOX)-dependent reactive oxygen species (ROS). Simultaneously, the activity of antioxidant enzymes (such as catalase (CAT) and glutathione (GSH)) is reduced, exacerbating oxidative damage and leading to the accumulation of malondialdehyde (MDA), the end product of lipid peroxidation. ROS decouple endothelial nitric oxide synthase (eNOS) by consuming tetrahydrobiopterin (BH4), inhibiting nitric oxide (NO) synthesis and promoting the synthesis and release of endothelin-1 (ET-1). Reduced NO secretion is a key hallmark of endothelial dysfunction. It not only impairs NO-mediated vasodilation and anti-inflammatory functions but also promotes monocyte adhesion and inflammatory infiltration by reducing its inhibitory effect on vascular cell adhesion molecule (VCAM-1), further exacerbating endothelial damage. Therefore, targeted inhibition of ACE activity, blocking AT1R signaling, restoring NO homeostasis, reducing ET-1 secretion, and enhancing antioxidant defenses have become key strategies for improving endothelial dysfunction. However, current clinical interventions are limited, primarily relying on ACE inhibitors such as captopril and plant-derived bioactive peptides.

[0004] Captopril is an angiotensin-converting enzyme inhibitor. Although it can improve endothelial dysfunction, it is often accompanied by adverse reactions such as cough, gastrointestinal problems, and hypotension, and even serious side effects such as renal damage and hyperkalemia. CN 117229355 A discloses an active peptide derived from pumpkin seed cake, its preparation method, and its use. Although the active peptide monomer prepared by this patented technology has a good ACE inhibitory effect, it reduces the production of ET-1 in EA.hy926 cells by more than 90% at an extremely low dose of 100 μg / mL. A significant reduction in ET-1 can also have an adverse effect on cardiovascular function, leading to the occurrence and development of a series of diseases (such as causing circulatory system symptoms such as hypotension), posing certain safety risks.

[0005] Therefore, there is an urgent need to develop new drugs with multi-target synergistic regulation for use in the preparation of products to improve vascular endothelial dysfunction. Summary of the Invention

[0006] The purpose of the present invention is to overcome the shortcomings of the prior art and provide an oligopeptide having the effect of improving vascular endothelial dysfunction and its use in the preparation of a product for improving vascular endothelial dysfunction.

[0007] To achieve the above object, the technical solution adopted by the present invention is:

[0008] In a first aspect, the present invention provides an oligopeptide having an amino acid sequence of Ala-Ile-Pro-Tyr-Leu.

[0009] The amino acid sequence of the oligopeptide of the present invention is Ala-Ile-Pro-Tyr-Leu, and experiments have confirmed that the oligopeptide has the activity of inhibiting angiotensin converting enzyme (ACE).

[0010] In a second aspect, the present invention provides the use of oligopeptides in the preparation of angiotensin-converting enzyme inhibitors.

[0011] In a third aspect, the present invention provides an angiotensin-converting enzyme inhibitor, comprising the above-mentioned oligopeptide.

[0012] In a fourth aspect, the present invention provides the use of the oligopeptide described above in the preparation of a product for improving endothelial dysfunction. Experiments conducted by the present invention demonstrate that the oligopeptide AIPYL has the following effects:

[0013] (1) It promotes the production of NO factor by endothelial cells, helps to dilate blood vessels and relieve endothelial dysfunction.

[0014] (2) Inhibits the production of endothelin ET-1, a potent vasoconstrictor factor whose overexpression is closely related to endothelial dysfunction.

[0015] (3) Excellent antioxidant effect, which can increase GSH content and CAT activity, while reducing MDA content, helping to reduce oxidative stress damage and restore the normal function of endothelial cells.

[0016] (4) Significantly reduce the production of TNF-α, thereby alleviating vascular inflammatory response.

[0017] (5) It significantly reduces the expression levels of adhesion factors VCAM-1 and ICAM-1, reduces the adhesion and migration of leukocytes to the vascular endothelium, and thus reduces the inflammatory response and endothelial damage. This effect helps to restore the normal function of endothelial cells.

