JP6961237B2 - Composition for promoting expression of brain-derived neurotrophic factor - Google Patents

Description

The present invention relates to a composition for promoting expression of brain-derived neurotrophic factor. Hereinafter, the composition for promoting the expression of brain-derived neurotrophic factor will be referred to as the composition for promoting the expression of brain-derived neurotrophic factor.

As described in Non-Patent Document 1, the brain-derived neurotrophic factor is a neurotrophic factor that controls the differentiation and growth of neural precursor cells and the promotion of neurite outgrowth. Increased brain-derived neurotrophic factors in the brain improve memory, prevent and improve depression, improve glucose and lipid metabolism, suppress appetite, reduce stroke-induced brain injury and sequelae, suppress chronic pain, post-stroke Function such as promotion of recovery of motor function or enhancement of viability occurs. As a substance that promotes the expression of brain-derived neurotrophic factor, for example, epinephrine, which is a hormone secreted from the adrenal medulla, is known.

Rakuwakai Hospital Medical Magazine Vol. 28: 7-24, 2017

The present invention was made based on the fact that, as a result of diligent research by the present researchers, it was newly found that a component contained in a specific algal body exerts an action of promoting the expression of brain-derived neurotrophic factor. It is a thing. An object of the present invention is to provide a novel composition for promoting brain-derived neurotrophic factor.

The composition for promoting brain-derived neurotrophic factor that solves the above problems is a composition for promoting brain-derived neurotrophic factor that promotes the expression of brain-derived neurotrophic factor, and is a composition for promoting brain-derived neurotrophic factor. It contains an extract of algae belonging to the genus Chinorimo, the genus Stigonema, the genus Nostocopsis, the genus Nenjumo, the genus Trebouxiophyceae, and the genus Chlorella, the genus Trebouxiophyceae.

In the above composition for promoting nerve growth factor, the extract is preferably an extract using an organic solvent or a mixed solvent of an organic solvent and water as an extraction solvent.
In the above composition for promoting neurotrophic factors derived from the brain, the algae are preferably those belonging to the genus Nostocales, the genus Nostocales, the genus Nostocales, and the genus Nostocales.

According to the present invention, a novel brain-derived neurotrophic factor promoting composition is provided.

The graph which shows the relationship between the type of algae and the amount of BDNF (brain-derived neurotrophic factor) production.

Hereinafter, the composition for promoting brain-derived neurotrophic factor of the present invention will be described. In the following, the brain-derived neurotrophic factor will be referred to as "BDNF", and the brain-derived neurotrophic factor promoting composition will be referred to as "BDNF promoting composition".

The composition for promoting BDNF is an alga belonging to the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Trebouxiophyceae. It contains an extract of (described as a specific alga) or a dimethylsulfoxide-soluble component of a specific alga as an active ingredient.

Among the specific algae, it is preferable to use the algae belonging to the genus Nostocales, the genus Nostocales, the genus Nostocales, and the genus Nostocales.
Examples of algae belonging to the order Nitzschia are Nitzschia filiformis, Nitzschia frustulum, Nitzschia levidensis, and Nitzschia levidensis. Miss (Nitzschia scalpeliformis), Nitzschia martiana, Nitzschia pungens, Nitzschia tenuiarcuata, Nitzschia tenuiarcuata, Pseudo Nitzschia multistrinita ), Phaeodactylum triconutum (Phaeodutylum triconutum) of the genus Pheodactylum.

Examples of algae belonging to the genus Porphyridium purpureum, Porphyridium aerugineum, and Porphyridium sordidum include Porphyridium purpureum, Porphyridium aerugineum, and Porphyridium sordidum.

Examples of algae belonging to the genus Nostochopsis of the order Cyanobacteria include Nostochopsis lobatus and Nostochopsis wichmannii.

Examples of Nostoc commune, Nostoc flagelliforme, Nostoc sphaericum, Nostoc velcosm (Nostoc commune), Nostoc flagelliforme, Nostoc sphaericum, Nostoc, etc. verrucosum), Nostoc linckia, Nostoc muscorum, Nostoc punctiforme.

Examples of the algae belonging to the genus Chlorella of the order Chlorella algae include Chlorella pyrenoidosa, Chlorella sorokiniana, and Chlorella lobophora.

The specific algae may be naturally occurring algae or artificially cultivated algae. It is industrially preferable to use artificially cultured algae from the viewpoints of stable supply and easy quality maintenance.

The compounding form of the specific algae in the BDNF promoting composition is not particularly limited, and for example, the state as it is collected, the state of being crushed after collection, the state of being dried after collection, the state of being crushed and dried after collection. It may be in any of the processed states. In addition, the specific algae may be blended in the form of an extract.

As the extraction solvent for extracting the extract from the specific algae, for example, an organic solvent and a mixed solvent of the organic solvent and water can be used. Examples of the organic solvent include lower alcohols having 1 to 5 carbon atoms, methyl acetate, ethyl acetate, hexane, cyclohexane, dimethylsulfoxide, acetonitrile, acetone, glycerin, propylene glycol, dimethyl ether, diethyl ether and dichloromethane. Examples of the lower alcohol include methanol, ethanol, 1-propanol, 2-propanol (isopropanol), 1-butanol and 2-butanol.

