CN115819508B - Isolated oligopeptides and their use in the preparation of hypoglycemic drugs or foods - Google Patents
Isolated oligopeptides and their use in the preparation of hypoglycemic drugs or foods Download PDFInfo
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- CN115819508B CN115819508B CN202211559666.1A CN202211559666A CN115819508B CN 115819508 B CN115819508 B CN 115819508B CN 202211559666 A CN202211559666 A CN 202211559666A CN 115819508 B CN115819508 B CN 115819508B
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
The invention provides an isolated oligopeptide and application thereof in hypoglycemic drugs or foods, wherein the isolated oligopeptide has a sequence shown in SEQ ID NO:1, and a polypeptide having the amino acid sequence shown in 1. The isolated oligopeptide has the function of reducing blood sugar, and has important significance for development and application of hypoglycemic drugs, health-care foods or special medical formula foods, diabetes research and the like.
Description
Technical Field
The present invention relates to the field of biology. In particular, the invention relates to isolated oligopeptides and their use in hypoglycemic drugs or foods.
Background
Diabetes is a metabolic disease characterized by relative or absolute deficiency of insulin, with hyperglycemia as the main symptom. The blood sugar rise caused by diabetes can cause chronic damage to human viscera, and cause dysfunction of blood vessels, hearts, livers, kidneys and other organs. The existing clinically used antidiabetic medicines are mostly chemical and biological preparations, have definite curative effect but high price, and often have side effects such as weight increase, hypoglycemia, gastrointestinal adverse reaction and the like. Therefore, the screening of low-cost hypoglycemic drugs with less side effects from natural products has become a focus of attention for researchers.
At present, researches report that some polypeptide substances have the effect of reducing blood sugar. Compared with the conventional chemical medicines, the hypoglycemic peptide medicine has the advantages of simple structure, no immunogenicity, low side effect and the like. However, most of the hypoglycemic peptide drugs are degraded by proteases in the gastrointestinal tract after oral intake, and cannot exert their physiological functions. Meanwhile, the hypoglycemic peptide medicine has stronger hydrophobicity and poorer intestinal tract absorption effect. Therefore, development of a hypoglycemic peptide medicament with both gastrointestinal enzymolysis resistance and good intestinal absorption effect is needed.
Disclosure of Invention
The present invention aims to solve, at least to some extent, the technical problems existing in the prior art. Therefore, the invention provides the isolated oligopeptide, the isolated nucleic acid molecule, the construct, the recombinant cell, the medicine, the health food or the special medical purpose formula food and the application, and the isolated oligopeptide has the blood sugar reducing effect and has important significance for development and application of the blood sugar reducing medicine, the health food or the special medical purpose formula food, diabetes research and the like.
In one aspect of the invention, the invention provides an isolated oligopeptide. According to an embodiment of the invention, the isolated oligopeptide has the sequence as set forth in SEQ ID NO:1, in particular the amino acid sequence of the isolated oligopeptide is Phe-Gly-Ala-Trp-Thr-Pro-Arg. The inventor of the present invention found that the above isolated oligopeptide (also referred to as "hypoglycemic peptide" in the present invention) can effectively reduce blood glucose level, relieve insulin resistance, and improve blood lipid metabolic disorder caused by hyperglycemia, and has important significance for development and application of hypoglycemic drugs, health foods or formula foods for special medical use, diabetes research, and the like.
In another aspect of the invention, the invention provides an isolated nucleic acid molecule. According to an embodiment of the invention, the isolated nucleic acid molecule encodes the aforementioned isolated oligopeptide. The isolated nucleic acid molecules according to embodiments of the present invention, after being introduced into a recipient cell, may express the isolated oligopeptides described above, in an environment suitable for protein expression, to exert their hypoglycemic effect.
In yet another aspect of the invention, the invention provides a construct. According to an embodiment of the invention, the construct comprises the isolated nucleic acid molecule as described above. After the construct according to the embodiment of the present invention is introduced into a cell, the isolated oligopeptide described above is expressed in an environment suitable for protein expression, which is helpful for exerting the hypoglycemic effect of the oligopeptide.
In yet another aspect of the invention, the invention provides a recombinant cell. According to an embodiment of the invention, the recombinant cell contains an isolated nucleic acid molecule as described above or a construct as described above. Thus, the above-described oligopeptide is expressed under an environment suitable for protein expression, thereby contributing to the hypoglycemic effect of the oligopeptide. The recombinant cells of the present invention do not comprise germ cells, fertilized egg cells, or embryonic cells.
