JNK Activation Composition

Abstract

To provide novel materials for JNK activation.SOLUTION: The invention provides a JNK activating composition comprising one or more components selected from the group consisting of an S-layer protein being a cell component of a Lactobacillus bacterium and decomposition products thereof. The invention also provides food and drinks for JNK activation, antioxidation or cell protection.SELECTED DRAWING: Figure 3A

Description

[Technical Field]

[0001] The present invention relates to a composition for activating JNK, and in particular to a composition for activating JNK comprising an S-layer protein of a lactic acid bacterium and a degradation product of the S-layer protein. [Background technology]

[0002] The mitogen-activated protein kinase (MAPK) pathway plays an important role in the expression of various cellular functions. MAPKs form a superfamily of structurally similar proteins, particularly JNK (c-Jun N-terminal kinase, hereafter simply referred to as JNK), p38MAPK (p38), and ERK proteins. JNK is activated by stresses such as radiation, cytokine stimulation, and heat shock. Abnormal activation of JNK is known to cause various diseases associated with chronic inflammation, while moderate activation of JNK has beneficial effects. Several beneficial effects mediated by JNK activation have been reported. Non-patent document 1 shows that the increased expression of interferon via JNK activation acts to protect against infection. Non-patent document 2 shows that Lactobacillus gasseri SBT2055 activates JNK, thereby enhancing the NRF2-ARE pathway and improving antioxidant capacity. Non-Patent Document 3 shows that lipoteichoic acid prepared from Lactobacillus lactic acid bacteria activates JNK and induces TNFα expression. Non-patent document 4 shows that soluble components produced by Lactobacillus rhamnosus GG act in cell defense by activating MAPK, including JNK, and inducing the production of heat shock proteins. Patent Document 1 shows that Lactobacillus helveticus has the ability to induce MKP-1. Since MKP-1 is a negative regulator of MAPK, it is suggested that it has the effect of suppressing MAPK activation. However, the solution provided by the present application is neither disclosed nor suggested in any of the documents. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 2017-171616 [Non-patent literature]

[0004] [Non-Patent Document 1] Fejer, G., et al., PLoS pathogens, 2008:e1000208 [Non-patent document 2] Kobatake,E.,et al.,PLoS One,2017:e0177106 [Non-patent document 3] Matsuguchi,T.,et al.,Clinical and diagnostic laboratory immunology,2003:259-266 [Non-patent document 4] Tao, Y., et al., American Journal of Physiology-Cell Physiology, 2006:C1018-C1030 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a novel material that activates JNK. [Means for solving the problem]

[0006] In order to solve the above problems, the present invention includes the following configurations. [1] A composition for activating JNK, characterized by comprising one or more components selected from the group consisting of S-layer proteins, which are components derived from Lactobacillus bacteria, and degradation products of the S-layer proteins. [2] The composition for activating JNK according to [1], wherein the lactic acid bacteria of the genus Lactobacillus are one or more selected from the group consisting of Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus amylovorus, Lactobacillus brevis, and Lactobacillus buchneri. [3] The composition for activating JNK according to [1], wherein the lactic acid bacterium of the genus Lactobacillus is Lactobacillus helveticus. [4] A composition for activating JNK, characterized by containing Lactobacillus helveticus cells or a culture thereof as an active ingredient. [5] A food or drink for activating JNK, comprising the composition for activating JNK described in any one of [1] to [4]. [6] An antioxidant food or drink comprising the composition for activating JNK described in any one of [1] to [4]. [7] A food or drink for cell protection, comprising the composition for JNK activation described in any one of [1] to [4]. [Effects of the Invention]

[0007] By ingesting materials that activate JNK, such as S-layer protein (SLP) derived from Lactobacillus lactic acid bacteria and its degradation products, or Lactobacillus helveticus lactic acid bacteria and its culture, JNK is activated, and various effects such as antioxidant and cell defense effects can be expected. [Brief explanation of the drawings]