[0018] The oligopeptide of the present invention exhibits comprehensive and effective therapeutic potential through multi-target synergistic regulation, including inhibiting ACE activity, promoting NO production, inhibiting ET-1 production, enhancing the antioxidant defense system, reducing inflammatory factors and reducing adhesion factor expression.

[0019] As a preferred embodiment of the application of the present invention, the products for improving vascular endothelial dysfunction include medicines, foods, health products and cosmetics.

[0020] As a preferred embodiment of the application of the present invention, the oligopeptide can be compounded with an ACE inhibitor and / or a drug for improving vascular endothelial dysfunction to form a product for improving vascular endothelial dysfunction.

[0021] In a fifth aspect, the present invention provides a product having the effect of improving vascular endothelial dysfunction, comprising the above-mentioned oligopeptide.

[0022] As a preferred embodiment of the product of the present invention, the product further comprises auxiliary materials.

[0023] As a preferred embodiment of the product of the present invention, the auxiliary material includes at least one of a flavoring agent, a thickener, a disintegrant, and a filler.

[0024] As a preferred embodiment of the product of the present invention, the dosage form of the composition for improving vascular endothelial cell dysfunction is at least one of capsules, pills, oral liquids, tablets, granules, powders and injections.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The oligopeptide AIPYL provided by this invention offers significant innovation and advantages in improving endothelial cell dysfunction. It demonstrates comprehensive and effective therapeutic potential through multi-target synergistic regulation, including inhibition of ACE activity, promotion of NO production, inhibition of ET-1 production, enhancement of the antioxidant defense system, reduction of inflammatory factors, and decreased expression of adhesion factors. Compared with existing technologies, the AIPYL peptide segment not only exhibits higher activity and efficacy but also has no toxic side effects, providing a new potential strategy for the treatment of endothelial dysfunction. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is a liquid chromatogram of the oligopeptide AIPYL in Example 1 of the present invention;

[0028] Figure 2 This is the mass spectrum of the oligopeptide AIPYL in Example 1 of the present invention;

[0029] Figure 3 The results of the determination of the ACE inhibition rate of oligopeptide AIPYL at different concentrations in Example 1 of the present invention are as follows;

[0030] Figure 4 The results of the measurement of the effect of AIPYL on NO factor production by vascular endothelial cells in Example 2 of the present invention;

[0031] Figure 5 The results of the measurement of the effect of AIPYL on the production of ET-1 by vascular endothelial cells in Example 2 of the present invention;

[0032] Figure 6 The results of the determination of the effect of AIPYL on the antioxidant factors of vascular endothelial cells in Example 2 of the present invention, wherein A is reduced glutathione, B is catalase, and C is malondialdehyde;

[0033] Figure 7 The results of the measurement of the effect of AIPYL on the production of inflammatory factors by vascular endothelial cells in Effect Example 2 of the present invention;

[0034] Figure 8 The results of the determination of the effect of AIPYL on the expression of adhesion factors by vascular endothelial cells in Example 2 of the present invention, wherein A is VCAM-1 and B is ICAM-1;

[0035] In the above figures, "#", "##" or "###" indicates that there is a significant difference compared with the blank control group (P < 0.05, P < 0.01 or P < 0.001); "*", "**" or "***" indicates that there is a significant difference compared with the model group (P < 0.05, P < 0.01 or P < 0.001);

[0036] In the above figure, a “-” in the horizontal axis indicates that the corresponding reagent was not added to the group, and a “+” indicates that the corresponding reagent was added to the group. DETAILED DESCRIPTION

[0037] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0038] Unless otherwise specified, other materials and reagents used in the examples can be obtained from commercial sources.

[0039] The techniques not described in detail in the following examples, comparative examples and effect examples are all commonly used techniques in the art. Please refer to "Molecular Biology Experiment Manual" (Ma Wenli, People's Military Medical Publishing House), "Molecular Biology Experiment (Second Edition)" (Zhejiang University Press), and "Cell Biology Experiment" (Yang Hongbing, Hou Lixia, Zhang Yuxi, Higher Education Press).

