JP5710091B2 - NO production promoter - Google Patents

Description

  The present invention relates to an immunostimulant containing an extract of a fruit of Matabi, and a food or drink containing the immunostimulant.

  In recent years, consumers' awareness of health has increased. On the other hand, in modern society, factors that damage the immune system, such as irregular lifestyles, dietary bias, and mental stress, are inundated. It is known that various illnesses such as cancer, infectious diseases, and allergic symptoms are induced by such a decrease in immunity. Conversely, by activating the immunity, carcinogenesis is suppressed and controlled. Various effects such as cancer action, anti-infection, anti-allergy action, recovery of physical condition rhythm, and maintenance of homeostasis can be expected.

  Many types of cells are involved in the immune system, but the role of leukocytes is particularly large, and macrophages are a type of important leukocytes that are involved in all stages, including the action in the early stages of the immune response. is there. For example, macrophages have the function of ingesting foreign substances such as bacteria and viruses that have entered the living body (phagocytic ability), and expressing the ingested antigen on the cell surface (antigen presentation ability). In recent years, the function of leukocytes has been elucidated at the substance level, and it has been found that the functions and intercellular interactions of leukocytes are borne by trace proteins (cytokines) secreted by leukocytes.

  There are many types of cytokines. Among them, inflammatory cytokines represented by tumor necrosis factor (TNF-α) are mainly released from macrophages. TNF-α production promotion is one of the indicators of immunostimulation, allergic diseases that are attributed to enhanced immune action against tumors, direct antitumor effect, and improved balance between Th1 and Th2 cells Improvement effects and immunostimulatory effects are known (see Patent Document 1). Conventionally, for example, an extract from a plant belonging to the genus Curiophyceae (see Patent Document 2) has been reported as having such a TNF-α production promoting action.

  Interferon (IFN) -γ is a cytokine that is produced by activated T cells and has a regulatory effect on the immune system. IFN-γ has an action of enhancing the antiviral action and antitumor action of IFN-α and β, and has an action of stimulating macrophages to phagocytose bacteria. The production promotion of IFN-γ is considered as one of the indicators of immunostimulation. Examples of those having such an activity of promoting IFN-γ production include conventionally plants of the genus Sendangsa or extracts thereof (Patent Document 3). Reference) etc. have been reported.

  Nitric oxide (NO) plays an important role in regulating blood pressure and the immune system, and macrophages produce NO in order to kill pathogens. NO is produced by nitric oxide synthase (NOS) using the guanidino group of L-arginine and molecular oxygen as a substrate, and immunity is activated through actions such as activation of helper T cells and promotion of synthesis of inflammatory cytokines. Work in the direction of increasing. Therefore, NO production promotion is considered as one of the indicators of immunostimulation, and examples of those having such NO production promotion action include herbal medicines such as tiger cane, jaundice, serpentine, malt, and extraction thereof. A thing (refer patent document 4) etc. are reported.

  In addition to the above, immunostimulatory action has been studied for many natural products, and several materials and extracts that have been found effective have already been put into practical use as raw materials for health foods and the like. However, some of these have insufficient immunostimulatory activity or have not been confirmed to be sufficiently safe, and thus have an excellent immunostimulatory action and high safety, At present, provision of immunostimulants that can be widely used for foods and drinks is still required.

JP 2007-131568 A JP 2004-107660 A JP 2005-298372 A JP 7-324039 A

  An object of the present invention is to solve the conventional problems and achieve the following objects. That is, the present invention has an excellent immunostimulatory action (NO production promoting action, TNF-α production promoting action, IFN-γ production promoting action, phagocytic ability activating action, etc.) and highly safe immune stimulation. It aims at providing the food / beverage products using the agent and the said immunostimulant.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that an extract of the fruit of Actinidia polygamama belonging to the genus Matatabi belongs to an excellent immunostimulatory action (NO production promoting action, TNF). -Α production promoting action, IFN-γ production promoting action, phagocytic ability activation action, etc.). Matabi ( Actinidia polygamama ) is a hermaphroditic deciduous plant that grows naturally in the mountains of Japan and also in the northern part of the Chinese continent from the Korean peninsula. In the Kampo field, it is used for the purpose of warming the body and for the purpose of analgesia. However, it has not been known so far that the fruit extract has an excellent immunostimulatory effect, which is a new finding by the present inventors.

