KR102507532B1 - Composition comprising Lactobacillus plantarum HAC03 and flavonoids for treating or preventing inflammatory bowel disease - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease and a health functional food composition comprising a Lactobacillus plantarum HAC03 strain and flavonoids as active ingredients. The combination of the Lactobacillus plantarum HAC03 strain and flavonoids of the present invention has an effect of effectively inhibiting or increasing the expression of various inflammatory cytokines, and thus can be used as a therapeutic agent for inflammatory diseases, a health functional food, and the like.

Description

Composition comprising Lactobacillus plantarum HAC03 and flavonoids for treating or preventing inflammatory bowel disease}

The present invention relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease and a health functional food composition comprising a Lactobacillus plantarum HAC03 strain and flavonoids as active ingredients.

Inflammatory bowel disease (IBD) is a painful disease in which symptoms improve and worsen repeatedly. There are more than 6 million patients with inflammatory bowel disease worldwide, and the incidence is also increasing. In Korea, as of 2019, there are more than 70,000 patients with inflammatory bowel disease, which is a 33% increase compared to 2015. Although the number of patients suffering from inflammatory bowel disease is increasing, it is impossible to cure it because there is no effective treatment.

In the domestic inflammatory bowel disease treatment guideline published in 2012, aminosalicylate (5-ASA) was suggested as the most important treatment for patients with mild to moderate ulcerative colitis. Regardless of the site of inflammation, 5-ASA is initially administered, steroids are administered for patients who do not respond to 5-ASA, immunomodulatory agents are administered for patients who are dependent or insufficiently responsive, and anti-TNF agents are administered if there is no response to treatment. Jenna considers surgery.

Although 5-ASA, an anti-inflammatory drug, has been used for a long time, it has a disadvantage that the therapeutic effect is not great, so corticosteroids are used together, but there may be side effects. Immunosuppressants, including steroids, are used as a treatment for inflammatory bowel disease, but they have minor side effects and can cause serious side effects if they exceed 12 weeks. In addition, anti-TNF-α therapeutic agents are also used, but they have disadvantages such as the inconvenience of having to be continuously injected to maintain the efficacy and the therapeutic efficacy of less than 40%, so their use is limited. In order to overcome the above limitations, various research teams around the world are conducting research to discover substances whose safety and efficacy have been verified.

Flavonoids are secondary metabolites produced by plants and are contained in various fruits and vegetables. Flavonoids are substances whose antioxidant, anti-inflammatory and anti-cancer effects have already been verified through various studies. However, there is one major limitation in using flavonoids as candidates for inflammatory bowel disease, which is that the bioavailability of flavonoids is low. Flavonoids can be divided into two types: glycosides with sugars bound to them and aglycones with no sugars attached. Most of the flavonoids present in nature take the form of sugar-linked glycosides. When flavonoids are ingested orally, they are absorbed after glycosides are hydrolyzed into aglycones in the small intestine or large intestine. It is not absorbed, but is hydrolyzed in the form of aglycone by intestinal microorganisms such as Bacteroides spp, Lactobacillus spp, and Enterococcus spp. When glycosides are maintained without being hydrolyzed, most of the flavonoids are excreted out of the body.

One of the ways to solve the low bioavailability of flavonoids is to use microorganisms capable of hydrolyzing glycoside-type flavonoids into aglycones. The enzymes that play the most pivotal role in hydrolyzing Rutin, a glycoside of quercetin, to form quercetin, an aglycone form, are α-L-rhamnosidase (EC 3.2.1.40) and β-D-glucosidase (EC 3.2.1.21 ), and in fact, there are research results in which rutin is hydrolyzed into quercetin using various microorganisms, including specific lactic acid bacteria, in vitro.

The inventors of the present invention confirmed that the anti-inflammatory effect was remarkably excellent due to the synergistic effect between the Lactobacillus plantarum HAC03 strain and flavonoids when the Lactobacillus plantarum HAC03 strain and flavonoids exhibiting anti-inflammatory effects were administered in combination. has been completed.