[0008] [Figure 1] 1 is a photograph showing the results of SDS-PAGE of SLP purified from Lactobacillus helveticus. [Figure 2] This is a photograph showing the results of SDS-PAGE of SLP, heated SLP, and SLP degradation products. [Figure 3] Photograph (A) and graph (B) show the results of Western blotting analysis of JNK phosphorylation when SLP purified from Lactobacillus helveticus was added to Caco-2 cells. [Figure 4] 1 is a graph showing the expression level of the hBD2 gene when Caco-2 cells were treated with a MAPK or NF-κB inhibitor and then SLP purified from Lactobacillus helveticus was added. [Figure 5] This photograph shows the results of Western blotting analysis of JNK phosphorylation when SLP purified from Lactobacillus helveticus SBT2171 (FERM BP-5445), Lactobacillus helveticus JCM1120, Lactobacillus acidophilus JCM1132, Lactobacillus amylovorus JCM1126, Lactobacillus brevis HYZ33043, and Lactobacillus buchneri JCM1115 was added to Caco-2 cells. [Figure 6] 1 is a graph showing the expression level of the hBD2 gene when SLP of Lactobacillus helveticus, heated SLP, or SLP degradation products were added to Caco-2 cells. [Figure 7] 1 is a graph showing the expression level of the hBD2 gene when Lactobacillus helveticus cells and SLP were added to Caco-2 cells. [Figure 8] 1 is a graph showing the expression level of the hBD2 gene when a skim milk culture of Lactobacillus helveticus is added to Caco-2 cells. DETAILED DESCRIPTION OF THE INVENTION

[0009] The present invention provides a novel composition for activating JNK. The composition for activating JNK of the present invention will be described in detail below. (JNK activation composition) S-layer proteins (hereinafter simply referred to as SLPs) are found in the outer layer of the cell walls of various bacteria and are characterized by their regular crystalline structure. Because SLPs are noncovalently bound to cell wall components, they can be extracted from bacterial cells using chaotropic agents such as lithium chloride. Furthermore, the extracted SLPs re-form their regular crystalline structure upon removal of the chaotropic agent. This characteristic allows for their purification from bacterial cells. Among lactic acid bacteria, the Lactobacillus genus has been found to express S-layers, and a report by Mukai et al. (Japanese Journal of Lactic Acid Bacteria, 19(1):21-29, 2008) confirmed or predicted the expression of SLPs in 13 bacterial species, including Lactobacillus acidophilus. The SLPs expressed by these lactic acid bacteria share common features, such as being basic proteins with an isoelectric point of 9-10 and possessing a signal peptide sequence of 23-30 amino acid residues in the N-terminal region. The SLP used in the JNK-activating composition of the present invention is derived from the genus Lactobacillus and any SLP that has the relevant activity can be used, but Lactobacillus helveticus is preferred, and among Lactobacillus helveticus, SBT2171 (FERM BP-5445) is the most preferred. Furthermore, the SLP, which is an active ingredient of the present invention and is a component derived from Lactobacillus cells, does not need to be purified from cells, and a crude fraction may be used, but purified SLP is more preferred. Furthermore, Lactobacillus helveticus cells or cultures thereof can be used as the active ingredient of the present invention. The cells themselves may be live or dead, and the culture may be either liquid or solid culture.

[0010] (Method of producing a composition for activating JNK) The SLP used in the JNK-activating composition of the present invention can be purified from lactic acid bacteria cells according to the following method. The target Lactobacillus lactic acid bacteria are thoroughly cultured in a liquid medium such as MRS liquid medium or in skim milk, and then the cells are collected and washed as necessary. The cells may also be collected from colonies grown on agar medium or the like. The obtained cells, either directly or after lyophilization, are suspended and stirred in a chaotropic reagent solution such as lithium chloride, urea, or guanidine hydrochloride to solubilize the SLP on the cell surface. After removing solids from the solution containing the solubilized SLP, the chaotropic reagent is removed by dialysis or the like to precipitate the SLP. The precipitated SLP is collected and washed as necessary to obtain purified SLP. The SLP used in the JNK-activating composition of the present invention may be heated, as its JNK-activating activity is maintained even when heated.

[0011] (SLP decomposition product) The SLP digests used in the JNK-activating composition of the present invention are prepared according to the following method. Various proteases are added to a suspension of SLP at appropriate concentrations, and the mixture is allowed to react as needed. The type of protease and the degree of protease degradation are not limited. For example, conditions for degradation with proteinase K are preferably 37°C for 2 to 24 hours, more preferably 3 to 20 hours.

[0012] (Intake amount) Because SLP's antimicrobial peptide production-promoting effect is exerted even in the form of degradation products, it is thought that degradation by gastric acid after oral ingestion would have little effect on its effect. For this reason, it is recommended that SLP or its degradation products be added to food and taken orally. There are no particular restrictions on the amount of intake, but in the case of Lactobacillus helveticus SBT2171, JNK activation can be expected by continuously ingesting approximately 1 mg of SLP per day.