The present invention is based on the above findings of the present inventors, and means for solving the above problems are as follows. That is,
<1> An immunostimulant characterized by containing an extract of a fruit of Matabi ( Actinidia polygam ).
<2> The immunostimulator according to <1>, which has at least one of NO production promoting action, TNF-α production promoting action, IFN-γ production promoting action, and phagocytic ability activating action.
<3> A food or drink comprising the immunostimulator according to any one of <1> to <2>.

  According to the present invention, conventional problems can be solved and the above-mentioned object can be achieved, and an excellent immunostimulatory action (NO production promoting action, TNF-α production promoting action, IFN-γ production promoting action, phagocytic activity) A highly safe immunostimulant and food and drink using the immunostimulant can be provided.

(Immunostimulator)
The immunostimulant of the present invention contains an extract of the fruit of Matabi, and further contains other components as necessary.

The immunostimulant has, as an immunostimulatory action, a nitric oxide (NO) production promoting action, a tumor necrosis factor (TNF) -α production promoting action, an interferon (IFN) -γ production promoting action, and a phagocytic ability activating action. It has at least any one of these.
Details of a substance that exerts at least one of NO production promoting action, TNF-α production promoting action, IFN-γ production promoting action, and phagocytic ability activating action, which is considered to be present in the extract of the fruit of the matabata Although it is unclear, it has not been known at all that the extract of the fruit of the matababi has these excellent actions and is useful as an immunostimulant, according to the present inventors. This is a new finding.

The matata ( Actinidia polygamama ) is a hermaphroditic deciduous plant belonging to the genus Matatabidae, which grows naturally in the mountain of Japan, and also inhabits the northern part of the Chinese continent from the Korean peninsula. For example, it is easily available from these areas. The fruit of the matababi is a berry, an oval shape or an oval shape, and the tip is thinned in a beak shape. The length is 2 to 2.5 cm, the diameter is about 1 cm, it is yellow-ripened, and has a pungent taste when eaten. Conventionally, the fruit of the matababi has been eaten raw or salted. In addition, there is a case where the matababi fruit fly parasitizes the above-mentioned matababi fruit, and there is a case where a bumpy surface with a bumpy surface can be formed. It has a warming action and an analgesic action, and has been conventionally used for medicinal liquors.
In the present invention, as the fruit of matatabi used as an extraction raw material, the above-described fruit itself may be used, or the one in the above-described state of an insect bump may be used.

  For example, the fruit of Matatabi, which is the raw material for extraction, can be subjected to solvent extraction as it is or after being dried or pulverized using a crusher. The drying may be performed, for example, in the sun or using a commonly used dryer. In addition, you may use the fruit of the said matababi as a raw material for extraction, after giving pretreatments, such as degreasing, with nonpolar solvents, such as hexane and benzene. By performing a pretreatment such as degreasing, the extraction treatment of the fruit of the matababi with a polar solvent can be performed efficiently.

  The extract of the fruit of the matabi can be easily obtained by utilizing a method generally used for extracting a plant. In addition, the extract of the matababi fruit includes an extract of the matababi fruit, a diluted or concentrated solution of the extract, a dried product of the extract, or a crudely purified product or a purified product thereof. included.

  There is no restriction | limiting in particular as a solvent used for the said extraction, According to the objective, it can select suitably, For example, water, a hydrophilic organic solvent, or these mixed solvents etc. can be used.

  The water that can be used as the extraction solvent is not particularly limited and can be appropriately selected depending on the purpose. For example, pure water, tap water, well water, mineral water, mineral water, hot spring water, spring water, fresh water, etc. In addition, those subjected to various treatments are included. Examples of the treatment applied to water include purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, and the like. The water that can be used as the extraction solvent includes purified water, hot water, ion exchange water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.