Further, as the organic solvent, a single species may be used, or a mixed solvent in which a plurality of species are mixed may be used. When a mixed solvent of water and an organic solvent is used as the extraction solvent, the content of the organic solvent in the mixed solvent is preferably 50% by volume or more, more preferably 80% by volume or more. Further, additives such as organic salts, inorganic salts, buffers, emulsifiers and the like may be dissolved in the extraction solvent.

As the extraction method for extracting the extract from the specific algae, any known extraction method, for example, cold extraction, room temperature extraction, or heat extraction may be used. The extraction temperature can be appropriately set according to the type of solvent, extraction efficiency, deterioration of components, and the like.

The extraction operation is performed by immersing a specific algae as a raw material in an extraction solvent for a predetermined time. At that time, the concentration of the specific algae in the extraction solvent can be appropriately set according to the type of the extraction solvent, the extraction efficiency, the efficiency of the concentration treatment after the extraction, and the like. In such an extraction operation, in order to improve the extraction efficiency, further treatments such as stirring treatment, pressure treatment, and ultrasonic treatment may be performed, if necessary.

Further, the extraction operation may be performed only once for the same specific algae, or may be repeated a plurality of times. Then, the solid-liquid separation operation is performed after the extraction operation to separate the extract (extract) and the residue of the specific algae. As a method of solid-liquid separation operation, a known separation method such as filtration or centrifugation can be used. Moreover, the obtained extract (extract) may be concentrated or dried if necessary.

Next, the action of the BDNF promoting composition will be described.
The extract of the specific algae contained in the composition for promoting BDNF or the dimethyl sulfoxide-soluble component of the specific algae has an action of promoting the expression of BDNF in vivo.

Here, BDNF is a neurotrophic factor that controls the differentiation and growth of neural precursor cells and the promotion of neurite outgrowth. When BDNF increases in the brain, it prevents and improves depression, improves glucose and lipid metabolism, suppresses appetite, reduces cerebral injury and sequelae due to stroke, suppresses chronic pain, promotes recovery of motor function after stroke, etc. Enhancement of function or viability occurs.

Therefore, the BDNF promoting composition is used for promoting the expression of BDNF, for example, prevention and improvement of depression, improvement of glucose / lipid metabolism, suppression of appetite, reduction of brain injury and sequelae due to stroke, suppression of chronic pain. , Can be applied to the purpose of promoting recovery of motor function after stroke. The BDNF-promoting composition can be applied as a food or drink, a pharmaceutical product, a quasi-drug, or a reagent for experiments or research.

Foods and drinks include, for example, various beverages (beverages containing fruit juice or vegetable juice, soft beverages, mineral beverages, sports drinks, tea beverages, coffee, carbonated beverages, dairy products such as milk and yogurt), jelly-like foods ( Jelly, agar, jelly-like beverages, etc.), capsules (soft capsules, hard capsules), and various confectioneries. Foods and drinks include gelling agents such as pectin and carrageenan, sugars and sweeteners such as glucose, sucrose, fructose, lactose, stevia, aspartame, and sugar alcohols, food additives such as fragrances, vegetable fats and oils, and animal fats and oils. It is possible to appropriately contain fats and oils such as. The use of foods and drinks is not particularly limited, and is used as so-called general foods, health foods, functional foods, nutritionally functional foods, dietary supplements, supplements, foods for specified health use, foods with functional claims, and foods for the sick. Can be applied.

The administration method when used as a drug or quasi-drug is not particularly limited. Specific administration methods include, for example, administration by administration (oral ingestion), intravascular administration, enteral administration, transdermal administration, and intraperitoneal administration. The dosage form when used as a drug or quasi-drug is not particularly limited. Specific dosage forms include, for example, powders, powders, granules, tablets, capsules, pills, suppositories, liquids and injections. Further, as the additive, for example, an excipient, a base, an emulsifier, a solvent, a stabilizer and the like may be contained.

Next, the effect of the BDNF promoting composition will be described.
(1) The BDNF promoting composition contains an extract of a specific algae or a dimethyl sulfoxide-soluble component of the specific algae as an active ingredient.

According to the above configuration, the effect of promoting the expression of BDNF in the living body can be obtained.
(2) The specific algae are preferably those belonging to the genus Nostocales, Nostocales, Nostocales, Nostocales, Nostocales, Nostocales, Nostocales, Nostocales.

In this case, the effect of promoting the expression of BDNF in the living body is more remarkable.
In addition, this embodiment can be implemented by changing as follows. The present embodiment and the following modified examples can be implemented in combination with each other within a technically consistent range.

-The BDNF promoting composition may contain other components as long as the desired action is not impaired.
-The intake amount and the intake period of the BDNF promoting composition are not particularly limited, and are appropriately determined in consideration of the state of physical function of the ingestor, age, gender, and other conditions.

-The BDNF promoting composition can be applied not only to humans but also to feeds, drugs and the like for domestic animals such as livestock.
Next, the technical idea that can be grasped from the above-described embodiment and modified example will be described.