In yet another aspect of the invention, the invention provides a pharmaceutical, health food or special medical use formula. According to an embodiment of the invention, the medicament, health food or special medical use formula comprises: an isolated oligopeptide, an isolated nucleic acid molecule or a recombinant cell as hereinbefore described. Thus, the medicament, the health food or the special medical purpose formula food according to the embodiment of the invention has the blood sugar reducing effect.
In a further aspect of the invention, the invention provides the use of the isolated oligopeptide, the isolated nucleic acid molecule or the recombinant cell as described above for the preparation of a medicament, a health food or a formulation for special medical use. According to an embodiment of the invention, the medicament, health food or special medical use formula is for lowering blood glucose.
According to an embodiment of the invention, the medicament is for preventing or treating diabetes.
Compared with the prior art, the invention has the beneficial effects that:
(1) The hypoglycemic peptide is obtained through gastrointestinal simulated digestion, can resist secondary hydrolysis of protease in gastrointestinal tract after being orally taken, and has the characteristics of stability, safety, no side effect and the like.
(2) The invention combines computer software to comprehensively evaluate isoelectric points, hydrophilia, stability, toxicity, steric hindrance and human intestinal absorbability of the hypoglycemic peptide, and knows that the hypoglycemic peptide meets the requirements of oral medicine or food development.
(3) The hypoglycemic peptide can improve fasting blood glucose level and insulin resistance of a diabetic mouse, reduce the content of total cholesterol and triglyceride in serum, and has wide application prospect in the fields of preparation of formula foods, health products and medicaments for preventing and treating diabetes in special medical applications.
Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.
Drawings
The foregoing and/or additional aspects and advantages of the invention will become apparent and may be better understood from the following description of embodiments taken in conjunction with the accompanying drawings in which:
figure 1 shows the effect of a hypoglycemic peptide on glucose tolerance of diabetic mice according to one embodiment of the invention, indicating significant differences compared to the normal group (P < 0.05); # represents significant differences compared to the model group (P < 0.05);
FIG. 2 shows the effect of a hypoglycemic peptide on insulin content in serum of diabetic mice according to one embodiment of the present invention, the different lowercase letters represent significant differences (P < 0.05);
FIG. 3 shows the effect of a hypoglycemic peptide on total cholesterol content in serum of diabetic mice according to one embodiment of the present invention, different lower case letters represent significant differences (P < 0.05);
figure 4 shows the effect of a hypoglycemic peptide according to one embodiment of the invention on triglyceride content in serum of diabetic mice, the different lowercase letters represent significant differences (P < 0.05).
Detailed Description
Embodiments of the present invention are described in detail below. The following examples are illustrative only and are not to be construed as limiting the invention.
The invention provides an isolated oligopeptide. According to an embodiment of the invention, the amino acid sequence of the isolated oligopeptide is SEQ ID NO:1, in particular, the amino acid sequence of the isolated oligopeptide is Phe-Gly-Ala-Trp-Thr-Pro-Arg (SEQ ID NO: 1). Wherein, the liquid crystal display device comprises a liquid crystal display device,
phe represents an amino acid residue named Phenylalanine in English and Phenylalanine in Chinese;
gly represents an amino acid residue with an English name of Glycine and a Chinese name of Glycine;
ala represents an amino acid residue with the English name Alanine and the Chinese name Alanine;
trp represents an amino acid residue named english as trytophan and chinese as Tryptophan;
thr represents an amino acid residue named Threonine in english and Threonine in chinese;
pro represents an amino acid residue named Proline in English and Proline in Chinese;
arg represents an amino acid residue named Arginine in English and Arginine in Chinese.
The separated oligopeptide has the molecular weight of 33.95Da, is easy to dissolve in water, has good stability, is used as an oligopeptide substance with small molecular weight and clear structure, has the characteristic of resisting enzymolysis of gastrointestinal tracts and good intestinal absorption effect due to the amino acid sequence, and is favorable for being developed into medicines, health-care foods or formula foods with special medical purposes.
The invention does not limit the source of the isolated oligopeptide strictly, and the oligopeptide can be obtained by extracting from natural substances, or can be obtained by adopting a chemical synthesis means, and the natural substances can be plants, such as millet, highland barley, oat and quinoa.
