JP2009046465A - Skin cosmetic and food/drink - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide antioxidants, anti-inflammatory agents, platelet coagulation inhibitors, immunoactivators, TNF-α production promoters, antiaging agents, antiobese agents, brightening agents, skin cosmetics or food/drink, each containing one or more kinds of natural extract. <P>SOLUTION: Extract(s) from one or more plants selected from the group consisting of Polygala chinensis L., Polygala japonica Houtt. and Polygala avensis is (are) included as the active ingredient in antioxidants, anti-inflammatory agents, platelet coagulation inhibitors, immunoactivators, TNF-α production promoters, antiaging agents, anti-obese agents, brightening agents, skin cosmetics or food/drink. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an antioxidant, an anti-inflammatory agent, an immunostimulant, an anti-aging agent, an anti-obesity agent, a whitening agent, a skin cosmetic, and a food and drink.

In recent years, active oxygen has attracted attention as a factor that particularly oxidizes biological components, and its adverse effect on living organisms has become a problem. Active oxygen is generated in the process of energy metabolism in living cells. Examples of active oxygen include superoxide (that is, superoxide anion generated by one-electron reduction of oxygen molecules: .O ₂ ⁻ ), hydrogen peroxide (H ₂ O ₂ ), hydroxy radical (.OH), singlet oxygen ( ¹ O ₂ ) and the like. These active oxygens are essential for the phagocytic sterilization mechanism and play an important role in removing viruses and cancer cells.

  However, excessive production of active oxygen attacks in vivo molecules constituting membranes and tissues in the living body and induces various diseases. Normally, superoxide produced in vivo and used as a starting material for other active oxygen is sequentially eliminated by the catalytic action of superoxide dismutase (SOD) contained in the cells. Is excessive or when the SOD action is reduced, superoxide elimination is insufficient, and the superoxide concentration increases, which may cause tissue damage such as rheumatoid arthritis and Behcet's disease, myocardial infarction, stroke Causes cataracts, spots, freckles, wrinkles, diabetes, arteriosclerosis, stiff shoulders, coldness, etc.

  In particular, since the skin is directly affected by environmental factors such as ultraviolet rays, it is an organ that easily generates superoxide, and therefore, by increasing the concentration of superoxide, for example, the biological tissue such as collagen is decomposed and denatured or It is thought to crosslink and oxidize fats and oils to produce lipid peroxides that damage cells, and the damage caused by active oxygen is the cause of aging such as skin wrinkle formation and skin elasticity reduction (See Non-Patent Document 1). Therefore, by inhibiting and suppressing the generation of active oxygen and in vivo radicals, skin aging such as wrinkle formation and reduced elasticity, tissue disorders such as rheumatoid arthritis and Behcet's disease, myocardial infarction, stroke, cataracts, spots, buckwheat It is considered that various disorders involving active oxygen such as diabetes, arteriosclerosis, stiff shoulders, and coldness can be prevented, treated or improved.

  Therefore, attempts have been made to obtain active oxygen scavenging substances, radical scavenging substances, and hydrogen peroxide scavenging substances from natural products that are advantageous in terms of safety. Extracts (see Patent Document 1), extracts from the plant belonging to the genus Ryukyu benkei (see Patent Document 2), extracts from the butterfly (see Patent Document 3), extracts from sulfur (see Patent Document 4) Etc. are known.

  Glutathione is a tripeptide composed of three amino acids, glutamic acid, cysteine, and glycine, and is a compound having a major cysteine residue in the cell. Intracellular glutathione functions as a radical donor, regulation of cell function by redox, and an SH donor for various enzymes, and is also known as an antioxidant component. Its action expression is thought to be derived from cysteine residues. However, it has been reported that the amount of glutathione in the skin decreases with aging, and this is one factor that reduces the oxidative defense ability in the skin and damages cellular components such as DNA and proteins. It is believed that.

  That is, promoting the production of glutathione in the skin increases the defense against oxidative stress that declines with aging and suppresses damage to oxidative stress caused by ultraviolet rays, and prevents skin aging from being prevented, treated, or stained. It is considered that improvement for pigmentation can be expected. Based on this idea, bilberry extract, walnut extract (see Patent Document 5), gardenia plant extract (see Patent Document 6), and the like are known as having glutathione production promoting action.

  One of the causes of inflammatory diseases is known to be due to platelet aggregation. Platelet aggregation and activation cause physiological hemostasis and pathological thrombus formation, and platelet aggregation is thought to be involved in the progression of arteriosclerosis, cancer metastasis, inflammation, etc. ing. For this reason, it is thought that an inflammatory disease can be prevented and improved by inhibiting and suppressing the aggregation of platelets. As what has a platelet aggregation inhibitory effect, for example, a Kangsanfu extract (refer patent document 7), a phlorizin, a phloretin (refer patent document 8), etc. are known.

  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. Thus, it is known that various illnesses such as cancer, infectious diseases and allergic symptoms are induced by a decrease in immunity, and conversely, when the immunity is activated, a carcinogenesis-suppressing action and control are suppressed. Various effects such as cancer action, anti-infective action, anti-allergic action, recovery of physical condition rhythm, and maintenance of homeostasis can be expected.

  Many types of cells are involved in the immune mechanism, but the role of leukocytes is particularly large, and macrophages are ubiquitous in all animals, including the actions at the early stages of the immune response. It is a kind of important white blood cell that is involved in every stage. 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 carried by trace proteins (cytokines) secreted by leukocytes.

  There are many types of cytokines, and among them, tumor necrosis factor (TNF) and interleukins are attracting attention. Among them, inflammatory cytokines typified by TNF-α are reported to be mainly released from macrophages and finally exhibit antitumor action and the like. Therefore, it is considered that by enhancing the production function of TNF-α, the immune function is activated and the growth of malignant tumor can be suppressed. Based on such an idea, as a TNF-α production promoter, an extract from a plant belonging to the genus Curranta (see Patent Document 9), an extract from a shellfish mother (see Patent Document 10), and the like are known. ing.

  One cause of skin aging with aging is a decrease in the secretion of estrogen, a female hormone. In other words, estrogen is deeply involved in maintaining the health of adult women, and its lack of secretion leads to various medical illnesses, as well as causes of unfavorable skin changes such as skin hypersensitivity, reduced elasticity, reduced moisture, etc. It is known that estrogen deficiency in postmenopausal women and the like causes coronary heart disease and osteoporosis.

  Therefore, a drug containing a substance having the same action as estrogen is transdermally or orally administered to women after menopause, whose estrogen secretion declines. As what has such an estrogen-like effect | action, the extract (refer patent document 11), the phlorizin, and phloretin (refer patent document 8) etc. from the leaf part of a quince are known, for example.

  The skin is composed of the epidermis, basement membrane, dermis, and subcutaneous tissue. The basement membrane is present at the boundary between the epidermis and the dermis, and its functions are diverse. Adhesion of the epidermis to the dermis, determination of the polarity of the epidermis, control of epidermal differentiation and proliferation, and factors produced by dermal cells It is involved in the control of nutrient supply derived from blood and blood components. Therefore, the basement membrane plays an extremely important role in maintaining the structure and homeostasis of the skin. Therefore, when the structure of the basement membrane changes, skin aging symptoms such as wrinkles and sagging appear. In particular, if the production of type IV collagen, the main component of the basement membrane, decreases, the structure of the basement membrane changes and skin aging symptoms such as wrinkles and sagging appear. By doing so, it is considered that these skin aging symptoms and the like can be prevented and improved. Examples of such a type IV collagen production-promoting action include hydrolyzed casein, beech bud, erythrina, soluble eggshell membranes, cuckoo, and western ivy extract (see Patent Document 12), phlorizin and phloretin ( Patent Document 8) is known.

  The dermis of the skin is composed of fibroblasts and an extracellular matrix such as collagen that is outside the cells and supports the skin structure. In young skin, fibroblasts are actively proliferating, and the moisture of skin is retained by the interaction of skin tissues such as fibroblasts and collagen, and the flexibility and elasticity of the skin are secured. , The skin is kept fresh and fresh with a firm and glossy appearance. However, when there is an influence of certain external factors such as ultraviolet rays, drastic drying of air, excessive skin washing, etc., or when aging progresses, the proliferation of fibroblasts is delayed, and the moisture retention function and elasticity of the skin are reduced. descend. The skin loses its tension and gloss, and exhibits aging symptoms such as rough skin and wrinkle formation. Therefore, it is considered that aging symptoms of skin can be prevented and improved by promoting the proliferation of fibroblasts. For example, corosolic acid (see Patent Document 13) is known as such a fibroblast proliferation promoting action.

  The epidermis has a four-layer structure that starts with the basal layer, the lowest layer, and continues to the spiny layer, the granule layer, and the stratum corneum. Most of the cells in each layer are keratinocytes differentiated from the basal layer. It is. Normally, keratinocytes are produced in the basal layer, and gradually move to differentiate into the upper layer to form horny cells to form the horny layer, and finally fall off from the horny layer as plaque.

  The stratum corneum is present in the outermost shell of the skin and serves as a physical barrier against irritation from the outside world. In order to have this barrier function in the skin, the cycle (keratinization) from the production of keratinocytes in the basal layer to the peeling off of the keratinocytes (keratinization) is usually repeated at a cycle of 4 weeks to perform epidermal metabolism. . However, the metabolic function of this stratum corneum also deteriorates with aging, and skin troubles such as wrinkles, dullness, pigmentation, and rough skin occur. Therefore, it is considered that skin aging such as wrinkles, dullness, and pigmentation can be improved by promoting the proliferation of keratinocytes and restoring the metabolic function of the skin. Based on such an idea, a lotus germ extract (see Patent Document 14), a lysium extract (see Patent Document 15), and the like are known as having an action of promoting epidermal keratinocyte proliferation.

  Hyaluronic acid is one of the major extracellular matrices that are deeply involved in skin moisture retention and viscoelasticity, and is known to be synthesized from epidermal keratinocytes in addition to dermal fibroblasts. It is also known that the function of hyaluronic acid in the epidermis is involved in maintaining skin homeostasis such as immune system and differentiation regulation. However, it is known that the hyaluronic acid content in the skin decreases with physiological aging, and the decrease in the hyaluronic acid content in the skin causes aging such as dryness / atrophy of the skin, decreased elasticity, and formation of fine lines. (See Non-Patent Document 2). Therefore, it is considered that aging of the skin can be prevented and improved by promoting the expression of hyaluronic acid synthase 3 (HAS3) involved in promoting the synthesis of epidermal hyaluronic acid. Based on this idea, for example, tocopheryl retinoate (see Patent Document 16) is known as one having hyaluronic acid synthase 3 (HAS3) expression promoting action.

  In skin cells, it is known that aquaporins, known as water channels, are expressed on the cell membrane and play a role of taking in low-molecular substances such as interstitial water into cells. In humans, the presence of 13 types of aquaporins (AQP0 to AQP12) is known. In epidermal cells, AQP3 is mainly present, and it is considered to play a role of taking in low-molecular compounds such as glycerol and urea involved in water retention action in addition to water. However, AQP3 decreases with aging, and it is suggested that this contributes to a decrease in water retention function. Therefore, by promoting the expression of AQP3, water retention ability and barrier function due to aging are increased. It is thought that it is possible to control etc. (refer nonpatent literature 3). Based on such an idea, extracts having an AQP3 expression promoting action are known, for example, an extract obtained from a Nozenhalenaceae plant (see Patent Document 17), tocopheryl retinoate (see Patent Document 16), and the like.

