KR20160037342A - Composition for Preventing, Treating or Improving Insulin Resistance or Insulin Resistance-Related Diseases Comprising Fermented Garlic using Saccharomyces cerevisiae - Google Patents
Composition for Preventing, Treating or Improving Insulin Resistance or Insulin Resistance-Related Diseases Comprising Fermented Garlic using Saccharomyces cerevisiae Download PDFInfo
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Abstract
The present invention relates to a composition comprising fermented garlic using Saccharomyces cerevisiae , which comprises a fermented garlic fermentation product obtained by inoculating Saccharomyces cerevisiae with a suspension of garlic powder or a garlic extract, A pharmaceutical composition for preventing or treating insulin resistance or insulin resistance-related diseases containing water as an active ingredient, and a functional food composition for prevention or improvement. The composition of the present invention has an effect of enhancing the expression of a receptor of a receptor, an effect of enhancing glucose uptake, a glucose controlling effect and a weight controlling effect.
Description
The present invention relates to a composition for preventing, treating or ameliorating insulin resistance or insulin resistance-related diseases, including garlic fermented products, using Saccharomyces cerevisiae.
Garlic ( Allium sativum L.) is a bulbous plant belonging to the genus Liliiaceae ( Allium ). Recently, many researchers have found that there are various pharmacological physiological activities such as cancer prevention effect, blood circulation prevention effect and antioxidant activity Are reported. The major component of the pharmacological activity of garlic is the s-allyl-cysteine sulfoxide (S-alkenyl-l-cysteine sulfoxides) L-cysteine sulfoxide (S-allyl-L-cysteine sulfoxide) is produced by the action of allinase, an enzyme in garlic, and the azoenes produced by polymerization and decomposition of allicin and allicin ajoene and vinyl dithiins (Lawson et al., Planta, Med., 57: 363-370 (1991)).
Diabetes mellitus (diabetes) is characterized by chronic hyperglycemia due to a lack of insulin action, and it is a group of diseases with various characteristic metabolic abnormalities. Since insulin is mainly involved in carbohydrate metabolism, diabetes is a general metabolic disease, since the abnormality of carbohydrate metabolism is a fundamental problem, and all the nutrient metabolism in the body is affected thereby. Diabetes is one of the most important chronic diseases in modern times, especially in advanced countries. Diabetes is largely classified as
Diabetes is a major cause of insulin deficiency or hyperglycemia due to cell resistance to insulin, which leads to metabolic changes as hyperglycemia persists. When the insulin action is lowered, when the excessive sugar is absorbed, the ability to maintain a constant blood sugar level is decreased, so that the blood glucose is increased and thus the glucose is excreted in the urine.
Early symptoms of diabetes include polyuria, polydipsia, polyphagia, and weight loss. Clinical symptoms include glucosuria, hyperglycemia, abnormal glucose tolerance test, and asthenia through urinary excretion.
Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.
The present inventors have sought to produce a fermented garlic product having an effect of improving, preventing or treating insulin resistance or insulin resistance-related diseases. As a result, the present invention has been completed by confirming the effect of enhancing expression of sugar receptors, enhancing glucose uptake, controlling blood glucose, and controlling body weight of fermented garlic fermented by inoculation with Saccharomyces cerevisiae .
Accordingly, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating insulin resistance or insulin resistance-related diseases.
Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.
According to one aspect of the present invention, there is provided a method for producing a fermented garlic fermented product, which comprises fermenting garlic fermented by inoculating Saccharomyces cerevisiae with a suspension or garlic extract of a pulverized garlic powder as an active ingredient, insulin resistance or insulin resistance There is provided a pharmaceutical composition for preventing or treating a related disease.
The present inventors have sought to produce a fermented garlic product having an effect of improving, preventing or treating insulin resistance or insulin resistance-related diseases. As a result, the effect of enhancing sugar receptor expression, glucose uptake, glucose control effect and weight control effect of fermented garlic fermented by inoculation with Saccharomyces cerevisiae was confirmed.
As used herein, the term " prophylactic " means any action that inhibits or delays progression of insulin resistance and / or insulin resistance-related diseases upon administration of the composition of the present invention.
