CN113005165A

CN113005165A - Alpha-lactalbumin hydrolysate, antihypertensive peptide and application thereof

Info

Publication number: CN113005165A
Application number: CN202110289201.8A
Authority: CN
Inventors: 谢静莉; 魏东芝; 谢德伟
Original assignee: East China University of Science and Technology
Current assignee: East China University of Science and Technology
Priority date: 2021-03-18
Filing date: 2021-03-18
Publication date: 2021-06-22

Abstract

The invention discloses alpha-lactalbumin hydrolysate and a peptide segment with the function of reducing blood pressure in vivo, wherein the alpha-lactalbumin hydrolysate is obtained by hydrolyzing alpha-lactalbumin by utilizing pepsin and pancreatin and then performing ultrafiltration separation on a hydrolysate to obtain a hydrolysate component with the molecular weight of less than 3 kDa. The amino acid sequence of the antihypertensive peptide is VGINYW. The alpha-lactalbumin hydrolysate and antihypertensive peptide can be used as ACE inhibitor, and can be used for preparing antihypertensive drugs and antihypertensive health products.

Description

Alpha-lactalbumin hydrolysate, antihypertensive peptide and application thereof

Technical Field

The invention belongs to the technical field of food and medicine, and particularly relates to alpha-lactalbumin hydrolysate capable of reducing blood pressure, a preparation method thereof, and high-activity antihypertensive peptide in the alpha-lactalbumin hydrolysate.

Background

Hypertension is a common cardiovascular disease, and can cause various complications of heart, brain, kidney and the like, as well as stroke, atherosclerosis and coronary heart disease. WHO reported that the prevention and treatment of hypertension was a global problem in 2019 for over 11.3 billion hypertensive patients worldwide. Some of the current clinical antihypertensive drugs are mainly Angiotensin Converting Enzyme (ACE) inhibitors (such as lisinopril), diuretics (such as hydrochlorothiazide), angiotensin ii (ang ii) receptor blockers (such as olmesartan medoxomil), calcium antagonists (nifedipine), and the like. These drugs are effective in lowering blood pressure, but do not solve the problems of prevention of hypertension and treatment of mild patients, and also cause side effects such as dizziness, allergy, gastrointestinal dysfunction and hepatotoxicity.

ACE is a Zn-containing²⁺The carboxypeptidase is a key enzyme of a renin-angiotensin-aldosterone system of a human blood pressure regulating system, can cut angiotensin I (Ang I) into Ang II and can inactivate bradykinin, and the two actions can cause vasoconstriction and increase blood pressure. ACE inhibitors act to lower blood pressure by inhibiting ACE activity, thereby preventing Ang II biogenesis and reducing inactivation of bradykinin. Compared with the traditional antihypertensive drugs, the natural food-derived ACE inhibitory peptide has the advantages of high specificity and small toxic and side effects, and can play a significant role in lowering blood pressure in hypertension animal models and clinical studies. The food-derived peptide and protein hydrolysate with the function of reducing blood pressure have great potential in the prevention and treatment of hypertension.

Disclosure of Invention

Aiming at the defects in the prior art, the invention provides alpha-lactalbumin hydrolysate, antihypertensive peptide and application thereof.

The technical scheme for solving the technical problems is as follows:

an alpha-lactalbumin hydrolysate is prepared through hydrolyzing alpha-lactalbumin by pepsin and pancreatin, and ultrafiltering to obtain the component of alpha-lactalbumin hydrolysate.

The alpha-lactalbumin hydrolysate is applied as an ACE inhibitor.

The application of the alpha-lactalbumin hydrolysate in preparing the antihypertensive drug.

The application of the alpha-lactalbumin hydrolysate in preparing the health care product for reducing blood pressure.

The preparation method of the alpha-lactalbumin hydrolysate comprises the following steps: dissolving alpha-lactalbumin in deionized water to prepare a solution, adjusting the pH to 1.5-2.5, and adding pepsin for enzymolysis; then, adjusting the pH value of the system to 6.5-7.5, and adding pancreatin for hydrolysis; after hydrolysis, adjusting the pH value of the system to 6.8-7.0, and inactivating in a water bath at 85-100 ℃; then the hydrolysate is centrifuged, and the supernatant is the alpha-lactalbumin hydrolysate.