  When the skin is irradiated with ultraviolet rays, the cells of the skin are damaged or cell death is caused, the skin loses its elasticity and elasticity, and exhibits aging symptoms such as rough skin and wrinkles. Therefore, prevention / improvement of skin aging can be expected by suppressing / recovering damage (for example, cell damage, cell death, etc.) caused by ultraviolet irradiation. As what has the damage recovery effect by ultraviolet irradiation, an oil-soluble licorice extract (refer patent document 18), a phlorizin, a phloretin (refer patent document 8), etc. are known, for example.

  When the intake energy is excessive with respect to the consumed energy, the excess fat accumulates as neutral fat in white fat cells. Obesity caused by the accumulation of body fat is not only cosmetically unfavorable, but also causes various diseases such as arteriosclerosis, diabetes, and metabolic syndrome. Recently, it is an era of satiety, and obesity due to overeating, lack of exercise, stress, etc. has increased, and it has become a big problem from the viewpoint of beauty regardless of gender. Therefore, accumulation of subcutaneous fat or the like is not preferable from the viewpoint of health, and reduction / decomposition of subcutaneous fat or the like, or prevention of accumulation is an important problem. In order to break down fat in the living body, the role of cyclic AMP is important. Cyclic AMP activates triglyceride lipase present in the living body, and fat is broken down into fatty acid and glycerol by the activated lipase. However, when cyclic AMP phosphodiesterase is activated, degradation of cyclic AMP is induced and lipase activation is inhibited. Therefore, it is considered that by inhibiting the activity of cyclic AMP phosphodiesterase, the amount of cyclic AMP in the cell can be increased and the decomposition of fat can be promoted. Based on such an idea, as having a cyclic AMP phosphodiesterase inhibitory action, for example, a monopod, an extract of Kojiro and Psycho (see Patent Document 19), a peanut astringent skin extract (see Patent Document 20), An extract of ginger family mango ginger (see Patent Document 21) and the like are known. In addition, as a substance having a lipolysis promoting action, for example, an extract of birch family birch and an extract of Gramineae (see Patent Document 22) are known.

Conventionally, in the development of whitening agents, tyrosinase, which is the rate-determining enzyme for melanin production, has been focused on. Recently, cytokines that are activated from epidermal keratinocytes and activate pigment cells (melanocytes) after UV-B irradiation. Α-melanocyte stimulating hormone (α-MSH), endothelin-1 (ET-1), stem cell growth factor (SCF), basic fibroblast growth factor (bFGF), granulocyte / macrophage / colony stimulating factor (GM) -CSF) and the like are known, and the development of a whitening agent that suppresses melanin production and exerts a whitening effect by blocking the information transmission system in which these are involved has been actively performed. Based on this idea, those having stem cell growth factor (SCF) expression inhibitory action include, for example, pentagonal, licorice leaf, oni strawberry, loquat, matils, melissa, moon peach, pearl barley, senkyu, tonin and gentian Extracts (see Patent Document 23) and the like are known.
JP 2003-81848 A JP 2005-29483 A JP 2006-321730 A JP 2007-8902 A JP 2006-241062 A JP 2006-347934 A JP 2002-53477 A JP 2007-106712 A JP 2004-107660 A JP 2006-56854 A JP 2002-302452 A JP 2004-107660 A JP 2006-265232 A JP 2002-68993 A JP 2006-316028 A JP 2006-290873 A JP 2004-168732 A JP 2004-250368 A JP 2003-261457 A JP 2004-26719 A JP 2005-104886 A JP 2006-45120 A Japanese Patent Application No. 2007-119579 "Fragrance Journal Extra Number", 1995, No.14, p.156 "Cosmetic Stage", 2007, Vol.1, No.3, p.45-46 "Fragrance Journal", 2006, Vol.34, No.10, p.19-23

  The first aspect of the present invention is one or two selected from the group consisting of SOD-like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action and glutathione production promoting action among highly safe natural products. An object of the present invention is to provide an antioxidant having an action more than that of a seed and using it as an active ingredient.

  Secondly, an object of the present invention is to find an anti-inflammatory agent or a platelet aggregation inhibitor that has a platelet aggregation inhibitory action from among highly safe natural products and uses it as an active ingredient.

  A third object of the present invention is to find a TNF-α production promoting action from highly safe natural products, and to provide an immunostimulatory agent or TNF-α production promoting agent using the same as an active ingredient. And

  Fourth, the present invention is a highly safe natural product that promotes type IV collagen production, estrogen-like action, epidermal keratinocyte proliferation promotion action, fibroblast proliferation promotion action, glutathione production promotion action, HAS3 mRNA expression promotion An object of the present invention is to provide an anti-aging agent which has one or two or more kinds of actions selected from the group consisting of action, aquaporin 3 mRNA expression promoting action and ultraviolet damage recovery action, and using it as an active ingredient.

  A fifth object of the present invention is to provide an anti-obesity agent comprising a highly safe natural product having a cyclic AMP phosphodiesterase inhibitory action and / or a lipolysis promoting action as an active ingredient. And

  A sixth object of the present invention is to provide a whitening agent having an SCF mRNA expression inhibitory action and / or a bFGF mRNA expression inhibitory action among highly safe natural products and using it as an active ingredient.

  Seventh, the present invention is a highly safe natural product, SOD-like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action, glutathione production promoting action, platelet aggregation inhibiting action, TNF-α production Promoting action, type IV collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting action, UV damage recovery action, cyclic AMP phosphodiesterase inhibition An object of the present invention is to find a substance having at least one of an action, a lipolysis promoting action, an SCF mRNA expression inhibitory action and a bFGF mRNA expression inhibitory action, and to provide a skin cosmetic or a food or drink containing the same.

  In order to solve the above problems, the antioxidant, anti-inflammatory agent, platelet aggregation inhibitor, immunostimulant, TNF-α production promoter, anti-aging agent, whitening agent and anti-obesity agent of the present invention include gold conversion, It contains an extract from one or more kinds of plants selected from the group consisting of Enshi Kobana as an active ingredient, and the skin cosmetics and beauty foods and beverages of the present invention are non-refundable, Himehagi and Enshi Kobana. Extracts from one or more plants selected from the group consisting of:

  In the antioxidant of the present invention, the extract is one or more selected from the group consisting of SOD-like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action, and glutathione production promoting action. In the anti-aging agent of the present invention, the above extract is a type IV collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, glutathione production It preferably has one or more actions selected from the group consisting of promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting action and ultraviolet damage recovery action. Has cyclic AMP phosphodiesterase inhibitory action and / or lipolysis promoting action DOO preferably, in the whitening agent of the present invention, the extract preferably has a SCFmRNA expression inhibitory activity and / or bFGFmRNA expression inhibitory action.

  According to the present invention, an anti-oxidant excellent in safety, containing as an active ingredient an extract from one or more kinds of plants selected from the group consisting of a natural product, gold inversion, himehagi, and floret An anti-inflammatory agent, a platelet aggregation inhibitor, an immunostimulant, a TNF-α production promoter, an anti-aging agent, an anti-obesity agent, a whitening agent, a skin cosmetic, or a food or drink can be provided.

The present invention will be described below.
[Antioxidants, anti-inflammatory agents, platelet aggregation inhibitors, immunostimulants, TNF-α production promoters, anti-aging agents, anti-obesity agents, whitening agents]
The antioxidant, anti-inflammatory agent, platelet aggregation inhibitor, immunostimulant, TNF-α production promoter, anti-aging agent, anti-obesity agent, or whitening agent of the present invention is selected from the group consisting of gold conversion, himehagi, and hanahana An extract from one or more kinds of plants is contained as an active ingredient.

  Here, in the present invention, “an extract from one or two or more plants selected from the group consisting of gold inversion, himehagi, and hanahana” is one or two selected from the group consisting of gold inversion, himehagi, and hanahana An extract obtained by using a plant or more of seeds or more as a raw material for extraction, a diluted solution or a concentrated solution of the extract, a dried product obtained by drying the extract, or a roughly purified product or a purified product thereof are included. .

  The raw materials for extraction used in the present invention are gold invariant (Kinfukan, scientific name: Polygala chinensis L.), himehagi (scientific name: Polygala japonica Houtt.) And Toshi Kobana (scientific name: Polygala avensis).

  Money conversion (Polygala chinensis L.) is an annual plant of 10 to 40 cm in height belonging to the genus Himehagi, also known as Daikin beef grass, and is wild in various Chinese provinces such as Hubei, Hunan, Guangdong and Guangxi. And can be easily obtained from these areas. Examples of the constituent parts of the gold substitution that can be used as the extraction raw material include leaves, branches, bark, trunks, stems, fruit parts, flower parts, above-ground parts, root parts, or a mixture of these parts. Preferably, it is the above-ground part.

  Himehagi (Polygala japonica Houtt.) Is a perennial plant with a height of 15 centimeters belonging to the genus Himehagi, also known as claws, and is distributed in various regions of China such as Tohoku, North China, and Southwest. It can be easily obtained from these areas. Examples of the constituent parts of the Japanese butterfly that can be used as the raw material for extraction include leaves, branches, barks, trunks, stems, fruit parts, flower parts, above-ground parts, root parts, or a mixture of these parts. Preferably, it is the above-ground part.

  Polygala avensis (Polygala avensis) is an annual vegetation of 5 to 15 cm in height belonging to the genus Himehagi, also known as Hoso Gold Beef Grass, which is distributed in Jiangxi, Hunan, Guangdong, Guangxi, etc. It can be easily obtained from the area. Examples of the constituent parts of Kobana Enshi that can be used as an extraction raw material include leaves, branches, bark parts, trunks, stems, fruit parts, flower parts, above-ground parts, root parts, or a mixture of these parts. Is preferably the above-ground part.

  SOD like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action, glutathione production promoting action, platelet aggregation inhibiting action, TNF-α production promoting action , Type IV collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting action, UV damage recovery action, cyclic AMP phosphodiesterase inhibitory action, Details of the substance having a lipolysis promoting action, an SCF mRNA expression suppressing action or a bFGF mRNA expression suppressing action are not known, but it has these actions from gold conversion, Himehagi or Kobana Enshi depending on the extraction method generally used for plant extraction Get an extract Door can be.

  For example, after drying the above plant, it is pulverized as it is or using a crusher, and is subjected to extraction with an extraction solvent, so that SOD-like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action, glutathione production Promoting action, platelet aggregation inhibiting action, TNF-α production promoting action, type IV collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting An extract having an action, a UV damage recovery action, a cyclic AMP phosphodiesterase inhibitory action, a lipolysis promoting action, an SCF mRNA expression suppressing action or a bFGF mRNA expression suppressing action can be obtained. Drying may be performed in the sun or using a commonly used dryer. Moreover, after performing pretreatment, such as degreasing, with a nonpolar solvent such as hexane, it may be used as an extraction raw material. By performing a pretreatment such as degreasing, extraction with a polar solvent such as gold inversion, Himehagi or Enshi Kobana can be performed efficiently.