[0013] (Food, medicine, and feed) Since purified SLP does not lose its JNK-activating activity even after heat treatment, it can be incorporated into foods, pharmaceuticals, and feeds according to standard methods. Foods and beverages containing the JNK-activating composition of the present invention are useful as JNK-activating foods and beverages, and ingesting these foods and beverages is expected to provide antioxidant and cytoprotective effects associated with JNK activation. That is, the present invention also relates to antioxidant foods and beverages containing the JNK-activating composition, as well as cytoprotective foods and beverages containing the JNK-activating composition. Furthermore, when the JNK-activating composition of the present invention is included in animal feed, similar effects can be expected in animals that ingest it. Furthermore, a pharmaceutical comprising the composition for activating JNK of the present invention can be used for diseases that can be treated or prevented by activating JNK.

[0014] (Evaluation method) The JNK activation effect of the present invention refers to the effect of enhancing JNK phosphorylation and activating JNK signaling in a subject who has ingested the Lactobacillus-derived SLP or SLP degradation product (SLP, etc.) of the present invention. The JNK activating effect of the present invention can be evaluated, for example, by the following method. SLP or the like derived from the Lactobacillus genus is added to cultured cells, and after a predetermined time, JNK phosphorylation is evaluated by Western blotting. In this case, if phosphorylation is enhanced when SLP or the like is added compared to when no addition is made, it can be evaluated that there is a JNK activating effect. Various cells can be used for the evaluation. [Example]

[0015] Examples of the present invention will be described in detail below, but the present invention is not limited to these examples. The preparation examples of Lactobacillus SLP and SLP degradation products used in this test are shown below. (Example of preparation of Lactobacillus lactic acid bacteria cells) Lactobacillus helveticus SBT2171 was cultured in 100 mL of MRS liquid medium at 37°C for 16 hours, and then the cells were collected by centrifugation (8,000 x g, 4°C, 10 minutes), washed twice with saline and once with sterilized MilliQ water, and then freeze-dried (freeze-dried cells). The freeze-dried cells were used in the following tests.

[0016] (Example of SLP preparation) Lactobacillus helveticus SBT2171 was cultured in 100 mL of MRS liquid medium at 37°C for 16 hours, and then the cells were collected by centrifugation (8,000 × g, 4°C, 10 minutes) and washed once with sterilized MilliQ water. TM The mixture was suspended in 10 mL of 1 M LiCl solution containing Protease Inhibitor Cocktail (Roche) and stirred at room temperature for 30 minutes. The suspension was centrifuged (10,000 × g, 4 °C, 20 minutes) and the supernatant was collected. The precipitate was then collected by centrifuging at 10,000 × g for 20 minutes at 4 °C. TM The cells were resuspended in 10 mL of 5 M LiCl solution containing Protease Inhibitor Cocktail (Roche) and stirred again at room temperature for 30 minutes. The stirred suspension was centrifuged (10,000 × g, 4°C, 20 minutes), and the supernatant was collected. The collected supernatants were combined, passed through a 0.2 μm filter, and then dialyzed against sterile MilliQ water using a Slide-A-Lyzer G2 10K (Pierce) to precipitate SLPs. The dialyzed solution was centrifuged (12,000 × g, 4°C, 20 minutes), and the precipitated SLPs were collected. The recovered SLPs were washed with 1 mL of sterile MilliQ water, suspended in 500 μL of 1 M LiCl solution, and kept on ice for 15 minutes with appropriate stirring. The LiCl solution was removed by centrifugation, washed again with 1 mL of sterile MilliQ water, resuspended in sterile MilliQ water, and lyophilized to obtain purified SLPs. After purification, SDS-PAGE confirmed that a band of the desired size, approximately 43 kDa, was observed (Figure 1). The yield of SLP obtained was 3 mg. Similarly, SLPs prepared from Lactobacillus helveticus JCM1120, Lactobacillus acidophilus JCM1132, Lactobacillus amylovorus JCM1126, Lactobacillus brevis HYZ33043, and Lactobacillus buchneri JCM1115 showed bands of the desired size, approximately 43–55 kDa, by SDS-PAGE. The yields of SLPs ranged from 1–9 mg.