Further, ultrafiltration is continuously carried out by using an ultrafiltration tube with the filter diameter of 3kDa, the filtrate is the hydrolysate component with the filter diameter of less than 3kDa, and the hydrolysate component is frozen and dried to obtain a powdery sample.

A peptide for lowering blood pressure has amino acid sequence of VGINYW.

The use of the above-mentioned antihypertensive peptides as ACE inhibitors.

The antihypertensive peptide is applied to the preparation of antihypertensive drugs.

The antihypertensive peptide is applied to the preparation of antihypertensive health products.

In the invention, pepsin and pancreatin are used for hydrolyzing alpha-lactalbumin, and then the hydrolysis product is ultrafiltered and separated to obtain the molecular weight<A 3kDa hydrolysate component, a hydrolysate component having a significant ACE inhibitory effect in vitro, IC₅₀It was 0.061 mg/mL.

Identifying the component sequence of the hydrolysate by LC-MS, and performing active screening to obtain high-activity ACE inhibitory peptide with sequence Val-Gly-Ile-Asn-Tyr-Trp, i.e. VGINYW, IC for inhibiting ACE₅₀It was 15.1. mu.M.

To verify the in vivo hypotensive effect of <3kDa hydrolysate fraction and VGINYW, it was verified by primary hypertensive rat (SHR) acute and subacute feeding experiments.

Research shows that the hydrolysate with the molecular weight of less than 3kDa obtained after the alpha-lactalbumin is hydrolyzed by pepsin and pancreatin, and VGINYW can stably reduce the Systolic Blood Pressure (SBP) and the Diastolic Blood Pressure (DBP) of SHR for a long time. Through research on an in-vivo action mechanism of the antihypertensive peptide, the hydrolysate of <3kDa and VGINYW are found to improve the expression level of ACE2 and an angiotensin type 2 receptor (AT2R), reduce the expression level of an angiotensin type 1 receptor (AT1R), remarkably improve the oxidative stress of SHR and regulate the composition of SHR intestinal tract microorganisms to realize the control of blood pressure mainly by remarkably reducing the serum ACE activity and the Ang II content of the SHR.

The hydrolysate and the antihypertensive peptide which are prepared by the enzymatic hydrolysis of the alpha-lactalbumin and have the effect of reducing blood pressure and the preparation method thereof have good potential and application prospect when being used as health care products and medicines for preventing and treating hypertension.

Drawings

FIGS. 1-4 are graphs showing the effect of hypotensive peptides on the expression level of SHR kidney-associated proteins; note: the same figure, which does not contain the same letters between groups, indicates that the two results differ significantly at p < 0.05. FIG. 1 shows ACE2 expression levels; FIG. 2 is AT1R expression level; FIG. 3 is AT2R expression levels;

FIGS. 4-8 are graphs showing the effect of hypotensive peptides on SHR gut microbiota; FIG. 4 is an alpha diversity index; FIG. 5 shows relative abundance of lactic acid bacteria; FIG. 6 is a gate level species stack; FIG. 7 is a phylum level species abundance heat map; FIG. 8 is a graph of PCA analysis.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

In the following examples. The principle and method for determining in vitro ACE inhibitory activity are as follows:

the principle of in vitro determination of ACE inhibitory activity is: hippuryl Histaminyl Leucine (HHL) is used as a substrate, hippuric acid and HL can be generated under the catalytic action of ACE, and the activity of the ACE is determined by measuring the content of hippuric acid through a liquid phase. When an ACE inhibitor is present, ACE activity is inhibited to decrease hippuric acid production, and the inhibitory activity is calculated by calculating the amount of decrease in product production.