  As the extraction solvent, it is preferable to use a polar solvent, and examples thereof include water and hydrophilic organic solvents. These may be used alone or in combination of two or more at room temperature or a temperature below the boiling point of the solvent. Is preferred.

  Examples of water that can be used as the extraction solvent include pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, and those subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, and the like. Therefore, the water that can be used as the extraction solvent in the present invention includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.

  Examples of hydrophilic organic solvents that can be used as the extraction solvent include lower aliphatic alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; -C2-C5 polyhydric alcohols, such as butylene glycol, propylene glycol, and glycerol, etc. are mentioned.

  When using the liquid mixture of 2 or more types of polar solvents as an extraction solvent, the mixing ratio can be adjusted suitably. For example, when using a liquid mixture of water and a lower aliphatic alcohol, it is preferable to mix 1 to 90 parts by weight of a lower aliphatic alcohol with respect to 10 parts by weight of water. When using a mixed solution, it is preferable to mix 1 to 40 parts by mass of a lower aliphatic ketone with 10 parts by mass of water, and when using a mixed solution of water and a polyhydric alcohol, water 10 It is preferable to mix 10 to 90 parts by mass of polyhydric alcohol with respect to parts by mass.

  The extraction treatment is not particularly limited as long as the soluble component contained in the extraction raw material can be eluted in the extraction solvent, and can be performed according to a conventional method. For example, the extraction raw material is immersed in an extraction solvent 5 to 15 times (mass ratio) of the extraction raw material, the soluble components are extracted at room temperature or under reflux, and then filtered to remove the extraction residue. A liquid can be obtained. The obtained extract is diluted, concentrated, dried, purified, etc. according to a conventional method in order to obtain a diluted or concentrated solution of the extract, a dried product of the extract, or a crude purified product or a purified product thereof. Processing may be performed.

  Purification can be performed by, for example, activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like. The obtained extract can be used as an active ingredient of an antioxidant, anti-inflammatory agent, platelet aggregation inhibitor, immunostimulant, TNF-α production promoter, anti-aging agent, anti-obesity agent or whitening agent as it is. However, it is easier to use a concentrated solution or a dried product.

  Extracts from gold incongruent, himehagi or kotohana have a peculiar odor, and it is possible to carry out purification for the purpose of decolorization, deodorization, etc. within a range that does not cause a decrease in the physiological activity. Since it is not used in a large amount when blended in cosmetics or foods and drinks, there is no practical problem even if it is not purified.

  The extract obtained from the above-described gold inversion, himehagi or kotobana is an antioxidant, anti-inflammatory, platelet aggregation inhibitory, immunostimulatory, TNF-α production promoting, anti-aging, anti-obesity Or, since it has a whitening action, an anti-oxidant, an anti-inflammatory agent, a platelet aggregation inhibitor, an immunostimulant, a TNF-α production promoter, an anti-aging agent, an anti-obesity agent, or a whitening is utilized by using each action. It can be used as an active ingredient of an agent. In the present invention, an extract from any one kind of plant selected from the group consisting of gold inversion, himehagi and kotohana may be used as the active ingredient, or from two or more of them. These extracts may be mixed and used as the active ingredient. When an extract from two or more kinds of plants selected from the group consisting of gold inversion, himehagi and kotohana is mixed and used as the active ingredient, the blending ratio may be appropriately determined according to the degree of their action. .

  Here, the antioxidative action of the extract from gold inversion, himehagi and kotohana is, for example, from the group consisting of SOD-like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action, and glutathione production promoting action. It is exhibited based on one or more selected actions. However, the antioxidant effect which the extract from gold inversion, Shimehagi and Enshi Kobana has is not limited to the antioxidant effect exhibited based on the said effect | action. In addition, since the extract from gold inversion, Himehagi and Enshi Kobana has SOD-like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action and glutathione production promoting action, using these actions, It can be used as an active ingredient of an SOD-like agent (superoxide scavenger), radical scavenger, hydrogen peroxide scavenger and glutathione production promoter.

  The anti-inflammatory action possessed by the extracts from the gold incongruent, himehagi and kotohana is exhibited based on, for example, the platelet aggregation inhibitory action. However, the anti-inflammatory action which the extract from gold conversion, Shimeji and Enshi Kobana has is not limited to the anti-inflammatory action exhibited based on the above action. It should be noted that extracts from one or more plants selected from the group consisting of gold inversion, himehagi, and hanahana are based on their platelet aggregation-inhibiting action, and diseases caused by platelet aggregation (for example, thrombosis And can be used as an active ingredient of a prophylactic / therapeutic agent for ischemic heart disease and the like.

  The immunostimulatory action possessed by the extracts from the gold incongruent, Japanese honeybee, and Kobana Enshi is exhibited based on, for example, a TNF-α production promoting action. However, the immunostimulatory action possessed by the extracts from the gold inversion, himehagi and kotohana is not limited to the immunostimulatory action exhibited based on the above action. In addition, the extract from 1 or 2 or more types of plants chosen from the group which consists of gold incongruity, Japanese butterfly, and Kobana is a disease caused by a deficiency of TNF-α based on their TNF-α production promoting action. It can be used as an active ingredient of a prophylactic / therapeutic agent (for example, cancer, infection, allergic symptoms, etc.).

  The anti-aging effect possessed by the extract from gold inversion, Himehagi and Enshi Kobana is, for example, type IV collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, glutathione production promoting action, It is exhibited based on one or more actions selected from the group consisting of HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting action and ultraviolet damage recovery action. However, the anti-aging action which the extract from gold conversion, a Japanese sword and Enshi Kobana has is not limited to the anti-aging action exhibited based on the said action. In addition, the extract from one or more plants selected from the group consisting of gold inversion, himehagi and floret is a type IV collagen production promoting action, an estrogen-like action, an epidermal keratinocyte proliferation promoting action, fibroblasts Since it has a growth promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting action and ultraviolet damage recovery action, these actions are used to promote type IV collagen production promoter, estrogen-like agent, epidermal keratinocyte growth promoter. It can be used as an active ingredient of a fibroblast proliferation promoter, a HAS3 mRNA expression promoter, an aquaporin 3 mRNA expression promoter and an ultraviolet damage recovery agent.

  The anti-obesity action possessed by the extracts from the gold incongruent, himehagi and kotohana is exhibited based on, for example, a cyclic AMP phosphodiesterase inhibitory action and / or a lipolysis promoting action. However, the anti-obesity action of the extracts from Kim Inchang, Himehagi and Kobana Enshi is not limited to the anti-obesity action exerted based on the above action. In addition, since the extract from 1 type or 2 or more types of plants chosen from the group which consists of gold incongruity, himehagi, and hanahana has cyclic AMP phosphodiesterase inhibitory action and lipolysis promotion action, using those actions, It can be used as an active ingredient of a cyclic AMP phosphodiesterase inhibitor and a lipolysis accelerator.

  The whitening action possessed by the extracts from the gold incongruent, himehagi and Enshi Kobana is exhibited based on, for example, an SCF mRNA expression inhibitory action and / or a bFGF mRNA expression inhibitory action. However, the whitening action of the extracts from the gold inversion, Himehagi and Enshi Kobana is not limited to the whitening action exhibited based on the above action. In addition, since the extract from 1 type or 2 or more types of plants chosen from the group which consists of gold inversion, Shimehagi, and Enshi Kobana has SCF mRNA expression inhibitory action and bFGF expression inhibitory action, SCF mRNA is utilized using those actions. It can be used as an active ingredient of an expression inhibitor and bFGF expression inhibitor. In addition, an extract from one or two or more plants selected from the group consisting of gold inversion, himehagi, and floret distantly suppresses abnormal growth of myeloblasts through an SCF mRNA expression inhibitory action, resulting from increased expression of SCF mRNA. It can also be used as an active ingredient of a prophylactic / therapeutic agent for a disease (eg, a myelodysplastic syndrome, a disease such as acute myeloid leukemia). Furthermore, an extract from one or more plants selected from the group consisting of gold inversion, himehagi, and floret distantly suppresses abnormal angiogenesis in tumor cells through bFGF mRNA expression-inhibiting action, and increases expression of bFGF mRNA. It can also be used as an active ingredient of a prophylactic / therapeutic agent for a disease caused by it (for example, cancer).

  The antioxidant, anti-inflammatory agent, platelet aggregation inhibitor, immunostimulant, TNF-α production promoter, anti-aging agent, anti-obesity agent, or whitening agent of the present invention is selected from the group consisting of gold conversion, himehagi, and hanahana It may be composed of only one or two or more kinds of plant extracts, or it may be a formulation of the above extract.

  Extracts from one or more plants selected from the group consisting of gold inversion, himehagi, and floret are used in a conventional manner using a pharmaceutically acceptable carrier such as dextrin, cyclodextrin, or any other auxiliary agent. Accordingly, it can be formulated into an arbitrary dosage form such as powder, granule, tablet, and liquid. In this case, as an auxiliary agent, for example, an excipient, a binder, a disintegrant, a lubricant, a stabilizer, a flavoring / flavoring agent, and the like can be used. Extracts from one or more kinds of plants selected from the group consisting of money conversion, himehagi and kotohana are used in combination with other compositions (for example, skin cosmetics, foods and drinks described later). In addition, it can be used as an ointment, a solution for external use, a patch and the like.

  The antioxidant, anti-inflammatory agent, platelet aggregation inhibitor, immunostimulant, TNF-α production promoter, anti-aging agent, anti-obesity agent or whitening agent of the present invention may have an antioxidant effect, SOD-like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action, glutathione production promoting action, anti-inflammatory action, platelet aggregation inhibiting action, immunostimulating action, TNF-α production promoting action, anti-aging action, IV Collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting action, UV damage recovery action, anti-obesity action, cyclic AMP phosphodiesterase inhibition Action, lipolysis action, whitening action, SCF mRNA expression inhibitory action or bFGF mRNA expression inhibitory action It can be used as an active ingredient by blending other natural extracts.

  As an administration method of the antioxidant, anti-inflammatory agent, platelet aggregation inhibitor, immunostimulant, TNF-α production promoter, anti-aging agent, anti-obesity agent or whitening agent of the present invention, generally transdermal administration, oral administration However, depending on the type of the disease, a suitable method for its prevention / treatment may be selected as appropriate. In addition, the dosage of the antioxidant, anti-inflammatory agent, platelet aggregation inhibitor, immunostimulant, TNF-α production promoter, anti-aging agent, anti-obesity agent or whitening agent of the present invention also depends on the type and severity of the disease. The dose may be appropriately increased or decreased depending on individual differences among patients, administration methods, administration periods, and the like.