Domestic Patent No. 10-2266314

The problem to be solved by the present invention is to provide a pharmaceutical composition or health functional food composition containing the Lactobacillus plantarum HAC03 strain and flavonoids having an effect of preventing or treating inflammatory bowel disease as active ingredients.

In order to solve the above problems, the present invention is selected from the group consisting of Lactobacillus plantarum HAC03 strain (accession number: KCTC 13242BP), a culture of the strain, a concentrate of the culture, a dried product of the culture, and an extract of the culture. one or more; And it provides a pharmaceutical composition for preventing or treating inflammatory bowel disease containing flavonoids as an active ingredient.

The flavonoid may be rutin.

The inflammatory bowel disease may be at least one selected from the group consisting of colitis, colitis, Crohn's disease, and Behcet's syndrome.

The colitis may be at least one selected from the group consisting of ulcerative colitis, collagenous colitis, lymphocytic colitis, ischemic colitis and converting colitis.

In addition, the present invention is a Lactobacillus plantarum HAC03 strain (accession number: KCTC 13242BP), a culture of the strain, a concentrate of the culture, a dried product of the culture, and at least one selected from the group consisting of an extract of the culture; And it provides a health functional food composition for preventing or improving inflammatory bowel disease containing flavonoids as active ingredients.

The flavonoid may be rutin.

The inflammatory bowel disease may be at least one selected from the group consisting of colitis, colitis, Crohn's disease, and Behcet's syndrome.

The colitis may be at least one selected from the group consisting of ulcerative colitis, collagenous colitis, lymphocytic colitis, ischemic colitis and converting colitis.

The combination of the Lactobacillus plantarum HAC03 strain and flavonoids of the present invention has an effect of effectively inhibiting or increasing the expression of various inflammatory cytokines, and thus can be used as a therapeutic agent for inflammatory diseases, a health functional food, and the like.

1 to 3 confirm changes in inflammatory cytokines in the colon by combined administration of Lactobacillus plantarum HAC03 and rutin. Figure 1 shows changes in the expression level of TNF-α, Figure 2 shows IL-1β, and Figure 3 shows IL-6.
Figure 4 confirms the change in the anti-inflammatory cytokine IL-10 expression level by combined administration of Lactobacillus plantarum HAC03 and rutin.
Figure 5 confirms the change in Muc2 expression level by combined administration of Lactobacillus plantarum HAC03 and rutin.
6 and 7 confirm changes in cytokines involved in tight junctions between colon cells by combined administration of Lactobacillus plantarum HAC03 and rutin. Figure 6 is ZO-1, Figure 7 confirms the change in Occludin expression level.

The present inventors have completed the present invention by confirming that the anti-inflammatory effect is remarkably excellent due to the synergistic effect between the Lactobacillus plantarum HAC03 strain and flavonoids when the Lactobacillus plantarum HAC03 strain and flavonoids are administered in combination. Specifically, when the strain and flavonoids are administered in combination, the strain or flavonoid is used alone due to the anti-inflammatory effect of the strain itself and the anti-inflammatory effect caused by the change of the flavonoid to an aglycone form with improved in vivo activity by the strain. It was experimentally confirmed that the anti-inflammatory effect was significantly better than that of administration.

Therefore, in one aspect, the present invention provides at least one selected from the group consisting of the Lactobacillus plantarum HAC03 strain (accession number: KCTC 13242BP), the culture solution of the strain, the concentrate of the culture solution, the dried product of the culture solution, and the extract of the culture solution. ; And it relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease comprising a flavonoid as an active ingredient.

Lactobacillus plantarum of the present invention may be used as a synonym for Lactobacillus plantarum .

The Lactobacillus plantarum HAC03 (accession number: KCTC 13242BP) strain was isolated from white kimchi, showed excellent acid resistance and bile resistance, had no antibiotic resistance, and had no ability to produce biogenic amines (Korean Patent No. 10 -2266314). In addition, the Lactobacillus plantarum HAC03 strain is characterized in that it comprises a 16s rDNA sequence represented by SEQ ID NO: 1 below.

