KR101918704B1 - Composition for preventing or treating disease induced by rotavirus infection comprising genipin as an active agent - Google Patents

Abstract

The present invention relates to novel uses of genipin compounds and, more particularly, to the use of genipin or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention and treatment of diseases caused by rotavirus infection Or improving compositions for the treatment of cancer. The Jennypin compound of the present invention is excellent in prevention and treatment of rotavirus infection.

Description

[0001] The present invention relates to a composition for preventing or treating a disease caused by rotavirus infection,

The present invention relates to a novel use of a genipin compound and more particularly to a method for preventing, treating or ameliorating a disease caused by rotavirus infection comprising as an active ingredient zenypin or a pharmaceutically acceptable salt thereof ≪ / RTI >

Rotavirus belongs to the genus Reoviridae and is known to be the most important cause of acute childhood enteritis. The double capsid of the viral particles is called a rotavirus, derived from a Latin rota (wheel of English), as if it were a wagon wheel. In 1943, Light and Hodes reported severe diarrhea in infants and isolated diarrhea-causing filterable pathogens, but their morphological characteristics were revealed by electron microscopy in 1973. Reovirus-like viruses have been isolated from mammals and birds. These viruses have been identified as rotaviruses and were classified in 1978 as Genus Rotaviruses in the family Reoviridae.

The rotavirus genome is composed of 11 segments of double-stranded RNA, and the rotavirus particles are spherical with a diameter of 70 nm. The outer capsid and the inner capsid It has two shells. The inner layer capsid is composed of VP6 protein and contains the core part containing 11 double RNA fragments and the structural proteins VP1, VP2 and VP3. The outer capsid is composed of VP7 and VP4 . Among VP4 and VP7, VP4 and VP7 are virus hemagglutinin, an attachment protein of the host cell, which spikes on the virus surface and accounts for 2.5% of all viruses. VP7 is a 37 kDa glycoprotein that forms a smooth outer capsid shell and accounts for 30% of all viruses. Because the VP4 protein is divided into VP5 and VP8 by the protease of the host, its serotype is called P type and the VP7 protein is glycosylated, so its serotype is called G type (Ciarlet, M. and Ester, MK Rotaviruses: basic biology, epidemiology and methodologies in encyclopedia of envirionmental microbiology. Pp. 2753-2773, 2002). VP4 and VP7 proteins are important for host defense by inducing neutralizing antibodies. The serotypes are divided into a total of seven species, from serotype to VP6, the middle-layer capsid protein, to A-G. Of these, serotyping A rotaviruses occur most commonly in humans and animals, causing annually 130 million worldwide to enteritis, of which 873,000 are known to be very important infectious agents leading to death.

In general, for the purpose of treating such viral diseases, methods such as inhibition of adsorption to epithelial cells, inhibition of invasion into cells, inhibition of gene transcription and replication, inhibition of protein synthesis, and release of cells are conceivable. Although the target of antivirals is reported, no clear target for rotavirus has been known to date.

Recently, treatment of rotavirus has nonspecific properties in HRV (human rotavirus) infection. Therefore, vaccination plays an important role in protecting children from illness and death from infection with HRV. HRV vaccines, including Rotarix ™ and RotaTeq ^® , have been used in 1990 and 2000, respectively. However, they can induce vaccine-induced illness as side effects, such as inactivation of HRV or dilution of HRV, requiring skill, and altering sensitivity to collective immunity and disease.

 To overcome the drawbacks of these vaccines, research is being conducted on natural materials that can inhibit rotavirus.

Accordingly, the inventors of the present invention have confirmed that genipin inhibits the replication of rotavirus by anti-rotavirus infection activity while studying anti-rotavirus preparations, thereby completing the present invention.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating diseases caused by rotavirus infection comprising genipin or a pharmaceutically acceptable salt thereof as an active ingredient.

It is another object of the present invention to provide a food composition for preventing or ameliorating a disease caused by rotavirus infection comprising genipin or a pharmaceutically acceptable salt thereof as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating diseases caused by rotavirus infection comprising genipin or a pharmaceutically acceptable salt thereof as an active ingredient.