  The antioxidant of the present invention has an SOD-like action (superoxide scavenging action), a radical scavenging action, a peroxidation possessed by an extract from one or more plants selected from the group consisting of gold inversion, himehagi and kotohana. Skin aging such as wrinkle formation and reduced elasticity, tissue damage such as rheumatoid arthritis and Behcet's disease, myocardial infarction, stroke through one or more actions selected from the group consisting of hydrogen scavenging action and glutathione production promoting action It is possible to prevent, treat or ameliorate various disorders involving active oxygen such as cataracts, spots, freckles, diabetes, arteriosclerosis, stiff shoulders and coldness. However, in addition to these uses, the antioxidant of the present invention is one or two selected from the group consisting of SOD-like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action, and glutathione production promoting action. It can be used for all purposes that are meaningful for exerting more than a kind of action.

  The anti-inflammatory agent of the present invention is a contact dermatitis (rash), psoriasis, through a platelet aggregation inhibitory action possessed by an extract from one or more plants selected from the group consisting of gold inversion, himehagi and kotohana. Various inflammatory diseases such as pemphigus vulgaris can be prevented, treated or ameliorated. However, the anti-inflammatory agent of the present invention can be used for all uses other than these uses that are meaningful for exhibiting the platelet aggregation inhibitory action.

  The platelet aggregation inhibitor of the present invention suppresses the aggregation of platelets through the platelet aggregation inhibitory action possessed by an extract from one or more plants selected from the group consisting of gold inversion, himehagi and kotohana. Various inflammatory diseases such as dermatitis (rash), psoriasis and pemphigus vulgaris can be prevented, treated or ameliorated. However, the platelet aggregation inhibitor of the present invention can be used for all applications other than these applications that are meaningful for exhibiting the platelet aggregation inhibitory action.

  The immunostimulatory agent of the present invention can be used for cancer, infectious diseases, allergic symptoms, etc. through the TNF-α production promoting action of an extract from one or more plants selected from the group consisting of gold inversion, himehagi and kotohana. It is possible to prevent, treat or improve various diseases. However, the immunostimulant of the present invention can be used for all purposes that are meaningful for exerting a TNF-α production promoting action in addition to these uses.

  The TNF-α production promoter of the present invention has a TNF-α production promoting action possessed by an extract from one or more plants selected from the group consisting of gold inversion, himehagi, and kotohana. Various diseases such as allergic symptoms can be prevented, treated or improved. However, the TNF-α production promoter of the present invention can be used for all purposes that are meaningful for exerting a TNF-α production promoting action in addition to these uses.

  The anti-aging agent of the present invention is a type IV collagen production-promoting action, estrogen-like action, epidermal keratinocyte proliferation possessed by an extract from one or more kinds of plants selected from the group consisting of gold inversion, himehagi and kotohana Skin aging through one or more actions selected from the group consisting of promoting action, fibroblast proliferation promoting action, glutathione production promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting action, and UV damage recovery action Can be prevented, treated or ameliorated. However, in addition to these uses, the anti-aging agent of the present invention has a type IV collagen production promoting action, an estrogen-like action, an epidermal keratinocyte proliferation promoting action, a fibroblast proliferation promoting action, a glutathione production promoting action, and a HAS3 mRNA expression promoting. It can be used for all purposes that are meaningful for exerting one or more kinds of actions selected from the group consisting of action, aquaporin 3 mRNA expression promoting action, and ultraviolet damage recovery action.

  The anti-obesity agent of the present invention is an obesity through a cyclic AMP phosphodiesterase inhibitory action and / or a lipolysis-promoting action possessed by an extract from one or two or more plants selected from the group consisting of gold inversion, Himehagi and Kobana Enshi. It is possible to prevent, treat or ameliorate various diseases such as symptom, associated arteriosclerosis, diabetes, and metabolic syndrome. However, the anti-obesity agent of the present invention can be used for all purposes that are meaningful for exerting a cyclic AMP phosphodiesterase inhibitory action and / or a lipolysis promoting action in addition to these uses.

  The whitening agent of the present invention has a skin pigmentation disease through an SCF mRNA expression inhibitory action and / or a bFGF expression inhibitory action possessed by an extract from one or two or more kinds of plants selected from the group consisting of gold inversion, Himehagi and Kobana Enshi. , Spots, buckwheat etc. can be prevented, treated or improved. However, the whitening agent of the present invention can be used for all purposes that are meaningful in exhibiting the SCF mRNA expression inhibitory action and / or bFGF expression inhibitory action in addition to these uses.

[Skin cosmetic]
Extracts from one or more plants selected from the group consisting of gold inversion, himehagi, and hanahana are SOD-like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action, glutathione production promoting action Platelet aggregation inhibitory action, TNF-α production promoting action, type IV collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting action, It has UV damage recovery action, cyclic AMP phosphodiesterase inhibitory action, lipolysis action, SCF mRNA expression inhibitory action or bFGF mRNA expression inhibitory action, and has excellent usability and safety when applied to the skin. Suitable for blending into cosmetics.

  In this case, the skin cosmetic may be blended with an extract from one or more plants selected from the group consisting of gold inversion, himehagi and floret distant, or a group consisting of gold inversion, himehagi and floret ambition. Antioxidants, anti-inflammatory agents, platelet aggregation inhibitors, immunostimulants, TNF-α production promoters, anti-aging agents, anti-obesity agents formulated from extracts from one or more selected plants Alternatively, a whitening agent may be blended.

  Extracts from one or more kinds of plants selected from the group consisting of gold inversion, himehagi and kotoko hana, or antioxidants, anti-inflammatory agents, platelet aggregation inhibitors, immunostimulants formulated from them, and TNF -By adding α production promoter, anti-aging agent, anti-obesity agent or whitening agent to skin cosmetics, SOD-like action (superoxide scavenging action), radical scavenging action, hydrogen peroxide scavenging action on skin cosmetics, Glutathione production promoting action, platelet aggregation inhibiting action, TNF-α production promoting action, type IV collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA Expression promoting action, UV damage recovery action, cyclic AMP phosphodiesterase inhibitory action, lipolytic action, SCF mRNA expression inhibitory action or bFGF mRNA expression inhibitory action can be imparted.

  There are no particular limitations on the type of skin cosmetic that can be blended with an extract from one or more plants selected from the group consisting of money conversion, himehagi, and kotohana, for example, ointments, creams, and emulsions. , Lotions, packs, jellies, foundations, lip balms, lipsticks, bath additives and the like.

  In the case where an extract from one or two or more plants selected from the group consisting of gold inversion, himehagi and kotohana is incorporated into skin cosmetics, the amount to be blended should be adjusted as appropriate according to the type of skin cosmetic. However, a suitable blending ratio is about 0.0001 to 10% by mass in terms of a standard extract, and a particularly suitable blending ratio is about 0.001 in terms of a standard extract. ˜1% by mass.

  The skin cosmetic composition of the present invention has an SOD-like action (superoxide scavenging action), radical scavenging action, and peroxidation possessed by an extract from one or more plants selected from the group consisting of gold inversion, himehagi and floret Hydrogen scavenging action, glutathione production promoting action, platelet aggregation inhibiting action, TNF-α production promoting action, type IV collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, HAS3 mRNA expression promoting Main agent used for the production of normal skin cosmetics, unless it interferes with the action, aquaporin 3 mRNA expression promoting action, UV damage recovery action, cyclic AMP phosphodiesterase inhibitory action, lipolysis action, SCF mRNA expression inhibitory action or bFGF mRNA expression inhibitory action, Auxiliaries or other ingredients, eg astringent , Disinfectant / antibacterial agent, whitening agent, UV absorber, moisturizer, cell activator, anti-inflammatory / antiallergic agent, antioxidant / active oxygen remover, fats and oils, waxes, hydrocarbons, fatty acids, alcohols, Esters, surfactants, fragrances and the like can be used in combination. By using in this way, it becomes a more general product, and a synergistic action with the above-mentioned components used in combination may bring about an excellent effect that is usually expected.

[Food and Drink]
Extracts from one or more kinds of plants selected from the group consisting of gold inversion, himehagi and kotohana are radical scavenging action, hydrogen peroxide scavenging action, glutathione production promoting action, platelet aggregation inhibiting action, TNF-α production Promoting action, type IV collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting action, UV damage recovery action, cyclic AMP phosphodiesterase inhibition It has been confirmed that it has an action, lipolysis action, SCF mRNA expression inhibitory action or bFGF mRNA expression inhibitory action and is not digested in the digestive tract, and is excellent in safety. It is suitable for blending.

  In this case, an extract from one or two or more kinds of plants selected from the group consisting of gold inversion, himehagi and hanahana may be blended as they are, or 1 selected from the group consisting of gold inversion, himehagi and hanahana Antioxidants, anti-inflammatory agents, platelet aggregation inhibitors, immunostimulants, TNF-α production promoters, anti-aging agents, anti-obesity agents or whitening agents formulated from seeds or extracts from two or more plants You may mix | blend.

  Extract from one or two or more kinds of plants selected from the group consisting of the above-mentioned gold inversion, himehagi and kotohana, or antioxidants, anti-inflammatory agents, platelet aggregation inhibitors, immunostimulants, and TNF- formulated therefrom When blending α production promoter, anti-aging agent, anti-obesity agent or whitening agent in foods and drinks, the amount of active ingredients in them can be appropriately changed in consideration of the purpose of use, symptoms, sex, etc. In consideration of the general intake amount of foods and drinks to be added, it is preferable that the extract intake amount per day for an adult is about 1 to 1000 mg.

  The food / beverage products of the present invention are blended with any food / beverage product that does not impede its activity with an extract from one or more kinds of plants selected from the group consisting of money conversion, himehagi and kotohana. Alternatively, it may be a dietary supplement mainly composed of an extract from one or two or more plants selected from the group consisting of money conversion, himehagi and kotohana.

  In producing the food and drink of the present invention, for example, sugars such as dextrin and starch; proteins such as gelatin, soy protein and corn protein; amino acids such as alanine, glutamine and isoleucine; polysaccharides such as cellulose and gum arabic Any additive such as oils and fats such as soybean oil and medium chain fatty acid triglycerides can be added to make foods and drinks of any shape.

  Although the food and drink which can mix | blend the extract from the 1 type (s) or 2 or more types of plant chosen from the group which consists of money conversion, himehagi, and hanahana is not specifically limited, As a specific example, a soft drink, a carbonated drink, a nutrition drink Beverages such as fruit drinks, lactic acid drinks (including concentrated concentrates and powders for preparation of these drinks); frozen desserts such as ice cream, ice sherbet and shaved ice; buckwheat, udon, harsame, gyoza skin, sushi husk, Chinese Noodles such as noodles and instant noodles; candy, chewing gum, candy, gum, chocolate, tablet confectionery, snacks, biscuits, jelly, jam, cream, baked confectionery, etc .; fishery and livestock processed foods such as kamaboko, ham, sausage Milk products such as processed milk and fermented milk; salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, Oils and processed foods such as lessings; seasonings such as sauces and sauces; soups, stews, salads, prepared dishes, pickles; various other forms of health and nutritional supplements; tablets, capsules, drinks, etc. When these foods and drinks are blended with extracts from one or more plants selected from the group consisting of the above-mentioned money conversion, himehagi and kotohana, the auxiliary ingredients and additives usually used are used in combination. Can do.

  The antioxidants, anti-inflammatory agents, platelet aggregation inhibitors, immunostimulants, TNF-α production promoters, anti-aging agents, anti-obesity agents, whitening agents, skin cosmetics or foods and beverages of the present invention are for humans. However, as long as each effect is exhibited, it can also be applied to animals other than humans.

