Substance for increasing enampt in living body

Abstract

To provide a lower-cost substance that increases eNAMPT in a living body.SOLUTION: A substance for increasing eNAMPT in a living body is composed of a product derived from a culture solution resulting from the culture of the lactic acid bacterium Lactobacillus kefiranofaciens in a medium prepared through the saccharification of rice. The medium can comprise yeast extract. The product comprises kefiran.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a substance that increases eNAMPT in the body. [Background technology]

[0002] Nicotinamide adenine dinucleotide (NAD) is an essential substance for life activities. It is known that NAD decreases with age, and that the decrease in NAD is known to cause the decline in organ and tissue function and aging-related diseases. Therefore, by suppressing the decrease in NAD and promoting NAD synthesis in the body, it is possible to prevent the decline in organ function and aging-related diseases, and increase the activity of SIRT1, which is related to longevity.

[0003] Nicotinamide phosphoribosyltransferase (NAMPT) is an important enzyme involved in the synthesis (production) of NAD in the body. NAMPT converts nicotinamide to nicotinamide mononucleotide (NMN), which is then converted to NAD by nicotinamide mononucleotide adenylyltransferase (NMNAT1). NAMPT is an important enzyme that controls the production of NAD by producing NMN.

[0004] There are two types of NAMPT: intracellular (iNAMPT) that exists within cells, and extracellular (eNAMPT) that exists in blood and cerebrospinal fluid. eNAMPT decreases with age. Furthermore, it is known that there is a strong positive correlation between the amount of eNAMPT and life expectancy in mice. Mice that have been made to produce a lot of eNAMPT have suppressed the decline in physical activity caused by aging, improved sleep quality, and improved memory and learning ability compared to normal mice (Non-Patent Document 1). An increase in eNAMPT leads to an increase in NAD, which is expected to suppress aging and prevent diseases associated with aging. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2023-058828 A [Patent Document 2] JP 2022-159178 A [Non-patent literature]

[0006] [Non-Patent Document 1] M. Yoshida et al., "Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice", Cell Metabolism, vol. 30, pp. 329-342, 2019. Summary of the Invention [Problem to be solved by the invention]

[0007] As described above, increasing eNAMPT in the body is effective in suppressing aging and preventing diseases associated with aging. For example, a technology has been proposed for obtaining extracellular vesicles (EVs) containing eNAMPT from a solution containing a human biological sample (Patent Document 1). In addition, for example, β-palmitic acid has been developed as a component that increases eNAMPT in the body (Patent Document 2). However, the above-mentioned technology has problems in that it is costly and difficult to use continuously.

[0008] The present invention has been made to solve the above problems, and aims to provide a cheaper substance that increases eNAMPT in the body. [Means for solving the problem]

[0009] The substance that increases eNAMPT in the body according to the present invention is composed of a product obtained from a culture medium obtained by culturing the lactic acid bacterium Lactobacillus kefiranofaciens in a medium obtained by saccharifying rice.

[0010] In one example of the above-mentioned substance for increasing eNAMPT in the living body, the medium contains yeast extract.

[0011] In one embodiment of the substance for increasing eNAMPT in a living body according to claim 1 or 2, the product contains kefiran. Effect of the Invention

[0012] As described above, according to the present invention, a purified product is obtained from the culture medium obtained by culturing the lactic acid bacterium Lactobacillus kefiranofaciens in a medium obtained by saccharifying rice, thereby providing a cheaper substance that increases eNAMPT in the body. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a characteristic diagram showing changes in blood eNAMPT levels in mice following administration tests of a substance according to an embodiment of the present invention. [Diagram 2] FIG. 2 is a characteristic diagram showing changes in body weight in mice after administration of a substance according to an embodiment of the present invention. [Diagram 3] FIG. 3 is a characteristic diagram showing changes in adipose tissue mass in mice after administration of a substance according to an embodiment of the present invention. [Figure 4] FIG. 4 is a characteristic diagram showing changes in blood cholesterol levels in mice in a test in which the substance according to the embodiment was administered. [Diagram 5] FIG. 5 is a characteristic diagram showing changes in blood triglyceride levels in mice after administration of a substance according to an embodiment of the present invention. [Figure 6] FIG. 6 is a characteristic diagram showing changes in the amount of free fatty acids in the blood in mice administered with the substance according to the embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] The following describes a substance that increases eNAMPT in a living body according to an embodiment of the present invention. This substance that increases eNAMPT in a living body is composed of a product obtained from a culture solution obtained by culturing lactic acid bacteria Lactobacillus kefiranofaciens in a medium obtained by saccharifying rice. The medium may contain yeast extract. The product has been found to contain kefiran.

[0015] A more detailed explanation is given below. First, a tank with an internal volume of about 500 liters is prepared, and in this tank, 36 kg of rice flour is suspended in 216 liters of water, to which 2.8 kg of lactic acid is added, and the mixture is emulsified by heating to 121°C and stirring for 30 minutes. Next, pepsin is added to the emulsified liquid to hydrolyze the proteins contained therein (pH 1.8, 50°C, 4 hours). After this, glucoamylase is added to the hydrolyzed liquid to saccharify it (pH 4.5, 50°C, 1 hour), producing rice saccharified liquid (approximately 270 liters).

[0016] Next, 4 kg of yeast extract (1%), 400 ml (0.1%) of "Tween 80", 800 g (0.2%) of dipotassium hydrogen phosphate, 2 kg (0.5%) of sodium acetate, 800 g (0.2%) of citrate, 80 g (0.02%) of magnesium sulfate, 60 g (0.01%) of agar, and 130 liters of water are added to the rice saccharification liquid in the tank, and the lactic acid bacteria Lactobacillus kefiranofaciens is cultivated using this medium composition.

