KR102085900B1 - Pharmaceutical composition for preventing or treating diabetes comprising as an active ingredient a compound isolated from Bacillus amyloliquefaciens RWL-1 culture medium - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating, and treating diabetes comprising a compound isolated from a Bacillus amyloliquefaciens RWL-1 strain culture medium, wherein the present invention is the first description of enzyme inhibitory activity of a bioactive compound isolated from Bacillus amyloliquefaciens species. The composition of the present invention has excellent alpha-glucosidase inhibitory activity and thus inhibits absorption of sugar in the intestine, thereby being effective in treating, preventing, and alleviating diabetes; and uses the secondary metabolite of microorganisms as an important source of bioactive metabolites with high therapeutic values, thereby being usefully used in medical and food industry fields.

Description

Pharmaceutical composition for preventing or treating diabetes comprising as an active ingredient a compound isolated from Bacillus amyloliquefaciens RWL- 1 culture medium}

The present invention relates to a composition for preventing, ameliorating or treating diabetes, comprising a compound isolated from a culture solution of Bacillus amyloliquefaciens RWL-1 strain.

Diabetes is a type of metabolic disease such as insufficient insulin secretion or normal functioning. It is characterized by high blood sugar, which increases the concentration of glucose in the blood, and causes various symptoms and signs and releases glucose from urine. . Type 1 diabetes requires insulin treatment, and type 2 diabetes is based on lifestyle modifications and may require additional drug administration. Alpha-glucosidase inhibitors are one of the drugs that break down starch in the gut. By preventing it, it helps to lower blood sugar by slowing blood sugar increase after a meal. Representative alpha-glucosidase inhibitors are acarbose.

On the other hand, plant endogenous (endophyte) refers to a microorganism having the ability to live in plant tissues and form colonies in the internal tissues of plants without causing obvious diseases. Plant endogenous organisms are spread throughout all parts of the plant and are separated from other parts of the plant. They do not damage plants and interact with host plants, but their interactions depend on many factors and can change over time. In this symbiotic relationship, plants provide shelter, protection, and essential nutrients to plant endogenous organisms. Instead, plant endogenous organisms form beneficial interactions with host plants through the regulation of endogenous plant hormones and nutrients, and the plant for fast changing environments. Improves its adaptability. Plant endogenous organisms are present in all plant species, but the interaction between plant endogenous organisms and the host has not been fully studied.

In addition, endogenous organisms show many important biological activities besides the interaction of plants and microorganisms. Many bacteria in endogenous organisms are known to produce various bioactive and health enhancing compounds such as volatile organic compounds, antibiotics, immunosuppressive compounds, anticancer agents, antiviral and antifungal agents. In clinical trials, exopolysaccharides with anti-tumor efficacy were found in the first study of Bacillus amyloliquefaciens, which is a natural product and more than 60% of anticancer drugs. In addition to these antitumor substances, plant endogens belonging to the genus Bacillus genus produce a variety of secondary metabolites. For example, Bacillus thuringiensis produces the anti-infective compound anthracene and B. subtilis produces the antibiotic protein YbdN, which suggests promising medical possibilities in the Bacillus genus. have.

In recent years, the isolation and identification of biologically active alpha-glucosidase inhibitors is of increasing interest as they can be used as tools for understanding biochemical processes and functioning as promising therapeutics. Although an important source, microorganisms are also considered to be important sources of biologically active metabolites with high therapeutic value. In this regard, although the biological potential of Bacillus amyloliquefaciens has been widely reported, studies on the enzymatic inhibitory activity of bioactive compounds isolated from Bacillus amyloliquefaciens species have been insufficient.