[0040] In the following examples and effect examples, "V" refers to valine (Val), "P" refers to proline (Pro), "G" refers to glycine (Gly), "H" refers to histidine (His), "R" refers to arginine (Arg), "K" refers to lysine (Lys), "I" refers to isoleucine (Ile), "F" refers to phenylalanine (Phe), "L" refers to leucine (Leu), "W" refers to tryptophan (Trp), "A" refers to alanine (Ala), "M" refers to methionine (Met), "C" refers to cysteine ​​(Cys), "N" refers to asparagine (Asn), "S" refers to serine (Ser), "Q" refers to glutamine (Gln), "Y" refers to tyrosine (Tyr), "D" refers to aspartic acid (Asp), "E" refers to glutamic acid (Glu), and "T" refers to threonine (Thr).

[0041] In the following examples and effects, AIPYL refers to the oligopeptide with the amino acid sequence of SEQ ID NO. 1.

[0042] HPLC-MS / MS parameters: Samples were separated and detected using a Waters 2695-ZQ2000 single quadrupole liquid chromatography-mass spectrometer (Waters, USA) using an ODS-SP column (4.6 × 250 mm × 5 μm) (Shimadzu, Japan). The mobile phase consisted of 0.1% (v / v) trifluoroacetic acid in water (A) and 0.1% (v / v) trifluoroacetic acid in acetonitrile (B). The elution ratio was 10% to 70% B (0–25.00 min), then 100% B (25.01–30.00 min). The flow rate was 1 mL / min, the injection volume was 30 μL, and the column temperature was 40°C. The percentages of mobile phases are expressed by volume, i.e., the volume of mobile phase B / (the total volume of mobile phases A and B). Mass spectrometry detection method: scan period 0.1S, ESI ion source temperature 100℃, positive ion mode, spray voltage 3000V, scanning range 300-1999Da.

[0043] In the following effect examples, the angiotensin-converting enzyme inhibitor activity detection kit was purchased from Beijing Solebow Technology Co., Ltd. with the catalog number BC5575;

[0044] The NO detection kit was purchased from Shanghai Biotech Biotechnology Co., Ltd., catalog number S0021S;

[0045] Human endothelin (ET-1) ELISA kit was purchased from Shanghai ELISA Biotechnology Co., Ltd., catalog number ml025101;

[0046] The reduced glutathione peptide detection kit was purchased from Beijing Solebow Technology Co., Ltd., catalog number BC1175;

[0047] The catalase activity detection kit was purchased from Beijing Box Biotechnology Co., Ltd., with the catalog number AKAO003-1U;

[0048] The lipid oxidation (malondialdehyde) activity detection kit was purchased from Shanghai Beyotime Biotechnology Co., Ltd., catalog number S0131S;

[0049] Human tumor necrosis factor (TNF-α) ELISA kit was purchased from Shanghai ELISA Biotechnology Co., Ltd., catalog number ml064303;

[0050] The reverse transcription kit was HiScript II Reverse Transcriptase purchased from Nanjing Novozymes Biotechnology Co., Ltd., catalog number R201-01;

[0051] Fluorescence quantitative PCR reagents were ChamQ Universal SYBR qPCR Master Mix purchased from Nanjing Novozymes Biotechnology Co., Ltd., catalog number Q711-02;

[0052] RNA extraction was completed using TRIzol reagent, and the source of TRIzol reagent was not limited.

[0053] The internal control for qRT-PCR was GAPDH. The primer sequences for VCAM-1 and ICAM-1 are as follows:

[0054] VCAM-1-F, 5'-TCTCATTGACTTGCAGCACCACAG-3';

[0055] VCAM-1-R, 5'-CCTCATTCGTCACCTTCCCATTCAG-3';

[0056] ICAM-1-F, 5′-GGTAGCAGCCGCAGTCATAATGG-3′;

[0057] ICAM-1-R, 5'-GTGGCTTGTGTGTTCGGTTTCATG-3'.

[0058] Example 1

[0059] This example provides an oligopeptide, which was synthesized by solid phase synthesis and commissioned to Nanjing Jiepeptide Biotechnology Co., Ltd. The synthesized oligopeptide was characterized by HPLC-MS / MS. The results are shown in Table 1 and Figure 1-2 The amino acid sequence of the oligopeptide is shown in SEQ ID NO.1.

