KR20170074209A - Composition for preventing, improving or treating depressive disorder comprising osmotin or its active peptide - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating depression comprising osmotin comprising the amino acid sequence of SEQ ID NO: 1 or osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 2 as an active ingredient.
The present invention also relates to a health functional food composition for preventing or ameliorating depression comprising osmotin comprising the amino acid sequence of SEQ ID NO: 1 or osmotin peptide consisting of amino acid sequence of SEQ ID NO: 2 as an active ingredient .

Description

TECHNICAL FIELD The present invention relates to a pharmaceutical composition for preventing, ameliorating or treating depression, which comprises osmotin or an activated peptide thereof,

The present invention relates to a pharmaceutical composition for preventing or treating depression comprising osmotin and an active osmotin peptide as an active ingredient, and a health functional food for preventing or ameliorating depression.

Various stresses prevalent in modern society cause depression. Already in the western world, drug prescriptions related to depression are increasing rapidly, and prescribing rates are considerably higher. The World Health Organization (WHO) estimates that by 2020 depression will be the most prevalent disease in the United States and Western Europe. As the urbanization of Korea accelerates, the incidence of depression is rapidly increasing due to the deepening of the gap between rich and poor, and the feeling of alienation. Currently, Korea belongs to the country with the highest suicide rate among OECD countries.

Until now, the mechanism of depression has not been elucidated yet. However, the mechanism of depression has not been clarified. However, in general, there is a lack of monoamine neurotransmitters such as serotonin, norepinephrin and dopamine in the synapses of the central nervous system This is a hypothesis that depression is induced. Therefore, current antidepressants have pharmacological actions that increase the concentration of neurotransmitters in central serotonin or norepinephrine synapses. Antidepressants can be classified as tricyclic antidepressants (TCA), monoamine oxidase inhibitors (MAOI), or selective serotonin reuptake inhibitors (SSRIs) depending on the mechanisms that increase the concentration of neurotransmitters. And so on.

Although these conventional antidepressants are relatively effective, some of them have serious side effects and effects that do not meet expectations. Drug administration increases the concentration of monoamine in synapses immediately, but it usually takes about two weeks to improve symptoms such as improvement in depression. In addition, many patients do not respond well to antidepressant drugs, have a high recurrence rate, and are unable to take medication due to severe side effects. The tricyclic antidepressants imipramine and desipramine have severe side effects such as hypotension and cardiac dysfunction. The most commonly used selective serotonin uptake inhibitors, such as fluoxetine or sertraline, cause zone, gastrointestinal bleeding or sexual dysfunction. Therefore, the development of new drugs which are more effective than the existing depressants and have less side effects is continuously being tried.

Plant derived osmotin is involved in fatty acid oxidation regulation, glucose uptake, phosphorylation (AMP kinase) and signal transduction pathways. Osmotin (24 kDa) is a stable protein contained in the PR-5 family, which is homologous to the sweet-testing protein thaumatin, and is known to induce intracellular signaling in yeast. Osmotin is resistant to heat, acidity and enzymes, meaning that it can circulate the body without fear of being crushed by digestion. These osmotins are known to be homologues of adiponectin present in animals. Adiponectin has been shown to have some anti-inflammatory, anti-diabetic, anti-atherosclerotic potential. However, in relation to osmotin, effects mainly related to obesity and diabetes have been studied, and other effects are not well known.

Accordingly, the inventors of the present invention have confirmed that osmotin-peptide inhibits apoptosis of cells induced by depression and has an effect of improving or treating depression, and is applied to a pharmaceutical composition for preventing or improving depression or a health functional food The present invention has been completed.

Korean Patent No. 10-0575229 (Food Composition for Prevention or Treatment of Cranial Neuropathy) includes a peptide as an active ingredient to inhibit neuronal cell death, thereby preventing cranial nerve diseases such as dementia, stroke, and depression .

It is an object of the present invention to provide a method for preventing and treating depression comprising osmotin (SEQ ID NO: 1) or activated osmotin-peptide (SEQ ID NO: 2) consisting of the amino acid sequence shown in SEQ ID NO: And to provide a therapeutic pharmaceutical composition.