[0017] The culture conditions for Lactobacillus kefiranofaciens in the above medium are a temperature of 33°C, an agitation speed of 30 rpm, and a pH of 5.0. Sodium hydroxide (5N) is used to adjust the pH.

[0018] This cultivation was continued for 7 days, yielding 1630 mg / liter of culture solution. 150 kg of dextrin was added to the sterilized culture solution, and the solution was dried by spray drying to obtain a powder (product). Approximately 200 kg of powder (product) was obtained by drying. Analysis of the purified product from the obtained powder revealed that it contained a polysaccharide (kefiran) with a monosaccharide composition of glucose (1.0) and galactose (1.4).

[0019] Next, the results of an experiment using the substance that increases eNAMPT in the living body according to the present embodiment will be described. In this experiment, a test was performed by administering the substance according to the embodiment to mice (C57 / BL6J). The experiment was performed in five groups (five mice per group) as shown below.

[0020] Group 1: After one week of preliminary rearing, the animals were fed a normal diet for three weeks. Group 2: After a week of pre-breeding, the mice were fed a high-fat diet for three weeks. Third group: After one week of preliminary breeding, the mice are fed a high-fat diet together with the substance according to the embodiment at 10 mg / kg body weight / day for three weeks. Fourth group: After one week of preliminary breeding, the mice are fed a high-fat diet together with the substance according to the embodiment at 50 mg / kg body weight / day for three weeks. · Fifth group: After one week of preliminary breeding, the mice are fed a normal diet along with the substance according to the embodiment at 50 mg / kg of body weight / day for three weeks.

[0021] As a result of the experiment, the third, fourth and fifth groups had higher levels of eNAMPT in the blood compared to the first and second groups (Figure 1). In addition, the third, fourth and fifth groups had lower body weight compared to the second group (Figure 2). In addition, the third, fourth and fifth groups had lower adipose tissue mass compared to the second group (Figure 3).

[0022] Next, the results of another experiment will be described. In this experiment, a test was also conducted in which the substance according to the embodiment of the present invention was administered to mice (C57 / BL6J). The experiment was conducted by dividing the mice into the following five groups (five mice per group).

[0023] Group 1: After one week of preliminary rearing, the animals were fed a normal diet for five weeks. Group 2: After a week of pre-breeding, the mice were fed a high-fat diet for five weeks. Third group: After a week of preliminary breeding, the mice are fed a high-fat diet together with the substance according to the embodiment at 10 mg / kg body weight / day for five weeks. Fourth group: After a week of preliminary breeding, the mice are fed a high-fat diet together with the substance according to the embodiment at 50 mg / kg body weight / day for five weeks. Fifth group: After a week of preliminary breeding, the mice are fed a high-fat diet together with the substance according to the embodiment at 100 mg / kg body weight / day for five weeks.

[0024] In addition, in the third and fourth groups, the amount of cholesterol in the blood decreased (Figure 4), the amount of triglycerides in the blood decreased (Figure 5), and the amount of free fatty acids in the blood decreased (Figure 6).

[0025] As described above, it was confirmed that the substance that increases eNAMPT in the living body according to the embodiment increases the amount of eNAMPT in the blood. Furthermore, it was confirmed that the substance that increases eNAMPT in the living body according to the embodiment improves obesity. Obesity is a risk factor for various diseases such as diabetes, hypertension, and dyslipidemia. According to the World Health Organization (WHO), more than one billion people in the world are obese, and improving obesity is an urgent and important issue. It can be seen that the substance that increases eNAMPT in the living body according to the embodiment is useful for this measure.

[0026] The substance that increases eNAMPT in the body described above is obtained from a culture medium obtained by culturing lactic acid bacteria Lactobacillus kefiranofaciens in a medium obtained by saccharifying rice. By ingesting this substance, the amount of eNAMPT in the blood can be increased. Here, as described above, it has been found by analysis that the main component of the substance that is the active ingredient of the substance that increases eNAMPT in the body of the present invention is a polysaccharide containing kefiran.

[0027] However, it cannot be said that all polysaccharides, including Kefiran, have the effect of increasing the amount of eNAMPT in the blood as described above. On the other hand, it is considered impossible to completely specify (identify) the components of the product obtained from the culture solution obtained by culturing the lactic acid bacteria Lactobacillus kefiranofaciens in the medium obtained by saccharifying rice using the current analytical technology. Therefore, it is considered to be practical to directly specify the substance that increases eNAMPT in the living body by its structure or characteristics, such as by clearly specifying the components that contribute to the effect of the present invention.

[0028] As described above, according to the present invention, a purified product is obtained from the culture medium obtained by culturing the lactic acid bacterium Lactobacillus kefiranofaciens in a medium obtained by saccharifying rice, making it possible to provide a cheaper substance that increases eNAMPT in the body.

[0029] It should be noted that the present invention is not limited to the above-described embodiments, and it is apparent that many modifications and combinations can be made by a person having ordinary knowledge in the art within the technical concept of the present invention.

Claims

1. A substance that increases eNAMPT in the body, composed of a product obtained from a culture medium obtained by culturing the lactic acid bacterium Lactobacillus kefiranofaciens in a medium obtained by saccharifying rice.

2. The substance according to claim 1 which increases eNAMPT in a living body, The medium contains a yeast extract, which is a substance that increases eNAMPT in a living body.

3. The substance according to claim 1 or 2 that increases eNAMPT in a living body, The product is a substance that increases eNAMPT in the body, including kefiran.

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