In order to accomplish still another object of the present invention, there is provided a food composition for preventing or ameliorating a disease caused by rotavirus infection comprising genipin or a pharmaceutically acceptable salt thereof as an active ingredient.

Hereinafter, the present invention will be described in detail.

The genipin of the present invention has a structure represented by the following general formula (1), and can be purified from natural sources, commercially available, or can be produced by chemical synthesis methods known in the art.

≪ Formula 1 >

The present inventors have for the first time identified the anti-rotavirus use of zeniprin, which is well illustrated in the specification examples of the present invention.

In one embodiment of the present invention, the JNP inhibits the production of NO (nitric oxide) and inhibits the secretion of cytokines promoting inflammatory responses such as IL-6, IL-10, IL-1β and PGE ₂ , (Example 2). ≪ tb >< TABLE >

In another embodiment of the present invention, MA104 cells were infected with rotavirus, treated with zeniprin alone or in parallel with virus before and after viral infection, and the effect thereof was measured (see Example 3). As a result, it was confirmed that Jeniprin inhibited rotavirus replication and had a therapeutic effect on rotavirus infection (see Example 3-1) as well as an excellent prophylactic effect (see Examples 3-2 and 3-3) . In particular, as shown in Examples 3-2 and 3-3, it was confirmed that the use of jennypin in combination with prophylactic and therapeutic treatment of rotavirus infection shows a greater disease inhibitory effect.

Accordingly, the present invention provides a pharmaceutical composition for preventing or treating diseases caused by rotavirus infection comprising genipin or a pharmaceutically acceptable salt thereof as an active ingredient.

The term " prophylactic " in the present invention means any action that inhibits or delays the onset of rotavirus infection by administration of the composition.

The term " treatment " in the present invention means any action that improves or alleviates symptoms caused by rotavirus infection by administration of the composition.

The rotavirus can be, for example, a human rotavirus, a Pocine rotavirus, a Bovine rotavirus, or a Goat rotavirus, although the resulting animal is not particularly limited. And preferably human rotavirus.

The disease caused by the rotavirus infection is not particularly limited as long as it is known as a disease caused by rotavirus in the art, but it is preferably selected from the group consisting of gastroenteritis, enteritis, diarrhea, cold, sore throat, bronchitis and pneumonia .

The pharmaceutical composition of the present invention is characterized by comprising zenypine or a pharmaceutically acceptable salt thereof. The term " pharmaceutically acceptable " as used herein means physiologically acceptable and does not usually cause an allergic reaction or a similar reaction when administered to humans, and the salt includes a pharmaceutically acceptable free acid, Lt; / RTI > is preferred. The free acid may be an organic acid or an inorganic acid. The organic acids include, but are not limited to, citric, acetic, lactic, tartaric, maleic, fumaric, formic, propionic, oxalic, trifluroacetic, benzoic, gluconic, methosulfonic, glycolic, succinic, Glutamic acid and aspartic acid. In addition, the inorganic acid includes, but is not limited to, hydrochloric acid, bromic acid, sulfuric acid, and phosphoric acid.

The pharmaceutical composition according to the present invention may contain, alone or in combination with one or more pharmaceutically acceptable carriers, excipients or diluents, xanthine or a pharmaceutically acceptable salt thereof. The pharmaceutically acceptable carrier may further include, for example, a carrier for oral administration or a carrier for parenteral administration. Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. In addition, the carrier for parenteral administration may contain water, a suitable oil, a saline solution, an aqueous glucose and a glycol, and may further contain a stabilizer and a preservative. Suitable stabilizers include antioxidants such as sodium hydrogen sulfite, sodium sulfite or ascorbic acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol. Other pharmaceutically acceptable carriers can be found in Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, Pa., 1995).