As used herein, the term " treatment " refers to the inhibition of the development of insulin resistance and / or insulin resistance related diseases; Alleviating insulin resistance and / or insulin resistance related diseases; And elimination of insulin resistance and / or insulin resistance related diseases.
As used herein, the term " insulin resistance " refers to the inability of cells to burn glucose effectively because of insulin's ability to lower blood glucose. When the insulin resistance is high, the human body produces too much insulin, which can lead to hypertension and abnormal lipidemia as well as heart disease and diabetes. In particular,
As used herein, the term " insulin resistance-related disease " is a concept collectively referred to as a disease caused, progressed and / or worsened by causing insulin resistance to be a direct / indirect cause.
According to one embodiment of the present invention, the insulin resistance-related disease is selected from the group consisting of diabetes mellitus, diabetic complication, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, insulin resistance syndrome, dyslipidemia, obesity, cardiovascular disease, low HDL cholesterol But are not limited to, one or more diseases selected from the group consisting of hyperlipidemia, hyperlipidemia, inflammation, breast cancer, prostate cancer and rheumatoid arthritis.
Insulin resistance is known to be a central cause of risk factors for
According to an embodiment of the present invention, the diabetic complication includes at least one disease selected from the group consisting of diabetic retinopathy, diabetic cataract, diabetic neuropathy, diabetic neuropathy and diabetic osteoporosis, It is not.
According to one embodiment of the present invention, the cardiovascular disease is selected from the group consisting of hypertension, heart disease, stroke, thrombosis, angina pectoris, heart failure, myocardial infarction, coronary artery disease, aneurysm, embolism, atherosclerosis, atherosclerosis and arteriosclerosis Including, but not limited to, one or more diseases.
As used herein, the term " insulin resistance syndrome " is a generic term for the diseases caused by insulin resistance, and includes the cell resistance to insulin action, hyperinsulinemia, very low density lipoprotein (VLDL) (HDL) and hypertension, and is a concept recognized as a risk factor for cardiovascular disease and
In addition, it is known that insulin resistance increases risk factors such as hypertension, diabetes and smoking, thereby increasing intracellular oxidative stress and altering the signal transduction system to induce an inflammatory reaction (Freeman BA et al., Biology Investig. 47: 412-26 (1982), Kawamura M et al., Pathophysiological concentrations of glucose promoting oxidative modification of low density lipoprotein by a superoxidedependent pathway, J. Clin. Invest. 94: 771-8 (1994)).
The present invention includes a fermented garlic fermented product obtained by inoculating a suspension of garlic powder or garlic extract with Saccharomyces cerevisiae as an active ingredient.
The garlic fermented product of the present invention may be fresh garlic or blanched garlic.
According to one embodiment of the present invention, the suspension or garlic extract of the garlic pulverizer is inactivated with allinase in garlic.
The inactivation of the alliinase inactivates the alliinase by heat treating the raw garlic. The heat treatment is performed by immersing in a solution at 80-100 ° C, 90-100 ° C, or 95-100 ° C for 5 minutes to 15 minutes, 5 minutes to 10 minutes, or 6 minutes to 8 minutes. The amount of time to devote can vary depending on the amount of garlic added to the hot water.
The garlic fermented product of the present invention uses a suspension of garlic powder or garlic extract.
The garlic pulverizer includes garlic produced by various processes. For example, garlic may be pulverized in various states such as powdered state, homogenized state, slicing state, and mash state after processing such as vacuum distillation, freeze drying, spray drying and the like .
According to an embodiment of the present invention, the garlic pulverizer is pulverized or homogenized after lyophilization. According to another embodiment of the present invention, the garlic pulverizer is pulverized after lyophilization.
In order to prepare the suspension of the above-mentioned garlic pulverizer, a solution for various garlic pulverizer may be used. The solution may be diluted with distilled water, a buffer (e.g., Tris buffer, HEPES buffer, etc.), a yeast culture medium (e.g., SD (Synthetic defined) medium, YPD (Yeast extract, peptone, dextrose)
According to one embodiment of the present invention, the suspension of the garlic pulverizer is distilled water or yeast culture medium. According to another embodiment of the present invention, the suspension of the garlic pulverizer is distilled water.