<SEQ ID NO: 1>

In addition, the Lactobacillus plantarum HAC03 strain (Lactobacillus plantarum HAC03) has a gene expressing an enzyme that plays a pivotal role in hydrolyzing rutin.

The flavonoid may be rutin. Rutin is a glycoside in which rutinose (a disaccharide composed of glucose and rhamnose) is bound to carbon 3 of quercetin. It was found in Ruta genus of Rutaceae, and was later isolated from many types of plants such as Sophora japonica flower buds and Buckwheat (Fagopyrum esculentum).

In the present invention, the term "inflammatory bowel disease" is a disease that repeats improvement and recurrence and causes chronic inflammation and ulceration in the intestine, which can be caused by environmental, immune and genetic factors. The inflammatory bowel disease may be at least one selected from the group consisting of colitis, colitis, Crohn's disease and Behcet's syndrome, but is not limited thereto. In addition, the colitis may be one selected from the group consisting of ulcerative colitis, collagenous colitis, lymphocytic colitis, ischemic colitis and convertible colitis, but is not limited thereto. Preferably, the inflammatory bowel disease is colitis, and in one embodiment of the present invention, the colitis improvement effect by combined administration of the Lactobacillus plantarum HAC03 strain and rutin was confirmed (Examples 1 and 2).

In the present invention, the term "prevention" refers to any action that suppresses or delays the onset of a disease by administering a pharmaceutical composition.

As used herein, the term "treatment" refers to abrogating, substantially inhibiting, slowing or reversing the progression of a disease, substantially improving the clinical or aesthetic symptoms of a disease, or substantially preventing the appearance of clinical or aesthetic symptoms of

The pharmaceutical composition is any one selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried agents, and suppositories. It may have a formulation, and may be of various oral or parenteral formulations. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

In the present invention, the term "administration" refers to introducing the pharmaceutical composition of the present invention to a subject by any appropriate method, and the route of administration may be administered through various oral or parenteral routes as long as it can reach the target tissue.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin It can be prepared by mixing etc. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, internal solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. there is. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used.

The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" refers to an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is dependent on the type and severity of the subject, age, sex, and type of disease. , activity of the drug, sensitivity to the drug, administration time, route of administration and excretion rate, duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And it can be single or multiple administrations. It is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects in consideration of all the above factors, and can be easily determined by those skilled in the art.

The pharmaceutical composition of the present invention is not particularly limited as long as it is a subject for the purpose of treating inflammatory diseases, and any may be applied. For example, non-human animals such as monkeys, dogs, cats, rabbits, guinea pigs, rats, mice, cows, sheep, pigs, goats, and the like, humans, birds, and fish may be used, and the pharmaceutical composition may be administered parenterally or subcutaneously. , can be administered intraperitoneally, intrapulmonaryly and intranasally, and for local treatment, if necessary, by any suitable method including intralesional administration. The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and body weight of the subject, the severity of the disease, the drug type, the route and duration of administration, but can be appropriately selected by those skilled in the art. For example, it may be administered by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine intrathecal or intracerebrovascular injection, but is not limited thereto.

A suitable total daily amount can be determined by treatment within the scope of sound medical judgment, and is generally in the range of 0.001 to 1000 mg/kg, preferably 0.05 to 200 mg/kg, more preferably 0.1 to 100 mg/kg. The amount of may be divided and administered once a day to several times.

In another aspect, the present invention is a Lactobacillus plantarum HAC03 strain (accession number: KCTC 13242BP), a culture of the strain, a concentrate of the culture, a dried product of the culture, and at least one selected from the group consisting of an extract of the culture; And it relates to a health functional food composition for preventing or improving inflammatory bowel disease containing flavonoids as an active ingredient.

The food composition means a natural product or processed product containing one or more nutrients, and preferably means a product that can be eaten directly through a certain degree of processing process, and in a conventional sense, food, food It includes all additives, health functional foods and functional beverages.