Yet another object of the present invention is to provide a health functional food for improving or preventing depression, which comprises osmotin or osmotin-peptide consisting of the amino acid sequence shown in SEQ ID NO: 1 or SEQ ID NO: 2 as an active ingredient.

In order to accomplish the object of the present invention, the present invention provides a method for producing an osmotin (SEQ ID NO: 1) or an activated osmotin peptide (SEQ ID NO: 2) comprising an amino acid sequence represented by SEQ ID NO: And a pharmaceutical composition for preventing or treating depression.

The present invention also provides a health food for preventing or ameliorating depression, comprising osmotin or osmotin-peptide consisting of the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 as an active ingredient.

The present invention also provides a method of preventing or treating depression, which comprises administering to an animal a composition comprising osmotin or osmotin-peptide consisting of the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 to provide.

The osmotin of SEQ ID NO: 1 or the osmotin peptide of SEQ ID NO: 2 has neuroprotective and depression improvement or therapeutic effect, so that a health functional food composition for preventing or ameliorating depression and a pharmaceutical composition for preventing or treating depression It can be usefully used as an active ingredient.

In addition, the osmotin and osmotin-peptide can be usefully used as a therapeutic method for the treatment of depression.

FIG. 1 shows the results of MTT assay to examine the cell survival rate of PC-12 cell line induced LPS with osmotin or osmotin-peptide addition.
FIG. 2 shows the results for cell viability when treated with osmotin or osmotin-peptide, FIG. 2 (b) shows the results on cytotoxicity, FIG. Figure 2 (c) is the result for caspase 3/7 activity associated with apoptosis.
FIG. 3 shows the results of Dopamine receptor 2 protein secretion activity when osmotin or osmotin-peptide was treated.
FIG. 4 shows in vivo experimental results for examining the behavioral changes of FST and TST.
Figure 5 shows the results of in vivo experiments to examine behavioral changes through anhedonia and olfactory tests.
FIG. 6 shows results of in vivo experiments to examine the activity of postsynaptic dysfunction by osmotin in mouse brain.
FIG. 7 shows experimental results for examining the effect of osmotin-peptide on the BDNF / Akt / PI3K signaling pathway in LPS / HFD treated mice.
Figure 8 is for an activated osmotin-peptide consisting of 9 amino acids.

Hereinafter, the present invention will be described in detail.

The present invention SEQ ID NO: 1 (SEQ ID NO: 1) agarose motin or SEQ ID NO: 2 is composed of the amino acid sequence represented by: OSU motin (osmotin) consisting of the amino acid sequence shown in (SEQ ID NO 2) - the peptide active ingredient A pharmaceutical composition for preventing or treating depression is provided.

In the present invention, osmorethin is a protein contained in a large amount in aged fruits such as grapes, and is a protein composed of about 150 to 250 amino acids depending on individuals.

 The osmotin-peptide of SEQ ID NO: 2 is a peptide consisting of nine amino acids from the 157th to the 165th in the sequence of the osmotin protein.

The osmotin or osmotin-peptide of the present invention may be a purified natural product or a chemically synthesized product and may be prepared by recombinant techniques.

In the present invention, osmotin-peptide treatment of PC-12 cell line induced by depression with LPS (lipopolysacccharide) resulted in the maintenance of cell survival and cytotoxicity of PC-12 cell line, Inhibiting activity and inhibiting apoptosis, and has the effect of improving or treating depression.

The PC-12 cell line is a cell line derived from chromaffinocytoma of the rat adrenal medulla and is a neural crest ) From the embryonic origin.

The inflammatory immune response in the brain is closely related to depression. LPS, a typical inflammation inducer, is known to cause depression-like behavior. Intracerebroventricular injection of LPS increases transcription of TNF-α and IL-6 and increases the expression of indoleamine 2,3 dioxygenase (IDO), leading to depression-like behavior in mice. Antidepressants such as clomipramine, imipramine, or citalopram significantly inhibited IL-1β, IL-6, and TNF-α production induced by LPS treatment and IL-2 and IFN- Secretion is suppressed.

In the case of treating osmotin comprising the amino acid sequence shown in SEQ ID NO: 1 or osmotin peptide shown in SEQ ID NO: 2 in the PC-12 cell line induced by LPS with LPS, cell death due to LPS is suppressed and neuroprotective effect And depression.