  Hereinafter, although a manufacture example, a test example, and a compounding example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to each following example at all.

[Production Example 1] Manufacture of gold-unconverted ground part extract To 100 g of coarsely ground product of gold-unconverted ground part, 1000 mL of extraction solvent was added, kept at 80 ° C for 2 hours with gentle stirring, and filtered while hot. The obtained extract was concentrated under reduced pressure at 40 ° C. and dried with a vacuum drier to obtain a gold-unconverted ground portion extract (Samples 1 to 3). The yield of each extract when water, 50 mass% ethanol (mass ratio of water and ethanol is 1: 1), and 80 mass% ethanol (mass ratio of water and ethanol is 1: 4) are used as the extraction solvent. Is shown in Table 1.

[Production Example 2] Production of Himehagi above-ground extract To 100 g of coarsely ground product of Himehagi, 1000 mL of extraction solvent was added, kept at 80 ° C for 2 hours with gentle stirring, and filtered while hot. The obtained extract was concentrated under reduced pressure at 40 ° C., and dried with a vacuum drier to obtain a gold-unconverted ground portion extract (samples 4 to 6). The yield of each extract when water, 50 mass% ethanol (mass ratio of water and ethanol is 1: 1), and 80 mass% ethanol (mass ratio of water and ethanol is 1: 4) are used as the extraction solvent. Is shown in Table 2.

[Production Example 3] Manufacture of the above-ground extract of Enshi Kobana To 100 g of the coarsely ground product of Enshi Obana, 1000 mL of extraction solvent was added, kept at 80 ° C for 2 hours with gentle stirring, and filtered while hot. The obtained extract was concentrated under reduced pressure at 40 ° C. and dried with a vacuum dryer to obtain the above-ground extract of Kobana Enshi (Samples 7 to 9). The yield of each extract when water, 50 mass% ethanol (mass ratio of water and ethanol is 1: 1), and 80 mass% ethanol (mass ratio of water and ethanol is 1: 4) are used as the extraction solvent. Is shown in Table 3.

[Test Example 1] Superoxide scavenging action test (NBT method)
Gold-unconverted ground extract obtained in Production Example 1 (Samples 1 to 3), Himehagi ground extract obtained in Production Example 2 (Samples 4 to 6), and Kohana Enshi ground product extraction obtained in Production Example 3 The product (samples 7 to 9) was tested for superoxide scavenging action as follows.

Add 0.1 mL of 3 mM xanthine, 0.05 M Na ₂ CO ₃ buffer (pH 10.2), 3 mM EDTA, bovine serum albumin solution, and 0.75 mM NBT (nitroblue tetrazolium) to the test tube. To each sample solution, 0.1 mL of each sample solution (Samples 1 to 9) was added and left at 25 ° C. for 10 minutes. After standing, a xanthine oxidase solution as an enzyme solution was added, stirred rapidly, and allowed to stand at 25 ° C. for 20 minutes. Thereafter, 0.1 mL of 6 mM copper chloride was added to stop the reaction, and the absorbance at a wavelength of 560 nm was measured.

  Even when the enzyme solution was not added, the same operation and absorbance were measured, and the same measurement was performed when distilled water was added without adding the sample solution. From the obtained results, the superoxide elimination rate (%) was calculated by the following formula.

Superoxide erasure rate (%) = {1- (AB) / (CD)} × 100
In the above formula, A is “absorbance when enzyme solution is added / sample solution is added”, B is “absorbance when enzyme solution is not added / sample solution is added”, and C is “absorbance when enzyme solution is added / sample solution is not added”. "Absorbance", D indicates "absorbance when no enzyme solution is added / sample solution is not added".

The concentration of the sample solution was decreased stepwise to measure the superoxide elimination rate, and the sample concentration IC ₅₀ (μg / mL) at which the superoxide elimination rate was 50% was determined by interpolation.
Table 4 shows the results of the above test.

  As shown in Table 4, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-extracted extract of Kobana Enshi have an excellent superoxide scavenging action. In addition, it was confirmed that the degree of superoxide scavenging action can be adjusted by the concentration of the gold-unconverted aboveground extract, the above ground extract, or the above-extracted floret.

[Test Example 2] Radical scavenging action test Gold-exchanging aboveground extract (Samples 1 to 3) obtained in Production Example 1, Himehagi aboveground extract (Samples 4 to 6) obtained in Production Example 2 and Production Example 3 The radical scavenging action of the Kobana Enshi ground extract (samples 7 to 9) obtained by the above was tested as follows.

After 3 mL of the sample solution (Samples 1 to 9) was added to 3 mL of 1.5 × 10 ⁻⁴ M DPPH (diphenyl-p-picrylhydrazyl) ethanol solution, the solution was tightly stoppered, shaken and allowed to stand for 30 minutes. After standing, the absorbance at a wavelength of 520 nm was measured. As a control, the same operation was performed using only the solvent in which the sample was dissolved instead of the sample solution, and the absorbance at a wavelength of 520 nm was measured. Further, as a blank, after adding 3 mL of the sample solution to ethanol, the absorbance at a wavelength of 520 nm was measured immediately. From the obtained results, the radical scavenging rate (%) was calculated by the following formula.

Radical scavenging rate (%) = {1- (BC) / A} × 100
In the above formula, A represents “absorbance of control”, B represents “absorbance upon addition of sample solution”, and C represents “absorbance of blank”.

The radical scavenging rate was measured by gradually decreasing the concentration of the sample solution, and the sample concentration IC ₅₀ (μg / mL) at which the radical scavenging rate was 50% was determined by interpolation.
The results of the above test are shown in Table 5.

  As shown in Table 5, it was confirmed that the gold-unconverted ground extract, the ground extract, and the Kobana ground extract have an excellent radical scavenging action. In addition, it was confirmed that the degree of radical scavenging action can be adjusted by the concentration of the gold-unconverted aboveground extract, the above-ground extract of Himehagi or the above-extracted extract of Kobana.

[Test Example 3] Hydrogen peroxide scavenging action Gold-exchanging aboveground extract (Samples 1 to 3) obtained in Production Example 1, Himehagi aboveground extract (Samples 4 to 6) obtained in Production Example 2 and Production Example The terrestrial extract of Kobana ground obtained by 3 (samples 7 to 9) was tested for hydrogen peroxide scavenging action as follows.

  10 μL of a sample solution (samples 1 to 9) was added to 10 μL of a 1.5 mM hydrogen peroxide solution and reacted at 37 ° C. for 20 minutes, and then a coloring solution (100 mM DA-64 (manufactured by Wako Pure Chemical Industries, Ltd.), 0. 1 unit of 100 units / mL peroxidase was added to 100 mL of 0.1 M PIPES buffer (pH 7.0) containing 5% by weight Triton X-100, and the total amount was adjusted to 100 mL). Incubated for 5 minutes at ° C. Thereafter, the absorbance at a wavelength of 727 nm was measured.

  The same operation and absorbance measurement were performed when no hydrogen peroxide standard solution was added, and the same measurement was also performed when distilled water was added without adding the sample solution. From the obtained results, the hydrogen peroxide elimination rate (%) was calculated by the following formula.

Hydrogen peroxide elimination rate (%) = {1- (A−B) / (C−D)} × 100
In the above formula, A is “absorbance when hydrogen peroxide standard solution is added / sample solution is added”, B is “absorbance when hydrogen peroxide standard solution is not added / sample solution is added”, and C is “hydrogen peroxide standard” D represents the “absorbance when no hydrogen peroxide standard solution is added / sample solution is added”.

The hydrogen peroxide erasure rate was measured by gradually reducing the sample concentration, and the sample concentration IC ₅₀ (μg / mL) at which the hydrogen peroxide erasure rate was 50% was determined by interpolation.
The results of the above test are shown in Table 6.

  As shown in Table 6, it was confirmed that the gold-convertible above-ground extract, the above-ground extract of Himehagi, and the above-extracted extract of Enshi Kobana have an excellent hydrogen peroxide scavenging action. In addition, it was confirmed that the degree of hydrogen peroxide scavenging action can be adjusted by the concentration of the gold-unconverted aboveground extract, the above ground extract, or the above-extracted floret.

[Test Example 4] Glutathione production promoting action test Gold-unconverted aboveground extract (samples 1 to 3) obtained in Production Example 1, citrus aboveground extract (Samples 4 to 6) obtained in Production Example 2 and Production Example With regard to the essence extract of Kobana Zoshi obtained from 3 (samples 7 to 9), the glutathione production promoting action was tested as follows.

Human normal skin fibroblasts (NB1RGB) were cultured using α-MEM containing 10% FBS, and then cells were collected by trypsin treatment. The recovered cells were diluted with α-MEM containing 10% FBS to a cell density of 2.0 × 10 ⁵ cells / mL, then seeded at 200 μL per well in a 48-well plate, and cultured overnight. After culturing, 200 μL of a sample solution (samples 1 to 9, sample concentration: 200 μg / mL) dissolved in D-MEM containing 1% FBS was added to each well and cultured for 24 hours. After completion of the culture, the medium was removed from each well, washed with 400 μL of PBS (−), and the cells were lysed using 150 μL of M-PER (PIERCE). Using 100 μL of the cell lysate thus obtained, total glutathione was quantified as follows.

  100 μL of cell lysate, 0.1 M phosphate buffer (50 μL), 2 mM NADPH 25 μL and glutathione reductase 25 μL (final concentration 17.5 units / mL) were added and heated at 37 ° C. for 10 minutes, followed by 10 mM 5, 25 μL of 5′-dithiobis (2-nitrobenzoic acid) was added, and the absorbance at a wavelength of 412 nm until 5 minutes later was measured to obtain ΔOD / min. The total glutathione concentration was calculated based on a calibration curve prepared using oxidized glutathione. After correcting the obtained value to the glutathione amount per total protein amount, the glutathione production promotion rate (%) was calculated by the following formula.

Glutathione production promotion rate (%) = B / A × 100
In the above formula, A represents “the amount of glutathione per total amount of protein in the cell when no sample is added” and B represents “the amount of glutathione per total amount of protein in the cell when added to the sample”.
Table 7 shows the results of the above test.

  As shown in Table 7, it was confirmed that the gold-unconverted aboveground extract, the above-ground extract of Himehagi, and the above-extracted extract of Kobana Enshi have an excellent glutathione production promoting action.

[Test Example 5] Platelet aggregation inhibitory action test Gold-extracted aboveground extract obtained from Production Example 1 (Samples 1 to 3), Himehagi aboveground extract obtained from Production Example 2 (Samples 4 to 6), and Production Example With regard to the Kobana distant ground extract (samples 7 to 9) obtained in step 3, the platelet aggregation inhibitory action was tested as follows.

(1) Preparation of platelet suspension 1/10 volume of heparin sodium injection solution (Japanese Pharmacopoeia) was added to the collected rabbit blood, centrifuged (180 × g, 10 minutes, room temperature), and platelet suspension (Platelet) Rich Plasma (PRP) was obtained.