The garlic extract used in the pharmaceutical composition for the prevention or treatment of insulin resistance or insulin resistance-related diseases of the present invention can be used in various extraction solvents when it is obtained by treating garlic with an extraction solvent. Preferably, a polar solvent or a non-polar solvent can be used. Suitable polar solvents are (i) water, (ii) alcohols (preferably methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, Or ethylene glycol), (iii) acetic acid, (iv) dimethyl-formamide (DMFO) and (v) dimethyl sulfoxide (DMSO). Suitable nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1- But are not limited to, pentane, 1-chlorobutane, 1-chloropentane, o -xylene, diisopropyl ether, 2- chloropropane, toluene, 1- chloropropane, chlorobenzene, benzene, diethyl ether, diethylsulfide, Methane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride, and THF.
More preferably, the extraction solvent used in the present invention is (a) water, (b) anhydrous or hydrated lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.) (E) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether. . Most preferably, the extract of the present invention is obtained by treating garlic with water, ethanol or a combination thereof.
As used herein, the term " extract " means that it is used in the art as a crude extract as described above, but broadly includes fractions obtained by further fractionating the extract. That is, the garlic extract includes not only those obtained by using the aforementioned extraction solvent but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the above extract through an ultrafiltration membrane having a constant molecular weight cut-off value, and a separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity) The fraction obtained by the purification method is also included in the garlic extract of the present invention.
The garlic extract used in the present invention may be prepared in powder form by an additional process such as vacuum distillation and freeze drying or spray drying.
The garlic fermented product of the present invention is fermented by inoculating a suspension of garlic powder or garlic extract with Saccharomyces cerevisiae.
According to one embodiment of the present invention, the Saccharomyces cerevisiae is Saccharomyces cerevisiae SAC (KFCC11565P).
According to one embodiment of the present invention, the fermentation has a reaction temperature of 10 to 30 DEG C, and according to another embodiment of the present invention, the fermentation is a reaction temperature of 15 to 30 DEG C, The fermentation is a reaction temperature of 20-30 ° C or 23-27 ° C.
According to one embodiment of the present invention, the fermentation has a reaction time of 1-20 days, according to another embodiment of the invention, the fermentation is a reaction time of 1-15 days, and in certain embodiments of the invention According to this, the fermentation is a reaction time of 2-12 days.
The composition of the present invention has an effect of preventing or treating insulin resistance or insulin resistance-related diseases.
According to one embodiment of the present invention, the composition has a blood glucose reducing activity.
According to one embodiment of the present invention, the composition has an activity of improving glucose tolerance.
According to one embodiment of the invention, the composition reduces weight gain.
As demonstrated in the following examples, the garlic fermented product exhibits improved glucose uptake (see Fig. 1), reduced blood glucose (see Fig. 2), improved glucose tolerance (see Fig. 3), increased insulin sensitivity (See Figure 5).
The compositions of the present invention may be prepared with pharmaceutical compositions.
According to a preferred embodiment of the present invention, the composition of the present invention comprises (a) a pharmaceutically effective amount of the above-described garlic fermented product of the present invention; And (b) a pharmaceutically acceptable carrier. As used herein, the term " pharmaceutically effective amount " means an amount sufficient to achieve efficacy or activity of the garlic fermentation product described above.
When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).
The pharmaceutical composition of the present invention can be administered orally or parenterally, and is preferably administered orally.
The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . Typical dosages of the pharmaceutical compositions of this invention are in the range of 0.001-100 mg / kg on an adult basis.
The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
According to another aspect of the present invention, there is provided a method for preventing or ameliorating insulin resistance or insulin resistance-related diseases comprising an effective ingredient of a fermented garlic fermented by inoculating a suspension of garlic powder or garlic extract with Saccharomyces cerevisiae To provide a functional food composition.
The functional food composition for preventing or ameliorating insulin resistance or insulin resistance-related diseases of the present invention uses the same active ingredient as the pharmaceutical composition for preventing or treating insulin resistance or insulin resistance-related diseases, In order to avoid the excessive complexity of the present description, the description thereof is omitted.