The invention does not limit the form of special medical food, health food or medicine strictly, and the special medical food can be gel-like food, porous food, powdery food, pasty food and the like; the health food can be tablet, capsule (soft or hard), watered pill, granule (powder), oral liquid, medicated wine, teabag, etc.; the dosage forms of the medicine can be mixture, injection, tablet, granule, syrup, capsule, oral liquid, aerosol, spray, etc.
The invention does not limit the ingestion mode of special medical food, health food or medicine strictly, and the health food only limits the entry of the food through the digestive tract, such as oral administration, chewing, lozenge and the like; the special medical food can be taken orally or fed by a tube feeding way, so that the special medical food is convenient for people with limited feeding; the administration mode of the medicine can be peritoneal, vein, muscle, subcutaneous, cortex, oral, nasal, lung, rectum, etc.
In the present invention, the term "treatment" is used to refer to obtaining a desired pharmacological and/or physiological effect. The effect may be prophylactic in terms of completely or partially preventing the disease or symptoms thereof, and/or may be therapeutic in terms of partially or completely curing the disease and/or adverse effects caused by the disease. As used herein, "treating" encompasses diseases in mammals, particularly humans, including: (a) Preventing the occurrence of a disease (e.g., preventing diabetes) or disorder in an individual susceptible to the disease but not yet diagnosed with the disease; (b) inhibiting disease, e.g., arresting disease progression; or (c) alleviating a disease, e.g., alleviating symptoms associated with a disease. As used herein, "treating" or "treatment" encompasses any administration of a drug or compound to an individual to treat, cure, alleviate, ameliorate, reduce or inhibit a disease in the individual, including, but not limited to, administration of a drug comprising an isolated oligopeptide, an isolated nucleic acid molecule or a recombinant cell as described herein to an individual in need thereof.
The scheme of the present invention will be explained below with reference to examples. It will be appreciated by those skilled in the art that the following examples are illustrative of the present invention and should not be construed as limiting the scope of the invention. The examples are not to be construed as limiting the specific techniques or conditions described in the literature in this field or as per the specifications of the product. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Example 1
Functional prediction of the hypoglycemic peptide (Phe-Gly-Ala-Trp-Thr-Pro-Arg) is carried out by computer software, wherein isoelectric point, hydrophilicity and stability are evaluated by an Expasy kit (https:// web. ExPasy org/protparam /). Toxicity and steric hindrance were assessed by the ToxinPred kit (https:// webs. Iitid. Edu. In/raghava/ToxinPred/index. Html); human intestinal absorption was assessed by the admetSAR kit (http:// lmmd. Ecust. Edu. Cn/admetSAR1/home /).
TABLE 1 functional prediction of glycopeptides
| Isoelectric point | Average hydrophilicity | Instability index | Toxicity of | Steric hindrance | Human intestinal tract absorbability |
| 9.75 | -0.50 | -35.80 | Without any means for | 0.57 | + |
Note that: a negative average hydrophilicity is greater, indicating greater hydrophilicity, and an instability index of less than 40 indicates stable presence.
As shown in Table 1, the hypoglycemic peptide is alkaline, has isoelectric point of 9.75, strong hydrophilicity and good stability. Meanwhile, the peptide is nontoxic, has good intestinal tract absorbability, and is favorable for combining with a specific receptor and generating physiological functions due to lower steric hindrance.
Example 2
The hypoglycemic peptide sequence (Phe-Gly-Ala-Trp-Thr-Pro-Arg) is chemically synthesized to obtain synthetic peptide, and animal experiments prove that the hypoglycemic peptide has the hypoglycemic effect, and the specific steps are as follows:
36 male mice of 4 weeks old C57BL/6J were supplied by Peking Vitre Liwa laboratory animal technologies Co. Mice were divided into 3 groups after 1 week of adaptive feeding: the normal control group was fed low-fat diet, the model group and the intervention group were fed high-fat diet. Model and intervention groups fasted 12h at week 5 and injected intraperitoneally with 100mg/kg STZ to establish a type II diabetes model. The intervention group irrigates 200mg/kg of the hypoglycemic peptide per day, and the model group irrigates the same amount of physiological saline per day. After 4 weeks of continuous gavage, mice were fasted for 12 hours with 1g/kg of a glucose solution and then blood glucose was measured at 0, 15, 30, 60, 90, 120 minutes using a blood glucose meter. After 5 weeks of continuous gastric lavage, orbital bleeding was performed, mice were euthanized for dislocation, and the serum levels of insulin, total cholesterol, and triglycerides were determined.