(2) Test for inhibiting platelet aggregation Next, 1 μL of 200 mmol / L calcium chloride solution was added to 223 μL of platelet suspension (PRP) and reacted at 37 ° C. for 1 minute. 1 μL of the sample solution (Samples 1 to 9) was added to this, reacted for another 2 minutes, stirred for 1 minute with a stir bar, added with 25 μL of collagen solution, and reacted for 10 minutes at 37 ° C. Aggregation rate was measured. Separately, the platelet aggregation rate was measured in the same manner as above except that the solvent of the sample solution was added instead of the sample solution as a control. From the obtained results, the platelet aggregation inhibition rate (%) was calculated by the following formula.

Platelet aggregation inhibition rate (%) = (A−B) / A × 100
In the above formula, A represents “control platelet aggregation rate”, and B represents “platelet aggregation rate at the time of sample addition”.

The above-mentioned platelet aggregation inhibition rate was measured by decreasing the sample concentration stepwise, and the sample concentration IC ₅₀ (μg / mL) at which the platelet aggregation inhibition rate was 50% was determined by interpolation.
The results of the above test are shown in Table 8.

  As shown in Table 8, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-extracted extract of Kobana Enshi have an excellent platelet aggregation inhibitory action. Moreover, it was confirmed that the degree of the platelet aggregation inhibitory effect can be adjusted by the concentration of the gold-unconverted aboveground extract, the above-ground extract of himehagi, or the above-ground extract of Kobana.

[Test Example 6] TNF-α production promoting action test Gold-extracted aboveground extract (samples 1 to 3) obtained by Production Example 1, eastern extract of sampled earth (Samples 4 to 6) obtained by Production Example 2 and About the small flower Enshi ground extract (samples 7-9) obtained by manufacture example 3, the TNF- (alpha) production promotion effect was tested as follows.

Mouse macrophage cells (RAW264.7 cells, manufactured by Dainippon Pharmaceutical Co., Ltd.) were cultured in a DMEM medium containing 10% FBS, and then the cells were collected with a cell scraper. The collected cells were diluted with 10% FBS-containing DMEM to a cell density of 1.0 × 10 ⁶ cells / mL, then seeded at 100 μL per well in a 96-well plate, and cultured for 4 hours.

  After completion of the culture, the medium was removed, and 200 μL of a sample solution (sample 1 to 9, sample concentration: 100 μg / mL) in which the sample was dissolved in DMEM containing 10% FBS containing DMSO having a final concentration of 1.0% was added to each well. Cultured for 24 hours. After completion of the culture, the amount of TNF-α in the culture supernatant of each well was measured using a sandwich ELISA method. By the same method, it measured also when the sample was not added. From the obtained results, the TNF-α production promotion rate (%) was calculated by the following formula.

TNF-α production promotion rate (%) = A / B × 100
In the above formula, A represents “TNF-α amount at the time of sample addition” and B represents “TNF-α amount at the time of no sample addition”.
Table 9 shows the results of the above test.

  As shown in Table 9, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-extracted extract of Kobana Enshi have an excellent TNF-α production promoting action.

[Test Example 7] Type IV collagen production promoting action test Gold-unconverted aboveground extract (Samples 1 to 3) obtained in Production Example 1, eastern ground extract (Samples 4 to 6) obtained in Production Example 2 and About the Kobana Enshi ground extract (samples 7-9) obtained by manufacture example 3, the IV type collagen production promotion effect was tested as follows.

Human normal fibroblasts (NB1RGB) were cultured using Dulbecco's MEM medium containing 10% FBS, and then cells were collected by trypsin treatment. The collected cells were diluted with Dulbecco's MEM medium to a cell density of 1.6 × 10 ⁵ cells / mL, then seeded at 100 μL per well in a 96-well microplate, and cultured overnight.

  After completion of the culture, the medium was removed, 150 μL of a sample solution (samples 1 to 9, sample concentration: 100 μg / mL) dissolved in 0.25% FBS-containing Dulbecco's MEM medium was added to each well and cultured for 3 days. After culture, the amount of type IV collagen in the medium of each well was measured by ELISA. From the obtained results, the type IV collagen production promotion rate (%) was calculated by the following formula.

Type IV collagen production promotion rate (%) = A / B × 100
In the above formula, A represents “amount of type IV collagen when a sample is added” and B represents a “amount of type IV collagen when no sample is added”.
The results of the above test are shown in Table 10.

  As shown in Table 10, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-extracted extract of Enshi Kobana have an excellent type IV collagen production promoting action.

[Test Example 8] Estrogen-like action test Gold-unconverted aboveground extract (samples 1 to 3) obtained by Production Example 1, himehaji aboveground extract (Samples 4 to 6) obtained by Production Example 2 and Production Example 3 The estrogen-like effect was tested as follows for the essence extract (samples 7 to 9) of the Kobana distant ground obtained by the above.

Human breast cancer-derived cells (MCF-7) were cultured in a MEM medium containing 10% FBS, 1% NEAA and 1 mmol / L sodium pyruvate, and then cells were collected by trypsin treatment. The recovered cells were treated with activated carbon-treated 10% FBS, 1% NEAA, and 1 mmol / L sodium pyruvate and no phenol red, and 3.0 × 10 ⁴ cells using MEM medium (T-MEM medium). After adjusting to a cell density of / mL, the cells were seeded in a 48-well plate at 450 μL per well and cultured to establish the cells. Six hours later (day 0), 50 μL of a sample solution (samples 1 to 9, sample concentration: 50 μg / mL) adjusted to 10 times the final concentration with T-MEM medium was added to each well, and the culture was continued. On the third day, the medium was removed, 0.5 mL of the sample solution (samples 1 to 9) adjusted to the final concentration with T-MEM medium was added to each well, and the culture was further continued.

Estrogen-like effects were measured using the MTT assay. After completion of the culture, the medium was removed, and 200 μL of MTT dissolved in a final concentration of 0.4 mg / mL in MEM medium containing 1% NEAA and 1 mmol / L sodium pyruvate was added to each well. After culturing for 2 hours, blue formazan produced in the cells was extracted with 200 μL of 2-propanol. After extraction, the absorbance at a wavelength of 570 nm was measured. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two was used as the amount of blue formazan produced. As a positive control, 1 × 10 ⁻⁹ M estradiol was used. From the obtained results, the estrogen-like action rate (%) was calculated by the following formula.

Estrogen-like action rate (%) = A / B × 100
In the above formula, A represents “absorbance when the sample solution is added”, and B represents “absorbance when no sample solution is added”.
The results of the above test are shown in Table 11.

  As shown in Table 11, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-extracted extract of Enshi Kobana have an excellent estrogen-like action.

[Test Example 9] Fibroblast proliferation promoting action test Gold-extracted above-ground extract (samples 1 to 3) obtained in Production Example 1, Himehagi above-ground extract (Samples 4 to 6) obtained in Production Example 2 and About the floret distant ground material extract (samples 7-9) obtained by manufacture example 3, the fibroblast proliferation promoting effect was tested as follows.

Human normal skin fibroblasts (NB1RGB) were cultured using α-MEM containing 10% FBS, and then cells were collected by trypsin treatment. The collected cells were diluted with α-MEM containing 5% FBS to a concentration of 7.0 × 10 ⁴ cells / mL, then seeded at 100 μL per well in a 96-well plate, and cultured overnight. After completion of the culture, 100 μL of a sample solution (samples 1 to 9, sample concentration: 200 μg / mL) dissolved in α-MEM containing 5% FBS was added to each well and cultured for 3 days.

  Fibroblast proliferation was measured using the MTT assay. After completion of the culture, 100 μL of the medium was removed from each well, and 20 μL of MTT dissolved in PBS (−) at a final concentration of 5 mg / mL was added to each well. After culturing for 4.5 hours, 100 μL of a 0.01 mol / L hydrochloric acid solution in which 10% SDS was dissolved was added to each well and incubated overnight, and then the absorbance at a wavelength of 570 nm was measured. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two was used as the amount of blue formazan produced. In addition, a blank test was performed and corrected in the same manner. From the obtained results, the fibroblast proliferation promotion rate (%) was calculated by the following formula.

Fibroblast proliferation promotion rate (%) = (St−Sb) / (Ct−Cb) × 100
In the above formula, St represents “absorbance in the cell to which the sample was added”, Sb represents “absorbance in the blank test to which the sample was added”, Ct represents “absorbance in the cell to which no sample was added”, and Cb Represents “absorbance of blank test without addition of sample”.
The results of the above test are shown in Table 12.

  As shown in Table 12, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-extracted extract of Enshi Kobana have an excellent fibroblast proliferation promoting action.

[Test Example 10] Epidermal keratinocyte proliferation promoting action test Gold-convertible above-ground extract obtained from Production Example 1 (Samples 1 to 3), Himehagi above-ground extract obtained from Production Example 2 (Samples 4 to 6) In addition, the epiphytic keratinocyte proliferating action of the floret distant ground extract (samples 7 to 9) obtained in Production Example 3 was tested as follows.

Normal human neonatal foreskin keratinocytes (NHEK) were used in a growth medium (Epilife-KG2) for long-term culture of normal human epidermal keratinocytes in an 80 cm ² flask at 37 ° C. and 5% CO ₂ -95% air. After culturing the cells, the cells were collected by trypsin treatment. The collected cells were diluted with Epilife-KG2 to a cell density of 2.0 × 10 ⁴ cells / mL, and then seeded at 100 μL per well in a collagen-coated 96-well plate and cultured overnight. Thereafter, 100 μL of a sample solution (samples 1 to 9, sample concentration: 12.5 μg / mL) in which the sample was dissolved in EpiLife-KG2 was added to each well and cultured for 3 days.

  Epidermal keratinocyte proliferation was measured using the MTT assay. After completion of the culture, the medium was removed, and 100 μL of MTT dissolved in PBS (−) at a final concentration of 0.4 mg / mL was added. After culturing for 2 hours, blue formazan produced in the cells was extracted with 100 μL of 2-propanol. After extraction, the absorbance at a wavelength of 570 nm was measured. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two was used as the amount of blue formazan produced. From the obtained results, the epidermal keratinocyte proliferation promotion rate (%) was calculated by the following formula.

Epidermal keratinocyte proliferation promotion rate (%) = St / Ct × 100
In the above formula, St represents “absorbance in cells to which a sample is added”, and Ct represents “absorbance in cells to which no sample is added”.
The results of the above test are shown in Table 13.

  As shown in Table 13, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of himehagi, and the above-extracted essence of Kobana have excellent epidermal keratinocyte proliferation promoting action.

[Test Example 11] HAS3 mRNA expression promoting action test Gold-unconverted aboveground extract (samples 1 to 3) obtained in Production Example 1, citrus aboveground extract (Samples 4 to 6) obtained in Production Example 2 and Production Example As for the essence extract of Kobana terrestrial matter (samples 7 to 9) obtained in step 3, the HAS3 mRNA expression promoting effect was tested as follows.

Normal human epidermal keratinocytes (NHEK) were cultured in a growth medium (Epilife-KG2) for long-term culture of normal human epidermal keratinocytes in an 80 cm ² flask at 37 ° C., 5% CO ₂ -95% air. The cells were precultured under the above conditions and cells were collected by trypsin treatment.

