JP2019137681A - Composition for promoting mesenchymal stem cell growth and composition for improving cognitive function - Google Patents

Abstract

To provide new means that contributes to effective utilization of mesenchymal stem cells.SOLUTION: The present invention provides a composition for promoting mesenchymal stem cell growth and a composition for improving a cognitive function, containing one or more food selected from the group consisting of beta-carotene containing food, rutin-containing food, anthocyanin-containing food and flavonol-containing food as an active ingredient; and a composition for promoting mesenchymal stem cell growth and a composition for improving the cognitive function, containing one or more material selected from the group consisting of beta-carotene, rutin, anthocyanin and flavonol as an active ingredient.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a composition for promoting proliferation of mesenchymal stem cells, in particular, proliferation of mesenchymal stem cells in vivo, and a composition for improving cognitive function of mammals, particularly humans.

  In today's rapidly aging society, the decline in cognitive function among the elderly is a social problem. The decline in function due to so-called dementia caused by Alzheimer's disease or the like is not only a decrease in the patient's QOL, but also causes an increase in the burden on the surroundings such as nursing care and an increase in medical expenses. In addition, even a relatively mild decline in cognitive function associated with natural aging can cause various obstacles in the daily life of the person, and the effect can be more serious with aging. Therefore, from the viewpoint of reducing social welfare costs such as medical expenses and improving the QOL of the subject, there is high expectation for means that can prevent or improve cognitive function.

  For patients who have been diagnosed with medical dementia, indications such as donepezil and galantamine, which exhibit acetylcholinesterase inhibitory action, have been applied. However, treatment with these drugs is symptomatic and has side effects.

  Ginkgo biloba flavonoid glycosides and terpene lactones (enhanced utilization of cholinergic neurotransmitters) and chicken-derived plasmalogens (promoting the development of hippocampal neurons) as functional ingredients in foods effective for improving cognitive function , Suppression of amyloid β accumulation, neuroinflammation, DHA derived from fish and auranthiochytrium (promoting neurogenesis in the hippocampus, suppression of amyloid β protein aggregation, synaptic membrane fluidity NMDA (N- Methyl-D-aspartate) receptor activation, promotion of oxygen supply to the brain by increasing cerebral blood flow), soybean-derived phosphatidylserine (activation of NMDA-type glutamate receptor of phosphatidylserine-derived D-serine), etc. Has been reported and is sold as a functional food.

  On the other hand, regenerative medicine using mesenchymal stem cells (MSCs) has been proposed as an effective means for treating or improving damaged brain function. For example, mesenchymal stem cells collected from living organisms and cultured and expanded outside the body can be systemically administered intravenously to various neurological disease model animals and humans to improve sequelae of cerebral infarction and spinal cord injury (Non-Patent Documents 1 to 5 as examples). However, preparation of mesenchymal stem cells for administration requires special equipment, and in the case of autologous transplantation, mesenchymal stem cells need to be collected and cultured from the patient before administration. Administration of mesenchymal stem cells remains in the treatment of patients who have already developed symptoms. Even in so-called chronic diseases that gradually develop and have a long course, such as neurodegenerative diseases and chronic inflammatory diseases, mesenchymal stem cells have various effects such as tissue repairing action, anti-inflammatory action, and fibrosis-suppressing action. Is expected to contribute to prevention of onset and suppression of disease progression, but therapeutically administering mesenchymal stem cells to those suffering from these diseases before their clear symptoms appear, and Prophylactic administration of mesenchymal stem cells to those who are likely to suffer from these diseases is not realistic in terms of difficulty in finding the subject and economics.

Iihoshi S. et al., Brain Res. 2004; 1007: 1-9. Nomura T. et al., Neuroscience. 2005; 136: 161-169. Honma T. et al., Exp. Neurol. 2006; 199: 56-66. Honmou O. et al., Brain. 2011; 134: 1790-1807. Morita T. et al., Neuroscience. 2016; 335: 221-31.

  An object of the present invention is to provide a new means that contributes to effective use of mesenchymal stem cells, particularly mesenchymal stem cells present in vivo.