Korean Patent Registration Publication 10-0943747

The present inventors confirmed the alpha-glucosidase inhibitory effect of crude extract of Bacillus amyloliquefaciens RWL-1 strain culture to separate the compound having a specific structure from the crude extract and the isolated compound was alpha- The present invention was completed by experimentally confirming the excellent glucosidase inhibitory activity.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating diabetes and a food composition for improving diabetes, comprising a compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problem, another task that is not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the object of the present invention as described above, the present invention provides a pharmaceutical composition for preventing or treating diabetes, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

In one embodiment of the present invention, the compound may be isolated from the culture of Bacillus amyloliquefaciens RWL-1 strain (KCTC 13637BP).

In another embodiment of the present invention, the composition may have an alpha-glucosidase inhibitory effect.

In another aspect, the present invention provides a food composition for improving diabetes comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

In one embodiment of the present invention, the compound may be isolated from the culture of Bacillus amyloliquefaciens RWL-1 strain (KCTC 13637BP).

In another embodiment of the present invention, the composition may have an alpha-glucosidase inhibitory effect.

In addition, the present invention provides a method for preventing or treating diabetes, comprising administering to a subject a pharmaceutical composition comprising a compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

In addition, the present invention provides a pharmaceutical composition comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient, preventing or treating diabetes.

[Formula 1]

The present invention relates to a composition for the prevention, improvement and treatment of diabetes, comprising a compound isolated from the culture medium of Bacillus amyloliquefaciens RWL-1 strain, the composition of the present invention is excellent alpha-glucosid By having an antase inhibitory activity, it is effective in treating, preventing and improving diabetes by inhibiting the absorption of sugar in the intestine and using the second metabolite of microorganisms, which can be used as an important source of biologically active metabolites with high therapeutic value. It is expected to be useful in the medical and food industries.

Figure 1 schematically shows an experimental method for separating the compounds of the present invention and confirm their structure.
Figure 2a is the result of experiments on the alpha-glucosidase inhibitory effect of the crude extract of Bacillus amyloliquefaciens RWL-1 culture.
Figure 2b is the result of experiments with the cytotoxicity of the crude extract of Bacillus amyloliquefaciens RWL-1 culture in an MTT assay.
Figure 2c is a test result of the AChE (acetylcholinesterase) inhibitory effect of the crude extract of Bacillus amyloliquefaciens RWL-1 culture.
Figure 3 shows the structure of the compound isolated from amyloliquefaciens RWL-1 culture crude extract.
4 shows the results of experiments on alpha-glucosidase inhibitory activity of the compounds isolated from the crude extract.

The present inventors confirmed the alpha-glucosidase inhibitory effect of the crude extract of Bacillus amyloliquefaciens RWL-1 strain culture, and separated the compound having a specific structure from the crude extract, and the isolated compound has alpha-glucosidase inhibitory activity. Experimentally confirmed this superiority to complete the present invention.

In one embodiment of the present invention, by treating the crude extract of Bacillus amyloliquefaciens RWL-1 strain cultures to test the alpha-glucosidase inhibitory activity, cytotoxicity, AChE inhibitory activity as a result of the crude extract alpha-glucosidase It was confirmed that the inhibitory activity was excellent (see Example 2).

In another embodiment of the present invention, the compound isolated from the crude extract of Bacillus amyloliquefaciens RWL-1 strain culture was analyzed to confirm its chemical structure (see Example 3).

In another embodiment of the present invention, the enzyme inhibitory activity of the compound was confirmed that the alpha-glucosidase inhibitory activity was excellent (see Example 4).

Therefore, in view of the above content, the compound is excellent in alpha-glucosidase inhibitory activity and thus can be used for the treatment, prevention, or improvement of diabetes.

Accordingly, the present invention provides a pharmaceutical composition for preventing or treating diabetes, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

As used herein, the term "prevention" means any action that inhibits or delays the onset of diabetes by administration of the pharmaceutical composition according to the present invention.

As used herein, the term "treatment" refers to any action by which administration of the pharmaceutical composition according to the present invention improves or beneficially changes the symptoms caused by diabetes.