Preferably, the composition of the present invention may further comprise a pharmaceutically acceptable carrier.

The composition of the present invention may be prepared into oral or parenteral formulations according to the route of administration by a person skilled in the art. In the case of formulation, it can be prepared by using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used

In addition, the present invention SEQ ID NO: 1 (SEQ ID NO: 1) agarose motin or SEQ ID NO: 2 is composed of the amino acid sequence represented by: OSU motin (osmotin) consisting of the amino acid sequence shown in (SEQ ID NO 2) - the peptide The present invention provides a composition for health food for preventing and ameliorating depression as an active ingredient.

When the composition for a health functional food of the present invention is used as a food additive, the composition may be added as it is, or may be used together with other food or food ingredients, and suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). In general, the composition of the present invention is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material, in the production of food or beverage. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of controlling health, it may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

There is no particular limitation on the kind of the food. Examples of the food to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Such natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharine and aspartame, and the like . The ratio of the natural carbohydrate can be appropriately determined by a person skilled in the art.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The ratios of these additives can also be appropriately selected by those skilled in the art.

In addition, the present invention SEQ ID NO: 1 (SEQ ID NO: 1) agarose motin or SEQ ID NO: 2 consisting of the amino acid sequence represented by: OSU motin (osmotin) consisting of the amino acid sequence shown in (SEQ ID NO 2) - the peptide The present invention relates to a method for preventing or treating depression, comprising administering to an animal a composition containing the active ingredient.

The animal may preferably comprise a mammal, more preferably a human.

Hereinafter, the present invention will be described in detail with reference to the following experimental examples.

However, the following experimental examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following experimental examples.

≪ Experimental Example 1 > Cell culture and drug treatment

PC-12 cell lines were harvested in DMEM medium containing 10% fetal bovine serum (FBS) and antibiotics (penicillin and streptomycin) and cultured for 4 days. Thereafter, the drug was treated as follows.

Control: culture for 48 hours in DMEM medium

LPS-treatment (LPS-treatment): Culture for 48 hours in DMEM medium containing LPS-supernatant (a mixture of LPS and supernatant in a ratio of 1: 4 (volume ratio)

LPS + osmotin treatment: The cells were cultured for 48 hours in DMEM medium containing LPS-supernatant (a mixture of LPS and supernatant at a ratio of 1: 4 (volume ratio)), And cultured with osmotin. At this time, concentrations of osmotin are 0.4 uM, 0.2 uM, 0.1 uM and 0.05 uM.

LPS + osmotin-peptide-9 treatment (LPS + osmotin-peptide-9 treatment): LPS-supernatant (solution mixed with LPS and supernatant at a ratio of 1: 4 (volume ratio) The cells were incubated in the medium for 48 hours, but the last 24 hours were incubated with the osmotin-peptide. At this time, the concentration of osmotin-peptide was 10 uM, 5 uM, 1 uM and 0.5 uM.

All cells were harvested after 6 days and used for the following analysis.

≪ Experimental Example 2 > MTT assay for measuring cell viability

 MTT reagent (3- [4,5-dimethylthiazol-2-yl] -2,5-diphenyl tetrazolium bromide) was used to measure living cells. PC12 cell lines were plated in 96-well plates (1 x 10 < 5 > cells / well) in 100 [mu] l DMEM medium. MTT reagent (5 mg / ml phosphate buffered saline, PBS) was added to each well and incubated at 37 [deg.] C for 4 hours after drug treatment in individual wells as in Example 1. Formazan was dissolved in DMSO and added to each well. The plate was stirred by a rotary stirrer for 10 to 20 minutes. Absorbance was measured for all cells at 550-570 nm (L1) and 620-650 nm (L2). Final OD values were calculated (OD = L1 - L2) and the percentage of cell viability compared to the control group was calculated.