The specific determination steps are as follows: using a 1.5mL EP tube as a reactor, 10. mu.L of ACE (310mU dissolved in 0.1M borate buffer at pH 8) and 25. mu.L of a sample to be tested (blank 25. mu.L deionized water) were added, incubated at 37 ℃ for 10min, 50. mu.L of HHL (5 mM in 0.1M borate buffer at pH 8.3) was added, the reaction was stopped at 37 ℃ by adding 500. mu.L of 0.5M HCl after the reaction was completed. The reaction mixture was centrifuged at 14000rpm, and the supernatant was collected and subjected to HPLC analysis. The high performance chromatographic determination conditions are as follows: mobile phase 25% acetonitrile: 75% water (containing 0.1% trifluoroacetic acid), a detection wavelength of 228nm, a column temperature of 30 ℃ and a sample loading of 10. mu.L. ACE inhibition (X) was calculated as follows:

x ═ (a control-a 1)/a control × 100%

In the formula: x is ACE inhibitory rate (%), A control is blank control substrate peak area, and A1 is experimental group substrate peak area.

IC₅₀The calculation of (2): IC (integrated circuit)₅₀Is the concentration of the inhibitor when inhibiting 50 percent of ACE activity and is obtained by measuring the ACE inhibition rate corresponding to different concentrations of a sample.

Example 1 hydrolysis solution of alpha-lactalbumin<Preparation of the 3kDa component

Dissolving alpha-lactalbumin in deionized water to prepare a 40mg/mL solution, adjusting the pH to 2.0 by using 5M HCl, adding pepsin (250U/mg) with the enzyme-substrate ratio of 1:30(w/w), and carrying out enzymolysis for 2 hours at 37 ℃ and the rotating speed of 170 rpm; the system was then adjusted to pH 7.0 with 6M NaOH solution and pancreatin (8 XSPS) was added in an enzyme to substrate ratio of 1:25(w/w) and hydrolyzed at 37 ℃ for 4h with a shaker speed of 170 rpm. After the hydrolysis is finished, the pH value of the system is adjusted to 7.0, and the system is inactivated in a water bath at 95 ℃ for 10 min. And then centrifuging the hydrolysate for 10min at the rotating speed of 12000rpm, and taking the supernatant to obtain the complete hydrolysate. And then, performing ultrafiltration by using an ultrafiltration tube (the specification is 50mL) with the filter diameter of 3kDa, wherein the filtrate is a hydrolysate component with the filter diameter of less than 3kDa, and performing freeze drying on the hydrolysate component to obtain a powdery sample for later use.

Example 2 Mass Spectrometry identification of VGINYW

The lyophilized <3kDa hydrolysate fraction was redissolved with 0.1% formic acid solution, desalted with a ZipTip desalting column, equilibrated with 0.1% formic acid and acetonitrile respectively, adsorbed the sample, washed with 0.1% formic acid, eluted with 20% acetonitrile and 0.1% formic acid elution buffer, and the eluted sample was dried with a centrifuge concentrator. After drying, the sample was dissolved in 30. mu.L of a buffer containing 2% acetonitrile and 0.1% formic acid and analyzed by LC-MS.

NanoLC-MS conditions and procedures: the liquid chromatographic column is a C18 reversed phase analytical column (75mm × 15 cm × 3 μm); the polypeptide enrichment column is a C18 reversed phase column (75mm × 2cm × 3 μm). The mobile phase A is a mixed solution of 99.9 percent of water and 0.1 percent of formic acid, and the mobile phase B is a mixed solution of 99.9 percent of acetonitrile and 0.1 percent of formic acid. The flow rate of the mobile phase was 300 nL/min. The instrument is set to be in an ESI + mode, the voltage of a mass spectrum electrospray capillary is set to be 2000V, the gas flow rate is set to be 2.0L/min, the ion source temperature is 150 ℃, the secondary fragmentation is carried out by selecting parent ions with the charge number of 1-3 and the mass-nucleus ratio of 350-1800, and a data dependence scanning mode is adopted. Data Analysis 4.1 software is used to extract ion Peaks to generate mgf files, and Peaks 8.5 search engine searches alignment sequences. Finally obtaining a sequence Val-Gly-Ile-Asn-Tyr-Trp, namely VGINYW.

Example 3 in vitro determination of ACE Activity

Respectively taking complete alpha-lactalbumin hydrolysate,<3kDa hydrolysate and synthesized VGINYW, ACE inhibitory activity was determined at various concentrations, and IC was calculated₅₀The results are shown in Table 1.

TABLE 1 IC of different samples₅₀

Relative molecular weight of VGINYW is 750.85, IC of VGINYW is calculated by mol concentration₅₀It was 15.1. mu.M.