The food composition of the present invention may include pills, powders, granules, infusions, tablets, capsules or liquids, and the type of food is not particularly limited. For example, various beverages, gums, teas, vitamin complexes, There are health supplement foods, etc.

Other ingredients may be added to the food composition, and the type is not particularly limited. For example, it may contain various herbal extracts, food additives or natural carbohydrates, etc., as additional components, as in conventional foods, but are not limited thereto.

In the present invention, the term "food supplement additive" refers to a component that can be added to food supplementally, and can be appropriately selected and used by those skilled in the art as being added to prepare a health functional food of each formulation. Examples of food additives include various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners , pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, etc. are included, but the types of food additives of the present invention are not limited by the above examples.

Examples of the natural carbohydrate include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (thaumatin, etc.), stevia extract (rebaudioside A, glycir hijin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can advantageously be used.

The food composition of the present invention may include health functional food. In the present invention, the term "health functional food" refers to food manufactured and processed in the form of tablets, capsules, powders, granules, liquids and pills using raw materials or ingredients having useful functionality for the human body. Here, functional means obtaining useful effects for health purposes such as adjusting nutrients for the structure and function of the human body or physiological functions. The health functional food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and components commonly added in the art during the preparation. In addition, unlike general drugs, there is an advantage in that there is no side effect that may occur when taking a drug for a long time by using food as a raw material, and it can be excellent in portability.

In general, the amount of the Lactobacillus plantarum HAC03 strain included in the food composition may be added to 0.1 to 90% by weight of the total food weight. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be less than the above range. In addition, the food composition according to the present invention, in addition to the Lactobacillus plantarum HAC03 strain, preferably contains other ingredients that can synergize the main effect within the range of not impairing the main effect intended by the present invention. free

Hereinafter, the configuration and effects of the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and the scope of the present invention is not limited by these examples.

<Experiment method>

1. Isolation and identification of strains

About 10 to 15 days after manufacture, after purchasing white kimchi, which is undergoing fermentation, the pH was measured to confirm the decrease in pH due to lactic acid production, and then the lactic acid bacteria were isolated. 90 mL physiological saline solution (0.85% NaCl/L) was put into a high-pressure sterilized plastic bag, and 10 g of white kimchi sample was added and mixed uniformly at 200 rpm for 5 minutes (Stomacher® 400 Circulator, Seward, UK). 1 ml was dispensed, diluted 10 times in 9 ml of physiological saline (0.85% NaCl/L), and spread on MRS solid medium (5.5% Lactobacillus MRS broth, BD Difco, USA and 1.5% Bacteriological Agar, Affymetrix, USA). . After that, they were grown for 24 to 48 hours in a 37℃ incubator, separated and identified.

First, in order to estimate the type of strain on the plate, the colony morphology was compared through observation under a microscope (Imager.A2, ZEISS, Germany). brevis), the convex short or medium length rod shape was assumed to be Lactobacillus plantarum, and the spherical rod shape was assumed to be Lactobacillus sakei.

Next, while culturing the grown bacteria at 37° C. for 24 to 48 hours using 3% hydrogen peroxide, analysis of catalase activity and Gram staining was performed. The catalase-negative strain was identified as a taxonomic species through bidirectional 16S rDNA gene sequence analysis. Identification of the nucleotide sequence of the strain was performed by requesting Solgent Co., Ltd. (Korea).

As a result, the strain of the present invention isolated from white kimchi was identified as Lactobacillus plantarum as a catalase-negative, Gram-positive, and rod-shaped strain, and was named Lactobacillus plantarum HAC03. The strain was deposited with the Korea Research Institute of Bioscience and Biotechnology on December 28, 2020 (accession number: KCTC 13242BP).

