Composition for preventing, ameliorating or treating inflammatory diseases comprising lactobacillus plantarum wikim0175

The novel Lactobacillus plantarum WiKim0175 strain, isolated from kimchi, addresses the limitations of current osteoarthritis treatments by inhibiting inflammation and cartilage damage genes, thereby improving joint health and reducing arthritis symptoms.

WO2025110672A1PCT designated stage expired Publication Date: 2025-05-30KOREA FOOD RES INST
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Patent Information

Application Number
PCT/KR2024/018255
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-11-20
Filing Date
2024-11-19
Publication Date
2025-05-30

AI Technical Summary

Technical Problem

Current treatments for osteoarthritis, including pain relief medications and chondroprotectors, are insufficient in preventing cell and tissue degeneration and promoting cartilage production and regeneration, leading to ongoing limitations in treatment efficacy.

Method used

A novel Lactobacillus plantarum strain, WiKim0175, isolated from kimchi, is used in a composition to inhibit the expression of inflammation-related and cartilage damage-related genes, thereby improving joint and cartilage health.

Benefits of technology

The Lactobacillus plantarum WiKim0175 strain effectively reduces cartilage matrix decomposition and improves joint and cartilage functions, demonstrating arthritis-reducing activity and anti-inflammatory effects.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention relates to a Lactobacillus plantarum WiKim0175 strain isolated from Kimchi and a composition comprising same. Lactobacillus plantarum WiKim0175 according to the present invention inhibits inflammatory responses, and thus can have various applications for the prevention, amelioration and treatment of inflammatory diseases.
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Description

Composition for preventing, improving or treating inflammatory diseases comprising Lactobacillus plantarum WIKIM0175

[0001] The present invention relates to a Lactobacillus plantarum strain, a lactic acid bacterium isolated from kimchi, and a composition containing the same for preventing, improving, or treating inflammatory diseases.

[0002] Osteoarthritis is a degenerative disease in which the cartilage tissue protecting the joints gradually and irreversibly wears away. Approximately 10-15% of the world's population and 31% of the Korean adult population have symptoms, and the number of arthritis patients worldwide is continuously increasing due to the aging population and extended life expectancy.

[0003] Although much research and effort has been made recently to identify the pathological cause of arthritis, a fundamental treatment method has not been developed.

[0004] Up to now, the most common treatment for arthritis, other than artificial joint surgery, is pain relief through anti-inflammatory drugs (non-steroidal anti-inflammatory drugs, COX-2 selective inhibitors, combination drugs, natural products). Recently, chondroprotectors (hyaluronic acid, glucosamine, chondroitin) have been developed and are effective in cell protection, shock relief, cartilage nutrition supply, and cartilage metabolism enhancement. However, they are still insufficient in preventing cell and tissue degeneration and promoting cartilage production and inducing regeneration.

[0005] Additionally, although cutting-edge treatments such as cell and tissue engineering therapies or gene cell therapies have been developed recently for the treatment of arthritis, there are still many issues that need to be resolved before commercialization.

[0006] Due to the continuous increase in demand for arthritis treatment, various treatments have been launched, but they are still unable to sufficiently satisfy market demand due to limitations in their therapeutic effects.

[0007] In particular, in the case of domestic arthritis treatment, the domestic market share is being increased only with natural-based pain relief and anti-inflammatory products, but in order to target the global market in the future, it is necessary to develop new improvement methods that can induce or prevent improvement of symptoms in the early stages of arthritis using food ingredients.

[0008] The present invention provides a novel Lactobacillus plantarum WiKim0175 strain with accession number KCCM13151P, which has excellent efficacy in preventing or improving inflammatory diseases.

[0009] Accordingly, the inventors of the present invention have attempted to find a lactic acid bacteria strain that exhibits a preventive or improving effect on inflammatory diseases from traditional fermented foods, and as a result, have isolated and identified a novel lactic acid bacteria strain of the genus Lactobacillus, Lactobacillus plantarum WiKim0175, thereby completing the present invention.

[0010] The present invention provides Lactobacillus plantarum WiKim0175.