Example 4 measurement of antihypertensive peptide Effect in vivo lowering blood pressure

Influence of one-time administration on primary hypertension rats

The model group, the positive control group and the experimental group adopt male essential hypertension rats (SHR) with the cleaning grade, the age of 9 weeks and the weight of 250 +/-15 g. The normal group used male Wistar rats of clean grade, 9 weeks of age, and a body weight of 250 ± 15 g. All experimental animals were fed water freely, with an environment of 24 + -2 deg.C, and illuminated daily for 12 h. The animals are adapted for 7 days after transportation, the blood pressure is measured by a tail artery pressure measurement method in the last three days, and the rats are preheated for 15min in a 37 ℃ environment before the pressure measurement for pressure measurement training. Then, the groups were randomly grouped into 6 individuals according to the weight and blood pressure of the SHR. The specific grouping is as follows:

1) normal group: the normal saline with the same volume is perfused every day in the experimental period;

2) model group: the normal saline with the same volume is perfused every day in the experimental period;

3) positive control group: the daily gavage dose of lisinopril with 5mg/kg BW in the experimental period;

4) hydrolysate group of <3 kDa: the daily gavage dosage is 100mg/kg BW hydrolysis liquid of <3kDa in the experimental period;

5) VGINYW group: the daily gavage dose was 5mg/kg BW VGINYW over the experimental period.

All the above reagents were dissolved by physiological saline. The above groups were subjected to corresponding samples for gastric perfusion, and Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at 0, 1, 2, 4, 6, 8h after gastric perfusion were measured by the tail artery pressure measurement method, respectively, 5 times, and the results were averaged as shown in tables 2 and 3.

TABLE 2 Effect of one administration of different ACE inhibitors on SHR systolic blood pressure (mmHg)

Note: the results in table 2, which are in the same column (i.e., SBP at different times after intragroup gavage), do not contain the same lower case letters, indicating that there is a significant difference between the two results at p < 0.05; the same row of results (i.e., different groups of SBPs at the same time) do not contain the same capital letter, indicating that the two results differ significantly at p < 0.05.

TABLE 3 Effect of one administration of different ACE inhibitors on SHR diastolic blood pressure (mmHg)

Note: the results in table 3, which are in the same column (i.e., DBP at different times after intragroup gavage) do not contain the same lower case letters, indicating that there is a significant difference between the two results at p < 0.05; the same row of results (i.e., different groups of DBPs at the same time) do not contain the same capital letter, indicating that the two results differ significantly at p < 0.05.

The acute experimental result of one-time administration shows that VGINYW of 5mg/kg BW after gastric lavage can obviously reduce SBP and DBP of SHR rats, the SBP reduction amplitude is maximum after 2h administration and is 21mmHg, and the DBP reduction amplitude is maximum after 4h administration and is 17 mmHg. The <3kDa hydrolysate of 100mg/kg BW by intragastric administration can also obviously reduce the blood pressure of SHR rats, the SBP reduction amplitude is 21mmHg after 4 hours of administration, and the DBP reduction amplitude is maximum and is 12mmHg after 2 hours of administration.

Second, the effect of continuous administration on Primary hypertensive rats

After completing the acute experiment of one administration, except that the dose of SHR intragastric lisinopril in the positive control group is reduced to 2.5mg/kg BW, the other groups continue to perform intragastric gavage with the same sample and dose every day for 4 weeks, and on days 7, 14, 21 and 28, the systolic pressure and diastolic pressure of the rats in each group are measured 24h after the previous administration, and are respectively measured for 5 times, and the results are averaged as shown in tables 4 and 5.

TABLE 4 Effect of continuous administration of different ACE inhibitors on SHR systolic blood pressure (mmHg)

Note: the results in table 4, which are in the same column (i.e., SBP at different times after successive administrations in the group), do not contain the same lower case letters, indicating that the two results differ significantly at p < 0.05; the same row of results (i.e., different groups of SBPs at the same time) do not contain the same capital letters, indicating that the two results differ significantly at p < 0.05.