The present inventors have found a new finding that a food containing a specific component promotes the proliferation of mesenchymal stem cells in vivo, and that the food improves cognitive function, and has completed the following invention. It was.
(1) A mesenchymal stem cell proliferation promoting composition containing, as an active ingredient, one or more foods selected from the group consisting of β-carotene-containing foods, rutin-containing foods, anthocyanin-containing foods, and flavonol-containing foods.
(2) The composition according to (1), wherein the β-carotene-containing food is carrot.
(3) The composition according to (1), wherein the rutin-containing food is tartary buckwheat.
(4) Anthocyanin-containing foods include tea variety San Rouge (variety registration No. 21262) and its varieties, potato variety shadow queen (variety registration No. 17574) and its varieties, and potato variety Northern Ruby (variety registration No. 17447) And a composition selected from the group consisting of the strains thereof.
(5) The composition according to (1) or (4), wherein the aglycone of anthocyanin is delphinidin, cyanidin, petunidin or pelargonidin.
(6) The composition according to (1), wherein the flavonol-containing food is tea cultivar Saint Rouge (variety registration No. 21262) or tea of its cultivar.
(7) The composition according to (1) or (6), wherein the flavonol is myricetin, kaempferol or quercetin.
(8) A composition for improving cognitive function comprising, as an active ingredient, one or more foods selected from the group consisting of β-carotene-containing foods, rutin-containing foods, anthocyanin-containing foods, and flavonol-containing foods.
(9) The composition according to (8), wherein the β-carotene-containing food is carrot.
(10) The composition according to (8), wherein the rutin-containing food is tartary buckwheat.
(11) Anthocyanin-containing foods include tea cultivar Saint Rouge (variety registration No. 21262) and its varieties, potato variety shadow queen (variety registration No. 17574) and its varieties, and potato varieties Northern Ruby (variety registration No. 17447) ) And its strain varieties, the composition according to (8).
(12) The composition according to (8) or (11), wherein the aglycone of anthocyanin is delphinidin, cyanidin, petunidin or pelargonidin.
(13) The composition according to (8), wherein the flavonol-containing food is tea cultivar Saint Rouge (variety registration No. 21262) or tea of its cultivar.
(14) The composition according to (8) or (13), wherein the flavonol is myricetin, kaempferol or quercetin.
(15) A mesenchymal stem cell proliferation promoting composition containing, as an active ingredient, one or more substances selected from the group consisting of β-carotene, rutin, anthocyanin and flavonol.
(16) The composition according to (15), wherein the aglycone of anthocyanin is delphinidin, cyanidin, petunidin or pelargonidin.
(17) The composition according to (15), wherein the flavonol is myricetin, kaempferol or quercetin.
(18) A composition for improving cognitive function comprising, as an active ingredient, one or more substances selected from the group consisting of β-carotene, rutin, anthocyanin and flavonol.
(19) The composition according to (18), wherein the aglycone of anthocyanin is delphinidin, cyanidin, petunidin or pelargonidin.
(20) The composition according to (18), wherein the flavonol is myricetin, kaempferol or quercetin.

  The mesenchymal stem cell proliferation promoting composition of the present invention can increase the number of mesenchymal stem cells in the body of a mammal administered or ingested, thereby preventing various diseases and / or Expected to exert therapeutic effects. Moreover, the mesenchymal stem cell proliferation promoting composition of the present invention can increase the number of cells by culturing mesenchymal stem cells in an appropriate medium containing the composition. An increase in the number of cells in the culture of mesenchymal stem cells is advantageous in the production of a medicament containing mesenchymal stem cells. Furthermore, the composition for improving cognitive function of the present invention can improve the cognitive function of a mammal administered or ingested.

It is a graph which shows the number of mesenchymal stem cells in 1 mL of bone marrow or peripheral blood in rats fed with carrot-containing food, sun rouge-containing food, tartary buckwheat-containing food or shadow queen-containing food for 10 weeks. It is a graph which shows the number of mesenchymal stem cells in the bone marrow in a rat fed with carrot-containing food, sunrouge-containing food, northern ruby-containing food, shadow queen-containing food or tartary buckwheat-containing food for 10 weeks, or administered β-carotene. It is a graph which shows the result of the novel object recognition test and the Morris water maze test in the rat which took carrot juice for 5 weeks. It is a graph which shows the number of mesenchymal stem cells in 1 mL of bone marrow or peripheral blood in a rat ingested with carrot juice for 5 weeks. It is a graph which shows the result of the novel object recognition test and the Morris water maze test in the rat ingested the carrot containing feed, the sun rouge containing feed, the tartary buckwheat containing feed or the shadow queen containing feed for 5 weeks. It is a graph which shows the number of mesenchymal stem cells in 1 mL of bone marrow or peripheral blood in a rat fed with carrot-containing food, sun rouge-containing food, tartary buckwheat-containing food or shadow queen-containing food for 5 weeks.