[0011] The present invention provides an anti-inflammatory food composition for improving joint and cartilage health, comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

[0012] In addition, the present invention provides an anti-inflammatory; health functional food composition for improving joint and cartilage health, comprising a culture, a lysate or an extract of Lactobacillus plantarum WiKim0175 strain as an active ingredient.

[0013] In order to achieve the above purpose, a method for improving anti-inflammatory and joint and cartilage health is provided, comprising a step of administering to a subject a composition comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

[0014] In order to achieve the above purpose, the present invention provides a composition comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient for producing an anti-inflammatory food for improving joint and cartilage health; or a health functional food.

[0015] In addition, the present invention provides a lactic acid bacteria starter for fermentation comprising Lactobacillus plantarum WiKim0175 strain or a culture thereof.

[0016] In addition, the present invention provides a feed or feed additive composition comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

[0017] In addition, the present invention provides a pharmaceutical composition for preventing or treating an inflammatory disease, comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

[0018] In order to achieve the above purpose, a method for preventing or treating an inflammatory disease is provided, comprising a step of administering to a subject a composition comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

[0019] In order to achieve the above purpose, the present invention provides a use of a composition comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient for manufacturing a pharmaceutical composition for preventing or treating an inflammatory disease.

[0020] Lactobacillus plantarum WiKim0175 according to the present invention is a lactic acid bacterium isolated from kimchi, which reduces the expression of inflammation-related genes and cartilage damage-related genes, thereby inhibiting cartilage matrix decomposition, and consequently improving joint and cartilage functions and having arthritis-reducing activity, and therefore can be utilized in various ways for the prevention, improvement, and treatment of inflammatory diseases that include lactic acid bacteria as an active ingredient.

[0021] Figure 1 is a graph showing the time (Sec, (a)) and force (PW, (b)) that the experimental group of arthritis mice endured to mechanical stimulation at the paw site as converted values.

[0022] Figure 2 is a graph showing the results of measuring the weight bearing value of the hind limbs of the arthritis mouse experimental group.

[0023] Figure 3 is a photograph (a) showing knee tissue damage observed in an experimental group of arthritis mice and a graph (b) showing the results of knee tissue thickness.

[0024] Figure 4 is a graph showing the level of gene expression related to cartilage damage in damaged cartilage tissue of the arthritis mouse experimental group.

[0025] Figure 5 is a graph showing the level of inflammation-related gene expression in damaged cartilage tissue of the arthritis mouse experimental group.

[0026] Hereinafter, the present invention will be described in detail through examples. The following examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention.

[0027] As a result of 16S rDNA base sequence analysis for identification and classification of microorganisms, the strain isolated from kimchi through an example of the present invention was found to have a nucleic acid sequence of SEQ ID NO: 1.

[0028] Accordingly, the microorganism of the present invention having the 16S rDNA base sequence of SEQ ID NO: 1 was named Lactobacillus plantarum WiKim0175 and deposited at the Korea Microbiological Conservation Center on March 23, 2022 (deposit number KCCM13151P).

[0029] SEQ ID NO: 1

[0030]

[0031] The Lactobacillus plantarum WiKim0175 of the present invention is a gram-positive bacterium and a facultative anaerobe capable of growing under both aerobic and anaerobic conditions. It does not form spores, is not motile, and its cells take the form of rods.

[0032] In the following examples, it was confirmed that the group administered Lactobacillus plantarum WiKim0175 of the present invention to mice in which arthritis was induced by administering MIA (monosodium iodoacetate) showed a higher arthritis pain improvement effect than the group administered PBS as a control group (Figs. 1 and 2), and it was confirmed that when Lactobacillus plantarum WiKim0175 was administered, the expression of cartilage damage-related genes (Adamts4, Adamts5, MMP3, MMP9, MMP13) and inflammation-related genes (IL-1β, IL-6, TNF-α, COX-2, iNOS) was also reduced. Therefore, Lactobacillus plantarum WiKim0175 of the present invention can be utilized in various ways for improving joint and cartilage health of humans or animals, preventing or improving arthritis disease, anti-inflammation, and preventing or improving inflammatory disease.