The collected cells were seeded at 40 × 10 ⁴ cells / 2 mL each in a 35 mm petri dish (manufactured by FALCON), and cultured overnight at 37 ° C. under 5% CO 2 -95% air using Epilife-KG2. After 24 hours, the culture solution was discarded, and 2 mL each of sample solutions (samples 1 to 9, sample concentration: 1 μg / mL) dissolved in Epilife-KG2 were added to each petri dish at 37 ° C., 5% CO ₂ -95% air. Cultured for 24 hours under the conditions. After culturing, the culture solution is discarded, and total RNA is extracted with ISOGEN (Nippon Gene, Cat. No. 311-02501), and the amount of each RNA is measured with a spectrophotometer so that it becomes 200 μg / mL. Total RNA was prepared.

  Using this total RNA as a template, the expression levels of HAS3 (Hyaluronan Synthase 3) and GAPDH as an internal standard were measured. Detection was performed by real-time 2 Step RT-PCR reaction using TaKaRa SYBER Prime Script RT-PCR kit (Perfect Real Time, code No. RR063A) using a real-time PCR device Smart cycler (Cepheid). The expression level of HAS3 was determined based on the total RNA preparation prepared from the cells cultured with “no sample added” and “added sample”, respectively, and a correction value was obtained from the GAPDH value. The correction value of “sample addition” when the correction value was 100 was calculated. From the obtained results, the HAS3 mRNA expression promotion rate (%) was calculated by the following formula.

HAS3 mRNA expression promotion rate (%) = A / B × 100
In the above formula, A represents “correction value when sample is added”, and B represents “correction value when sample is not added”.
The results of the above test are shown in Table 14.

  As shown in Table 14, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-ground extract of Enshi Kobana have an excellent HAS3 mRNA expression promoting action.

[Test Example 12] AQP3 mRNA expression promoting action test Gold-extracted aboveground extract obtained from Production Example 1 (Samples 1 to 3), Himehagi aboveground extract obtained from Production Example 2 (Samples 4 to 6) and Production Example About the Kobana Enshi ground extract (samples 7-9) obtained by No. 3, the AQP3 mRNA expression promotion effect was tested as follows.

Normal human epidermal keratinocytes (NHEK) were cultured in a growth medium (Epilife-KG2) for long-term culture of normal human epidermal keratinocytes in an 80 cm ² flask at 37 ° C., 5% CO ₂ -95% air. The cells were precultured under the above conditions and cells were collected by trypsin treatment.

The collected cells were seeded at 40 × 10 ⁴ cells / 2 mL in a 35 mm petri dish (manufactured by FALCON), and cultured overnight at 37 ° C. and 5% CO ₂ -95% air using Epilife-KG2. After 24 hours, the culture solution was discarded, and 2 mL each of sample solutions (samples 1 to 9, sample concentration: 1 μg / mL) dissolved in Epilife-KG2 were added to each petri dish at 37 ° C., 5% CO ₂ -95% air. Cultured for 24 hours under the conditions. After culturing, the culture solution is discarded, and total RNA is extracted with ISOGEN (Nippon Gene, Cat. No. 311-02501), and the amount of each RNA is measured with a spectrophotometer so that it becomes 200 μg / mL. Total RNA was prepared.

  Using this total RNA as a template, the expression levels of AQP3 (aquaporin3) and the internal standard GAPDH mRNA were measured. Detection was performed by real-time 2 Step RT-PCR reaction using TaKaRa SYBER Prime Script RT-PCR kit (Perfect Real Time, code No. RR063A) using a real-time PCR device Smart Cycler (Cepheid). The expression level of AQP3 was determined based on the total RNA preparation prepared from the cells cultured with “no sample added” and “added sample”, respectively, and a correction value was obtained from the GAPDH value. The correction value of “sample addition” when the correction value was 100 was calculated. From the obtained results, the AQP3 mRNA expression promotion rate (%) was calculated by the following formula.

AQP3 mRNA expression promotion rate (%) = A / B × 100
In the above formula, A represents “correction value when sample is added”, and B represents “correction value when sample is not added”.
The results of the above test are shown in Table 15.

  As shown in Table 15, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-ground extract of Enshi Kobana have an excellent AQP3 mRNA expression promoting action.

[Test Example 13] Damage recovery action test by ultraviolet irradiation Gold-exchanging aboveground extract (Samples 1 to 3) obtained in Production Example 1, Himehagi aboveground extract (Samples 4 to 6) obtained in Production Example 2 and About the Kobana Enshi ground extract (samples 7-9) obtained by manufacture example 3, the damage recovery effect by ultraviolet irradiation was tested as follows.

Human normal skin fibroblasts (NB1RGB) were cultured using α-MEM medium containing 10% FBS, and then cells were collected by trypsin treatment. The collected cells were diluted with α-MEM medium to a cell density of 2.0 × 10 ⁵ cells / mL, and then seeded at 200 μL per well in a 48-well plate. After culturing for 24 hours, the medium was replaced with 100 μL of PBS (−) and irradiated with 1.0 J / cm ² of UV-B. Immediately after irradiation, PBS (-) was removed, 400 µL of sample solution (sample 1-9, sample concentration; 25 µg / mL) dissolved in 10% FBS-containing D-MEM was added to each well, and cultured for 24 hours. .

  The damage recovery effect by ultraviolet (UV-B) irradiation was measured using an MTT assay. After completion of the culture, the medium was removed, and 200 μL of MTT dissolved at a final concentration of 0.4 mg / mL was added to each well. After culturing for 2 hours, blue formazan produced in the cells was extracted with 200 μL of 2-propanol, and after extraction, absorbance at a wavelength of 570 nm was measured. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two was used as the amount of blue formazan produced. Similarly, after seeding the cells, the cells not irradiated with UV-B and the cells irradiated with UV-B but not added with the sample solution were also measured in the same manner, and were set as a non-irradiated group and an irradiated group, respectively. From the obtained results, the damage recovery rate (%) by ultraviolet (UV-B) irradiation was calculated by the following formula.

Damage recovery rate (%) = {(Nt−C) − (Nt−Sa)} / (Nt−C) × 100
In the above formula, Nt represents “absorbance in cells not irradiated with UV-B”, C represents “absorbance in cells irradiated with UV-B but not added with a sample solution”, and Sa represents “ Absorbance at “cells irradiated with UV-B and added with sample solution” is shown.
The results of the above test are shown in Table 16.

  As shown in Table 16, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-extracted extract of Kobana distant ground have an excellent damage recovery effect by ultraviolet irradiation.

[Test Example 14] Cyclic AMP phosphodiesterase inhibitory effect test Gold-unconverted aboveground extract obtained from Production Example 1 (Samples 1 to 3), Himehagi aboveground extract obtained from Production Example 2 (Samples 4 to 6) and About the small flower Enshi ground extract (samples 7-9) obtained by manufacture example 3, the cyclic AMP phosphodiesterase inhibitory effect was tested as follows.

  0.1 mL of a 2.5 mg / mL bovine serum albumin solution, 0.1 mg / mL cyclic AMP phosphodiesterase solution in 0.2 mL of 50 mM Tris-HCl buffer (pH 7.5) containing 5 mM magnesium chloride A sample solution (samples 1 to 9) dissolved in 1 mL and 50% DMSO was added in an amount of 0.05 mL, and incubated at 37 ° C. for 5 minutes. To this reaction solution, 0.05 mL of a 0.5 mg / mL cyclic AMP solution was added and incubated at 37 ° C. for 60 minutes. The reaction was stopped by boiling on a boiling water bath for 3 minutes, this was centrifuged (2260 × g, 10 minutes, 4 ° C.), and cyclic AMP, which is a reaction substrate in the supernatant, was subjected to a high-speed liquid under the following conditions. Analyzed using chromatography. In addition, a blank test was performed in the same manner without adding the sample solution.

<High performance liquid chromatography conditions>
Product name: Chromatocorder 12 (manufactured by SYSTEM INSTRUMENTS)
Stationary phase: Wakosil 5C ₁₈ (Wako Pure Chemical Industries, Ltd.)
Column diameter: 4.6 mm
Column length: 250mm
Mobile phase: 1 mM TBAP in 25 mM KH ₂ PO ₄ : CH ₃ CN = 90: 10
Mobile phase flow rate: 1.0 mL / min
Detection: UV, 260nm

  Next, the peak area (A) of the cyclic AMP standard product, the peak area (B1) of the supernatant of the reaction solution of the cyclic AMP standard product and cyclic AMP phosphodiesterase when no sample is added, and the cyclic when the sample is added The peak area (B2) of the supernatant of the reaction solution of AMP standard product and cyclic AMP phosphodiesterase was determined. From the obtained results, the decomposition rate (C) of the cyclic AMP standard product when no sample was added and the decomposition rate (D) of the cyclic AMP standard product when the sample was added were calculated according to the following equations.

Standard product decomposition rate when no sample is added (C,%) = (1−B1 / A) × 100
Decomposition rate of standard product at the time of sample addition (D,%) = (1−B2 / A) × 100

Thereafter, the cyclic AMP phosphodiesterase inhibition rate (%) was calculated by the following formula based on the respective degradation rates (C, D) calculated by the above formula.
Cyclic AMP phosphodiesterase inhibition rate (%) = (1-D / C) × 100

The cyclic AMP phosphodiesterase inhibition rate is calculated by gradually reducing the concentration of the sample solution, and the sample concentration IC ₅₀ (μg / mL; ppm) at which the cyclic AMP phosphodiesterase inhibition rate becomes 50% is calculated by interpolation. Asked.
The results of the above test are shown in Table 17.

  As shown in Table 17, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-ground extract of Enshi Kobana have an excellent cyclic AMP phosphodiesterase inhibitory action. In addition, it was confirmed that the degree of cyclic AMP phosphodiesterase inhibitory action can be adjusted by the concentration of the gold-unconverted ground extract, the ground extract of Himehagi, or the above-ground extract of Enshi Kobana.

[Test Example 15] Lipolysis accelerating action test Gold-extracted aboveground extract obtained from Production Example 1 (Samples 1 to 3), Himehagi aboveground extract obtained from Production Example 2 (Samples 4 to 6) and Production Example With respect to the essence extract of Kobana distant ground obtained by 3 (samples 7 to 9), the lipolysis promoting action was tested as follows.

  Free adipocytes were prepared from the testicular adipose tissue of male Wistar rats (body weight 150-200 g) using collagenase solution by the method of Rodbell (Rodbell M., J. Biol. Chem., 239, 375 (1964)). did. 10 μL of a sample solution (samples 1 to 9) prepared with 50% DMSO was added to 90 μL of the obtained suspension of free adipocytes so that the final sample concentration was 400 μg / mL, and the mixture was reacted at 37 ° C. for 90 minutes. . After the reaction, the amount of fatty acid liberated in the reaction solution was measured using NEFA-C-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.). Similarly, the measurement was also performed when no sample was added. From the obtained results, the lipolysis promotion rate (%) was calculated by the following formula.

Lipolysis promotion rate (%) = A / B × 100
In the formula, A represents “the amount of free fatty acid when the sample is added”, and B represents “the amount of free fatty acid when no sample is added”.
The results of the above test are shown in Table 18.