  The present invention relates to a mesenchymal stem cell proliferation promoting composition containing, as an active ingredient, one or more foods selected from the group consisting of β-carotene-containing foods, rutin-containing foods, anthocyanin-containing foods, and flavonol-containing foods. .

  A mesenchymal stem cell is a stem cell having pluripotency and self-renewal ability present in stromal cells of mesenchymal tissue. It is known that mesenchymal stem cells not only differentiate into cells belonging to the mesenchymal system such as osteoblasts, chondrocytes, fat cells, and muscle cells, but also differentiate into neurons and liver cells beyond the germ layer. ing.

  The composition for proliferating mesenchymal stem cells of the present invention has an action of promoting the proliferation of mesenchymal stem cells, that is, an action of improving the proliferation ability of mesenchymal stem cells and increasing the number thereof. The composition for proliferating mesenchymal stem cells of the present invention can be used for any mesenchymal stem cells present in body tissues such as bone marrow, peripheral blood, fat, and brain, preferably derived from bone marrow or It can be used for mesenchymal stem cells derived from peripheral blood, particularly mesenchymal stem cells derived from bone marrow.

  The composition for promoting the proliferation of mesenchymal stem cells of the present invention can be used for both in vitro culture of mesenchymal stem cells and in vivo proliferation of mesenchymal stem cells in vivo. The subject to be administered or ingested with the composition for promoting mesenchymal stem cell proliferation of the present invention is a mammal for which the proliferation promotion of mesenchymal stem cells in the body is desired, and examples thereof include mice, rats, hamsters, dogs, cats, Cattle, pigs, monkeys, humans and the like can be mentioned, and humans are particularly preferable.

  The proliferation promoting effect on mesenchymal stem cells in vitro is compared to the case where the mesenchymal stem cells are cultured in the presence of the composition for promoting proliferation of mesenchymal stem cells of the present invention and cultured in the absence of the composition. This can be confirmed by the larger number of mesenchymal stem cells.

  The growth promoting effect on mesenchymal stem cells in vivo is determined when the composition for promoting proliferation of mesenchymal stem cells of the present invention is administered to or consumed by a suitable animal, preferably a mouse, rat or other experimental animal. It can be confirmed that the number of mesenchymal stem cells in the living body is preferably larger in the bone marrow or peripheral blood than in the case where no product is administered or taken. The number of mesenchymal stem cells in vivo can be measured by applying a known method such as culture to bone marrow or peripheral blood collected from a model animal.

  The composition for promoting proliferation of mesenchymal stem cells of the present invention exerts functions such as tissue repair, anti-inflammation and fibrosis suppression by promoting proliferation of mesenchymal stem cells in vivo, and prevents various diseases. Are expected to act in a therapeutic and / or therapeutic manner. Examples of the diseases that can be prevented and / or treated by the composition for promoting proliferation of mesenchymal stem cells of the present invention include neurological diseases such as cerebral infarction, spinal cord injury, dementia, and neurodegenerative diseases; cardiovascular diseases such as myocardial infarction. Inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease; diabetes and its complications; kidney disease and the like.

  The present invention further provides a composition for improving cognitive function comprising, as an active ingredient, one or more foods selected from the group consisting of β-carotene-containing foods, rutin-containing foods, anthocyanin-containing foods, and flavonol-containing foods. .

  The composition for improving cognitive function of the present invention can improve the cognitive function of the animal by administering or ingesting it to the mammal. In the present invention, the cognitive function refers to higher-order functions of the brain including memory, judgment, calculation, understanding, learning, thinking, language, etc., and the improvement thereof maintains any of those functions or decreases the function. , And reducing the rate of progression of functional degradation, and restoring the degraded functionality. Therefore, the composition for improving cognitive function of the present invention can also be expressed as a composition for maintaining cognitive function and a composition for suppressing cognitive function deterioration.