[0033] The present invention provides an anti-inflammatory food composition for improving joint and cartilage health, comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

[0034] The anti-inflammatory; joint and cartilage health improvement of the present invention may be due to inhibition of the expression of one or more genes selected from the group consisting of Adamts4, Adamts5, MMP3, MMP9, MMP13, IL-1β, IL-6, TNF-α, COX-2 and iNOS.

[0035] The above food composition may be in the form of a beverage or bar, etc.

[0036] In the present invention, a food composition containing the strain as an active ingredient may include a beverage such as fermented milk.

[0037] The food composition according to the present invention can be formulated in the same manner as the pharmaceutical composition described above and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, vitamin complexes, and health supplements.

[0038] The food composition of the present invention may include ingredients commonly added during food manufacturing, such as proteins, carbohydrates, fats, nutrients, seasonings, and flavoring agents. Examples of the carbohydrates mentioned above include monosaccharides such as glucose, fructose, etc.; disaccharides such as maltose, sucrose, oligosaccharides, etc.; and polysaccharides such as dextrin, cyclodextrin, etc., and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [thaumatin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.]) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is manufactured into drinks and beverages, citric acid, high fructose corn syrup, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts, etc. can be additionally included.

[0039] The above food composition may additionally contain food additives, and its suitability as a “food additive” is determined by the specifications and standards for the relevant item in accordance with the general provisions and general test methods of the Food Additives Codex approved by the Ministry of Food and Drug Safety, unless otherwise provided.

[0040] Examples of items listed in the above "Food Additives Codex" include chemically synthesized products such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, and guar gum; and mixed preparations such as sodium L-glutamate preparations, alkaline agents for noodles, preservative preparations, and tar color preparations.

[0041] Foods containing the active ingredient of the present invention include confectionery such as bread, rice cakes, dried fruits, candies, chocolates, chewing gums, and jams; ice cream products such as ice cream, frozen desserts, and ice cream powders; dairy products such as milk, low-fat milk, lactose-hydrolyzed milk, processed milk, goat milk, fermented milk, buttermilk, condensed milk, milk cream, buttermilk, natural cheese, processed cheese, powdered milk, and whey; meat products such as processed meat products, processed egg products, and hamburgers; fish products such as processed fish products such as fish cakes, ham, sausage, and bacon; noodles such as ramen, dried noodles, fresh noodles, fried noodles, luxurious dried noodles, improved boiled noodles, frozen noodles, and pasta; beverages such as fruit drinks, vegetable drinks, carbonated drinks, soy milk, and yogurt, and mixed drinks; soy sauce, soybean paste, red pepper paste, soybean paste, cheonggukjang, and mixed sauce; Condiments such as vinegar, sauces, tomato ketchup, curry, dressings, margarine, shortening, and pizza are included, but are not limited to these.

[0042] In addition to the above, the composition of the present invention may include various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the composition of the present invention may include fruit pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients may be used independently or in combination.

[0043] The beverage composition including the active ingredient of the present invention has no particular limitations on other ingredients, and may contain various flavoring agents or natural carbohydrates as additional ingredients, like conventional beverages. Examples of the above-mentioned natural carbohydrates include conventional sugars such as monosaccharides (e.g., glucose, fructose, etc.); disaccharides (e.g., maltose, sucrose, etc.); and polysaccharides (e.g., dextrin, cyclodextrin, etc.), and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (thaumatin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.

[0044] The present invention provides an anti-inflammatory; health functional food composition for improving joint and cartilage health, comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

[0045] The anti-inflammatory; joint and cartilage health improvement of the present invention may be due to inhibition of the expression of one or more genes selected from the group consisting of Adamts4, Adamts5, MMP3, MMP9, MMP13, IL-1β, IL-6, TNF-α, COX-2 and iNOS.

[0046] The above “health functional food” refers to a food manufactured and processed using raw materials or ingredients with functionality useful to the human body in accordance with the Health Functional Food Act (Article 3, Paragraph 1), and “functionality” refers to obtaining a useful effect for health purposes, such as regulating nutrients or physiological effects for the structure and function of the human body (Article 2, Paragraph 2).

[0047] The present invention provides a lactic acid bacteria starter for fermentation comprising Lactobacillus plantarum WiKim0175 strain or a culture thereof.