The pharmaceutical composition of the present invention can be administered to mammals including humans by any method. For example, it can be administered orally or parenterally. Parenteral administration methods include, but are not limited to, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual or rectal administration Lt; / RTI >

In addition, the pharmaceutical composition may be formulated into oral or parenteral formulations according to the route of administration as described above. In the case of a preparation for oral administration, the composition of the present invention may be formulated into a powder, a granule, a tablet, a pill, a sugar, a tablet, a liquid, a gel, a syrup, a slurry, . For example, an oral preparation can be obtained by combining the active ingredient with a solid excipient, then milling it, adding suitable auxiliaries, and then processing the mixture into a granular mixture. Examples of suitable excipients include, but are not limited to, sugars including lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol and maltitol, and starches including corn starch, wheat starch, rice starch and potato starch, Cellulose such as methylcellulose, sodium carboxymethylcellulose and hydroxypropylmethyl-cellulose and the like, fillers such as gelatin, polyvinylpyrrolidone and the like. In addition, crosslinked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate may optionally be added as a disintegrant. Further, the pharmaceutical composition of the present invention may further comprise an anti-coagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent and an antiseptic agent.

In the case of a preparation for parenteral administration, it can be formulated by a method known in the art in the form of injection, cream, lotion, external ointment, oil, moisturizer, gel, aerosol and nasal aspirate. These formulations are described in Remington's Pharmaceutical Science, 15th edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour, a commonly known formulary for all pharmaceutical chemistries.

In the present invention, the total effective amount of zenithrin or a pharmaceutically acceptable salt thereof may be administered to a patient in a single dose, and may be administered in a fractionated treatment protocol administered for a long period in multiple doses, ≪ / RTI > In the pharmaceutical composition of the present invention, the content of the active ingredient may be varied depending on the degree of the disease. Preferably, the preferred total dose of the present zenith fins or pharmaceutically acceptable salts thereof is from about 0.01 to 1,000 mg, and most preferably from 0.1 to 100 mg, per kg body weight of the patient per day. However, since the dose is determined in consideration of various factors such as the patient's age, body weight, health condition, sex, severity of disease, diet and excretion rate as well as administration route and treatment frequency of the pharmaceutical composition, In view of this, one of ordinary skill in the art will be able to determine the appropriate effective dose according to the particular use as a prophylactic or therapeutic agent for a disease caused by rotavirus infection with respect to the zenithrin or a pharmaceutically acceptable salt thereof There will be. The pharmaceutical composition according to the present invention is not particularly limited to its formulation, administration route and administration method as long as the effect of the present invention is exhibited.

The present invention also provides a food composition for preventing or ameliorating diseases caused by rotavirus infection comprising as an active ingredient zenypin or a pharmaceutically acceptable salt thereof.

The food composition of the present invention includes all forms such as functional food, nutritional supplement, health food and food additives. Food compositions of this type may be prepared in a variety of forms according to conventional methods known in the art. For example, the health food may be prepared by liquefying, encapsulating, and pulverizing liquified to make Jenny fin or a pharmaceutically acceptable salt thereof of the present invention in the form of tea, juice, and drink for drinking. It is also possible to combine the inventive jenipine or a pharmaceutically acceptable salt thereof with known substances or active ingredients known to be effective for anti-viral (including rotavirus as well as other antiviral agents) Can be manufactured.

Functional foods also include but are not limited to beverages (including alcoholic beverages), fruits and processed foods (e.g., canned fruits, jams, maamarade, etc.), fish, meat and processed foods (Eg butter, chewing), edible vegetable oil, margarine (for example, sausage, noodles, etc.), breads and noodles (eg udon, buckwheat noodles, ramen noodles, spaghetti, macaroni, , Vegetable protein, retort food, frozen food, various kinds of seasonings (for example, soybean paste, soy sauce, sauce, etc.). In order to use the jenny pin of the present invention in the form of a food additive, it may be prepared in the form of a powder or a concentrated liquid.