[0017] (Example of preparation of SLP decomposition product) SLP was suspended in PBS at 5 mg / mL, and proteinase K (from Tritirachium album, P6556: Sigma) (10 mg / mL) was added to a final concentration of 100 μg / mL, followed by incubation at 37°C overnight. After incubation, the SLP was heated at 96°C for 10 minutes to inactivate proteinase K, yielding an SLP digest. For comparison, SLP suspended in PBS, SLP suspended in PBS and heated at 96°C for 10 minutes, and SLP digested with proteinase K were analyzed by SDS-PAGE (Figure 2). The heated SLP showed bands at approximately 37 kDa and 5 kDa, in addition to the bands at approximately 43 kDa seen in SLP. Furthermore, no clear bands above 5 kDa were observed in the SLP digests.

[0018] (Example of preparation of skim milk culture) Lactobacillus helveticus SBT2171 was cultured in 15 mL of 10% reduced skim milk medium (sterilized at 110°C for 20 minutes) at 37°C for 16 hours to prepare a skim milk culture.

[0019] [Test Example 1] Evaluation of JNK activation ability Subcultured Caco-2 cells (human intestinal epithelial cells) were cultured at 4.0 × 10 5Cells were seeded into 6-well plates at 100 cells / well and cultured overnight at 37°C in a 5% CO2 incubator. DMEM-high glucose medium (D5796: Sigma) supplemented with FBS (final concentration 10%) (Lot. 11D264: Sigma), NEAA (M7145: Sigma), and penicillin-streptomycin (final concentration 100 U-100 μg / mL) (15140-122: Life Technologies) was used for culture. After confirming that the cells had reached 70-80% confluence, the medium was removed and replaced with medium (DMEM-high glucose supplemented with NEAA) without FBS or antibiotics and cultured for an additional 24 hours at 37°C. After culture, the medium was removed from the 6-well plate and medium containing 10 μg / mL of SLP purified from Lactobacillus helveticus SBT2171 was added and cultured for 1 hour. After culturing, the medium was removed from the 6-well plate, washed with PBS, and then TM Protease Inhibitor Cocktail (Roche) and PhosSTOP TM The cells were lysed and collected in RIPA buffer containing RIPA (Roche). The collected cells were left on ice for 1 hour, then sonicated and centrifuged (7,500 × g, 4°C, 5 minutes) to remove the precipitate. The resulting supernatant was mixed with sample buffer and heated at 95°C for 5 minutes to prepare the sample. The resulting samples were electrophoresed on a Mini-Protean TGX gel (BIO-RAD). After transfer to an Immobilon-P membrane (Merck), bound proteins were assayed by Western blotting using an anti-p-JNK antibody. The p-JNK band intensity was normalized to that of β-actin. Immobilon Western chemiluminescent HRP substrate (Merck) was used for detection.

[0020] 2. Test Results As a result of the evaluation, a significant increase in JNK phosphorylation was observed in cells treated with SLP from Lactobacillus helveticus compared to untreated cells (Figure 3). These results suggest that SLP purified from Lactobacillus helveticus has JNK activating activity.

[0021] [Test Example 2] Examination of effects mediated by JNK activation (increased expression of antimicrobial peptides) 1. Test Method Subcultured Caco-2 cells (human intestinal epithelial cells) were cultured at 2.0 × 10 5 Cells were seeded into 12-well plates at 100 cells / well and cultured overnight at 37°C in a 5% CO2 incubator. For culture, DMEM-high glucose (D5796: Sigma) was supplemented with FBS (final concentration 10%) (Lot. 11D264: Sigma), NEAA (M7145: Sigma), and penicillin-streptomycin (final concentration 100 U-100 μg / mL) (15140-122: Life Technologies). After confirming that the cells had reached 70-80% confluence, the medium was removed and replaced with medium (DMEM-high glucose + 1x NEAA) without FBS or antibiotics, and cultured for an additional 24 hours at 37°C. After incubation, the medium was removed from the 12-well plates, and medium containing 20 μM MAPK or NF-κB inhibitors (p38 inhibitor: SB202190, JNK inhibitor: SP600125, ERK inhibitor: PD98059, NF-κB inhibitor: JSH23) was added and treated for 1 hour. After inhibitor treatment, Lactobacillus helveticus SBT2171SLP was added to the cells at a final concentration of 10 μg / mL and cultured for 6 hours. After incubation, the medium was removed from the 12-well plates, washed with PBS, and total RNA was extracted from the cells using an RNeasy Mini Kit (Qiagen). The concentration of the extracted total RNA was measured using a NanoDrop2000 (Thermo Fisher Scientific). cDNA was synthesized from the extracted total RNA solution using ReverTra Ace qPCR RT Master Mix with gDNA Remover (Toyobo). A TaKaRa PCR Thermal Cycler Dice® Gradient (Takara Bio) was used for the reverse transcription reaction. The resulting reverse transcription reaction solution was used as template cDNA for real-time PCR. For real-time PCR, TaqMan® Fast Advanced Master Mix (Life Technologies, Cat. #4444556) and TaqMan Gene Expression Assay (hBD2: Hs00175474_m1, GAPDH: Hs03929097_g1) (Life Technologies) were used. Reactions were performed in a 384-well plate (Life Technologies, Cat. #4309849) using ViiA TM 7 (Life Technologies) was used. LPS was added at a concentration of 10 μg / mL as a positive control, and gene expression at each level was evaluated as the relative expression level to the positive control using the ΔΔCt method. Tests were performed in triplicate, and levels including samples in which no amplification was observed were recorded as not detected (nd).