[0048] The present invention provides an anti-inflammatory; feed or feed additive composition for improving joint and cartilage health, comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

[0049] The anti-inflammatory; joint and cartilage health improvement of the present invention may be due to inhibition of the expression of one or more genes selected from the group consisting of Adamts4, Adamts5, MMP3, MMP9, MMP13, IL-1β, IL-6, TNF-α, COX-2 and iNOS.

[0050] When used as a feed additive, the composition may be a highly concentrated solution of 20 to 90% or may be manufactured in the form of powder or granules. The feed additive may further include one or more of organic acids such as citric acid, fumaric acid, adipic acid, lactic acid, and malic acid; phosphates such as sodium phosphate, potassium phosphate, acid pyrophosphate, and polyphosphate (polyphosphate); and natural antioxidants such as polyphenol, catechin, alpha-tocopherol, rosemary extract, vitamin C, green tea extract, licorice extract, chitosan, tannic acid, and phytic acid. When used as a feed, the composition may be formulated in the form of a conventional feed and may include conventional feed ingredients together.

[0051] The above feed additives and feeds may further include grains, such as ground or crushed wheat, oats, barley, corn and rice; plant-based protein feeds, such as feeds mainly composed of rapeseed, soybeans and sunflower; animal-based protein feeds, such as blood meal, meat meal, bone meal and fish meal; dry ingredients composed of sugars and dairy products, such as various types of milk powder and whey powder, and may further include nutritional supplements, digestion and absorption enhancers, growth promoters and the like.

[0052] The feed additive may be administered to animals alone or in combination with other feed additives in an edible carrier. Furthermore, the feed additive may be easily administered to animals as a top dressing, by mixing it directly into animal feed, or in an oral formulation separate from the feed. When the feed additive is administered separately from animal feed, it may be prepared as an immediate-release or sustained-release formulation by combining it with a pharmaceutically acceptable edible carrier, as is well known in the art. Such edible carriers may be solid or liquid, such as cornstarch, lactose, sucrose, soybean flakes, peanut oil, olive oil, sesame oil, and propylene glycol. When a solid carrier is used, the feed additive may be in the form of a tablet, capsule, powder, troche, or saccharide tablet, or a top dressing in the form of a microdispersible. When a liquid carrier is used, the feed additive may be in the form of a gelatin soft capsule, or a syrup, suspension, emulsion, or solution.

[0053] In addition, the feed additive and feed may contain auxiliary agents, such as preservatives, stabilizers, wetting agents or emulsifiers, and solution accelerators. The feed additive may be added to animal feed by injection, spraying, or mixing.

[0054] The feed or feed additive of the present invention can be applied to a number of animal diets including mammals, poultry, and fish.

[0055] In the present invention, the animal includes mammals, and as mammals, pigs, cows, sheep, goats, laboratory rodents, and laboratory rodents, as well as pets (e.g., dogs, cats), etc., but is not limited thereto.

[0056] The present invention provides a pharmaceutical composition for preventing or treating inflammatory diseases, comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

[0057] The inflammatory disease of the present invention may be caused by the expression of one or more inflammation-related genes selected from the group consisting of IL-1β, IL-6, TNF-α, COX-2, and iNOS.

[0058] The inflammatory disease of the present invention is gastritis, stomatitis, atopic dermatitis, acne, psoriasis, sinusitis, rhinitis, conjunctivitis, asthma, dermatitis, inflammatory collagen vascular disease, glomerulonephritis, encephalitis, inflammatory enteritis, chronic obstructive pulmonary disease, sepsis, septic shock, pulmonary fibrosis, undifferentiated spondyloarthropathy, undifferentiated arthropathy, arthritis, osteoarthritis, inflammatory osteolysis, chronic inflammatory disease caused by viral or bacterial infection, ulcerative colitis, inflammatory bowel disease, rheumatoid arthritis, reactive arthritis, osteoarthritis, scleroderma, osteoporosis, atherosclerosis, myocarditis, endocarditis, pericarditis, cystic fibrosis, Hashimoto's thyroiditis, Graves' disease, leprosy, syphilis, Lyme disease, borreliosis, neurogenic borreliosis, tuberculosis, sarcoidosis, lupus, It may be at least one selected from the group consisting of chilblains lupus, tuberculous lupus, lupus nephritis, systemic lupus erythematosus, macular degeneration, uveitis, irritable bowel syndrome, Crohn's disease, Sjogren's syndrome, fibromyalgia, chronic fatigue syndrome, chronic fatigue immunodeficiency syndrome, myalgic encephalomyelitis, amyotrophic lateral sclerosis, Parkinson's disease, and multiple sclerosis.