[0060] Table 1 Oligopeptide identification results

[0061]

[0062] As shown in Table 1 and Figure 1-2 As shown, a solid-phase synthesis method was used to successfully prepare an oligopeptide with a purity of 97.05% and an amino acid sequence of Ala-Ile-Pro-Tyr-Leu, hereinafter referred to as AIPYL.

[0063] Effect Example 1

[0064] The efficacy of the oligopeptide AIPYL obtained in Example 1 was determined, and the specific protocol is as follows:

[0065] Effects on angiotensin-converting enzyme (ACE).

[0066] A 1 mg / mL oligopeptide solution was prepared by combining oligopeptide AIPYL with a buffer reagent. The 1 mg / mL oligopeptide solution was then diluted to 0.03125, 0.0625, 0.125, 0.25, and 0.5 mg / mL oligopeptide solutions, respectively. The 0.03125-1.0 mg / mL oligopeptide solutions were used as test samples. The inhibitory effect of oligopeptide AIPYL on ACE was determined by the microassay method described in the instructions of the angiotensin converting enzyme inhibitor activity assay kit. The results are shown in Tables 2 and Figure 3 .

[0067] Table 2 Effects of oligopeptide AIPYL on ACE inhibitory activity

[0068] Oligopeptide AIPYL concentration (mg / mL) ACE inhibition rate (%) 0.03125 43.41 0.06250 60.11 0.12500 63.64 0.25000 68.27 0.50000 75.51 1.00000 84.60

[0069] As shown in Table 2 and Figure 3 As shown in the results, oligopeptide AIPYL has a very strong ACE inhibitory effect. At a concentration of 1 mg / mL, the ACE inhibition rate is 84.60%. This shows that oligopeptide AIPYL inhibits the activity of ACE, reduces the production of angiotensin II, and reduces the degradation of bradykinin, thereby improving cardiovascular function.

[0070] Effect Example 2

[0071] In order to evaluate the effect of the oligopeptide AIPYL obtained in Example 1 on vascular endothelial cells, the oligopeptide AIPYL was co-cultured with vascular endothelial cells and relevant indicators were detected. The specific protocol is as follows:

[0072] In this example, human umbilical vein endothelial cells (HUVEC) were selected and cultured in DMEM containing 10% (v / v) fetal bovine serum at 37° C. and 5% CO 2 .

[0073] 1. NO factor.

[0074] HUVEC cells were plated and cultured in 6-well plates for 24 h. The culture medium was aspirated and culture medium (control group), hydrogen peroxide solution (model group, 6 mM hydrogen peroxide solution prepared with culture medium as solvent) or test sample solution (treatment group, 6 mM hydrogen peroxide solution and AIPYL solution prepared with culture medium as solvent, with AIPYL concentrations of 50, 100 and 200 μM, respectively) were added to each well. After incubation for 24 h, the NO content was detected according to the instructions of the NO kit. The results are shown in Tables 4 and Figure 4 .

[0075] Table 4 NO content detection results of HUVEC cells in different treatment groups

[0076]

[0077] As shown in Table 4 and Figure 4 As shown, there was a significant difference between the blank control group and the model group, indicating that hydrogen peroxide successfully induced endothelial cell dysfunction. Hydrogen peroxide causes endothelial cells to produce excessive reactive oxygen species (ROS), which oxidize BH4 and uncouple and inactivate endothelial nitric oxide synthase (eNOS), thereby reducing NO production and leading to endothelial dysfunction. The oligopeptide AIPYL exhibited significant effects on NO production at three different doses (50, 100, and 200 μM), and this effect was clearly dose-dependent. In particular, the 100 μM and 200 μM doses of AIPYL significantly increased NO production by 122.10% and 151.11%, respectively, compared to the model group. These results suggest that the AIPYL peptide has a very strong ability to promote NO production in vascular endothelial cells. Its mechanism of action may be related to activating endothelial nitric oxide synthase (eNOS) and increasing NO bioavailability, thereby contributing to vasodilation and alleviating endothelial dysfunction.

[0078] 2. Endothelin-1 (ET-1) factor.