  The hydrophilic organic solvent is not particularly restricted and may be appropriately selected according to purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol and isopropyl alcohol; acetone, methyl ethyl ketone and the like Lower aliphatic ketones; C2-C5 polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, glycerin and the like, and a mixed solvent of these hydrophilic organic solvents and water can be used. . In addition, when using the mixed solvent of the said water and the said hydrophilic organic solvent, in the case of a lower alcohol, 1 mass part-90 mass parts with respect to 10 mass parts of water, and the water 10 in the case of a lower aliphatic ketone. It is preferable to use what mixed 1 mass part-40 mass parts with respect to the mass part. In the case of a polyhydric alcohol, it is preferable to use a mixture of 1 part by mass to 90 parts by mass with respect to 10 parts by mass of water.

When extracting an extract having at least one of NO production promoting action, TNF-α production promoting action, IFN-γ production promoting action, and phagocytic ability activating action, from the fruit of Matatabi which is the extraction raw material, It is not necessary to employ a simple extraction method, and the extraction can be performed using any extraction device at room temperature or under reflux heating.
Specifically, in the processing tank filled with the extraction solvent, the matababi fruit as an extraction raw material is added, and further, with occasional stirring as necessary, it is allowed to stand for 30 minutes to 2 hours to elute soluble components. Thereafter, the solid matter is removed by filtration, the extraction solvent is distilled off from the obtained extract, and the extract can be obtained by drying. The amount of the extraction solvent is usually 5 to 15 times (mass ratio) of the extraction raw material. The extraction conditions are usually about 1 to 4 hours at 50 to 95 ° C. when water is used as the extraction solvent. Moreover, when the mixed solvent of water and ethanol is used as an extraction solvent, it is normally 30 minutes-about 4 hours at 40 to 80 degreeC. In addition, the extract obtained by extracting with a solvent can be used as it is as an immunostimulator of the present invention as long as the extraction solvent is highly safe.

  In order to obtain a diluted liquid or concentrated liquid of the extracted liquid, a dried liquid of the extracted liquid, or a crudely purified or purified product thereof, the extract of the fruit of Matatabi obtained by the extraction is diluted and concentrated according to a conventional method. You may give processes, such as drying and refinement | purification. In addition, although the extract of the matababi fruit obtained can be used as it is as an immunostimulant, it is easier to use a concentrated solution or a dried product thereof. In obtaining the dried extract, a conventional method can be used, and carriers such as dextrin and cyclodextrin may be added to improve hygroscopicity. In addition, it is possible to carry out purification for the purpose of decolorization, deodorization and the like within a range that does not cause a decrease in the physiological activity of the extract of the matababi fruit, but there is no practical problem even if it is not purified. Specifically, purification can be performed by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like.

The extract of the fruit of Matatabi obtained as described above has at least one of NO production promoting action, TNF-α production promoting action, IFN-γ production promoting action, and phagocytic ability activating action. Based on these actions, it can be suitably used as an active ingredient of the immunostimulant of the present invention.
In addition, the content of the extract of the fruit of Matatabi in the immunostimulant is not particularly limited and can be appropriately selected depending on the purpose, and the immunostimulant is the fruit of Matatabi The extract itself may be used.

  In addition, other components other than the fruit of the matabavi that can be included in the immunostimulant are not particularly limited as long as they do not impair the effects of the present invention, and are appropriately selected according to the purpose. Examples thereof include a physiological saline solution for diluting the extract of the fruit of the matabata to a desired concentration. Moreover, there is no restriction | limiting in particular also in content of the said other component in the said immunostimulant, According to the objective, it can select suitably.

  Since the immunostimulant of the present invention has an excellent immunostimulatory action and is excellent in safety, it is suitable for use in, for example, the food and drink of the present invention described later.

(Food)
The food / beverage products of this invention contain the above-mentioned immunostimulant of this invention, and also contain another component suitably as needed.
Here, the food and drink are those which are less likely to harm human health and are taken by oral or gastrointestinal administration in normal social life. It is not limited to the category of products, etc., and means, for example, a wide range of foods that are taken orally, including general foods, health foods, health functional foods, quasi drugs, pharmaceuticals, and the like.
The food and drink may be a food supplement containing a matababi fruit extract as a main component of a matabi fruit extract so as not to interfere with its activity. There may be. In addition, the food or drink may be an extract of a fruit of Matabi.