[0059] The present invention provides a pharmaceutical composition for preventing or improving arthritis disease, comprising Lactobacillus plantarum WiKim0175 strain, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

[0060] The arthritis disease of the present invention may be caused by the expression of one or more genes selected from the group consisting of Adamts4, Adamts5, MMP3, MMP9, MMP13, IL-1β, IL-6, TNF-α, COX-2, and iNOS.

[0061] The Lactobacillus plantarum WiKim0175 strain included in the composition according to the present invention may exist as a live cell or a dead cell, and may also exist in a dried or lyophilized form. In addition, a culture of the Lactobacillus plantarum WiKim0175 strain may be the active ingredient, and the culture may include a live cell culture solution or a dead cell supernatant. The form and formulation method of lactic acid bacteria suitable for inclusion in various compositions are well known to those skilled in the art. For example, Lactobacillus plantarum WiKim0175 may be a culture obtained by culturing in a known liquid medium or solid medium, a fermented product obtained by culturing the strain together with an additional component, an extract obtained by extracting the strain with an organic solvent, a lysate (or lysate) obtained by dissolving, crushing, or homogenizing the cell membrane of the strain, but is not limited thereto.

[0062] When the composition according to the present invention is used as a pharmaceutical composition, the pharmaceutical composition of the present invention can be prepared using a pharmaceutically suitable and physiologically acceptable auxiliary agent in addition to the Lactobacillus plantarum WiKim0175 strain, and the auxiliary agent can be an excipient, a disintegrant, a sweetener, a binder, a coating agent, a swelling agent, a lubricant, a glidant, or a flavoring agent.

[0063] The above pharmaceutical composition may be preferably formulated as a pharmaceutical composition by including one or more pharmaceutically acceptable carriers in addition to the above-described effective ingredients for administration.

[0064] For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an orally acceptable, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants, and coloring agents may also be included in the mixture. Suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracheacanth, or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methylcellulose, agar, bentonite, xanthan gum, and the like. In the composition to be formulated as a liquid solution, acceptable pharmaceutical carriers include those that are sterile and biocompatible, such as saline solution, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and mixtures of one or more of these components. If necessary, other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate the composition into injectable formulations such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, or tablets.

[0065] Furthermore, it can be preferably formulated according to each disease or ingredient using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA, as an appropriate method in the relevant field.

[0066] [Example]

[0067] Example 1: Isolation and cultivation of Lactobacillus plantarum WiKim0175

[0068] The inventors isolated kimchi lactic acid bacteria from kimchi. The kimchi sample was crushed, and the kimchi extract was spread on MRS agar medium (Difco) and cultured at 30°C for at least 24 hours. A single colony formed after cultivation was subcultured and identified through 16S RNA sequencing.

[0069] A single colony of Lactobacillus plantarum cultured on MRS agar medium (Difco) was cultured in MRS medium at 30°C for 24 hours, and the cells were centrifuged at 8,000 rpm for 5 minutes and rinsed with PBS to remove any remaining medium components.

[0070] The strain isolated through the example of the present invention was found to have a nucleic acid sequence of SEQ ID NO: 1 as a result of 16S rDNA base sequence analysis for identification of microorganisms.

[0071] Accordingly, the microorganism of the present invention was named Lactobacillus plantarum WiKim0175 and deposited at the Korea Microbiological Conservation Center on March 23, 2022 (deposit number KCCM13151P).

[0072] Example 2: Avoidance response to mechanical stimulation and hindlimb weight-bearing experiment

[0073] In order to confirm the arthritis-improving effect of Lactobacillus plantarum WiKim0175 of the present invention, an experimental group was prepared using C57BL / 6N, male, 8-week-old mice through the following procedure.