[0079] HUVEC cells were treated according to the above NO factor determination experiment, and the level of ET-1 factor in cells was detected using ELISA kit. The results are shown in Table 5 and Figure 5 .

[0080] Table 5 ET-1 content detection results of HUVEC cells in different treatment groups

[0081]

[0082] As shown in Table 5 and Figure 5As shown, there was a significant difference between the blank control group and the model group, indicating that hydrogen peroxide successfully induced endothelial cell dysfunction, leading to a significant increase in endothelin-1 (ET-1) production. ET-1 is a potent vasoconstrictor, and its overexpression is often closely associated with endothelial dysfunction. The oligopeptide AIPYL exhibited a significant inhibitory effect on ET-1 production at three different doses (50, 100, and 200 μM), and this effect was clearly dose-dependent. Specifically, the oligopeptide AIPYL at doses of 50 μM, 100 μM, and 200 μM significantly reduced ET-1 production by 20.17%, 24.33%, and 32.15%, respectively. In particular, at the 200 μM dose, ET-1 production did not differ significantly from the blank control group, indicating that at this dose, the AIPYL peptide can restore ET-1 secretion from endothelial dysfunction cells to normal levels. Increased ET-1 production is often associated with oxidative stress and inflammation. By inhibiting ET-1 production, the oligopeptide AIPYL may play an important role in reducing oxidative stress, suppressing inflammation, and improving vascular tone. This mechanism of action helps alleviate endothelial dysfunction and restore normal vascular physiological function.

[0083] 3. Antioxidant factors.

[0084] HUVEC cells were treated according to the above NO factor determination experiment, and the contents of cellular reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) were determined according to the kit instructions. The results are shown in Tables 6 and Figure 6 .

[0085] Table 6 Results of GSH, CAT and MDA content detection in HUVEC cells in different treatment groups

[0086]

[0087]

[0088] AIPYL peptides showed significant antioxidant effects in improving endothelial cell dysfunction. Figure 6 As shown in the results, oligopeptide AIPYL could significantly increase GSH content and CAT activity, while significantly reducing MDA content at three different doses (50, 100, and 200 μM), indicating that it has strong antioxidant capacity.

[0089] Specifically, the oligopeptide AIPYL significantly increased the GSH content by 19.18% and 29.33% at doses of 100μM and 200μM, respectively, even exceeding the level of the normal group, indicating that the oligopeptide AIPYL can effectively enhance the antioxidant capacity of cells and protect cells from oxidative stress damage. In addition, the oligopeptide AIPYL significantly increased CAT activity, especially at a dose of 200μM, the CAT content increased by 237.89% relative to the model group, and the activity returned to the level of the normal group, further confirming its effectiveness in enhancing antioxidant enzyme activity. At the same time, the oligopeptide AIPYL significantly reduced the MDA content, and this reduction effect was significantly dose-dependent. At a dose of 200μM, the MDA content almost returned to the level of the blank control group, indicating that the AIPYL peptide can effectively inhibit lipid peroxidation and reduce oxidative stress damage.

[0090] Oxidative stress is a key mechanism of endothelial dysfunction. Excessive reactive oxygen species (ROS) can damage cell membranes and proteins, leading to endothelial dysfunction. The oligopeptide AIPYL enhances the antioxidant capacity of cells, inhibits lipid peroxidation, and alleviates oxidative stress damage, thereby helping to restore normal endothelial cell function. These results demonstrate that the oligopeptide AIPYL has significant antioxidant effects and can effectively improve endothelial cell dysfunction.

[0091] 4. Inflammatory factors.

[0092] HUVEC cells were plated and cultured in 6-well plates for 24 h. The culture medium was aspirated, and culture medium (control group), angiotensin II (Ang II) solution (model group, 10 μM angiotensin II solution prepared with culture medium as solvent) or test sample solution (treatment group, 10 μM Ang II solution and AIPYL solution prepared with culture medium as solvent, with AIPYL concentrations of 50, 100, and 200 μM, respectively) were added to each well. After incubation for 24 h, TNF-α content was detected according to the instructions of the ELISA kit. The results are shown in Tables 7 and Figure 7 .