TABLE 5 Effect of successive administration of different ACE inhibitors on SHR diastolic blood pressure (mmHg)

Note: the results in table 5, which are in the same column (i.e., DBP at different times after successive administrations in the group) do not contain the same lower case letters, indicating that the two results differ significantly at p < 0.05; the same row of results (i.e., different groups of DBPs at the same time) do not contain the same capital letter, indicating that the two results differ significantly at p < 0.05.

Continuous administration experiments demonstrated that the blood pressure of SHR rats was stably lowered for a long period after continuous 4-week administration of <3kDa hydrolysate and VGINYW.

In conclusion, the hydrolysis liquid of <3kDa and VGINYW have potential as blood pressure lowering drugs or functional health foods, which are proved by experiments of one-time administration and continuous administration.

Example 5 Effect of antihypertensive peptides on the SHR renin-angiotensin System

After 4 weeks of continuous administration, the rats in each group were bled after fasting for 12h on the last day, centrifuged at 3000rpm to obtain serum, sacrificed and dissected according to the management rules of the experimental animals, and the kidneys, colon and liver of the rats were collected and stored at-80 ℃.

First, the influence of antihypertensive peptide on ACE activity and Ang II content in SHR body

Determination of serum ACE activity: the ACE activity of each group of sera was measured by enzymatic reaction of the sera obtained from the fourth rat with HHL as a substrate according to the definition of the enzyme activity, and the results are shown in Table 6.

Determination of serum Ang II content: the serum obtained from the fourth rat was assayed for Ang II content according to the requirements and procedures of the ELISA kit for Ang II assay, and the results are shown in table 6.

TABLE 6 Effect of antihypertensive peptides on ACE activity and Ang II content in SHR

Note: the results in table 6 in the same column do not contain the same capital letters, indicating that the two results differ significantly at p < 0.05.

Results of determination of serum ACE activity and Ang II content show that after SHR is continuously administered with 3kDa hydrolysate and VGINYW for 4 weeks, serum ACE activity is remarkably reduced compared with a model control, and serum Ang II level is further remarkably reduced. The hydrolysate of <3kDa and VGINYW are shown to be capable of inhibiting the activity of ACE in SHR body and reducing the content of Ang II, thereby realizing the reduction of blood pressure.

Second, the influence of antihypertensive peptides on the expression of key proteins of the renin-angiotensin system

Determination of key protein expression levels in kidney: taking a proper amount of kidney samples, grinding by liquid nitrogen and crushing tissue lysate to obtain tissue disruption solution, then centrifuging at the rotating speed of 12000rpm, and taking supernate, namely the whole protein extracting solution. The expression levels of angiotensin converting enzyme 2(ACE2), angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) were determined by Western blotting using β -actin (β -actin) as an internal reference protein. The results of the experiment are shown in FIGS. 1 to 3.

ACE2 inactivates Ang II in vivo to modulate blood pressure lowering, AT1R being a receptor that transmits a vasoconstrictive signal and AT2R being a receptor that transmits a vasodilative signal. The experimental results show that after SHR is continuously administered with <3kDa hydrolysate and VGINYW for 4 weeks, the expression levels of ACE2 and AT2R are increased, and the expression level of AT1R is reduced. The above results indicate that <3kDa hydrolysate and VGINYW are able to lower blood pressure by regulating key protein expression in RAS system of SHR.

Example 6 Effect of antihypertensive peptides on the level of oxidative stress of SHR

Determination of oxidative stress-related indicators: rat serum after 4 weeks of administration was subjected to MDA, Glutathione (GSH) and superoxide dismutase (SOD) activity assay according to the requirements and procedures of Malondialdehyde (MDA) assay kit, Glutathione (GSH) assay kit and superoxide dismutase (SOD) activity assay kit, and the results are shown in Table 7.

TABLE 7 Effect of antihypertensive peptides on oxidative stress levels in SHR

Note: the results in table 7 in the same column do not contain the same capital letters, indicating that the two results differ significantly at p < 0.05.

The determination result shows that after the SHR is continuously administered with <3kDa hydrolysate and VGINYW for 4 weeks, the content of MDA in serum can be obviously reduced, and the content of GSH and the activity of SOD can be improved. MDA is a product of oxidative stress of cells, GSH is a key antioxidant in an animal body, SOD can catalyze superoxide anion to have disproportionation effect, and the SOD is an important antioxidant enzyme in the organism. The oxidative stress induces the blood pressure to rise, and the <3kDa hydrolysate and VGINYW can remarkably reduce the oxidative stress in the SHR body, thereby being beneficial to the reduction of the blood pressure.