≪ Experimental Example 3 > ApoTox-Glo, triplex assay

ApoTox-GLO triplex assay (Promega, Promega BioSciences, LLC. San Luis Obispo, CA, USA). Briefly, the PC12 cell line was dispensed into 96-well plates (1 x 10 ⁵ cells / well) in 200 μl DMEM containing 10% fetal bovine serum (FBS) and antibiotics (penicillin and streptomycin). Survival / toxic reagents, including both GF-AFC substrate and bis-AAF-R110 substrate, were added to all wells after drug treatment in each well as in Experimental Example 1, stirred for 30 seconds, ≪ / RTI > Fluorescence spectra were measured at 400/505 nm for survival analysis and at 485/520 nm for toxicity analysis. To determine caspase 3/7 activity, caspase-Glo 3/7 reagent (100 μl) was then added to all wells and the% cell viability,% cytotoxicity,% caspase-3 / 7 activity was calculated.

<Experimental Example 4> Dopamine receptor 2 protein secretion activity

Dopamine receptor 2 protein secretion activity was measured in PC-12 cells secreting dopamine by inducing depression with LPS followed by treatment with osmotin (0.2 μM, 0.4 μM) or osmotin-peptide (5 μM, 10 μM).

 EXPERIMENTAL EXAMPLE 5 Forced Swim Test

The forced swim test (FST) was performed in principle as described in Porsolt RD 2000. Briefly, each mouse was individually placed in a cylinder (23 cm in diameter, 31 cm in height) containing 15 cm of water maintained at 23 1 ° C. Water was replaced between test sessions. The mice were placed in water for 6 minutes and then returned to the cage. During the test, the mice were recorded video above and the immobility time was measured for the last 5 minutes.

<Experimental Example 6> Tail Suspension Test

An adhesive tape was attached to a portion 2 cm away from the distal end of the tail of the mouse taken out from the cage. One hole was made in the tape and the mouse was suspended in a loop connected to a strain gauge for 10 minutes. A computer system for processing external forces acting on the gauge collected and analyzed the movement of each rat. Immobility time was measured manually by a person who did not see the experimental group.

<Experimental Example 7> Sucrose preference test

To perform the sucrose preference test, mice were administered either two solutions (water in a 50 ml conical tube fitted with a ball-type sipper tube or water added with 2% sucrose). Prior to this test, all mice were adhered to two bottle selection tests. All mice drank both water and 2% sucrose solution, but preferred to drink sucrose rather than water. On the day of testing, the mice were given no fluid and food for two hours before testing. At the beginning of the dark phase of the photoperiod, drinking water and 2% sucrose solution were placed overnight (15 hours) in the home cage. Prior to LPS administration, mice were given water / water (w / w) or water / sucrose (w / s) for 2 consecutive days for 24 hours to allow the mice to become familiar with the sucrose solution. At the end of each test, the fluid volume of the conical tube was measured and sucrose preference was measured using sucrose intake / total fluid intake (water + sucrose intake) * 100.

<Experimental Example 8> Olfactory Test / Buried Food Test

The Olfactory Test / buried food test measures how quickly an overnight fast can find a familiar and tasteful food hidden under bedclothes. It is assumed that fasting mice that fail to use odor signals to find food within 15 minutes may have a deficit in olfactory ability. Most of the mice with normal olfactory can find hidden food pieces within a few minutes.

<Experimental Example 9> In vivo model an drug treatment

At the start of the experiment, C657LB male mice (Gyeongsang National University Animal Breeding Center, Korea, Pearl, 40 grains), weighing 25-30g, were kept in a controlled temperature environment, We managed to eat food freely. The mice were randomly divided into four groups as described below.

One. Control group (i.p. saline for 1 week)

2. LPS group (i.p. 250 ug / kg for 1 week)

3. HF diet (4 weeks, oral) + LPS (250 pg / kg for 1 week) + osmotin (10 pg / g for 2 times weekly X 2 week)

4. Osmotin peptide (i.p. 3 ug / g, 3 times weekly) X 4 week

The experimental procedure was carried out according to the rules established by the Animal Ethics Committee (IACUC) of the Department of Biology, Gyeongsang National University. All the in vivo experimental techniques were approved (approval ID: 125) by the Animal Ethics Committee (IACUC) of Gyeongsang National University.

<Experimental Example 10> Western blot analysis

Mice were anesthetized after treatment, sacrificed, and brain samples were differentiated. The cortices and hippocampi were removed and frozen with dry ice. All brain tissues were homogenized in pro-prep extraction solution (iNtRON Biotechnology). Proteins were treated for immunoblotting as described above.