  There is no restriction | limiting in particular as said food-drinks, According to the objective, it can select suitably, For example, drinks, such as a soft drink, a carbonated drink, a nutritive drink, a fruit drink, a lactic acid drink; Ice cream, ice sherbet, shaved ice, etc. Noodles such as buckwheat, udon, harusame, gyoza skin, sushi mai, Chinese noodles, instant noodles, etc. Sweets such as bread; crab, salmon, clams, tuna, sardines, shrimp, skipjack, mackerel, whale, oyster, saury, squid, red sea bream, scallops, abalone, sea urchin, crabs, tocobushi, etc .; kamaboko, ham, sausage Processed fishery and livestock products such as dairy products such as processed milk and fermented milk; salad oil, tempura oil, margarine, mayonnaise, and short nibs Fats and processed oils such as whipped cream and dressings; seasonings such as sauces and sauces; curry, stew, oyakodon, rice cakes, miso cooked rice, Chinese rice cakes, and rice cakes, tempura, eel rice cakes, coconut rice, oden Retort pouch foods such as beef bowl, meat sauce, egg soup, omelet rice, dumplings, shumai, hamburger, meatballs; various forms of health foods and nutritional supplements; pharmaceuticals such as tablets, capsules, drinks, troches, etc. Examples include foreign products.

There is no restriction | limiting in particular as said other component, According to the objective, it can select suitably, For example, the auxiliary | assistant raw material or additive etc. which are normally used in manufacturing the said food / beverage products are mentioned.
The auxiliary raw material or additive is not particularly limited and may be appropriately selected depending on the intended purpose. For example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, rubusoside, corn syrup, lactose, citric acid , Tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, Arabia Examples include gum, carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances, preservatives and the like.

  As content of the said immunostimulant in the said food / beverage products, it differs according to the kind of object food / beverage products, and cannot be prescribed unconditionally, For example, in the range which does not impair the original taste of food / beverage products When it is intended to be blended in any food or drink, the amount of the extract of the fruit of Matabi, which is an active ingredient, is preferably 0.001% by mass to 50% by mass, 0.01% by mass to 20% by mass. % Is more preferable. In addition, for example, for the purpose of producing dietary supplement foods and drinks in the form of granules, tablets, capsules and the like, which are mainly composed of an extract of the fruit of the matababi, As a quantity, 0.01 mass%-100 mass% are preferable, and 5 mass%-100 mass% are more preferable.

(effect)
The immunostimulant of the present invention and the food and drink of the present invention can be orally ingested on a daily basis, and the action of the extract of the fruit of Matabi, which is an active ingredient, promotes NO production, TNF-α Immunostimulatory effects such as production promoting action, IFN-γ production promoting action, and phagocytic ability activating action can be exhibited extremely effectively. Therefore, the immunostimulant of the present invention and the food and drink of the present invention are widely effective for, for example, increasing the decreased immunity of the elderly and sick who have been weakened, and preventing or early treatment of the disease. It is thought that. In addition, although the immunostimulant of this invention and the food-drinks of this invention are applied suitably with respect to a human, as long as each effect is show | played, animals other than a human (for example, mouse | mouth) , Rat, hamster, dog, cat, cow, pig, monkey, etc.). Moreover, the immunostimulant of this invention and the food-drinks of this invention use the extract of the fruit of a natural origin matababi as an active ingredient, and are advantageous also in the point which is excellent in safety | security.

  Examples of the present invention will be described below, but the present invention is not limited to these examples.

(Production Example 1)
-Manufacture of hot water extract of matatabi fruit-
As a raw material for extraction, 100 g of pulverized material of Matatabi fruit was put into 1000 mL of hot water, kept at 90 ° C. for 2 hours with stirring, and then filtered. The filtrate was concentrated under reduced pressure at 60 ° C. and further dried with a vacuum dryer to obtain an extract (powder). The yield of the obtained extract is shown in Table 1.