Example 7 Effect of antihypertensive peptides on SHR intestinal microorganisms

Determination of intestinal microbial diversity: the colon contents of each group of rats were taken out, and genome in colon was extracted by fecal DNA extraction kit, followed by DNA amplification, purification and quantification of V3-V4 region of bacterial 16S rRNA gene. The purified samples were sequenced on an Illumina PE250 machine. And after sequencing to obtain Raw Reads, filtering the low-quality Reads, assembling and filtering the low-quality Reads, and obtaining effective data to perform OTU clustering. And after obtaining the OTU, carrying out species injection, alpha diversity analysis and related microorganism abundance analysis in sequence. The analysis results are shown in FIGS. 4 to 8.

The species stacking plot and the species abundance heat map show that the gut microbiota of SHR more trended towards normal rat gut microbiota after 4 consecutive weeks of administration of <3kDa hydrolysate and VGINYW. The results of Principal Component Analysis (PCA) also showed that the <3kDa hydrolysate group and VGINYW group had intestinal microbial composition closer to the normal group. Alpha diversity analysis showed that <3kDa hydrolysate and VGINYW were able to increase gut microbial diversity of SHR. The abundance analysis of each group of lactic acid bacteria shows that the hydrolysate with the molecular weight of <3kDa can obviously improve the abundance of the lactic acid bacteria.

The intestinal microorganisms have the function of regulating blood pressure, and the composition of the intestinal microorganisms of SHR rats is greatly different from that of normal rats. And the intestinal microbial diversity analysis result shows that the <3kDa hydrolysate and VGINYW can improve the intestinal microbial diversity of SHR, and make the composition of the SHR more approximate to the intestinal microbial composition of normal rats, thereby being beneficial to blood pressure regulation. In addition, the short-chain fatty acid produced by the intestinal microorganisms can have a positive effect on the regulation of blood pressure, the lactic acid bacteria are main bacteria for producing the short-chain fatty acid in the intestinal tract, and the hydrolysate with the molecular weight of <3kDa can obviously improve the abundance of the lactic acid bacteria in the SHR intestinal tract, so that the reduction of the blood pressure is facilitated.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims

1. An alpha-lactalbumin hydrolysate is characterized in that pepsin and pancreatin are used for hydrolyzing alpha-lactalbumin, and the hydrolysate is subjected to ultrafiltration separation to obtain the component of the alpha-lactalbumin hydrolysate.

2. Use of an alpha-lactalbumin hydrolysate as claimed in claim 1 as an ACE inhibitor.

3. Use of the α -lactalbumin hydrolysate as claimed in claim 1 in the preparation of a medicament for lowering blood pressure.

4. The use of the α -lactalbumin hydrolysate of claim 1 in the preparation of a health product for lowering blood pressure.

5. The method for preparing an α -lactalbumin hydrolysate as claimed in claim 1, comprising the steps of: dissolving alpha-lactalbumin in deionized water to prepare a solution, adjusting the pH to 1.5-2.5, and adding pepsin for enzymolysis; then, adjusting the pH value of the system to 6.5-7.5, and adding pancreatin for hydrolysis; after hydrolysis, adjusting the pH value of the system to 6.8-7.0, and inactivating in a water bath at 85-100 ℃; then the hydrolysate is centrifuged, and the supernatant is the alpha-lactalbumin hydrolysate.

6. The method for preparing α -lactalbumin hydrolysate as claimed in claim 5, wherein ultrafiltration is continued using an ultrafiltration tube with a filter diameter of 3kDa, and the filtrate is the <3kDa hydrolysate component, which is freeze-dried to obtain a powdered sample.

7. A peptide for lowering blood pressure, characterized in that its amino acid sequence is VGINYW.

8. Use of the antihypertensive peptide according to claim 7 as an ACE inhibitor.

9. Use of the antihypertensive peptide according to claim 7 for the preparation of a medicament for lowering blood pressure.

10. The use of the antihypertensive peptide according to claim 7 for the preparation of a health product for lowering blood pressure.