[0022] 2. Test Results The results of the evaluation showed that the addition of SLP purified from Lactobacillus helveticus increased the expression of the antimicrobial peptide hBD2 gene. On the other hand, treatment with a JNK inhibitor (SP600125) significantly suppressed the increase in hBD2 gene expression (Figure 4). Furthermore, MAPK or NF-κB inhibitors (p38 inhibitor: SB202190, ERK inhibitor: PD98059, NF-κB inhibitor: JSH23) did not suppress the increase in hBD2 gene expression. These results suggest that the induction of hBD2 expression by SLP from Lactobacillus helveticus is due to the effects of JNK activation.

[0023] [Test Example 3] Evaluation of JNK activation ability - Comparison of bacterial species 1. Test Method As in "Test Example 1: Evaluation of JNK activation ability," Caco-2 cells were seeded and the medium was changed. SLPs prepared from Lactobacillus helveticus SBT2171, Lactobacillus helveticus JCM1120, Lactobacillus acidophilus JCM1132, Lactobacillus amylovorus JCM1126, Lactobacillus brevis HYZ33043, and Lactobacillus buchneri JCM1115 were added to a concentration of 10 μg / mL and cultured for 1 hour. Sample preparation, SDS-PAGE, and Western blotting were then performed as described above.

[0024] 2. Test Results As a result of the evaluation, JNK activation was observed even when SLP purified from Lactobacillus lactic acid bacteria other than Lactobacillus helveticus was added (Figure 5). These results suggest that the JNK activation effect of SLP purified from lactic acid bacteria is broadly common to the Lactobacillus genus. The molecular weight of SLPs produced by lactic acid bacteria varies greatly between bacterial species, and their genetic structures have been shown to be highly diverse even within the same bacterial species. Therefore, it was surprising that the JNK activation effect of the SLPs of the present invention was found to be widespread among the Lactobacillus genus.

[0025] [Test Example 4] Evaluation of JNK activation ability - Evaluation of SLP digestion products 1. Test Method As in "Test Example 1: Evaluation of JNK activation ability," Caco-2 cells were seeded and the medium was changed. SLP from Lactobacillus helveticus SBT2171 was then added to the cells at a concentration of 50 μg / mL, either intact or after heating at 96°C for 10 minutes, or after decomposition by proteinase K treatment. The cells were then cultured for 6 hours. Total RNA was then extracted, cDNA was synthesized, and hBD2 gene expression was analyzed by real-time PCR, as described above.

[0026] 2. Test Results As a result of the evaluation, not only untreated SLP but also heat-treated SLP and SLP digested with proteinase K showed significantly higher hBD2 gene expression compared to the positive control (Figure 6). In the figure, the symbols a, b, and c indicate significant differences (P<0.05) between the different symbols. These results indicate that SLP purified from Lactobacillus helveticus SBT2171, even in its digested form, has the ability to upregulate the hBD2 gene. Since the induction of hBD2 expression by SLP from SBT2171 is due to JNK activation, it is thought that SLP digests from SBT2171 also have the ability to activate JNK.

[0027] [Test Example 5] Evaluation of JNK activation ability - Evaluation of Lactobacillus helveticus cells 1. Test Method As in the above "Test Example 1: Evaluation of JNK activation ability," Caco-2 cells were seeded and the medium was replaced, followed by the addition of medium containing Lactobacillus helveticus SBT2171 cells or SLP purified from Lactobacillus helveticus SBT2171 at 10 or 50 μg / mL, and the cells were cultured for 6 hours. Then, as in Test Example 1, total RNA extraction, cDNA synthesis, and hBD2 gene expression analysis by real-time PCR were performed.