  The subject to which the composition for improving cognitive function of the present invention is administered or ingested is a mammal whose cognitive function is desired to be improved, such as mouse, rat, hamster, dog, cat, cow, pig, monkey, human, etc. Humans are particularly preferred. The cognitive function improving action is carried out by performing a known method for measuring cognitive function in a suitable animal, preferably mouse, rat or other model animal administered or ingested with the composition for improving cognitive function of the present invention. This can be confirmed by evaluating the cognitive function and comparing it with the evaluation of the cognitive function of the model animal to which the composition was not administered. Known methods for measuring the cognitive function of model animals include a novel object recognition test, a Morris water maze test, a radial maze test, and the like.

  The mesenchymal stem cell proliferation promoting composition and the cognitive function improving composition of the present invention are one or more selected from the group consisting of β-carotene-containing foods, rutin-containing foods, anthocyanin-containing foods, and flavonol-containing foods. Contains food as an active ingredient.

  β-carotene is a kind of carotenoid that exists in plants and is known as one of the red-orange pigments and is also called provitamin A. Examples of edible plants containing a large amount of β-carotene include carrots (Daucus carota subsp. Sativus), perilla, moroheiya, parsley, basil, spinach, garlic, leek, pumpkin, komatsuna, chingensai and other green-yellow vegetables. Carrot is preferable.

  Rutin is a kind of flavonoid glycoside present in plants, and consists of quercetin and rutinose. Examples of edible plants containing a large amount of rutin include buckwheat, asparagus, citrus, etc., including tartary buckwheat (Fagopyrum tataricum), preferably tartary buckwheat, especially the variety name “Manten Kirari” (variety registration No. 23414) or That strain is tartary buckwheat.

  Anthocyanins are a kind of flavonoids present in plants, and have a structure in which sugar chains, organic acids, and the like are bound to anthocyanidins, which are aglycones. A preferred anthocyanin in the present invention is anthocyanin whose aglycon is delphinidin, cyanidin, petunidin or pelargonidin. Examples of delphinidin anthocyanins include delphinidin-3-O-β-galactopyranoside, delphinidin-3-O-β- (6-trans-p-coumaroyl) galactopyranoside, delphinidin-3-O-β. -(6-cis-p-coumaroyl) galactopyranoside, delphinidin-3-O-β-glucopyranoside, delphinidin-3-O-β- (6-trans-p-coumaroyl) glucopyranoside and the like. Examples of the cyanidin-based anthocyanins include cyanidin-3-O-β-galactopyranoside, cyanidin-3-O-β-glucopyranoside, cyanidin-3-O-β- (6-trans-p-coumaroyl) galactopila. Noside, cyanidin-3-O-β- (6-trans-p-coumaroyl) glucopyranoside, and the like.

  In the present invention, in particular delphinidin-3-O-β-galactopyranoside, cyanidin-3-O-β-galactopyranoside, delphinidin-3-O-β-glucopyranoside, cyanidin-3-O-β- Preferred are glucopyranoside, delphinidin-3-O-β- (6-trans-p-coumaroyl) galactopyranoside, delphinidin-3-O-β- (6-cis-p-coumaroyl) galactopyranoside, and the like. As the pelargonidin-based anthocyanin, petanin is preferable, and as the petunidin-based anthocyanin, peranine is preferable.

  Examples of edible plants containing a large amount of delphinidin and cyanidin anthocyanins include berries such as cassis, blueberry, bilberry, raspberry, cranberry, cassis and acai, lotus cup, grape, pomegranate, eggplant, mulberry, black beans and other reddish purple. Or tea (Camellia sinensis, Camellia taliensis) such as blue-purple vegetables or fruits, and cultivar name “Tea intermediate mother farm 6” (variety registration No. 16016), cultivar name “Saint Rouge” (variety registration No. 21262) Preferably, it is a tea of the cultivar name “Saint Rouge” or its cultivar. In addition, as edible plants containing a large amount of petunidin-based anthocyanin petanin and pelargonidin-based anthocyanin peranine, varieties "Inca Purple" (variety registration No. 8550), "Kitamurasaki" (variety registration No. 14041), Variety name "Shadow Queen" (variety registration No. 17574), variety name "Inca Red" (variety registration No. 8551), variety name "Northern Ruby" (variety registration No. 17447), etc. (Solanum tuberosum L.) Preferably, the cultivar name is “Shadow Queen”, the cultivar name “Northern Ruby”, or a potato of those strains.

