Method of enhancing a brain or cognitive function

Abstract

There is provided a composition for improving memory, learning ability, and cognitive ability and a method of enhancing a brain or cognitive function by administering the composition to a subject in need thereof. It has been confirmed that a peptide having a C-terminal region ended to GAG had an effect of improving the memory. In order for the peptide to have the effect, it has been confirmed that the peptide should be a peptide of which the length consists of at least 4 amino acids. Further, it has been confirmed that a peptide of which the length of the peptide having the C-terminal region ended to GAG consists of 5 to 9 amino acids has the same effect. As a result, the peptide of the present invention can be used as the composition for improving memory, learning ability, and cognitive ability, and the method of enhancing a brain or cognitive function.

Claims

1. A method of enhancing a brain or cognitive function in a subject in need thereof, comprising administering a peptide consisting of SEQ ID NO: 3 (AGAG) or SEQ ID NO:7 (QAGAG) to the subject.

2. The method of claim 1, wherein the subject suffers from a memory, cognitive, or learning disorder caused by aging, Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, pick disease, Creutzfeldt-Jakob disease, depression, head injury, stroke, CNS hypoxia, cerebral ischemia, encephalitis, forgetfulness, traumatic brain injury, hypoglycaemia, Wernicke-Korsakoff syndrome, drug addiction, epilepsy, Fasciola hepatica, hippocampal sclerosis, headache, brain aging, dementia, frontotemporal lobar degeneration, tumor, normal pressure hydrocephalus, HIV, cerebrovascular disease, cerebral disease, cardiovascular disease, amnesia, radiation exposure, metabolic disease, hypothyroidism, mild cognitive impairment, cognitive deficiency, or attention deficit.

3. The method of claim 1, wherein the peptide is administered in a food composition or a health drink composition to the subject.

4. The method of claim 1, wherein the peptide is administered in a food composition, wherein said peptide is 0.01 to 15 wt % of the food composition.

5. The method of claim 1, wherein the peptide is administered in a health drink composition, wherein the health drink composition contains the peptide at a concentration of 0.02 g to 5 g based on 100 ml of the health drink composition.

6. The method of claim 1, wherein the peptide is administered in a health drink composition, wherein the health drink composition contains the peptide at a concentration of 0.3 g to 1 g based on 100 ml of the health drink composition.

7. The method of claim 1 wherein the peptide is administered in a food composition, wherein the food composition comprises a cytologically acceptable supplementary additive.

8. The method of claim 3, wherein the food composition or health drink composition further contains one or more flavoring agents, starches, carbohydrates, nutrients, vitamins, minerals, electrolytes, coloring agents, thickening agents, pectic acid or a salt thereof, alginic acid or a salt thereof, an organic acid, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, and carbonic acid agents.

9. The method of claim 1, wherein the peptide is administered in a health drink composition, wherein the health drink composition contains one or more carbohydrates at a concentration of 1 g to 20 g based on 100 ml of the health drink composition.

10. The method of claim 1, wherein the peptide is administered in a food composition, wherein the food composition is in the form of a tablet, capsule, pill, liquid, jelly, powder, or granule.

11. The method of claim 3, wherein the food composition or health drink composition comprises one or more monosaccharides, disaccharides, polysaccharides, and sugar alcohols.

12. The method of claim 3, wherein the food composition or health drink composition comprises one or more of glucose, fructose, maltose, sucrose, dextrin, cyclodextrin, xylitol, sorbitol, erythritol, thaumatin, stevia extract, saccharin, and aspartame.

13. The method of claim 3, wherein the food composition or health drink composition comprises one or more of rebaudioside A, glycyrrhizin, cheese, chocolate, fruit juice, and vegetable juice.

14. The method of claim 1, wherein the peptide consists of SEQ ID NO: 3 (AGAG).

15. The method of claim 1, wherein the peptide consists of SEQ ID NO:7 (QAGAG).

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a diagram illustrating a memory enhancing effect of a peptide of which an amino acid sequence of a C-terminal region is GAG through a passive avoidance test. A y axis is time (sec).

(2) FIG. 2 is a diagram illustrating a memory enhancing effect of a peptide of which an amino acid sequence of a C-terminal region is GAG through a Y maze test. A y axis is spontaneous alternation (%).

(3) FIG. 3 is a diagram illustrating a memory enhancing effect of a peptide of which an amino acid sequence of a C-terminal region consisting of 5 to 9 amino acids is GAG through a passive avoidance test, including QAGAG (SEQ ID NO:7) and SGGAG (SEQ ID NO:8).

(4) FIG. 4 is a diagram illustrating a memory enhancing effect of a peptide of which an amino acid sequence of a C-terminal region consisting of 5 to 9 amino acids is GAG through a Y maze test, including QAGAG (SEQ ID NO:7) and SGGAG (SEQ ID NO:8).

DETAILED DESCRIPTION OF THE INVENTION

(5) Hereinafter, the present invention will be described in more detail through Examples. However, these Examples are to exemplify the present invention and the scope of the present invention is not limited to these Examples.

Example 1

Synthesis of Peptides

(6) Synthesized peptides were obtained from Genscript (New Jersey, USA). The peptides were synthesized by a flexpeptide technology method and confirmed by using high pressure liquid chromatography and mass spectrometry. Amino acid sequences of the synthesized peptides are as listed in Table 1.