[0074] 1)-Normal mouse

[0075] 1-1) After removing hair around the left knee of an anesthetized mouse, 10ul of PBS was injected into the knee joint space (PBS group).

[0076] 2) - Arthritis-induced mice

[0077] After removing hair around the left knee of an anesthetized mouse, 1 mg / 10 ul of MIA was injected once into the knee joint space to induce osteoarthritis, and then Indo or WiKim0175 was administered.

[0078] 2-1) After intra-articular injection of MIA, an arthritis-inducing substance, indomethacin was administered orally at a dose of 2 mg / kg, 5 times a week for a total of 3 weeks (Indo group).

[0079] 2-2) WiKim0175 was administered 2 times a week for a total of 5 weeks, starting from 2 weeks before the induction of osteoarthritis, and then 3 weeks after the injection of MIA into the joint, 2X10 9 CFU oral administration (WiKim0175 group).

[0080] To confirm the improvement in osteoarthritis pain in the arthritic mouse group prepared through the above process, the paw withdrawal threshold (PWT, paw withdrawal threshold, 50% PWT in this experiment, an indicator of pain threshold conversion) value in response to mechanical stimulation was measured through Mechanical Hypersensitivity (Allodynia). The measurement was conducted as follows.

[0081] The paw pads of each group were pricked with a blunt-tipped needle, and the time (sec) the mice could tolerate the pain induced and the pain level (PW) they could tolerate as the intensity of the pricking pain increased were measured. As the pain induced increased, the time (sec) to tolerate the stimulus decreased and the tolerable stimulus magnitude (PW) decreased. The measured values ​​are shown in Figure 1.

[0082] Figure 1(a) is a value converted into a threshold value for the time (sec) required to withstand pain due to mechanical stimulation, and Figure 1(b) is a value converted into a threshold value for the degree of withstandability for the pain intensity (PW) of mechanical stimulation.

[0083] In the WiKim0175 group, compared to the PBS group, the pain avoidance threshold value increased according to stimulation time in Fig. 1(a) and stimulation intensity in Fig. 1(b). Compared to the positive control group, the Indo group, the pain avoidance threshold value according to stimulation intensity was found to be at an equivalent or higher level. This confirmed the pain-improving effect of WiKim0175 in osteoarthritis.

[0084] Furthermore, the improvement in osteoarthritis pain was confirmed by measuring hindlimb weight-bearing values ​​through a weight-bearing load experiment. In the WiKim0175 group, the weight-bearing value increased compared to the PBS group, and also compared to the positive control group, the Indo group. This result also confirms the osteoarthritis pain-improving effect of WiKim0175 (Fig. 2).

[0085] Example 3: Observation results of knee tissue damage

[0086] Knee tissue damage was observed in the group of arthritic mice prepared in Example 2 (Fig. 3(a)). In cases of arthritis, knee tissue damage occurs, resulting in thickening of the knee.

[0087] In the WiKim0175 group, it was confirmed that the knee tissue thickness was reduced compared to the PBS group and that there was an effect of improving joint damage (Fig. 3(b)).

[0088] Example 4: Experimental results on the expression level of genes related to cartilage damage and inflammation in Lactobacillus plantarum WiKim0175.

[0089] In the above example, damaged cartilage tissues were collected from arthritis mice injected with MIA, and the expression of cartilage damage-related genes (Adamts4, Adamts5, MMP3, MMP9, MMP13) and inflammation-related genes (IL-1β, IL-6, TNF-α, COX-2, iNOS) was confirmed. In the cartilage tissues of the WiKim0175 group, a decrease in the expression of cartilage damage-related genes and inflammation-related genes was confirmed. The WiKim0175 group showed a significant level of expression inhibition effect on cartilage damage-related genes and inflammation-related genes compared to the PBS group (Figs. 4 and 5).