The pharmaceutical composition according to the present invention includes a compound isolated from the culture solution of Bacillus amyloliquefaciens RWL-1 strain (KCTC 13637BP) as an active ingredient, and may include a pharmaceutically acceptable carrier. . The pharmaceutically acceptable carrier is conventionally used in the preparation, and includes, but is not limited to, saline solution, sterile water, Ringer's solution, buffered saline, cyclodextrin, dextrose solution, maltodextrin solution, glycerol, ethanol, liposomes, and the like. If necessary, other conventional additives such as antioxidants and buffers may be further included. In addition, diluents, dispersants, surfactants, binders, lubricants and the like may be additionally added to formulate injectable formulations, pills, capsules, granules, or tablets such as aqueous solutions, suspensions, emulsions and the like. Suitable pharmaceutically acceptable carriers and formulations can be preferably formulated according to the individual components using methods disclosed in Remington's literature. The pharmaceutical composition of the present invention is not particularly limited in formulation, but may be formulated as an injection or oral ingestion.

The pharmaceutical composition of the present invention can be administered orally or parenterally (eg, intravenously, subcutaneously) according to the desired method, and the dosage is based on the condition and weight of the patient, the extent of the disease, the form of the drug, Depending on the route and time of administration, it may be appropriately selected by those skilled in the art.

The composition according to the invention is administered in a pharmaceutically effective amount. In the present invention, “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level means the type of disease, the severity, and the activity of the drug. , Drug sensitivity, time of administration, route of administration and rate of release, duration of treatment, factors including concurrent use of drugs, and other factors well known in the medical arts. The composition according to the present invention may be administered as a separate therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can achieve the maximum effect with a minimum amount without side effects, which can be readily determined by one skilled in the art.

Specifically, the effective amount of the composition according to the present invention may vary depending on the age, sex, and weight of the patient and may be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, and the like.

The term "pharmaceutically acceptable salts thereof" used in the present invention may be prepared by conventional methods in the art, for example, hydrochloric acid, hydrogen bromide, sulfuric acid, sodium hydrogen sulfate, phosphoric acid, carbonic acid. Medicaments with salts with inorganic acids or with organic acids such as formic acid, acetic acid, oxalic acid, benzoic acid, citric acid, tartaric acid, gluconic acid, gestyic acid, fumaric acid, lactobionic acid, salicylic acid, or acetylsalicylic acid (aspirin) To form salts of these pharmaceutically acceptable acids, or to react with alkali metal ions such as sodium and potassium to form their metal salts, or to react with ammonium ions to form another form of a pharmaceutically acceptable salt thereof. It means to form.

In the present invention, the compound may be isolated from the culture solution of Bacillus amyloliquefaciens RWL-1 strain (KCTC 13637BP), but is not limited thereto.

In the present invention, the Bacillus amyloliquefaciens RWL-1 strain was deposited with the Korea Institute of Bioscience and Biotechnology (KCTC) on September 06, 2018 and received accession number KCTC 13637BP.

The strain of the present invention may be isolated from rice seeds, but is not limited thereto.

The composition of the present invention may have an alpha-glucosidase inhibitory activity.

The term "glucosidase" used in the present invention refers to an enzyme that decomposes monosaccharides or other absorbable polysaccharides by hydrolyzing the binding portion of sugars in the metabolic process of carbohydrates and glycoproteins. They are responsible for the processing and synthesis of complex carbohydrates, and are known as essential enzymes in many biological molecular recognition processes. Α-glycosidase is in serous fluids, and β-glycosidase is in various tissues such as liver, kidney and spleen. . In addition, since various kinds of glucosidase are involved in food digestive system through the decomposition of starch, polysaccharides such as sucrose, and oligosaccharides, inhibitors against them inhibit the absorption of sugars in the intestine, which is used as antidiabetic and anti-obesity agents. It is reported to be useful.

As another aspect of the present invention, the present invention provides a food composition for improving diabetes comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

The food composition comprises a health functional food composition.