As shown in fig. 1, the mice in the model group showed a sharp rise in blood glucose after glucose injection compared to the normal group, indicating that their glucose tolerance was significantly impaired. The blood glucose level of the mice in the intervention group is lower than that in the model group, and the blood glucose level of the mice in the intervention group is obviously reduced compared with that in the model group at 120min, which indicates that the blood glucose reducing peptide has the effect of improving glucose tolerance of the diabetic mice.
As shown in fig. 2, the insulin content of mice in the model group was significantly increased compared to the normal group, indicating that insulin resistance occurred. After the intervention of the hypoglycemic peptide, the insulin content of the mice in the intervention group is obviously reduced compared with that of the model group, which shows that the hypoglycemic peptide has the effect of improving the insulin resistance of the diabetic mice.
As shown in fig. 3 and 4, the total cholesterol and triglyceride levels of mice in the model group were significantly elevated compared to the normal group, indicating a disturbance in blood lipid metabolism. The total cholesterol and triglyceride content of the mice in the intervention group is obviously lower than that of the mice in the model group, which shows that the hypoglycemic peptide has the effect of improving the blood lipid metabolic disorder of the diabetic mice.
While embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and not to be construed as limiting the invention, and that variations, modifications, alternatives and variations may be made to the above embodiments by one of ordinary skill in the art within the scope of the invention.
Claims (7)
1. An isolated oligopeptide, wherein the amino acid sequence of the isolated oligopeptide is as set forth in SEQ ID NO: 1.
2. An isolated nucleic acid molecule encoding the isolated oligopeptide of claim 1.
3. A construct comprising the isolated nucleic acid molecule of claim 2.
4. A recombinant cell comprising the isolated nucleic acid molecule of claim 2 or the construct of claim 3.
5. A medicament, comprising: the isolated oligopeptide of claim 1, the isolated nucleic acid molecule of claim 2 or the recombinant cell of claim 4.
6. Use of the isolated oligopeptide according to claim 1, the isolated nucleic acid molecule according to claim 2 or the recombinant cell according to claim 4 for the preparation of a medicament for reducing blood glucose.
7. The use according to claim 6, wherein the medicament is for the prevention or treatment of type II diabetes.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101029081A (en) * | 2007-02-05 | 2007-09-05 | 上海国佳生化工程技术研究中心有限公司 | Recombinant incretin peptide and method for constructing and culturing producing strain |
| CN109456395A (en) * | 2018-12-21 | 2019-03-12 | 南京财经大学 | A kind of incretin peptide and its application |
| CN110669105A (en) * | 2019-10-31 | 2020-01-10 | 华中科技大学 | Long-acting polypeptide construction and application thereof in resisting acute kidney injury and diabetic complication nephropathy |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090087878A9 (en) * | 1999-05-06 | 2009-04-02 | La Rosa Thomas J | Nucleic acid molecules associated with plants |
| EP3285795B1 (en) * | 2015-04-22 | 2022-11-16 | Cedars-Sinai Medical Center | Enterically delivered bitter oligopeptides for the treatment for type 2 diabetes and obesity |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101029081A (en) * | 2007-02-05 | 2007-09-05 | 上海国佳生化工程技术研究中心有限公司 | Recombinant incretin peptide and method for constructing and culturing producing strain |
| CN109456395A (en) * | 2018-12-21 | 2019-03-12 | 南京财经大学 | A kind of incretin peptide and its application |
| CN110669105A (en) * | 2019-10-31 | 2020-01-10 | 华中科技大学 | Long-acting polypeptide construction and application thereof in resisting acute kidney injury and diabetic complication nephropathy |
Non-Patent Citations (2)
| Title |
|---|
| Critical Review for the Production of Antidiabetic Peptides by a Bibliometric Approach;Ticiane Carvalho Farias et al.;《Nutrients》;第14卷(第4275期);第1-19页 * |
| 动物源性降糖肽的研究进展;马昕悦 等;《食品工业科技》;第43卷(第22期);第438−444页 * |
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