  Flavonol is a kind of flavonoid having a 3-hydroxyflavone skeleton contained in various vegetables and fruits, and there are many substances depending on the position of phenolic OH. Preferred flavonols in the present invention are myricetin (IUPAC; 3,3 ′, 4 ′, 5 ′, 5,7-hexahydroxy-2-phenylchromen-4-one), kaempferol (3,4 ′, 5,7-tetrahydroxy). -2-phenylchromen-4-one), quercetin (3,3 ', 4', 5,7-pentahydroxy-2-phenylchromen-4-one), and as edible plants rich in these flavonols, for example, tea , Walnuts, broccoli, cabbage, kale, onion, beans, grapes, berries, tomatoes, strawberries, apples, citrus fruits, buckwheat etc. ) Or a tea of that kind.

  The lineage varieties in the present invention mean the parent varieties of the varieties, and the breeding lines and varieties of progeny generated from the varieties and the parent varieties. For example, because San Rouge is a breed bred by crossing of the tea intermediate mother farm No. 6, tea intermediate mother farm No. 6 is a lineage of San Rouge, and Shadow Queen is breeding by crossing of Kitamurasaki Kitamurasaki is a lineage of Shadow Queen.

  β-carotene-containing foods, rutin-containing foods, anthocyanin-containing foods, and flavonol-containing foods refer to edible organisms (animals, plants, fungi, etc.) that contain a large amount of β-carotene, rutin, anthocyanins, flavonols, or processed products thereof. Preferably, one or two or more kinds of edible plants containing a large amount of each of the components listed above can be appropriately selected and used. The β-carotene-containing food, rutin-containing food, anthocyanin-containing food, and flavonol-containing food are not limited in form and shape unless the composition of the present invention is an organism such as an animal or a plant. Can be used.

  As described above, β-carotene-containing foods, rutin-containing foods, anthocyanin-containing foods and flavonol-containing foods all show mesenchymal stem cell proliferation promoting action and cognitive function improving action as foods containing many components, It is considered that β-carotene, rutin, anthocyanin and flavonol contained in a large amount in each food are involved in the above action. As described above, the present invention provides a mesenchymal stem cell proliferation promoting composition or a cognitive function improving composition comprising one or more substances selected from the group consisting of β-carotene, rutin, anthocyanin and flavonol as an active ingredient. Things are also provided. In these compositions, β-carotene, rutin, anthocyanin and flavonol can all be used after being purified or partially purified from plants or other biological materials containing them by methods known to those skilled in the art.

  The mesenchymal stem cell proliferation promoting composition and the cognitive function improving composition of the present invention can be provided as a food / beverage product, a pharmaceutical product or a quasi-drug, and thus the food / beverage product composition, pharmaceutical composition or quasi-drug. It can also be expressed as a product composition. The composition of the present invention may be a composition for oral or enteral consumption. There is no restriction | limiting in the form of the composition of this invention, For example, it may be forms, such as squeezing (juice), a paste, a dry powder, an extract. In addition, the composition of the present invention may be formulated, preferably an oral preparation such as a tablet, capsule, powder, granule, fine granule, pill, suspension, emulsion, liquid, syrup and the like. It can be in form. The composition for promoting mesenchymal stem cell proliferation and the composition for improving cognitive function of the present invention can also be expressed as a mesenchymal stem cell proliferation promoting agent and a cognitive function improving agent, respectively, depending on the mode.

  The food / beverage composition in the present invention has only a low risk of harming human health and can be taken orally or by tube feeding in normal social life. It can contain food and drink other than the excipient or active ingredient. In the present invention, the food / beverage composition comprises beverages (including beverage concentrates and adjustment powders), general processed foods including seasonings, supplements, health foods (functional foods / beverages), health functional foods (specific It is understood as including a wide range of foods for health, functional nutritional foods, and functional labeling foods.

  In the present invention, particularly preferred food and drink composition is a health functional food (specific health food, functional indication food) that displays a mesenchymal stem cell proliferation promoting action, a cognitive function improving action, or a preferred action scientifically derived therefrom. , Nutritional functional food).