As used herein, the term " improvement " means any action that at least reduces the parameters associated with the condition being treated, such as the extent of symptoms.

In the food composition of the present invention, the active ingredient may be added to the food as it is, or may be used together with other foods or food ingredients, and may be appropriately used according to conventional methods. The mixing amount of the active ingredient can be suitably determined according to the purpose of use (prevention or improvement). In general, in the manufacture of food or beverages the compositions of the invention are added in amounts of up to 15% by weight, preferably up to 10% by weight relative to the raw materials. However, for long term intakes for health and hygiene purposes or for health control purposes, the amount may be below this range.

The health functional food composition of the present invention, in addition to containing the active ingredient as an essential ingredient in the indicated ratio, there are no particular restrictions on other ingredients, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. have. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of the natural carbohydrate can be appropriately determined by the choice of those skilled in the art.

In addition to the above, the health functional food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, Alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. These components can be used independently or in combination. The proportion of such additives may also be appropriately selected by those skilled in the art.

Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the following examples.

[ Example ]

Example  1. Experimental Materials and Methods

Example  1-1. Bacillus Amyloliquefaciens RWL -1 Strain Culture and Secondary Metabolite Extraction

Endogenous bacterium Bacillus amyloliquefaciens RWL-1 isolated from rice seeds was incubated in 8 liters of LB medium (tryptone, 10 g; yeast extract, 5 g; sodium chloride ), 10 g; autoclave for 15 minutes at pH 7.0 ± 0.2, 121 ° C). The inoculated RWL-1 was incubated in a shaker (120 rpm) for 7 days at 28 ° C, and then cells were separated by centrifugation at 5000 × g for 15 minutes, and the culture medium from which the RWL-1 cells were removed was adjusted to pH 2.5. Was extracted three times with the same amount of ethyl acetate (ethyl acetate). The ethyl acetate extract was then completely dried in a rotary evaporator to give a concentrated extract (1.6 g).

Example  1-2. Isolation of Secondary Metabolites

Based on the bioassay results, crude ethyl acetate extract was subjected to silica gel column chromatography using a solvent gradient (1% ethyl acetate / n-hexane to 85% ethyl acetate / n-hexane). Analyzed using. Thin layer chromatography (TLC) experiments were performed to investigate and determine different fractions of bacterial culture extracts. TLC plates were observed under ultraviolet light at 254 nm and 365 nm. For further purification, bioactive fractions were obtained using high performance liquid chromatography (HPLC) combined with a UV-VIS detector (SPD-10A) and Shimadzu CBM-10. Samples were analyzed on a C18 column (Luna 5 μm, 100 mm 3, 250 × 4.6 mm). Solvent was used as solvent B-Water (solvent A-100% methanol (MeOH) and 5% acetic acid), solvent program (0-20 min (50% = A; 50% = B), Analysis was performed using 20-40 min (80% A, 20% B), 40-60 min (100% A, 0% B), flow rate of 1 mL / min). The remaining impurities were removed by loading semi-purified secondary metabolites into preparative TLC plates and 4.5 mg of compound was purified in DCM / n-hexane (95: 5) (see FIG. 1).

Example  1-3. From crude extract  Confirmation of structure of separated compound

Spectral analysis (Ultraviolet Ray), IR (infrared), nuclear magnetic resonance (1H-NMR), 13C-NMR, electrospray ionization (ESI) and mass spectrometry (MS) / MS to identify and characterize purified compounds Study). Optical measurements were performed using a polarimeter (JASCO DIP360) and a Bruker ATR-Tensor 37 spectrophotometer to record the IR spectrum. A 5-5.5 kV QSTAR mass spectrometer was used to obtain the ESI mass spectrum. NMR spectra (1H and 13C) were obtained using a Bruker NMR spectrometer operating at 600 MHz and 150 MHz, respectively.