(7) TABLE-US-00001 TABLE 1 Peptide name (sequence number) Amino acid sequence Peptide-I AG (SEQ ID NO: 1) Peptide-2 GAG (SEQ ID NO: 2) Peptide-3 AGAG (SEQ ID NO: 3) Peptide-4 QGAG (SEQ ID NO: 4) Peptide-5 GGAG (SEQ ID NO: 5) Peptide-6 SGAGAG (SEQ ID NO: 6)

(8) Further, the present inventors additionally synthesized peptides (sequence numbers 7 to 9) of amino acid sequences 5 to 9 to perform an additional test. These synthesized peptides were obtained from Genscript (New Jersey, USA). The peptides were synthesized by a flexpeptide technology method and confirmed by using high pressure liquid chromatography and mass spectrometry. The amino acid sequences of the synthesized peptides are as follows;

(9) TABLE-US-00002 (SEQ ID NO: 7) QAGAG (SEQ ID NO: 8) SGGAG (SEQ ID NO: 9) GAGGAGGAG

Example 2

Reagents and Animals

(10) Scopolamine was purchased from Sigma-Aldrich (St. Louis, Mo., USA). 4-week-old male ICR mice were purchased from Korean BioLink Co. (Chungbuk, Korea). After an adaptation period of one week, the mice were used in a test and all reagents were administered intraperitoneally. Memory disorder was induced by injection of scopolamine before 30 minutes of the test and the synthesized peptides were injected before 30 minutes of the injection of scopolamine.

Example 3

Confirmation of Effect of Peptides in Passive Avoidance Test

(11) A passive avoidance test was performed in the same bright room and dark room. A floor of each room was formed in a shape in which 2-mm stainless steel rods were separated from each other at 1-cm intervals. Bright squares (20×20×20 cm) had 100-W bulbs. These squares were connected to a guillotine door.

(12) For an acquisition trial, the mouse was placed in the bright room after injection of the reagents and the door was opened after 10 seconds. When the mouse completely entered the dark room, the door was closed and electric shock was applied for 3 seconds. A retention trial was performed after 24 hours of the acquisition trial and the mouse was positioned in the bright room. A latency time of the acquisition and retention trials was measured by a time until the mouse entered the dark room of the box after the door was opened.

(13) The retention latency in the passive avoidance test represents a long-term memory function in rodents. Accordingly, an effect of a silk fibroin peptide on scopolamine-induced memory deterioration was confirmed by using a step-through passive avoidance test and the result was illustrated in FIG. 1.

(14) As illustrated in FIG. 1, in the retention trial, a latency time of a normal saline-treated mouse was 180 seconds (maximum cut-off time). It was confirmed that an average of the step-through responses in a scopolamine-injected group with memory deterioration due to injection of scopolamine was significantly lowered as compared with a normal saline-treated group. Before administration of scopolamine, in groups administered with the synthesized peptides, in a peptide-I-administered group consisting of two amino acids, slight improvement was achieved compared with the scopolamine-administered group, and in a peptide-3-administered group, there was a little effect as compared with the scopolamine-administered group. However, it was confirmed that in peptide-2 and peptide-4 to 6-administered groups, the deteriorated memory by scopolamine was improved to be close to a normal group administered with saline. From the above result, it was confirmed that there was a memory improving effect of the peptide of which the C-terminal region ended to GAG, and in order to have the effect, it is confirmed that the peptide should be a peptide in which the length consists of at least four amino acids.

(15) As illustrated in FIG. 3, in the retention trial, a latency time of a normal saline-treated mouse was 180 seconds (maximum cut-off time). It was confirmed that an average of the step-through responses in a scopolamine-injected group with memory deterioration due to injection of scopolamine was significantly lowered as compared with a normal saline-treated group. Before administration of scopolamine, it was confirmed that in a group administered with the peptide consisting of 5 to 9 amino acids of the present invention, the memory deteriorated by scopolamine was improved to be close to the normal group administered with saline. From the above result, the memory improving effect of the peptide of which the C terminal region ended to GAG was confirmed.

Example 4

Confirmation of Effect of Peptide in Y Maze Test

(16) The mouse was placed at one end of a Y maze with a length of one branch of 30 cm, a width of 5 cm, and a height of 13 cm and the order of entry into each branch was recorded. Alternation was judged to be successful if the mouse sequentially entered three different branches. Spontaneous alternation was defined as Equation below.
Spontaneous alternation (%)=the number of alternations/(total number of entries−2)×100

(17) As illustrated in FIG. 2, it was confirmed that the mean of spontaneous alternations of a scopolamine-injected group with memory deterioration due to the injection of scopolamine was significantly lower than that of the normal saline group. In groups administered with the synthesized peptides before administration of scopolamine, it was confirmed that in a peptide-I and 2 administered group consisting of 2 and 3 amino acids, slight improvement was achieved as compared with the scopolamine-administered group, but in a peptide-3 to 6 administered group consisting of the number of amino acids of 4 to 6, the memory deteriorated by scopolamine was significantly improved. From the above result, it was confirmed that there was a memory improving effect of the peptide of which the C-terminal region ended to GAG, and in order to have the effect, it is confirmed that the peptide should be a peptide in which the length consists of at least four amino acids.

(18) Further, as illustrated in FIG. 4, it was confirmed that the mean of spontaneous alternations of a scopolamine-injected group with memory deterioration due to the injection of scopolamine was significantly lowered as compared with the normal saline group. In the group administered with the peptide consisting of 5 to 9 amino acids of the present invention before administration of scopolamine, the memory deteriorated by scopolamine was significantly improved, and in the group administered with peptides of sequence numbers 2 and 3, there was an excellent effect as compared with a control group. From the above result, the memory improving effect of the peptide of which the C terminal region ended to GAG was confirmed.