  The food and drink composition includes, for example, sugars such as dextrin and starch; proteins such as gelatin, soybean protein and corn protein; amino acids such as alanine, glutamine and isoleucine; polysaccharides such as cellulose and gum arabic; soybean oil and medium chain Arbitrary adjuvants, such as fats and oils, such as fatty acid triglyceride, can be added and it can manufacture as a food-drinks composition of arbitrary shapes.

  The pharmaceutical composition and quasi-drug composition of the present invention can contain a pharmaceutically acceptable carrier or additive, or a physiologically active substance other than the active ingredient. Pharmaceutically acceptable carriers or additives are well known to those skilled in the art, and those skilled in the art will be able to prepare pharmaceutical preparations from ingredients described in, for example, the 17th revised Japanese Pharmacopoeia and other standards, within the scope of normal performance. It can be appropriately selected and used according to the form. Moreover, the administration method of a pharmaceutical composition and a quasi-drug composition is not specifically limited, It determines suitably according to the form of a formulation.

  The physiologically active substance other than the active ingredient of the present invention in the pharmaceutical composition and quasi-drug composition is preferably a therapeutic agent for dementia or other neurodegenerative diseases, such as donepezil and galantamine, which exhibit acetylcholinesterase inhibitory action. Can be mentioned.

  The content of each active ingredient in the composition of the present invention and the dose or intake to the subject depend on the type of composition, usage, subject age, route of administration and other conditions, etc. The daily dose or intake should be adjusted appropriately so that it is within the range of 1 mg to 100 mg in terms of β-carotene, 50 mg to 1000 mg in terms of rutin, 1 mg to 500 mg in terms of anthocyanin, and 2 mg to 500 mg in terms of flavonol. That's fine. These amounts can be administered or ingested once or multiple times daily, or intermittently.

  The present invention will be described in more detail by the following examples, but the present invention is not limited to these examples.

Example 1-1. Evaluation of the mesenchymal stem cell growth promoting effect Carrot juice (trade name "Completely squeezed juice" (straight juice of carrot 100%), Ibashi Sangyo Co., Ltd., variety name Mukai Yoji), Mikka Nissan Unshu oranges 6 times concentrated juice, green tea (Variety name Saint Rouge), tartary buckwheat (variety name Manten Kirari) and potato (variety name Shadow Queen), and 10% each of these dry powder or steamed pulverized food (HOKUDO AIN-76A) Base). Table 1 shows the results of component analysis of each bait.

  SD rats (male, 33 weeks old) were divided into control group, carrot juice intake group, saint rouge intake group, tartary buckwheat intake group, Wenzhou mandarin orange intake group and shadow queen intake group (n = 10 / group), prepared above Each pellet food was fed freely and bred for 10 weeks. The control group received a standard pellet diet without any agricultural product. The estimated daily intake of functional components calculated from the amount of pelleted food in each group in terms of body weight of 60 kg is carrot β-carotene: 7 mg, saint rouge anthocyanin: 12 mg, saint rouge flavonol: 40 mg, tartary buckwheat rutin: 150 mg, shadow queen anthocyanin: 50 mg.

Bone marrow (2 femurs, 2 tibias) and peripheral blood were collected from each group of rats after breeding and reported previously (Kim S. et al., Brain Res. 2006; 1123, 27-33. Ukai R et al., J. Neurotrauma. 2007; 24: 508-520.) 10% FBS diluted to 25 mL with Dulbecco's Modified Eagle Medium (DMEM) and heat-inactivated (30% FBS for peripheral blood), After adding 2 mL L-glutamine, 100 U / mL penicillin, 0.1 mg / mL streptomycin, and incubating at 37 ° C. in a 5% CO ₂ atmosphere for 10 days, the number of cells was counted.

  The results are shown in FIG. Compared with the control group, the number of bone marrow mesenchymal stem cells and peripheral blood mesenchymal stem cells in the rat body increased in the carrot juice intake group, the sun rouge intake group, the tartary buckwheat intake group, and the shadow queen intake group. It was confirmed that

Example 1-2. Evaluation of Mesenchymal Stem Cell Growth Promoting Action In addition to the agricultural products prepared in Example 1-1, green tea (variety name Benifuuki) and potato (variety name Inokameme, Northern Ruby) are prepared, Rat pellet food (based on HOKUDO AIN-76A) containing 10% each was produced. .