(Production Example 2)
-Manufacture of 30% by mass (50% by mass, 70% by mass) ethanol extract of fruit of Matatabi-
As a raw material for extraction, 100 g of pulverized material of Matabi was added to 1000 mL of 30% by mass ethanol (mass ratio of water to ethanol: 7: 3), kept at 80 ° C. for 2 hours with stirring, and then filtered. The filtrate was concentrated under reduced pressure at 60 ° C. and further dried with a vacuum dryer to obtain an extract (powder). Further, instead of 30% by mass ethanol, 50% by mass ethanol (mass ratio of water and ethanol is 1: 1) or 70% by mass ethanol (mass ratio of water and ethanol is 3: 7) Similarly, each extract (powder form) was obtained. The yield of each extract obtained is shown in Table 1.

(Example 1)
-Nitric oxide (NO) production promoting test-
Using each matatabi fruit extract of Production Examples 1 and 2 as a test sample, the nitric oxide (NO) production promoting effect was tested by the following test method.
Mouse macrophage cells (RAW264.7) were cultured using Dulbecco's MEM containing 10% FBS, and then the cells were collected with a cell scraper. The collected cells were diluted with 10% FBS-containing phenol red-free Dulbecco's MEM to a concentration of 3.0 × 10 ⁶ cells / mL, and then seeded at 100 μL per well on a 96-well plate and cultured for 4 hours. After completion of the culture, the medium was removed, 50 μL of each concentration of test sample dissolved in 10% FBS-containing phenol red-free Dulbecco MEM containing a final concentration of 0.5% DMSO was added to each well, and cultured for 48 hours. Further, as a control, no test sample was added, and only 10% FBS-containing phenol red-free Dulbecco MEM containing a final concentration of 0.5% DMSO was added, and the same experiment was performed.
The amount of NO production was measured using the amount of nitrite ion (NO ₂ ⁻ ) as an index. After completion of the culture, the same amount of grease reagent (1% sulfanilamide, 0.1% N-1-naphthylethylenedihydride in 5% phosphoric acid solution) is added to the culture medium of each well and reacted at room temperature for 10 minutes. did. After the reaction, absorbance at a wavelength of 540 nm was measured. A calibration curve was prepared using NO ₂ ⁻ as an index, and the amount of NO produced in the culture supernatant was determined. The results are shown in Table 2.

  From the results of Table 2, a very strong NO production promoting action was observed in any of the matababi fruit extracts. In addition, the action was particularly strong in the 30% by mass ethanol extract of the matababi fruit.

( Reference Example 2)
-Tumor necrosis factor (TNF-α) production promoting action test-
Using each matababi fruit extract of Production Examples 1 and 2 as a test sample, the tumor necrosis factor (TNF-α) production promoting effect was tested by the following test method.
Mouse macrophage cells (RAW264.7) were cultured using Dulbecco's MEM containing 10% FBS, and then the cells were collected with a cell scraper. The collected cells were diluted with Dulbecco's MEM containing 10% FBS to a concentration of 1.0 × 10 ⁶ cells / mL, then seeded at 100 μL per well on a 96-well plate, and cultured for 4 hours. After completion of the culture, 100 μL of each concentration of test sample dissolved in 10% FBS-containing Dulbecco MEM containing a final concentration of 0.5% DMSO was added to each well and cultured for 24 hours. Further, as a control, a test sample was not added, and only a 10% FBS-containing Dulbecco MEM containing a final concentration of 1% DMSO was added, and the same experiment was performed.
After completion of the culture, the amount of TNF-α in the culture supernatant of each well was measured using a sandwich ELISA method. The results are shown in Table 3.

  From the results of Table 3, a very strong TNF-α production promoting action was observed in any of the matababi fruit extracts.

(Example 3)
-INF-γ production promoting action test-
Using each matatabi fruit extract of Production Examples 1 and 2 as a test sample, the INF-γ production promoting action was tested by the following test method.
Spleen cells were removed from C57BL / 6 mice (7 weeks old, female), and dispensed 6 × 10 ⁵ cells / 100 μL / well into 96-well microplates using RPMI1640 + 10% FBS culture solution. Further, 100 μL of concanavalin A added at a final concentration of 0.2 μg / mL to RPMI1640 + 10% FBS culture solution in which the test sample was dissolved at each concentration was added to each well at 37 ° C., 5% CO _2. The cells were cultured for 3 days. In addition, as a control, a test sample was not added, and the same experiment was carried out by adding only RPMI1640 + 10% FBS culture medium added with concanavalin A to a final concentration of 0.2 μg / mL. .
Thereafter, 150 μL each of the culture solution was collected, and the amount of IFN-γ produced was measured using the culture solution using a mouse Interferon gamma (IFN-γ) ELISA system (amersham pharmacia biotech). The IFN-γ production promotion rate was calculated by the following formula 1. The results are shown in Table 4.
[Formula 1]
IFN-γ production promotion rate (%) = (A / B) × 100
A: IFN-γ production amount during sample treatment B: IFN-γ production amount when sample is not treated

  From the results of Table 4, a very strong IFN-γ production promoting action was observed in any of the matababi fruit extracts.