[0028] 2. Test Results The evaluation results showed that both Lactobacillus helveticus cells and SLP increased hBD2 gene expression (Figure 7). At an added concentration of 10 μg / mL, Lactobacillus helveticus cells showed approximately three times higher hBD2 gene expression than the positive control, and at an added concentration of 50 μg / mL, approximately 28 times higher. At an added concentration of 10 μg / mL, SLP showed approximately 19 times higher gene expression and at 50 μg / mL, approximately 45 times higher gene expression. These results suggest that not only purified SLP from Lactobacillus helveticus but also cultured cells have the ability to activate JNK. In the figure, symbols a, b, c, and d indicate significant differences (P<0.05) between different symbols.

[0029] [Test Example 6] Evaluation of JNK activation ability - Evaluation of Lactobacillus helveticus skim milk culture 1. Test Method As in the above "Test Example 1: Evaluation of JNK activation ability," Caco-2 cells were seeded and the medium was replaced, followed by the addition of a medium containing 5% Lactobacillus helveticus SBT2171 skim milk culture and incubation for 6 hours. Then, as in Test Example 1, total RNA was extracted, cDNA was synthesized, and hBD2 gene expression was analyzed by real-time PCR.

[0030] 2. Test Results As a result of the evaluation, increased expression of the hBD2 gene was observed in the Lactobacillus helveticus skim milk culture (Figure 8). These results suggest that not only SLP purified from Lactobacillus helveticus and the cultured cells, but also the culture itself, have the ability to activate JNK.

[0031] (Example of food incorporation) 10 mg of SLP purified from Lactobacillus helveticus SBT2171 was mixed with 30 g of skim milk powder, 40 g of an equal mixture of vitamin C and citric acid, 100 g of granulated sugar, and 60 g of an equal mixture of cornstarch and lactose. The mixture was packed into a stick-shaped bag to produce the JNK-activating health food of the present invention.

[0032] (Example of mixing into feed) Two grams of purified SLP from Lactobacillus helveticus SBT2171 was suspended in 3998 g of deionized water, heated to 40°C, and mixed in a TK homogenizer (Model MARK II 160; Tokushu Kika Kogyo Co., Ltd.) at 3,600 rpm for 20 minutes to obtain a 2 g / 4 kg SLP solution. This SLP solution (2 kg) was then combined with 1 kg soybean meal, 1 kg skim milk powder, 0.4 kg soybean oil, 0.2 kg corn oil, 2.3 kg palm oil, 1 kg corn starch, 0.9 kg wheat flour, 0.2 kg bran, 0.5 kg vitamin mixture, 0.3 kg cellulose, and 0.2 kg mineral mixture. The mixture was then sterilized at 120°C for 4 minutes to produce 10 kg of the JNK-activating feed of the present invention.

[0033] (Example of compounding into pharmaceuticals) A liquid culture of Lactobacillus helveticus SBT2171 was centrifuged at 7,000 rpm at 4°C for 15 minutes, followed by three cycles of washing with sterile water and centrifugation to obtain washed bacterial cells. These washed bacterial cells were then freeze-dried to obtain bacterial cell powder. One part of this bacterial cell powder was mixed with four parts of skim milk powder, and the resulting powder mixture was compressed into 1g tablets in a tablet press using standard methods to prepare the JNK-activating tablets of the present invention. [Industrial Applicability]

[0034] By ingesting SLP derived from Lactobacillus lactic acid bacteria, or SLP decomposition products, Lactobacillus helveticus lactic acid bacteria cells, and materials that activate NK, antioxidant and cell protective effects can be expected.

Claims

1. A composition for activating JNK, characterized by containing, as an active ingredient, one or more selected from the group consisting of S-layer proteins, which are components derived from bacteria of the genus Lactobacillus, and degradation products of the S-layer proteins.

2. 2. The composition for activating JNK according to claim 1, wherein the lactic acid bacteria of the genus Lactobacillus are one or more selected from the group consisting of Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus amylovorus, Lactobacillus brevis, and Lactobacillus buchneri.

3. The composition for activating JNK according to claim 1, wherein the lactic acid bacterium of the genus Lactobacillus is Lactobacillus helveticus.

4. A composition for activating JNK, comprising Lactobacillus helveticus cells or a culture thereof as an active ingredient.

5. A food or drink for activating JNK, comprising the composition for activating JNK according to any one of claims 1 to 4.

6. An antioxidant food or drink comprising the JNK activating composition according to any one of claims 1 to 3.

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