  SD rats (male, 33 weeks old) were divided into 10 groups (n = 10 / group), and 8 groups were allowed to freely ingest any of the 8 pellet diets prepared above or in Example 1-1. Raised for 10 weeks. The remaining two groups were fed standard pellet food, and one group was given 0.1 μg / 0.5 ml of β-carotene by intraperitoneal injection every day (Kyowa Hakko Bio Co., Ltd .: Dunaliella carotene water-soluble biocarotene 02 (Dunaliella derived β-carotene containing 2% emulsion diluted with raw food), 1 group was a control group.

  After the breeding, the number of bone marrow mesenchymal stem cells of each group of rats was counted in the same manner as in Example 1-1. The results are shown in FIG. Compared with the control group, the number of bone marrow mesenchymal stem cells in rats increased in the β-carotene, carrot juice intake, sun rouge intake, northern ruby intake, shadow queen intake and tartary buckwheat intake groups. It was confirmed that

Example 2-1. Evaluation of cognitive function improving action (1) Novel object recognition test SHR rats exhibiting cognitive decline in addition to hypertension were used as dementia model animals. SHR rats (male, 20 weeks old, purchased from Sankyo Lab Service Co., Ltd.) are divided into a control group and a carrot juice intake group (n = 7 / group). For 14 days (from 20 to 22 weeks of age) from the start of test breeding, standard carrot diet (after 23 weeks of age) and carrot juice instead of water (trade name “Tokubetsu Premium Carrot Juice” (carrot) 100% straight juice, varietal name Akemi 5 inch), and a single grain of 10,000 times) were bred for 5 weeks.

  The rats of both groups were subjected to a novel object recognition test at the start of test breeding and every week during the test breeding period, and changes in cognitive function were examined over time. The contents of the novel object recognition test are as follows. First, two identical objects (plastic toys; 2 cm long, 3 cm wide, 5 cm high) were placed in the open field, and the rats were allowed to explore freely for 10 minutes. After 24 hours, the rats were trained in the same manner for 10 minutes, and after 4 hours, one of the objects in the open field was changed to a novel object, and allowed to search freely for 5 minutes in this test. The ratio of new object search time to new object search time (new / new + existing object search time) was calculated, and more than 50% was regarded as normal cognitive function. The location of the object was set in exactly the same position for both the training test and the main test.

(2) Morris water maze test The Morris water maze test was conducted for 5 days on dementia model rats raised in water or carrot juice for 5 weeks in the same manner as in (1) to examine changes in cognitive function. The Morris water maze test was carried out by filling a circular pool with water, creating a scaffold for the rat to evacuate at a location about 1 cm below the surface of the water, and measuring the time taken for the rat to reach the evacuation site. Only the first day was searched for 60 seconds, and the arrival time was recorded from the second day.

  The results are shown in FIG. The vertical axis of the upper graph in the figure represents the ratio (%) of the search time to the novel object in the total search time, and the horizontal axis represents the breeding time (weeks) after the start of the test breeding. The vertical axis of the lower graph represents the swimming time (seconds), and the horizontal axis represents the learning time (days) after the start of the Morris water maze test. In any of the tests, improvement in cognitive function was confirmed in the carrot juice intake group as compared with the progression of cognitive decline in the control group.

(3) Measurement of the number of mesenchymal stem cells The bone marrow according to the method described in Example 1-1, using a dementia model rat raised for 5 weeks on a standard pellet diet or carrot juice-containing pellet diet as in (1) The number of mesenchymal stem cells and the number of peripheral blood mesenchymal stem cells were measured. The results are shown in FIG. It was confirmed that both the number of bone marrow mesenchymal stem cells and the number of peripheral blood mesenchymal stem cells in the rat body increased in the carrot juice intake group as compared with the control group.