( Reference Example 4)
-Test for phagocytic activation-
Using each matatabi fruit extract of Production Examples 1 and 2 as a test sample, the phagocytic ability activation action was tested by the following test method.
Murine macrophage cells (RAW264.7) were cultured using Dulbecco's MEM containing 10% FBS, and then the cells were collected with a cell scraper. The recovered cells were seeded on a ^6- well plate in an amount of 1.5 × 10 ⁶ cells / well and cultured for 1 hour. After completion of the culture, 200 μL of a test sample dissolved in 10% FBS-containing Dulbecco MEM containing a final concentration of 0.5% DMSO was added to each well and cultured for 4 hours. After completion of the culture, the medium was removed, 1.0 mL of fresh 10% FBS-containing Dulbecco MEM was added to each well, and 10 μL of diluted fluorescent beads (Fluoresbrite YG carboxylate microspheres, 2 μm; Polyscience) was added to each well. The 6-well plate was cultured with shaking at 37 ° C. for 1 hour. After completion of the culture, the medium was removed, and 1 mL of 0.1% NaN ₃ was added to stop the reaction. Next, after washing with 1 mL of PBS, the cells were photographed under a microscope. The number of cells that phagocytosed the beads in each well was visually counted for 2 visual fields per well, and the phagocytic activation rate was calculated by the following formula 2. The results are shown in Table 5.
[Formula 2]
貪 Eating ability activation rate (%) = A / B × 100
A: Bead phagocytic cell rate when test sample is added B: Bead phagocytic cell rate when no test sample is added In addition, in the above formula 2, the phagocytic activation rate when no test sample is added (control) is 100%.

  From the results of Table 5, a very strong phagocytic activity activating effect was observed in any of the matababi fruit extracts. In addition, the action was particularly strong in the 30% by mass ethanol extract of the matababi fruit.

  From the results of Examples 1 to 4, the extract of the fruit of Matabi is the NO production promoting action, the TNF-α production promoting action, the IFN-γ production promoting action, and the phagocytic activation, which are indicators of the immunostimulatory action. In each evaluation of the action, it was found to have a very strong action. From this, it was suggested that the extract of the fruit of Matabi was very useful as an immunostimulant and could be widely used for health foods, nutritional supplements and the like for the purpose of enhancing immunity.

(Formulation Example 1)
-Tablet dietary supplements-
The following mixture was tableted to produce a tablet-shaped dietary supplement.
-Hot water extract of the fruit of Matatabi of Production Example 1 11% by mass
・ Powdered sugar (sucrose): 52% by mass
・ Guar gum decomposition product: 33% by mass
・ Glycerin fatty acid ester: 4% by mass

(Formulation Example 2)
-Granular dietary supplement-
The following mixture was formed into granules to produce a dietary supplement.
-Hot water extract of fruit of Mata tabi in Production Example 1 6.7% by mass
・ Beat oligosaccharide: 59.3 mass%
・ Vitamin C: 33.3% by mass
-Stevia extract: 0.7% by mass

  The immunostimulant of the present invention contains an extract of the fruit of Matabi, and has at least one of an excellent NO production promoting action, a TNF-α production promoting action, an IFN-γ production promoting action, and a phagocytic ability activating action. It has excellent safety. Therefore, the immunostimulant of the present invention can be widely used for health foods, dietary supplements, and the like for the purpose of enhancing the decreased immunity of, for example, the elderly and sick who have been weakened.

Claims (1)

The NO production promoter characterized by containing the 30 mass% ethanol extract of the fruit of a matabi (Actinidia polygamama).