The preferable content of the above-mentioned jenifine or pharmaceutically acceptable salt thereof in the food composition of the present invention is not particularly limited, but is preferably 0.01 to 90% by weight, and preferably 0.5 to 60% by weight in the finally prepared food.

The present invention relates to the anti-rotavirus effect of Jeniprin, and Jeniprin is excellent in prevention and treatment of rotavirus infection.

FIG. 1 is a graph showing the toxicity of geniprin to RAW 264.7 cells. FIG.
FIG. 2 is a graph showing the toxicity of Jeniphin against MA104 cells. FIG.
FIG. 3 is a graph showing the inhibitory effect of zeniprin on NO production in RAW 264.7 cells induced by LPS.
FIG. 4 is a graph showing inhibition of IL-6 production of geniprin in RAW 264.7 cells induced by LPS.
FIG. 5 is a graph showing inhibition of IL-10 production by zenith in RAW 264.7 cells induced by LPS.
FIG. 6 is a graph showing inhibition of IL-1β production by xeninthin in RAW 264.7 cells induced by LPS.
FIG. 7 is a graph showing inhibition of PGE ₂ production by genistin in RAW 264.7 cells induced by LPS.
FIG. 8 is a graph showing the ability of jeniphin to maintain TNF-a secretion level in RAW 264.7 cells induced by LPS.
FIG. 9 is a graph showing the therapeutic effect of MA104 cells infected with rotavirus Wa strain and treated with zeniprin.
FIG. 10A shows the results of pretreatment of a rotavirus Wa strain and a genitin mixture with MA104 cells, followed by infecting the Wa strain, and then reprocessing the genitin by concentration to prevent and protect against rotavirus infection (improvement and treatment) This is the graph I checked.
10B shows the pretreatment effect of Jenny pin (prevention of rotavirus infection of jennifin) in MA104 cells after pretreatment of a rotavirus Wa strain and a jennypin mixture and then infecting Wa strain, Respectively.
FIG. 11A is a graph showing inhibition of rotavirus infection and inhibition of virus growth (improvement and treatment) by pretreating genistein in MA104 cells for 24 hours, infecting Wa strain, to be.
FIG. 11B is a graph showing the pretreatment effect of Jenny pin (preventing the rotavirus infection of Jenny pin) in an experiment group in which MA104 cells were pretreated with JENNTPIN for 24 hours, infected with Wa strain, to be.

Hereinafter, the present invention will be described in detail.

However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

≪ Example 1 >

Evaluation of cytotoxicity of Jeniphin

Mouse macrophage RAW 264.7 cells were transfected three to four times a week and the medium was DMEM (Dulbecco's Modified Eagle's Medium) containing 20 μg / ml Gentamicin Reagent Solution (Gibco BRL) and 10% FBS (Gibco BRL) ) Medium at 37 ° C and 5% CO ₂ . MA104 cells were obtained from the Korean Cell Line Bank. And cultured in minimal essential medium alpha (MEM-alpha; Gibco BRL) containing 5% FBS and 20 g / ml gentamycin. Virus was used as the group A human rotavirus strain G1P1A (hereinafter 'strain Wa', ATCC VR-2018 ™ ^ⓡ).

RAW 264.7 cells were seeded in 96-well plates at a concentration of 2 × 10 ³ cells / well and cultured for 24 hours. The final concentration of Genipin powder (Sigma-aldrich) was dissolved in new DMEM medium without FBS to give 10, 50, 100, 150, 160, 180, 200 μM / Lt; / RTI > To determine the survival rate of the cell line, a microplate reader (model Infinite® F200, Tecan, Mannedorf, Switzerland) was used with MTT [3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide] The absorbance was measured. The cytotoxicity of MA104 cells was also measured in the same manner.

As a result, as shown in FIG . 1 and FIG. 2 , the survival rate of cells in RAW 264.7 cells and MA104 cells treated with JENYPIN tended to decrease from 160 μM / ml to concentration, The survival rate showed the same cell viability as the non-treated group, indicating no cytotoxicity.