Example  1-4. Alpha-glucosidase inhibitory activity evaluation

The inhibitory effect on the alpha-glucosidase activity of the compound separated from the crude ethyl acetate crude extract of RWL-1 was evaluated. First, alpha-glucosidase was mixed with various concentrations of crude extract of RWL-1 and incubated at 37 ° C. for 10 minutes. Acarbose was used as a positive control, p-nitrophenyl alpha-D-glucopyranoside (PNP-G) was used as a substrate and p released from PNP-G. The absorbance of -nitrophenol was measured at 405 nm every 5 minutes and the inhibition rate was calculated by writing a standard curve. The graph values were expressed as the average of three repetitions with standard error.

Example  1-5. Cytotoxicity Assessment

Cytotoxicity evaluation of the compound isolated from crude ethyl acetate extract was carried out by MTT assay. HCT-15 cells were purchased from the American Type Culture Collection CCL-25 (USA), with atmospheric conditions humidified subconfluent at 95% air and 5% CO ₂ at 37 ° C. RPM-1640 medium with 10% fetal bovine serum and 1% (v / v) streptomycin was used for subculture. HCT-15 cells were treated with 24 mL, 48 and 72 hours of ethyl acetate crude extract of RWL-1 at respective concentrations (250, 500, 750 μg / mL) and 10 ⁵ cells / well in an untreated 96-well plate. Subcultured at density. The medium was removed and 20 μL MTT solution (5 mg / mL in phosphate buffered saline) was added to each well of a 96-well plate and incubated at 37 ° C. for 2 hours. After incubation, MTT medium was replaced with dimethylsulfoxide (DMSO; 200 μl).

The plate was then gently shaken for 1 min and the absorbance was measured at 540 nm and the following formula was used to calculate cell viability and the graph values were expressed as the average of three replicates with standard error.

Viable cells% = (OD treated sample / OD untreated sample) × 100

Example  1-6. AChE ( acetylcholinesterase Inhibitory Activity Assessment

Evaluation of AChE inhibitory activity was performed based on Elman's colorimetric method. 15 mM acetylthiocholine iodide-deionized water (25 μL) solution containing 0.1 M sodium chloride (NaCl) and 0.02 M MgCl ₂ 6H ₂ O, 3 mM 5,5-diti Obis-2-nitrobenzoic acid (5,5-dithiobis-2-nitrobenzoic acid (DTNB, 125 μL), 50 mM Tris-hydrogen chloride buffer (Tris-HCl buffer, pH 8.0) was added to the 96-well plate It was. 50 mM tris-hydrogen chloride buffer (pH 8.0) containing 0.1% bovine serum albumin (50 μL) and ethyl acetate crude extract (25 μL) were added at different concentrations (50 μg / g to 600 μg / g) It was. AChE (25 μL, 0.2 U / mL) was added and absorbance was measured at 412 nm at 45 second intervals. Galantamine (Galantamine, 0.5-5 μg / mL) was used as a standard inhibitor. The graph values are expressed as the average of three repetitions with standard error.

AChE inhibitory activity (%) = 1-(sample reaction rate / blank reaction rate) × 100

Example  2. Bacillus Amyloliquefaciens RWL -One Crude extract  Biological activity assessment

The biological potential of Bacillus amyloliquefaciens RWL-1 crude extract was assessed through inhibitory activity and cytotoxicity against various enzymes, and through the treatment of various concentrations of RWL-1 crude extract, according to the method of Example 1-4 -Glucosidase inhibitory activity was examined for cytotoxicity against HCT-15 cells by the method of Example 1-5, and AChE inhibitory activity by the method of Example 1-6.

As a result, as shown in Figure 2a, RWL-1 crude extract showed a high inhibitory effect of alpha-glucosidase as the concentration was increased (10-100 μg / mL) and at a high dose (100 μg / mL) Alpha-glucosidase (37 ± 0.09%) was significantly inhibited and the positive control showed 74.85 ± 0.06% inhibition.

