KIMCHI LACTOBACILLUS SAKEI HAVING PROPHYLACTIC, AMELIORATING OR THERAPEUTIC EFFECT ON DEPRESSION AND ANXIETY DISORDERS

Abstract

The present disclosure relates to a composition for preventing, alleviating or treating depression or anxiety disorder, which contains Lactobacillus sakei as an active ingredient. The Lactobacillus sakei strain according to the present disclosure can be used to prevent, alleviate or treat a mental disorder such as depression or anxiety disorder.

Claims

1. A pharmaceutical composition for preventing or treating depression or anxiety disorder, comprising Lactobacillus sakei, a culture thereof, a lysate thereof, a fermentation product thereof or an extract thereof as an active ingredient.

2. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises 1×10.sup.2 to 1×10.sup.15 CFU/mL of Lactobacillus sakei and the pharmaceutical composition prevents or alleviates depression or anxiety disorder when administered to a subject 3 or more times a week.

3. The pharmaceutical composition according to claim 1, wherein the Lactobacillus sakei is Lactobacillus sakei WIKIM31 deposited with an accession number KCCM12654P.

4. The pharmaceutical composition according to claim 1, wherein the depression or anxiety disorder is depression or anxiety disorder in a subject having a neurodegenerative disease.

5. The pharmaceutical composition according to claim 4, wherein the neurodegenerative disease is one or more selected from a group consisting of Parkinson's disease, Alzheimer's disease, Huntington's disease, Lou Gehrig's disease (amyotrophic lateral sclerosis), Creutzfeldt-Jakob disease, stroke, multiple sclerosis, learning disorder, cognitive impairment and memory impairment.

6. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is administered via an administration route selected from oral administration, intravenous administration, intraperitoneal administration, intramuscular administration, subcutaneous administration, intradermal administration, topical administration, intranasal administration, intrapulmonary administration and intrarectal administration.

7. A food composition for preventing or alleviating depression or anxiety disorder, comprising Lactobacillus sakei, a culture thereof, a lysate thereof, a fermentation product thereof or an extract thereof as an active ingredient.

8. The food composition according to claim 7, wherein the Lactobacillus sakei is Lactobacillus sakei WIKIM31 deposited with an accession number KCCM12654P.

9. The food composition according to claim 7, wherein the food is a functional health food.

10. The food composition according to claim 7, wherein the food is a beverage, a bar or a fermented milk.

11. The food composition according to claim 7, wherein the depression or anxiety disorder is depression or anxiety disorder of a subject having a neurodegenerative disease.

12. The food composition according to claim 11, wherein the neurodegenerative disease is one or more selected from a group consisting of Parkinson's disease, Alzheimer's disease, Huntington's disease, Lou Gehrig's disease (amyotrophic lateral sclerosis), Creutzfeldt-Jakob disease, stroke, multiple sclerosis, learning disorder, cognitive impairment and memory impairment.

13. The food composition according to claim 7, wherein the food composition comprises 1×10.sup.2 to 1×10.sup.15 CFU/mL of Lactobacillus sakei and the food composition prevents or alleviates depression or anxiety disorder when orally administered to a subject 3 or more times a week.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0061] FIG. 1 shows a result of conducting open field test on a mouse model of Parkinson's disease (brown: general movement of mouse (movement in X and Y axes detected by far infrared sensor); blue: exploratory behavior of mouse (movement in X, Y and Z.sub.1 axes detected by far infrared sensor), Naive: non-treatment group, MPTP: negative control group (Parkinson's disease induced after ingestion of PBS), WIKIM31: WIKIM31 ingestion group (Parkinson's disease induced after ingestion of WIKIM31)).

[0062] FIG. 2 shows a result of conducting open field test on a mouse model of Parkinson's disease. (a) shows the total distance traveled by a mouse in a plastic cage, (b) shows residence time in the center zone, and (c) shows rearing time during which the mouse stood on hind legs.