2. Animal Testing

Animal experiments were performed to confirm the effects of preventing and improving inflammatory bowel disease of the Lactobacillus plantarum HAC03 strain and Rutin. As an enteritis model, a colitis model induced by DSS (dextran sulfate sodium) feeding was selected. Specifically, PBS or Lactobacillus plantarum HAC03 strain suspension was added to 5-week-old C57BL/6J female mice at a concentration of 1x10 ⁹ CFU/mouse. , Rutin was administered at a concentration of 200 mg/kg. After oral administration for 7 days, DSS was turbid by 3% in drinking water and fed autonomously. Even during the voluntary DSS feeding, Lactobacillus plantarum HAC03 strain and rutin were administered once a day. At the time of feeding about 30~40ml of DSS (5th day), it was replaced with normal drinking water for 2 days. Lactobacillus plantarum HAC03 and rutin were not administered during the regular drinking water replacement period. During the DSS treatment period, body weight was measured every day at 10 am. After the end of the breeding period, the colon length corresponding to the cecum distal rectum was measured and stored at -80 ° C to observe changes in gene expression.

3. Cytokine measurement

Ct법을 사용하여 계산하였다.Enteritis-related marker genes were identified in the colon in order to confirm the molecular mechanism involved in the prevention and improvement of inflammatory bowel disease of the Lactobacillus plantarum HAC03 strain and Rutin. Specifically, the large intestine of each experimental group was homogenized, dissolved in Trizol® (RNA extraction buffer, Thermo Fisher), and RNA was extracted according to the protocol provided by the manufacturer. The extracted RNA was quantified, and the same amount of RNA was synthesized into cDNA by reverse transcription using the SuperiorScript III cDNA synthesis Kit (Enzynomics, Daejeon, South Korea). Then, real-time PCR was performed using each gene-specific primer, TOPreal qPCR 2X premix (SYBR Green with high ROX) (Enzynomics, Daejeon, South Korea) and cDNA. ABI 7500 Fast Real time PCR system (Applied Biosystems, Waltham, MA, USA) was used for real-time PCR. The relative gene expression level is

It was calculated using the Ct method.

target Forward
(5' → 3') Reverse
(5' → 3') TNF-α CACAAGATGCTGGGGACAGTGA (SEQ ID NO: 2) GAGGCTCCAGTGAATTCGGA
(SEQ ID NO: 3) IL-1β CCTCTCCAGCCAAGCTTCCT (SEQ ID NO: 4) TTTGGAAGCAGCCCTTCATC
(SEQ ID NO: 5) IL-6 TCCAGTTGCCTTCTTGGAC (SEQ ID NO: 6) AGTCTCCTCTCCGGACTTGT
(SEQ ID NO: 7) IL-10 GTTGCCAAGCCTTATCGGAA (SEQ ID NO: 8) CCAGGGAATTCAAATGCTCCT
(SEQ ID NO: 9) Muc2 GCTGACGAGTGGTTGGTGAATG (SEQ ID NO: 10) GATGAGGTGGCAGACAGGAGAC
(SEQ ID NO: 11) Occludin AGACTACACGACAGGTGGGG (SEQ ID NO: 12) CTGCAGACCTGCATCAAAAT
(SEQ ID NO: 13) ZO-1 GCCGCTAAGAGCACAGCAA (SEQ ID NO: 14) TCCCCACTCTGAAAATGAGGA
(SEQ ID NO: 15)

[Example 1] Weight change and intestinal length change

Tables 3 and 4 confirm the inflammatory bowel disease prevention and improvement effects of the Lactobacillus plantarum HAC03 strain and Rutin.

Compared to the control group administered only with DSS, it was confirmed that the weight loss of mice administered with Lactobacillus plantarum HAC03 strain and rutin in combination was significantly reduced (Table 3). In addition, it was confirmed that the combined administration of the Lactobacillus plantarum HAC03 strain and rutin significantly improved weight loss due to DSS-induced enteritis compared to the group administered with the Lactobacillus plantarum HAC03 strain or rutin alone. (Table 3).

group Weight Loss (g) Normal control - DSS treat control 4.1 ± 1.2 Lactobacillus plantarum HAC03 administration group 3.37 ± 0.7 Rutin administration group 3.16 ± 0.5 Combined administration group (HAC03 + Rutin administration group) 2.42 ± 0.3