[0090] Name of depositor: Korea Center for Microbiological Conservation (KCCM)

[0091] Accession number: KCCM13151P

[0092] Date of acceptance: 20220323

Claims

1. Lactobacillus plantarum WiKim0175 {Lactobacillus plantarum WiKim0175}, accession number KCCM13151P.

2. An anti-inflammatory; or food composition for improving joint and cartilage health, comprising Lactobacillus plantarum WiKim0175 (Accession No. KCCM13151P), a culture thereof, a pulverized product thereof, or an extract thereof as an active ingredient.

3. In paragraph 2, A food composition wherein the anti-inflammatory; or improvement of joint and cartilage health is achieved by inhibition of the expression of one or more genes selected from the group consisting of Adamts4, Adamts5, MMP3, MMP9, MMP13, IL-1β, IL-6, TNF-α, COX-2 and iNOS.

4. An anti-inflammatory; or health functional food composition for improving joint and cartilage health, comprising Lactobacillus plantarum WiKim0175 (Accession No. KCCM13151P), a culture thereof, a pulverized product thereof, or an extract thereof as an active ingredient.

5. In paragraph 4, A health functional food composition wherein the anti-inflammation or improvement of joint and cartilage health is achieved by suppressing the expression of one or more genes selected from the group consisting of Adamts4, Adamts5, MMP3, MMP9, MMP13, IL-1β, IL-6, TNF-α, COX-2 and iNOS.

6. A lactic acid bacteria starter for fermentation comprising Lactobacillus plantarum WiKim0175 (accession number KCCM13151P) or a culture thereof.

7. A feed or feed additive composition comprising a culture, a pulverized product or an extract of Lactobacillus plantarum WiKim0175 (accession number KCCM13151P) as an active ingredient.

8. A pharmaceutical composition for preventing or treating inflammatory diseases, comprising Lactobacillus plantarum WiKim0175 (Accession No. KCCM13151P), a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.

9. In paragraph 8, A pharmaceutical composition, wherein the above inflammatory disease is caused by the expression of one or more inflammation-related genes selected from the group consisting of IL-1β, IL-6, TNF-α, COX-2, and iNOS.

10. In paragraph 8, The above inflammatory diseases include gastritis, stomatitis, atopic dermatitis, acne, psoriasis, sinusitis, rhinitis, conjunctivitis, asthma, dermatitis, inflammatory collagen vascular disease, glomerulonephritis, encephalitis, inflammatory enteritis, chronic obstructive pulmonary disease, sepsis, septic shock, pulmonary fibrosis, undifferentiated spondyloarthropathy, undifferentiated arthropathy, arthritis, osteoarthritis, inflammatory osteolysis, chronic inflammatory diseases caused by viral or bacterial infection, ulcerative colitis, inflammatory bowel disease, rheumatoid arthritis, reactive arthritis, scleroderma, osteoporosis, atherosclerosis, myocarditis, endocarditis, pericarditis, cystic fibrosis, Hashimoto's thyroiditis, Graves' disease, leprosy, syphilis, Lyme disease, borreliosis, neurogenic borreliosis, tuberculosis, sarcoidosis, lupus, chilblain lupus, A pharmaceutical composition comprising at least one selected from the group consisting of tuberculous lupus, lupus nephritis, systemic lupus erythematosus, macular degeneration, uveitis, irritable bowel syndrome, Crohn's disease, Sjogren's syndrome, fibromyalgia, chronic fatigue syndrome, chronic fatigue immunodeficiency syndrome, myalgic encephalomyelitis, amyotrophic lateral sclerosis, Parkinson's disease, and multiple sclerosis.

11. In paragraph 8, A pharmaceutical composition wherein the above inflammatory disease is an arthritis disease.

12. In paragraph 11, A pharmaceutical composition, wherein the above-mentioned arthritis disease is caused by the expression of one or more genes selected from the group consisting of Adamts4, Adamts5, MMP3, MMP9, MMP13, IL-1β, IL-6, TNF-α, COX-2 and iNOS.

13. In paragraph 11, A pharmaceutical composition, wherein the arthritic disease is at least one selected from the group consisting of undifferentiated spondyloarthrosis, undifferentiated arthropathy, arthritis, osteoarthritis, inflammatory osteolysis, rheumatoid arthritis, and reactive arthritis.

Citation Information

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