&Lt; Experimental Example 10 > Data analysis and statistics

The Western-blot band was scanned and analyzed using a computer-based Sigma Gel System (SPSS Inc., Chicago, IL) using densitometry. Immunofluorescence results were evaluated using computer-based ImageJ software and the density was calculated in arbitrary units. Data are expressed as mean ± standard error of the mean (SEM). Data were analyzed using ANOVA and Student's t-test.

&Lt; Effect of osmotin and osmotin-peptide on LPS-induced apoptosis in PC-12 cell line >

1. Results of MTT Assay

The effect of LPS-supernatant on the proliferation of PC12 cell line and the effect of osmotin and osmotin-peptide on cell proliferation (MTT assays) were analyzed.

In the spectrophotometric analysis, the% cell survival rate of the LPS-treated group was drastically decreased as compared with the control group. Compared with the LPS-treated group, the osmotin or osmotin-peptide treated group showed a dose-related increase in% cell viability (Figure 1).

2. Results of ApoTox-Glo triplex assay

The Apo-Tox Glo triplex assay was used to measure the PC12 cell viability, cytotoxicity and caspase 3/7 activity of the control, LPS and osmotin treatment groups, LPS and osmotin-peptide treatment groups. Osmotin or osmotin-peptide maintains cell survival after LPS treatment (Fig. 2A), reduces cytotoxicity (Fig. 2B), inhibits caspase 3/7 activity (Fig. 2C) . In addition, the dose-dependent neuroprotective activity of osmotin and osmotin-peptide was demonstrated to be superior at 0.4 uM (osmotin) and 10 uM (osmotin-peptide) concentrations.

3. Dopamine receptor 2 protein secretion activity

Dopamine receptor 2 protein secretion activity was increased when PC-12 cells secreted dopamine were depressed by LPS and treated with osmotin or 9 amino acid active osmotin-peptide. More Dopamine receptor 2 protein was secreted from cells treated with osmotin than with PC-12 treated with LPS alone, and secreted the most Dopamine receptor 2 protein in osmotin-peptide treated cells (Fig. 3).

< Results of in vivo mouse test >

1. Forced Swim Test (FST) and Tail Suspension Test (TST)

Forced Swim Test (FST) and Tail Suspension Test (TST) were used to determine whether HFD (high calorie diet, HF diet) treatment or LPS + HFD treatment contributed to acute behavioral despair. TST) was used. Applicants have found that the immobilization period is reduced compared to HFD treated mice and LPS + HFD treated mice in osmotin treated mice (FIGS. 4A and 4B).

2. Sucrose preference test and Olfactory test / Buried food test

With respect to asthenia (a phenomenon of diminished ability to experience pleasure), one of the key symptoms of depression, HFD-treated mice or LPS + HFD-treated mice show a significant reduction in sucrose preference. Administration of osmotin or osmotin-peptide significantly increased sucrose preference in HFD treated mice and had little effect on LPS + HFD treated mice (Figure 5a).

Also, in the olfactory test, HFD treated mice or LPS + HFD treated mice took considerable time to find food. However, in osmotin-treated mice, the food search time was greatly reduced (Fig. 5B).

3. Results of activity of postsynaptic dysfunction

Synaptic integrity was tested with the postsynaptic marker Postsynaptic Density Protein 95 (PSD95) in the mouse brain hippocampal region. Western blot analysis showed that PSD95 levels were significantly reduced in HFD- and LPS-treated mice compared to the control group. HFD treatment and LPS treatment could induce synaptic dysfunction, but treating osmotin with HFD or LPS greatly increased the expression of PSD95 (Fig. 6).

4. Effect of Osmotin Peptides on BDNF / Akt / PI3K signaling pathways in LPS / HFD treated mice

The effects of HFD treatment / LPS treatment and osmotin-peptide on BDNF / PI3k signaling were evaluated in the brain hippocampal region of mice via Western blotting technique. Immunoblot results indicate that HFD treatment and LPS treatment reduced BDNF expression and ultimately inhibited PI3k. The effects of HFD treatment, HFD treatment / LPS treatment (HFD treatment + LPS treatment) on BDNF-PI3k signaling were reversed when osmotin-peptide (9aa) was administered (Fig. 7).