≪ Example 2 >

Analysis of NO and cytokine effects of zeniprin

<2-1> NO assay

Cultured RAW 264.7 cells were plated at a concentration of 3 × 10 ⁵ cells / well in a 24-well plate and cultured for 24 hours. To induce inflammation, LPS was added to a fresh DMEM medium containing no FBS at a concentration of 0.1 μg / ml, and the cells were treated with final concentrations of 0, 10, 50, 100, and 150 μM / ml And cultured for 24 hours. After 24 hours, the Griess reagent was mixed 1: 1 to measure the NO production in the supernatant of the cells, reacted for 10 minutes, and absorbance was measured at 540 nm with a microplate reader. In addition, the efficacy of jeniphin for the expression of iNOS (inducible nitric oxide synthase) was carried out by the following method. RAW 264.7 cells at 3 × 10 ⁵ cells / well were treated with LPS in the same manner as described above, and cultured for 24 hours at the final concentration of each of the zenith fins. After 24 hours, the cells were centrifuged and 900 ㎕ of TRIZOL Reagent (MRC, Cincinnati, OH) was added and homogenized. 100 쨉 l of chloroform was added thereto, and the mixture was allowed to stand at room temperature for 5 minutes. The mixture was centrifuged at 13,000 rpm for 10 minutes, and the supernatant was collected. The same amount of isopropanol was added, and the mixture was allowed to stand at room temperature for 5 minutes and centrifuged. Washed once with 70% DEPC-ethanol, centrifuged and dried at room temperature, and 30 쨉 l of distilled water containing 70% DEPC was added. To carry out the reverse transcription-PCR assay, 1.4 μl of DMSO was added to 5 μl of RNA and denatured at 97 ° C. for 5 minutes. (10 μl total) containing 1 μl of 10 × buffer, 0.4 μl of 1 × dNTPs, 0.2 μl of forward primer specific for iNOS and reverse primer, 0.1 μl of enzyme AMV (Promega, Medison, USA) and RNase free water Transcription-PCR assay (42 ° C for 60 min, 95 ° C for 5 min) was performed to generate cDNA and the results were confirmed by electrophoresis.

As shown in FIG. 3, in the test group treated with JNP, the concentration-dependent inhibition of NO production and the inhibition of iNOS expression were observed compared with the control group treated with LPS alone. In particular, the treatment group with 100 μM / ml of jennypin showed a NO level of 10%, indicating a NO level similar to that of the LPS-untreated group.

<2-2> cytokine assay

Cultured RAW 264.7 cells were plated at a concentration of 3 × 10 ⁵ cells / well in a 24-well plate and cultured for 24 hours. To induce inflammation, LPS was added to a fresh DMEM medium containing no FBS at a concentration of 0.1 μg / ml. The cells were treated with the final concentrations of 0, 10, 50, 100, and 150 μM / Lt; / RTI &gt; To determine the degree of production of IL-6, IL-10, IL-1β, TNF-α and PGE-2 in the supernatant of cells 24 hours later, the Parameter ^™ Immunoassay kit and Quantikine® Immunoassay kit (R & D Systems, Minneapolis, ) Was used for the experiment according to the manual. The amount of each cytokine protein was measured at 450 nm using a microplate reader.

As a result, if the bioactive factor, IL-6 (Fig. 4), IL-10 (Fig. 5), IL-1β (Figure 6), PGE ₂ (FIG. 7) to promote inflammatory responses in cells, process the Jenny pin In one experimental group, the concentration-dependent inhibition of Cytokine secretion was observed compared to the control group treated with LPS only. In particular, at 100 and 150 μM / ml, the levels were similar to those of the LPS-untreated group, and the cytokine secretion was reduced by 75%, 83%, 77%, and 75%, respectively, at a concentration of 150 μM / ml. FIG. 8 shows the results of confirming the secretion of TNF-α and maintained high values at all concentrations of 10, 50, 100 and 150 μM / ml. These results indicate that the Xenopin of the present invention inhibits IL-6, IL-10, IL-1 beta, PGE ₂ And inhibit the secretion of cytokines, which promote inflammatory reactions, while maintaining the secretion of cytokines that inhibit the intracellular replication of viruses such as TNF-α, which may have an effect on rotavirus and, more broadly, It can be used as a composition.