Compared to the control group administered with only DSS, it was confirmed that the decrease in intestinal length was reduced in mice administered with Lactobacillus plantarum HAC03 strain and rutin in combination (Table 4). In addition, when combined administration of Lactobacillus plantarum HAC03 strain and rutin, compared to the group administered with Lactobacillus plantarum HAC03 strain or rutin alone, the decrease in intestinal length caused by DSS-induced enteritis was significantly improved. confirmed (Table 4).

group Chapter length (cm) Normal control 9.5 ± 0.6 DSS treat control 6.34 ± 0.2 Lactobacillus plantarum HAC03 administration group 7.1±0.3 Rutin administration group 7.6 ± 0.6 Combined administration group (HAC03 + Rutin administration group) 8.11 ± 0.6

[Example 2] Gene expression change

As a result of confirming cytokine changes in the extracted colon tissue, the expression of inflammatory cytokines (TNFα, IL-1β, IL-6) induced by DSS was significantly reduced in the Lactobacillus plantarum HAC03 strain and rutin combined administration group. , the expression of IL-10, an anti-inflammatory cytokine, was significantly increased. In addition, the expression of mucin (Muc2) and intestinal tight junction proteins (Occludin, ZO-1) was significantly increased.

Specifically, it was confirmed that the expression levels of inflammatory cytokines TNFα, IL-1β, and IL-6 were increased in mice administered with DSS compared to normal mice. At this time, compared to the DSS-administered control group, when Lactobacillus plantarum HAC03 strain and rutin were administered in combination, the expression level of inflammatory cytokines (TNFα, IL-1β, IL-6) decreased, indicating that the Lactobacillus plantarum HAC03 strain or It was confirmed that it was significantly reduced even compared to the group administered with rutin alone (FIGS. 1 to 3).

In addition, compared to the control group to which DSS was administered, when the Lactobacillus plantarum HAC03 strain and rutin were administered in combination, the expression of the anti-inflammatory cytokine IL-10 was significantly increased, indicating that the Lactobacillus plantarum HAC03 strain or It was also confirmed that it increased significantly compared to the group administered with rutin alone (FIG. 4).

In addition, in mice administered with DSS, it was confirmed that the expression level of Muc2, which is involved in the production of mucin, a mucus material secreted from the mucous membrane, was decreased compared to normal mice. At this time, compared to the DSS-administered control group, when the Lactobacillus plantarum HAC03 strain and rutin were administered in combination, the Muc2 expression level increased, which was significantly increased compared to the group administered with the Lactobacillus plantarum HAC03 strain or rutin alone. It was confirmed that it was (FIG. 5).

In addition, it was confirmed that the expression level of cytokines (ZO-1, Occludin) involved in tight junctions between colon cells was decreased in mice administered with DSS compared to normal mice. At this time, compared to the DSS-administered control group, when the Lactobacillus plantarum HAC03 strain and rutin were administered in combination, the expression levels of ZO-1 and Occludin increased, which was even compared to the group administered with the Lactobacillus plantarum HAC03 strain or rutin alone. It was confirmed that it was significantly increased (Figs. 6 and 7).

Through this, it was confirmed that tissue inflammation can be effectively inhibited when the Lactobacillus plantarum HAC03 strain and rutin are administered in combination.

Korea Research Institute of Bioscience and Biotechnology Biological Resources Center (KCTC) KCTC13242BP 20201228

Claims (8)

A pharmaceutical composition for preventing or treating colitis comprising Lactobacillus plantarum HAC03 strain (accession number: KCTC 13242BP) and rutin as active ingredients.
delete delete The pharmaceutical composition according to claim 1, wherein the colitis is at least one selected from the group consisting of ulcerative colitis, collagenous colitis, lymphocytic colitis, ischemic colitis and converting colitis.
A health functional food composition for preventing or improving colitis comprising Lactobacillus plantarum HAC03 strain (accession number: KCTC 13242BP) and rutin as active ingredients.
delete delete According to claim 5, wherein the colitis is characterized in that at least one selected from the group consisting of ulcerative colitis, collagenous colitis, lymphocytic colitis, ischemic colitis and converting colitis, functional health food composition.

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