[0093] Table 7 TNF-α content detection results of HUVEC cells in different treatment groups

[0094]

[0095]

[0096] As shown in Table 7 and Figure 7As shown, the oligopeptide AIPYL exhibits a significant effect in reducing the production of tumor necrosis factor (TNF-α) by vascular endothelial cells, thereby having a good effect in improving vascular endothelial cell dysfunction. Experimental data showed that the AIPYL peptide segment can significantly reduce the production of TNF-α at three different doses (50, 100, and 200 μM), and this reduction effect is clearly dose-dependent. The oligopeptide AIPYL at doses of 50 μM, 100 μM, and 200 μM significantly reduced the production of TNF-α by 22.67%, 29.34%, and 39.45%, respectively. In particular, at a dose of 200 μM, the production of TNF-α returned to the level of the blank control group, indicating that the oligopeptide AIPYL can effectively inhibit the overexpression of TNF-α.

[0097] TNF-α, as an important pro-inflammatory cytokine, plays a key role in endothelial dysfunction. Its overexpression can exacerbate vascular inflammation and further damage endothelial cells. The oligopeptide AIPYL, by significantly reducing TNF-α production, may play an important role in alleviating vascular inflammation, inhibiting endothelial cell damage, and improving vascular tone.

[0098] 5. Adhesion factors.

[0099] HUVEC cells were treated according to the above-mentioned inflammatory factor determination experiment, and total RNA of the cells was extracted. After reverse transcription, qRT-PCR was performed. The adhesion factors measured included VCAM-1 and ICAM-1. The results are shown in Figure 8 and Table 8.

[0100] Table 8 Relative expression results of VCAM-1 and ICAM-1 in HUVEC cells of different treatment groups

[0101]

[0102] like Figure 8 As shown in Table 8, the oligopeptide AIPYL reduced the mRNA expression of VCAM-1 and ICAM-1 at three different doses, and the reduction increased with increasing concentration. At a dose of 200 μM, there was a significant statistical difference compared to the model group, indicating that the AIPYL peptide can effectively inhibit the overexpression of these adhesion molecules, VCAM-1 and ICAM-1. VCAM-1 and ICAM-1, as important inflammation-related adhesion molecules, play a key role in endothelial dysfunction. Their overexpression can cause leukocyte adhesion and migration to the vascular endothelium, exacerbating the inflammatory response and endothelial damage. By significantly reducing the expression of VCAM-1 and ICAM-1, the oligopeptide AIPYL helps restore the normal function of endothelial cells.

[0103] In summary, the oligopeptide AIPYL of the present invention exhibits significant ACE inhibition, promoting NO production in endothelial cells, inhibiting ET-1 production, and reducing TNF-α production and adhesion cytokine expression. It also possesses excellent antioxidant properties and, through multi-target synergistic regulation, demonstrates comprehensive and effective therapeutic potential. The oligopeptide exhibits enhanced activity, efficiency, and safety, providing a new potential strategy for the treatment of endothelial dysfunction.

[0104] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. An oligopeptide, characterized in that: The amino acid sequence of the oligopeptide is Ala-Ile-Pro-Tyr-Leu.

2. Use of the oligopeptide according to claim 1 in the preparation of angiotensin-converting enzyme inhibitors.

3. An angiotensin-converting enzyme inhibitor, characterized in that The inhibitor comprises the oligopeptide according to claim 1.

4. Use of the oligopeptide according to claim 1 in the preparation of a product for improving vascular endothelial dysfunction.

5. Use of the oligopeptide according to claim 1 in the preparation of a product for improving cardiovascular function.

6. The use according to claim 5 or 6, characterized in that The products for improving vascular endothelial dysfunction include medicines, foods, health products and cosmetics.

7. A product having the effect of improving vascular endothelial dysfunction, characterized in that: The method comprises the oligopeptide according to claim 1.

8. The product according to claim 7, wherein The product also includes auxiliary materials.

9. The product according to claim 8, wherein The auxiliary materials include at least one of flavoring agents, thickeners, disintegrants, and fillers.

10. The product according to claim 7, wherein The dosage form of the product is at least one of capsule, pill, oral solution, tablet, granule, powder and injection.

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