On the other hand, in the case of cytotoxicity, as shown in Figure 2b RWL-1 crude extract showed a small cytotoxic effect (25 ± 0.16%) at high concentration (750 ㎍ / mL) compared to the control (100%). AChE inhibitory activity occurred dose-dependently at relatively high doses (250-750 μg / mL) as shown in FIG. 2C, but the positive control compound significantly inhibited AChE activity (94.45 ± 0.31%). No reduction was confirmed.

Example  3. From crude extract  Structural Analysis of Isolated Compounds

The structure of the compound was performed by analysis of NMR and MS spectral data according to the method of Examples 1-3 compared to the data reported in previous studies. The 1 H-NMR spectrum showed signals for five protons in the aromatic region (δ8.76-7.59) due to benzene and unsaturated γlactone residues with three substituents and in the downfield region of δ9.15. The wide singlet was assigned to the amide proton NH in the molecule. In addition to these aromatic signals, three oxy-methine protons (δ 4.24-3.84) and two methyl groups (6H, d, J = 7.4 Hz) were observed in the 1H-NMR spectrum.

Furthermore, in the 13C-NMR spectrum, unsaturated γ lactones were shown in the presence of carbonyl carbon at δ176.2 in addition to the two characteristic sp2 methine signals at δ 157.7 and 132.4. δ 139.3, 129.9 and 125.3.

In addition, the compound (name: (S) -2-hydroxy-N-((S) -1-((S) -8-hydroxy-1-oxoisochroman-3-yl) -3-methylbutyl) ) -2-((S) -5-oxo-2,5-dihydrofuran-2-yl) acetamide, (S) -2-hydroxy-N-((S) -1-((S)- 8-hydroxy-1-oxoisochroman-3-yl) -3-methylbutyl) -2-((S) -5-oxo-2,5-dihydrofuran-2-yl) acetamide) was compared with those reported in the literature .

As a result, the overall physical and spectral data of the compound were found to be identical to the antibiotic Al 77F previously isolated from bacterial strains of Bacillus pumilus and strains of Alternaria tenuis (see FIG. 3).

Example  4. From crude extract  Evaluation of Enzyme Inhibitory Activity of Isolated Compounds

Based on the biological potential of the RWL-1 crude extract, the alpha-glucosidase inhibitory activity of the compounds was tested at various concentrations by the method of Examples 1-4.

As a result, as shown in FIG. 4, the inhibition rate of alpha-glucosidase was increased as the concentration of the compound (Compound 1) was increased at 94.37 μg / mL of the IC50 value. 52.98 ± 0.8%). On the other hand, the standard drug used as a positive control showed 79.14 ± 1.9% at the IC50 values of 62.03 μg / mL and 80 μg / mL, and the negative control showed 0.08 ± 0.1% inhibition.

The above description of the present invention is intended for illustration, and it will be understood by those skilled in the art that the present invention may be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive.

Depositary Name: Korea Research Institute of Bioscience and Biotechnology

Accession number: KCTC13637BP

Deposit Date: 20180906

Claims (6)

A pharmaceutical composition for preventing or treating diabetes, comprising a compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

The method of claim 1,
The compound is characterized in that isolated from the culture of Bacillus amyloliquefaciens RWL-1 strain (KCTC 13637BP), diabetes prevention or treatment pharmaceutical composition.
The method of claim 1,
The composition is characterized in that the alpha-glucosidase (α-Glucosidase) inhibitory effect, characterized in that for preventing or treating diabetes pharmaceutical composition.
To include a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient, diabetic improvement food composition.
[Formula 1]

The method of claim 4, wherein
The compound is characterized in that isolated from the culture medium of Bacillus amyloliquefaciens RWL-1 strain (KCTC 13637BP), diabetic improvement food composition.
The method of claim 4, wherein
The composition is characterized in that the alpha-glucosidase (α-Glucosidase) inhibitory effect, food composition for diabetic improvement.

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