<110> INDUSTRY-ACADEMIC COOPERATION FOUNDATION GYEONGSANG NATIONAL UNIVERSITY <120> Composition for prevention, improving or treating depressive          bozuk comprising osmotin peptide <130> 16P1257 <160> 2 <170> Kopatentin 2.0 <210> 1 <211> 205 <212> PRT <213> Artificial Sequence <220> <223> synthetic peptide <400> 1 Ala Thr Ile Glu Val Arg Asn Asn Cys Pro Tyr Thr Val Trp Ala Ala   1 5 10 15 Ser Thr Pro Ile Gly Gly Gly Arg Arg Leu Asp Arg Gly Gln Thr Trp              20 25 30 Val Ile Asn Ala Pro Arg Gly Thr Lys Met Ala Arg Val Trp Gly Arg          35 40 45 Thr Asn Cys Asn Phe Asn Ala Ala Gly Arg Gly Thr Cys Gln Thr Gly      50 55 60 Asp Cys Gly Gly Val Leu Gln Cys Thr Gly Trp Gly Lys Pro Pro Asn  65 70 75 80 Thr Leu Ala Glu Tyr Ala Leu Asp Gln Phe Ser Gly Leu Asp Phe Trp                  85 90 95 Asp Ile Ser Leu Val Asp Gly Phe Asn Ile Pro Met Thr Phe Ala Pro             100 105 110 Thr Asn Pro Ser Gly Gly Lys Cys His Ala Ile His Cys Thr Ala Asn         115 120 125 Ile Asn Gly Glu Cys Pro Arg Glu Leu Arg Val Pro Gly Gly Cys Asn     130 135 140 Asn Pro Cys Thr Thr Phe Gly Gly Gln Gln Tyr Cys Cys Thr Gln Gly 145 150 155 160 Pro Cys Gly Pro Thr Phe Phe Ser Lys Phe Phe Lys Gln Arg Cys Pro                 165 170 175 Asp Ala Tyr Ser Tyr Pro Gln Asp Asp Pro Thr Ser Thr Phe Thr Cys             180 185 190 Pro Gly Gly Ser Thr Asn Tyr Arg Val Ile Phe Cys Pro         195 200 205 <210> 2 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> synthetic peptide <400> 2 Cys Thr Gln Gly Pro Cys Gly Pro Thr   1 5

Claims (9)

A pharmaceutical composition for preventing or treating depression, comprising osmotin comprising an amino acid sequence represented by SEQ ID NO: 1 or osmotin peptide consisting of an amino acid sequence represented by SEQ ID NO: 2 as an active ingredient. The pharmaceutical composition for preventing or treating depression according to claim 1, wherein the osmotin or osmotin-peptide is contained in an amount of 0.1 to 100% by weight based on the total weight of the composition. The pharmaceutical composition for preventing or treating depression according to claim 1, further comprising a pharmaceutically acceptable carrier in addition to the active ingredient. The pharmaceutical composition for preventing or treating depression according to claim 1, further comprising a pharmaceutically acceptable adjuvant in addition to the active ingredient. Comprising administering to an animal a composition comprising osmotin comprising an amino acid sequence represented by SEQ ID NO: 1 or osmotin peptide consisting of an amino acid sequence represented by SEQ ID NO: 2 as an active ingredient Methods for the prevention or treatment of depression. A health functional food composition for preventing or ameliorating depression characterized by containing osmotin comprising an amino acid sequence represented by SEQ ID NO: 1 or osmotin peptide consisting of an amino acid sequence represented by SEQ ID NO: 2 as an active ingredient. 7. The health functional food composition according to claim 6, wherein the osmotin or osmotin-peptide is contained in an amount of 0.1 to 100% by weight based on the total weight of the composition. The health functional food composition for preventing or improving depression according to claim 6, wherein the composition is any one of beverage, tablet, capsule, and powder. The health functional food composition for preventing or improving depression according to claim 6, further comprising a pharmaceutically acceptable adjuvant in addition to the active ingredient.

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