&Lt; Example 3 >

Measurement of rotavirus replication inferiority of Jennifer

The inhibitory effect of zeniprin on viral replication was confirmed in MA104 cells infected with rotavirus. MA104 cells were infected with rotavirus Wa strain at an MOI of 0.01, and the experiment was carried out in three ways as follows. Quantification of rotavirus in each experiment was confirmed by real-time RT-PCR. Specifically, Viral RNA was extracted using QIA amp Viral RNA Mini Kit (Qiagen, Valencia, CA, USA). First, 140 μl of supernatant was added to 560 μl of AVL solution containing 5.6 μg of carrier RNA (Qiagen, Valencia, CA, USA) and mixed for 15 seconds. After 10 minutes of incubation, 560 μl of ethanol was added and mixed for 15 seconds. The mixture was transferred to a 2 ml tube and centrifuged at 8000 rpm for 1 minute. After 2 washes, the cells were resuspended in 50 μl of RNase-free water and stored at -80 ° C. for RT (reverse transcription) -PCR.

The reverse transcription-PCR assay was performed using the rotavirus VP6 gene as a template. First, 1.4 μl of DMSO was added to 5 μl of viral RNA and denatured at 97 ° C. for 5 minutes. (5'-AAGGAGTAGCGCCACAATC-3 ') and reverse primer (5'-TAAGCCACATGGTTCCCATT-3'), 0.1 μl of enzyme AMV (Promega, Medison, USA), and 1 μl of 10 × buffer, 0.4 μl of 1 × dNTPs, and 0.2 μl of forward primer , And reverse transcription-PCR assay (42 ° C for 60 min, 95 ° C for 5 min) with a mixture containing RNase free water (total 10 μl). 2 μl of cDNA, 5 μl of master mix (Applied Biosystems, USA), 0.2 μl of forward and reverse primers (10 μM, the same as above), 1.5 μl of probe (6FAM-GCACCGGATTTGTTTTTCAT-MGBNFQ ) (2pM), and RNase free water. (50 ° C for 2 minutes, 95 ° C for 10 minutes) using an ABI 7500 real-time thermocycler (Biosystems, Foster City, CA, USA) Denaturation was carried out at 94 ° C for 15 seconds and annealing was carried out for 40 cycles (60 ° C for 1 minute).

3-1. Jenny pin treatment after rotavirus infection

MA104 cells were seeded in a 24-well plate at a concentration of 3 × 10 ⁵ cells / well and cultured at 37 ° C. for 24 hours. MA104 cells were infected with rotavirus Wa strain at an MOI of 0.01 and reacted for 1 hour. The unattached virus was then washed twice. Jenny pins were treated (24 hours) to 0, 10, 50, 100, 130, and 150 μM / ml in rotavirus Wa strain infected cells.

As a result, as shown in FIG. 9 , the number of viral replication was decreased depending on the concentration of the JENNIFIN, and the decrease was 62% at the highest concentration of 150 μM / ml.

3-2. After pre-treatment of rotavirus and genitin mixture, rotavirus infection and reprocessing of genitin

MA104 cells were seeded in a 24-well plate at a concentration of 3 × 10 ⁵ cells / well and cultured at 37 ° C. for 24 hours. Rotavirus and zeniprin at concentrations of 0, 10, 50, 100, 130 and 150 μM / ml were mixed in the medium and cultured at 37 ° C. for 4 hours. After MA104 cells were washed, the virus and zenithin mixture prepared above was pretreated and incubated for 1 hour. One hour later, MA104 cells were infected with rotavirus Wa strain of MOI 0.01 and reacted for 1 hour, after which the unattached virus was washed twice. The cells infected with the rotavirus Wa strain prepared as described above were divided into groups treated with JNP (0, 10, 50, 100, 130 and 150 μM / ml) Were measured.