[0063] FIG. 3 shows a result of analyzing the blood level of corticosterone which is a stress hormone in a rat model of general depression and/or anxiety disorder.

[0064] FIG. 4 shows a result of conducting open field test on a rat model of general depression and/or anxiety disorder.

[0065] FIG. 5 shows a result of conducting forced swim test on a rat model of general depression and/or anxiety disorder.

BEST MODE

[0066] Hereinafter, the present disclosure is described in detail through examples. The following examples merely illustrate the present disclosure, and the scope of the present disclosure is not limited by the examples.

EXAMPLES

Example 1: Preparation of Culture of Lactobacillus sakei WIKIM31 Strain

[0067] A Lactobacillus sakei WIKIM31 strain, which is derived from kimchi and is deposited in the Korea Culture Center of Microorganisms with the accession numbers KFCC11654P (domestic deposit) and KCCM12654P (international deposit), was used for experiment. After culturing the Lactobacillus sakei WIKIM31 strain in MRS medium at 30° C. for 24 hours, the cells were centrifuged at 8,000 rpm for 5 minutes and the remaining medium was removed by rinsing with PBS. 1×10.sup.10 CFU/mL of cells were quantitated using PBS. 0.2 mL (1×10.sup.9 CFU) was orally administered to an experimental animal 5 times a week. Sterilized PBS was administered to negative and positive control groups.

Example 2: Investigation of Effect of Preventing or Alleviating Depression and Anxiety Disorder in Animal Model

[0068] After accustoming 8-week-old male mice (C57BL/6) in a laboratory room for a week, Lactobacillus sakei WIKIM31 (KFCC11654P) was orally administered for 30 days. Then, after inducing Parkinson's disease by intraperitoneally injecting MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), the effect of Lactobacillus sakei WIKIM31 was investigated. The result is shown in FIGS. 1 and 2. In FIGS. 1 and 2, Naive stands for a normal mouse model, MPTP a mouse model with Parkinson's disease induced after oral administration of PBS, and WIKIM31 a mouse model with Parkinson's disease induced after oral administration of Lactobacillus sakei WIKIM31.

[0069] Open field test was conducted to evaluate the symptoms of anxiety in an animal model of Parkinson's disease. The open field test was conducted by exposing an experimental animal to a new spacious environment with no place to escape or hide and the level of anxiety of the experimental animal was investigated by monitoring exploratory behavior. A plastic cage (45 cm×45 cm×40 cm) used for the open field test was divided into 3×3 zones. The anxiety level of the experimental animal was estimated by analyzing the zones where the mouse resided within the open field, the activity of the mouse such as traveled distance, and the rearing time during which the mouse stood on hind legs for exploratory behavior. The behavior of the animal was monitored using the TSE multi-conditioning system (TSE Systems, USA) and the Actimot video tracking system. A video camera was installed in the center of the ceiling at a height of 100 cm from the bottom so as to record each plastic cage (45 cm×45 cm×40 cm) for the open field test. The location of the animal in the open field was analyzed automatically using a far infrared sensor of the ActiMot frame (TSE Systems,

[0070] USA). After accustoming the mouse in the plastic cage for 1 minute, its behavior was recorded for 10 minutes. The center zone of the plastic cage was set to 15 cm×15 cm.

[0071] As a result of the open field test, it was confirmed that overall movement was increased (FIG. 1 and FIG. 2(a)) and residence time in the center zone was increased (FIG. 2(b)) in the Lactobacillus sakei WIKIM31 ingestion group as compared to the PBS-treated negative control group. In addition, the time spent on exploratory behavior was increased significantly as compared to the negative control group (FIG. 2(c)). Therefore, it was confirmed that the ingestion of Lactobacillus sakei WIKIM31 significantly alleviates the symptoms of depression and anxiety disorder induced by MPTP (p<0.05).