Can be produced from a functional food composition for preventing or ameliorating insulin resistance or insulin resistance-related diseases comprising the fermented garlic product of the present invention as an active ingredient. When the composition of the present invention is prepared with a functional food composition, it includes components that are conventionally added in food production, and includes, for example, proteins, carbohydrates, fats, nutrients, and seasonings. For example, in the case of a drink, a flavoring agent or a natural carbohydrate may be added as an additional ingredient in addition to the fermented garlic as an active ingredient. For example, natural carbohydrates include monosaccharides (e.g., glucose, fructose, etc.); Disaccharides (e.g., maltose, sucrose, etc.); oligosaccharide; Polysaccharides (e.g., dextrin, cyclodextrin and the like); And sugar alcohols (e.g., xylitol, sorbitol, erythritol, etc.). Natural flavoring agents (e.g., tau marin, stevia extract, etc.) and synthetic flavoring agents (e.g., saccharin, aspartame, etc.) may be used as flavorings.
The features and advantages of the present invention are summarized as follows:
(a) The present invention provides a pharmaceutical composition and a functional food composition for preventing or treating insulin resistance or insulin resistance-related diseases.
(b) The composition of the present invention has an effect of enhancing the expression of a receptor of the sugar, an effect of enhancing sugar absorption, a blood glucose controlling effect and a body weight controlling effect.
Fig. 1 shows the effect of enhancing expression of a sugar receptor in a fermented product obtained by inoculating S. cerevisiae SAC into garlic.
Fig. 2 shows the sugar absorption enhancement effect of the fermented product fermented by inoculating S. cerevisiae SAC into garlic. In FIG. 2, 'IN' is insulin and 'PA' is palmitic acid.
Fig. 3 shows the effect of increasing the glucose tolerance of the fermented product obtained by inoculating S. cerevisiae SAC into garlic.
Fig. 4 shows the effect of increasing the insulin sensitivity of the fermented product fermented by inoculating S. cerevisiae SAC into garlic.
FIG. 5 shows the effect of reducing the insulin concentration in blood of the fermented product fermented by inoculating S. cerevisiae SAC into garlic.
Fig. 6 shows the effect of controlling the body weight of the fermented product fermented by inoculating S. cerevisiae SAC into garlic.
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
Example 1: Preparation of fermented garlic
I purchased a garlic group harvested in June 2012 from a garlic grower in the South Sea of the Republic of Korea. Peeled garlic bulbs were boiled for 7 minutes in boiling water to inactivate allinase, and all samples were lyophilized and stored at -20 ° C. To 20 g of the lyophilized garlic powder, 180 ml of distilled water was prepared in a 500 ml flask. Saccharomyces cerevisiae SAC (KFCC11565P) was inoculated at 1.0 × 10 5 CFU / ml and fermented at 25 ° C for 10 days. Samples were taken at 0, 2, 4, 7 and 10 days after fermentation, Respectively. This sample is referred to as "garlic- S. cerevisiae SAC fermentation product" below.
Example 2: Garlic -S. cerevisiae SAC fermentation product Enhancing effect of the receptor
Research method
L6-GLUT4myc cells (GLUT4 (Glucose transporter type 4) expressing L6 cells) (J Nutr Biochem, 2014 http://www.ncbi.nlm.nih.gov/pubmed/25034503) were inoculated with garlic- S. cerevisiae SAC fermentation SC) were pretreated for 24 hours and then starvated for 3 hours in serum-free medium. As a control, insulin is treated at a concentration of 100 nM for 20 minutes. After 3 washes with ice-cold PBS, the cells were reacted with anti-myc monoclonal antibody for 1 hour at 4 ° C and HRP-conjugated anti-mouse IgG for 45 minutes. After treatment with OPD (ο-Phenylenediamine dihydrochloride) buffer, absorbance is measured at 492 ㎚.
Results
The expression of GLUT4myc was increased in the insulin - treated group compared to NC (Negative Control), and the expression of GLUT4myc was increased in the treated with garlic - S. cerevisiae SAC fermented product compared to NC. The GLUT4 expression enhancing effect was highest in the experimental group treated with garlic- S. cerevisiae SAC fermentation for 4 days (Fig. 1).