(B) A composition for promoting brain-derived neurotrophic factors that promotes the expression of brain-derived neurotrophic factors. A composition for promoting neurotrophic factors derived from the brain, which comprises a dimethylsulfoxide-soluble component contained in an alga belonging to the genus Nenjumo, Trebouxiophyceae, Chlorella, as an active ingredient.

(B) Organic solvents for algae belonging to the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Nostoc, the genus Chlorella, the genus Chlorella, the genus Chlorella, the genus Nostoc, the genus Chlorella. Alternatively, a method for producing a composition for promoting brain-derived neurotrophic factor, which comprises an extraction step of performing an extraction treatment using a mixed solvent of an organic solvent and water.

(Preparation of algae sample solution)
1000 μl of dimethyl sulfoxide was added to 0.0106 g of the algae dry powder shown in the algae column of Table 1, and the mixture was stirred with a vortex mixer for 5 minutes and then centrifuged (3000 rpm, 5 minutes). The supernatant after the treatment was filtered and sterilized using a 0.22 μm filter, and this was used as the algae sample solution of Test Examples 1 to 12.

(BDNF production test)
Mouse-derived 3T3-L1 (mouse fibroblast JCRB9014) cells were cultured in Dulbecco's modified Eagle's medium containing 0.5% bovine serum albumin (protease-free). After 24 hours, the medium was exchanged, and the algae sample solution of the test example was added to the medium to a concentration of 5 μl / ml, and the culture was continued. After 24 hours, the medium was collected and centrifuged (5200 xg, 15 minutes). The supernatant after the treatment was collected.

As a control example 1, dimethyl sulfoxide was added to the medium so as to have a concentration of 5 μl / ml instead of the algae sample solution, and the same treatment was carried out, and the supernatant was recovered. In addition, as a control example 2, instead of the algae sample solution, epinephrine, which is a substance that promotes the expression of BDNF, was added to the medium so as to have a concentration of 30 μg / ml, and the same treatment was performed to prepare the supernatant. Recovered.

The amount of BDNF (BDNF production amount) contained in the obtained supernatant was measured using a commercially available measurement kit (BDNF Emax ImmunoAssay System manufactured by Promega). The results are shown in the BDNF production amount column of Table 1 and the graph of FIG. Then, the action of promoting BDNF expression in the algae sample solution of each test example was evaluated. The results are shown in the evaluation column of Table 1. In the evaluation column of Table 1, when the amount of BDNF produced is higher than that of Control Example 1 and there is a significant difference from the amount of BDNF produced in Control Example 1 (p value is less than 0.05), it is "○". Cases other than are indicated by "x".

珪藻綱羽状目の藻体（試験例１）、原始紅藻綱チノリモ目チノリモ属の藻体（試験例４）、藍藻綱スチゴネマ目ノストコプシス属の藻体（試験例８）、藍藻綱ネンジュモ目ネンジュモ属の藻体（試験例９〜１０）、トレボウクシア藻綱クロレラ目クロレラ属の藻体（試験例１１）の藻体試料液は、エピネフリンと同様にＢＤＮＦの発現を促進する作用を示した。

Algae of the order Feathered Algae (Test Example 1), Algae of the genus Nostoc of the order Primordial Red Algae (Test Example 4), Algae of the genus Nostocpsis of the order Algae (Test Example 8), Nostoc of the order Algae The algae sample solutions of Nostoc algae (Test Examples 9 to 10) and Trebouxia algae Chlorella order Chlorella algae (Test Example 11) showed an action of promoting the expression of BDNF in the same manner as epinephrine.

In particular, algae of the order Nostocales (Test Example 1), algae of the genus Nostocales of the order Red algae (Test Example 4), and algae of the genus Nostocles of the order Cyanobacteria (Test Examples 9 to 10). The algae sample solution showed an action of promoting the expression of BDNF more remarkably.

On the other hand, algae of the genus Dunariella of the order Oohigemawari (Test Example 2), algae of the genus Preurocrisis of the order Hapto algae, the algae of the genus Preurocrisis (Test Example 3), and the algae of the genus Desmodesmus of the order Yokowamidoro (Test Example 5). Algae sample solution of Algae (Test Example 6), Algae (Test Example 6), Algae (Test Example 7), Algae (Test Example 7), Algae (Test Example 12) Did not show any effect of promoting the expression of BDNF.

Claims (3)

A brain-derived neurotrophic factor expression promoting composition for promoting the expression of brain-derived neurotrophic factor,
Contains algae extracts selected from Porphyridium purpureum, Nostochopsis lobatus, Nostoc commune, and Nostoc flagelliforme as active ingredients. A composition for promoting the expression of brain-derived neurotrophic factor, which is characterized by the fact that The composition for promoting expression of brain-derived neurotrophic factor according to claim 1, wherein the extract is an extract using an organic solvent or a mixed solvent of an organic solvent and water as an extraction solvent. Claim 1 or claim 1, wherein the algae is an alga selected from Porphyridium purpureum, Nostoc commune, and Nostoc flagelliforme. The composition for promoting the expression of brain-derived neurotrophic factor according to claim 2.

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