Example 3: Investigation of Effect of Preventing or Alleviating Symptoms of Depression and Anxiety Disorder in Normal Animal Model

3-1. Induction of Depression in Normal Animal Model

[0072] After accustoming 6-week-old male rats (Sprague-Dawley) in a laboratory room for a week, chronic stress was applied from week 7. Stress was applied randomly to the experimental animals in a non-regular manner by depriving water or feed, providing empty water bottles, reversing dark-light cycles, flickering lights, providing noise frequently, providing wet bedding, tilting the cage, providing restrain stress, etc. every day. The stress was applied for a total of 6 weeks and different stress was applied every day. In the first two weeks, depression was induced by applying stress without ingestion of Lactobacillus sakei WIKIM31. After ingesting Lactobacillus sakei WIKIM31 (KCCM12654P) for the subsequent 4 weeks while applying stress, the alleviation of depression was measured.

3-2. Analysis of Blood Corticosterone Level

[0073] After the induction of stress, blood corticosterone level was measured to evaluate of the antidepressant effect of the administered strain. The blood corticosterone level was analyzed using an ELISA kit (corticosterone assay, Ca:KGE009, RND Systems, USA) by extracting blood. The blood was taken via the jugular vein. 300 μL of whole blood was taken and serum was separated for analysis by centrifuging at 4,500 rpm for 10 minutes.

[0074] As a result of the blood corticosterone level analysis, it was confirmed that the stress hormone was decreased in the Lactobacillus sakei WIKIM31 ingestion group as compared to the PBS-treated negative control group (FIG. 3). Therefore, it was confirmed that the symptoms of depression and anxiety disorder induced by repeated stress can be alleviated through the ingestion of Lactobacillus sakei WIKIM31.

3-3. Open Field Test

[0075] Open field test was conducted to evaluate the symptoms of depression and anxiety in a depression-induced rat model. The open field test was conducted by exposing an experimental animal to a new spacious environment with no place to escape or hide and the level of depression of the experimental animal was investigated by monitoring behavior. The measurement was made in a cage of 50 cm×50 cm×50 cm for 15 minutes per rat. The center zone of the plastic cage was set to 25 cm×25 cm and the distance traveled in the center zone was analyzed. A smaller ratio of the distance traveled in the center zone to the total distance traveled can be determined as depression. The behavior of the animal was monitored using a video tracking system (Smart 3.0, Panlab, USA).

[0076] As a result of the open field test, it was confirmed that the residence time in the center zone was increased in the Lactobacillus sakei WIKIM31 ingestion group as compared to the PBS-treated negative control group (FIG. 4). Therefore, it was confirmed that the ingestion of Lactobacillus sakei WIKIM31 alleviates the symptoms of depression and anxiety disorder induced by repeated stress.

3-4. Forced Swim Test

[0077] Forced swim test was conducted for 10 minutes after filling water in a transparent acrylic cylinder (12 cm in diameter, 40 cm in height) to a height of 30 cm. After the experiment was completed, the animal was placed under an infrared lamp for 30 minutes for drying and then returned to the cage. The behavior of the animal during the 10 minutes was measured as immobility time and analyzed using an image analyzer (Smart 3.0, Panlab, USA).

[0078] As a result of the forced swim test, it was confirmed that the time of forced swimming was decreased in the Lactobacillus sakei WIKIM31 ingestion group as compared to the PBS-treated negative control group (FIG. 5). Therefore, it was confirmed that the ingestion of Lactobacillus sakei WIKIM31 alleviates the symptoms of depression and anxiety disorder induced by repeated stress.

[Accession Numbers]

[0079] Depository agency: Korea Culture Center of Microorganisms (domestic)

[0080] Accession number: KFCC11654P

[0081] Date of deposition: 20160304

[0082] Depository agency: Korea Culture Center of Microorganisms (international)

[0083] Accession number: KCCM12654P

[0084] Date of deposition: 20200114