Example 2-2. Evaluation of cognitive function improving action SHR rat (male, 20 weeks old, purchased from Sankyo Lab Service Co., Ltd.), a dementia model rat, control group, carrot juice intake group, saint rouge intake group, tartary buckwheat intake group and shadow Divided into queen ingestion groups (n = 7 / group), the control group was fed with standard pellet food ad libitum and bred for 5 weeks. The remaining group contains standard pellet food for 14 days (from 20 weeks to 22 weeks of age) from the start of test breeding, and then carrot juice prepared in Example 1-1 or 1-2 (from 23 weeks of age) Pellet baits, saint rouge blended pellet baits, tartary buckwheat blended pellet baits or shadow queen blended pellet baits were freely fed and bred for 5 weeks. Thereafter, a novel object recognition test was performed on the rats of each group in the same manner as in Example 2-1.

  Moreover, the Morris water maze test was done like Example 2-1, using the dementia model rat reared on the same conditions as the above.

  The results of both tests are shown in FIG. The result of the Morris water maze test is on the fifth day after the start of learning. In any of the carrot juice intake group, the sun rouge intake group, the tartary buckwheat intake group, and the shadow queen intake group, improvement in cognitive function was confirmed as compared with the control group.

  Furthermore, the number of bone marrow mesenchymal stem cells and the number of peripheral blood mesenchymal stem cells were measured according to the method described in Example 1-1 using dementia model rats reared under the same conditions as described above. The results are shown in FIG. The number of bone marrow mesenchymal stem cells and peripheral blood mesenchymal stem cells increased in the carrot juice intake group, sun rouge intake group, tartary buckwheat intake group, and shadow queen intake group compared to the control group. confirmed.

Claims (20)

  A composition for promoting mesenchymal stem cell proliferation containing, as an active ingredient, one or more foods selected from the group consisting of β-carotene-containing foods, rutin-containing foods, anthocyanin-containing foods, and flavonol-containing foods.   The composition according to claim 1, wherein the β-carotene-containing food is carrot.   The composition according to claim 1, wherein the rutin-containing food is tartary buckwheat.   Anthocyanin-containing foods include tea variety San Rouge (variety registration No. 21262) and its varieties, potato variety shadow queen (variety registration No. 17574) and its varieties, potato variety Northern Ruby (variety registration No. 17447) and its The composition according to claim 1, which is a food selected from the group consisting of lineages.   The composition according to claim 1 or 4, wherein the anglycone of anthocyanin is delphinidin, cyanidin, petunidin or pelargonidin.   The composition according to claim 1, wherein the flavonol-containing food is a tea cultivar Saint Rouge (variety registration No. 21262) or a tea of its cultivar.   The composition according to claim 1 or 6, wherein the flavonol is myricetin, kaempferol or quercetin.   A composition for improving cognitive function comprising, as an active ingredient, one or more foods selected from the group consisting of β-carotene-containing foods, rutin-containing foods, anthocyanin-containing foods, and flavonol-containing foods.   The composition according to claim 8, wherein the β-carotene-containing food is carrot.   The composition according to claim 8, wherein the rutin-containing food is tartary buckwheat.   Anthocyanin-containing foods include tea variety San Rouge (variety registration No. 21262) and its varieties, potato variety shadow queen (variety registration No. 17574) and its varieties, potato variety Northern Ruby (variety registration No. 17447) and its The composition according to claim 8, which is a food selected from the group consisting of strains.   The composition according to claim 8 or 11, wherein the aglycone of anthocyanin is delphinidin, cyanidin, petunidin or pelargonidin.   The composition according to claim 8, wherein the flavonol-containing food is a tea cultivar Saint Rouge (variety registration No. 21262) or a tea of its cultivar.   The composition according to claim 8 or 13, wherein the flavonol is myricetin, kaempferol or quercetin.   A mesenchymal stem cell proliferation promoting composition containing, as an active ingredient, one or more substances selected from the group consisting of β-carotene, rutin, anthocyanin and flavonol.   16. The composition of claim 15, wherein the anthocyanin aglycone is delphinidin, cyanidin, petunidin or pelargonidin.   16. A composition according to claim 15, wherein the flavonol is myricetin, kaempferol or quercetin.   A composition for improving cognitive function, comprising one or more substances selected from the group consisting of β-carotene, rutin, anthocyanin and flavonol as an active ingredient.   19. The composition of claim 18, wherein the anthocyanin aglycone is delphinidin, cyanidin, petunidin or pelargonidin. 19. A composition according to claim 18, wherein the flavonol is myricetin, kaempferol or quercetin.