FIG. 10A is a graph showing inhibition of infection and viral replication inhibition by pretreating rotavirus Wa strain and a genistein mixture with MA104 cells, infecting Wa strain, and then reprocessing the genistein by concentration. The number of viruses decreased depending on the concentration of zeniprin, especially at the concentration of 150 μM / ml, the effect was 88%. FIG. 10B is a graph showing the results of the experiment group without reprocessing the JENNY pin . As shown in FIG. 10B , the number of viruses was decreased depending on the concentration of JENNYPIN in comparison with the untreated group, and the reduction was 57% at the concentration of 150 μM / mL. In particular, as shown in FIG. 10B , inhibition of viral infection even after reprocessing of the genitin after the rotavirus infection shows the excellent effect of preventing the rotavirus infection of the genitin.

3-3. After the pretreatment of the jenny pin, the rotavirus infection and the reprocessing of the jenny pin

MA104 cells were seeded in a 24-well plate at a concentration of 3 × 10 ⁵ cells / well and cultured at 37 ° C. for 24 hours. MA104 cells were added to the medium in concentrations of 0, 10, 50, 100, 130, and 150 μM / ml, respectively, and cultured for 24 hours. Thereafter, virus infection and reprocessing of the jenny pin proceeded in the same manner as in Example 3-2.

FIG. 11A shows the results of pretreating genitin in MA104 cells for 24 hours, infecting the Wa strain, and reprocessing the genitin pin by concentration. The number of viruses decreased depending on the concentration of zeniprin, and the number of viruses decreased sharply at all concentrations compared with the untreated group. Especially, at the concentrations of 130 μM / ml and 150 μM / ml, the number of viruses decreased by 88%. FIG. 11B is a graph showing the results of the non-reprocessing of the JENNY pin. As a result, the number of viruses decreased and the effect was reduced by 76% at 150 μM / ml, in comparison with the untreated group. In particular, as shown in FIG. 11B , inhibition of viral infection despite the reprocessing of the genitin after the rotavirus infection shows an excellent effect of preventing the rotavirus infection of the genitin.

Through the experiments in Example 3, the Jenny pin inhibited rotavirus replication and not only had a therapeutic effect on rotavirus infection (see Example 3-1) but also prevented (see Examples 3-2 and 3-3) The effect was also confirmed to be excellent. In particular, as shown in Examples 3-2 and 3-3, it was confirmed that the use of jennypin in combination with prophylactic and therapeutic treatment of rotavirus infection shows a greater disease inhibitory effect.

As a result, the Jenny pin of the present invention has a preventive effect and an inhibitory effect on rotavirus, and shows a greater effect when the combination of prevention and treatment is performed.

As described above, the present invention relates to a novel use of a genipin compound, and more particularly to a novel use of a genipin compound for prevention of a disease caused by rotavirus infection comprising as an active ingredient jenipine or a pharmaceutically acceptable salt thereof , &Lt; / RTI &gt;

Since the Jennypin compound of the present invention has an excellent anti-rotavirus effect, the pharmaceutical or food composition for prevention, treatment and improvement of diseases caused by rotavirus infection (enteritis, diarrhea, cold, sore throat, bronchitis and pneumonia) And thus it is highly likely to be used industrially.

Claims (6)

A pharmaceutical composition for preventing or treating enteritis or diarrhea caused by rotavirus infection comprising genipin or a pharmaceutically acceptable salt thereof as an active ingredient.
The composition of claim 1, wherein the rotavirus is human, Pocine, Bovine or Goat rotavirus.
delete A food composition for preventing or ameliorating enteritis or diarrhea caused by rotavirus infection comprising as an active ingredient zeniprin or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition for preventing or treating rotavirus infection comprising genipin or a pharmaceutically acceptable salt thereof as an active ingredient.
A food composition for preventing or improving rotavirus infection comprising genipin or a pharmaceutically acceptable salt thereof as an active ingredient.

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