Example 3: Garlic -S. cerevisiae SAC fermentation product Of sugar absorption enhancement
Research method
The differentiated C2C12 cells were treated with garlic- S. cerevisiae SAC fermentation (SC) for 18 hours and treated with free fatty acid (palmitic acid) to induce insulin resistance. Glucose uptake was measured with 2-NBDG (fluorescent glucose analog). Glucose uptake in skeletal muscle cells was measured by fluorescence and the greater the fluorescence intensity, the greater the increase in glucose uptake.
Results
Glucose uptake after treatment with garlic - S. cerevisiae SAC fermented on
Example 4: Preparation of garlic- S. cerevisiae SAC fermentation product Blood sugar control effect
Research method
Five-week-old male C57 BL / 6J at birth was adapted to the environment for one week with solid feed. After that, each group was randomly divided into 4 groups of 10 rats, and fed with experimental diet for 8 weeks. Experimental diets were prepared according to the AIN-76 dietary composition, and 15% Lard and 0.25% cholesterol were added to induce hyperlipidemia and obesity. The control and experimental groups were divided into four groups: normal (NC), high fat diet control (HFD), HFD + garlic - S. cerevisiae SAC fermented water supplement group (SC, 2.5% at high concentration and 1% The garlic- S. cerevisiae SAC fermentation product was fermented for 4 days. Intraperitoneal glucose tolerance test (IPGTT) was performed to measure glucose tolerance in patients with hyperglycemia due to diabetes. After fasting for 4 hours, blood glucose was measured at 15, 30, 60, 90, 120 and 150 minutes after administration of a glucose solution having a glucose concentration of 2 g / kg in the intraperitoneal solution.
For insulin sensitivity, insulin solution was prepared at a concentration of 1.3 unit / kg, and blood glucose was measured at 15, 30, 60, 90 and 120 minutes by IP administration to mice fasted for 4 hours. Fasting serum insulin levels were measured using an ELISA kit.
Results
HFD + garlic - S. cerevisiae SAC fermented group showed a significant decrease in blood glucose per time compared with the control group. From these results, it was confirmed that garlic- S. cerevisiae SAC fermentation increases the glucose tolerance (Fig. 3).
HFD + garlic - S. cerevisiae SAC fermented group showed a significant decrease in blood glucose per time compared with the control group. These results confirmed that garlic- S. cerevisiae SAC fermentation increased insulin sensitivity (FIG. 4).
In the HFD + garlic- S. cerevisiae SAC fermentation low-concentration group and HFD + garlic- S. cerevisiae SAC fermentation high-concentration addition group, the blood insulin concentrations were decreased in both groups compared to the control group (FIG. 5) .
These results suggest that HFD supplementation induces insulin resistance and HFD + garlic - S. cerevisiae SAC fermented product improves insulin resistance by HFD alone.
Example 5: Preparation of garlic- S. cerevisiae Weight control effect of fermented SAC
Research method
Five-week-old male C57 BL / 6J at birth was adapted to the environment for one week with solid feed. After that, each group was randomly divided into 4 groups of 10 rats, and fed with experimental diet for 8 weeks. Experimental diets were prepared according to the AIN-76 dietary composition, and 15% Lard and 0.25% cholesterol were added to induce hyperlipidemia and obesity. Experimental groups were divided into four groups: normal group (NC), high fat diet control group (HFD) and HFD + garlic- S. cerevisiae SAC fermented product (SC, high concentration 2.5% and
Results
To evaluate the efficacy of garlic- S. cerevisiae SAC fermentation (SC) on obesity induced by high fat diet, C57 / BL6J mice were fed a high fat diet supplemented with fermented garlic- S. cerevisiae SAC for 8 weeks Results The weight gain due to high fat dietary intake was significantly reduced (Figure 6).
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
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US11295334B2 (en) * | 2019-04-30 | 2022-04-05 | Bank Of America Corporation | Batch transaction multiplexing engine |
US11587113B2 (en) | 2019-04-30 | 2023-02-21 | Bank Of America Corporation | Batch transaction multiplexing engine |
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