  As shown in Table 18, it was confirmed that the gold-unconverted ground extract, the ground extract, and the Kobana distant ground extract have an excellent lipolysis promoting action.

[Test Example 16] SCF mRNA expression inhibitory action test Gold-unconverted aboveground extract (Samples 1 to 3) obtained in Production Example 1, eastern ground extract (Samples 4 to 6) obtained in Production Example 2 and Production Example About the Kobana Enshi ground extract (samples 7-9) obtained by No. 3, the SCF mRNA expression inhibitory effect was tested as follows.

Normal human epidermal keratinocytes (NHEK) were cultured in a growth medium (Epilife-KG2) for long-term culture of normal human epidermal keratinocytes in an 80 cm ² flask at 37 ° C., 5% CO ₂ -95% air. The cells were precultured under the above conditions and cells were collected by trypsin treatment.

The collected cells were seeded at 40 × 10 ⁴ cells / 2 mL in a 35 mm petri dish (manufactured by FALCON), and cultured overnight at 37 ° C. and 5% CO ₂ -95% air using Epilife-KG2. After 24 hours, the culture solution was discarded, 1 mL of HEPES buffer was added, UV-B irradiation (50 mJ / cm ² ) was performed, and then the sample solution dissolved in Epilife-KG2 (samples 1 to 9, sample concentration: 1 μg / mL, 10 μg / mL) was added to each petri dish at a rate of 2 mL, and cultured for 24 hours under conditions of 37 ° C. and 5% CO ₂ -95% air. After culturing, the culture solution is discarded, and total RNA is extracted with ISOGEN (Nippon Gene, Cat. No. 311-02501), and the amount of each RNA is measured with a spectrophotometer so that it becomes 200 μg / mL. Total RNA was prepared.

  Using this total RNA as a template, the expression level of SCF (Stem Cell Factor) and GAPDH mRNA as an internal standard was measured. Detection was performed by real-time 2 Step RT-PCR reaction using TaKaRa SYBER Prime Script RT-PCR kit (Perfect Real Time, code No. RR063A) using a real-time PCR device Smart cycler (Cepheid). The expression level of SCF was determined based on the total RNA preparations prepared from cells cultured in “UV-irradiated / no sample added”, “UV-irradiated / sample-free” and “UV-irradiated / sample added”, respectively. Then, the correction value of “UV irradiation / no sample added” and “UV irradiation / sample addition” when the correction value of “UV non-irradiation / no sample added” was set to 100 was calculated. From the obtained results, the SCF mRNA expression inhibition rate (%) was calculated by the following formula.

SCF mRNA expression inhibition rate (%) = {(A−B) − (A−C)} / (A−B) × 100
In the formula, A represents “correction value when UV irradiation is not performed and no sample is added”, B is “correction value when UV irradiation is performed and no sample is added”, and C is “correction value when UV irradiation is performed and sample is not added”. ".
The results of the above test are shown in Table 19.

  As shown in Table 19, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-ground extract of Enshi Kobana have an excellent SCF mRNA expression inhibitory action.

[Test Example 17] bFGF mRNA expression inhibitory action test Gold-unconverted above-ground extract (Samples 1 to 3) obtained in Production Example 1, Himehagi above-ground extract (Samples 4 to 6) obtained in Production Example 2 and Production Example The blossom mRNA expression suppression effect was tested as follows for the Kohana Enshi ground extract (samples 7 to 9) obtained in 3.

Normal human epidermal keratinocytes (NHEK) were cultured in a growth medium (Epilife-KG2) for long-term culture of normal human epidermal keratinocytes in an 80 cm ² flask at 37 ° C., 5% CO ₂ -95% air. The cells were precultured under the above conditions and cells were collected by trypsin treatment.

The collected cells were seeded at 40 × 10 ⁴ cells / 2 mL in a 35 mm petri dish (manufactured by FALCON), and cultured overnight at 37 ° C. and 5% CO ₂ -95% air using Epilife-KG2. After 24 hours, the culture solution was discarded, 1 mL of HEPES buffer was added, UV-B irradiation (50 mJ / cm ² ) was performed, and then the sample solution dissolved in Epilife-KG2 (samples 1 to 9, sample concentration: 1 μg / mL, 10 μg / mL) was added to each petri dish at a rate of 2 mL, and cultured for 24 hours under conditions of 37 ° C. and 5% CO ₂ -95% air. After culturing, the culture solution is discarded, and total RNA is extracted with ISOGEN (Nippon Gene, Cat. No. 311-02501), and the amount of each RNA is measured with a spectrophotometer so that it becomes 200 μg / mL. Total RNA was prepared.

  Using this total RNA as a template, the expression level of bFGF (basic fibroblast growth factor) and the internal standard GAPDH mRNA was measured. Detection was performed by real-time 2 Step RT-PCR reaction using TaKaRa SYBER Prime Script RT-PCR kit (Perfect Real Time, code No. RR063A) using a real-time PCR device Smart cycler (Cepheid). The expression level of bFGF was determined based on the total RNA preparations prepared from cells cultured in “UV-irradiated / no sample added”, “UV-irradiated / sample-free” and “UV-irradiated / sample added”, respectively. Then, the correction value of “UV irradiation / no sample added” and “UV irradiation / sample addition” when the correction value of “UV non-irradiation / no sample added” was set to 100 was calculated. From the obtained results, the bFGF mRNA expression suppression rate (%) was calculated by the following formula.

bFGF mRNA expression inhibition rate (%) = {(A−B) − (A−C)} / (A−B) × 100
In the formula, A represents “correction value when UV irradiation is not performed and no sample is added”, B is “correction value when UV irradiation is performed and no sample is added”, and C is “correction value when UV irradiation is performed and sample is not added”. ".
The results of the above test are shown in Table 20.

  As shown in Table 20, it was confirmed that the gold-unconverted above-ground extract, the above-ground extract of Himehagi, and the above-extracted extract of Kobana Enshi have an excellent bFGF mRNA expression inhibitory action.

[Formulation Example 1]
An emulsion having the following composition was produced by a conventional method.
Gold-unconverted ground extract (Production Example 1)
Jojoba oil 4.0g
Placenta extract 0.1g
Chamomile extract 0.1g
Olive oil 2.0g
Squalane 2.0g
Cetanol 2.0g
Glyceryl monostearate 2.0g
Polyoxyethylene cetyl ether (20E.O.) 2.5g
Oleic acid polyoxyethylene sorbitan (20E.O.) 2.0g
1,3-butylene glycol 3.0 g
Hinokitiol 0.15g
Fragrance 0.05g
Purified water remainder (total amount is 100 g)

[Formulation Example 2]
A cream having the following composition was produced by a conventional method.
80g ethanol extract above ground part (Production Example 2) 0.1g
Carrot extract 0.1g
Walnut extract 0.1g
Liquid paraffin 5.0g
Salami beeswax 4.0g
Cetanol 3.0g
Squalane 10.0g
Lanolin 2.0g
Stearic acid 1.0g
Oleic acid polyoxyethylene sorbitan (20E.O.) 1.5g
3.0 g glyceryl monostearate
1,3-butylene glycol 6.0 g
1.5 g of methyl paraoxybenzoate
Fragrance 0.1g
Purified water remainder (total amount is 100 g)

[Composition Example 3]
A pack having the following composition was produced by a conventional method.
Yuka Kobana Aboveground Water Extract (Production Example 3) 0.05g
Aloe extract 0.1g
Polyvinyl alcohol 15.0g
Polyethylene glycol 3.0g
Propylene glycol 7.0g
Ethanol 10.0g
0.05 g of methyl paraoxybenzoate
Fragrance 0.05g
Purified water remainder (total amount is 100 g)

[Formulation Example 4]
A lotion having the following composition was produced by a conventional method.
Gold Substrate 80% Ethanol Extract (Production Example 1) 0.05g
0.1g dipotassium glycyrrhizinate
Oil soluble licorice extract 0.1g
Glycerin 5.0g
Propylene glycol 5.0g
Polyethylene glycol 2.0g
Polyoxyethylene glycol 2.0g
7.0g ethanol
Potassium hydroxide 0.01g
Fragrance 0.01g
Butyl paraoxybenzoate 0.05g
Water-soluble pigment 0.2g
Purified water remainder (total amount is 100 g)

[Formulation Example 5]
A tablet-shaped dietary supplement having the following composition was produced by a conventional method.
50g ethanol extract above ground part (Production Example 2) 30g
178g powdered sugar (sucrose)
Sorbit 10g
Glycerin fatty acid ester 12g

[Composition Example 6]
A granular dietary supplement having the following composition was produced by a conventional method.
Kobana Enshi above ground water extract (Production Example 3) 20g
1000g beet oligosaccharide
Vitamin C 167g
Stevia extract 10g

  The antioxidant of the present invention is used for the prevention, treatment or improvement of various disorders involving active oxygen, and the anti-inflammatory agent or the platelet aggregation inhibitor of the present invention is used for the prevention, treatment or improvement of various inflammatory diseases. The immunostimulant or TNF-α production promoter is for the prevention, treatment or improvement of various diseases such as cancer, infectious diseases and allergic symptoms, and the anti-aging agent of the present invention is for the prevention, treatment or improvement of skin aging. The anti-obesity agent of the present invention is used for the prevention, treatment or improvement of various diseases such as obesity and accompanying arteriosclerosis, diabetes, metabolic syndrome, etc., and the whitening agent of the present invention is used for skin pigmentation, stains, etc. It can greatly contribute to prevention, treatment or improvement.

Claims (14)

  An antioxidant comprising, as an active ingredient, an extract from one or two or more kinds of plants selected from the group consisting of gold incongruent, himehagi and florets.   2. The extract according to claim 1, wherein the extract has one or more actions selected from the group consisting of an SOD-like action, a hydrogen peroxide scavenging action, a radical scavenging action, and a glutathione production promoting action. Antioxidants.   An anti-inflammatory agent characterized by containing, as an active ingredient, an extract from one or more plants selected from the group consisting of gold inversion, himehagi and florets.   A platelet aggregation inhibitor characterized by containing, as an active ingredient, an extract from one or more kinds of plants selected from the group consisting of gold inversion, himehagi and kotohana.   An immunostimulant characterized by containing, as an active ingredient, an extract from one or more kinds of plants selected from the group consisting of gold inversion, himehagi and florets.   A TNF-α production promoter characterized by containing, as an active ingredient, an extract from one or more kinds of plants selected from the group consisting of gold inversion, himehagi and kotohana.   An anti-aging agent characterized by containing, as an active ingredient, an extract from one or more kinds of plants selected from the group consisting of gold inversion, himehagi, and hanahana.   The extract is a type IV collagen production promoting action, estrogen-like action, epidermal keratinocyte proliferation promoting action, fibroblast proliferation promoting action, glutathione production promoting action, HAS3 mRNA expression promoting action, aquaporin 3 mRNA expression promoting action and UV damage recovery The anti-aging agent according to claim 7, wherein the anti-aging agent has one or more actions selected from the group consisting of actions.   An anti-obesity agent comprising, as an active ingredient, an extract from one or two or more kinds of plants selected from the group consisting of gold inversion, himehagi, and kotohana.   The anti-obesity agent according to claim 9, wherein the extract has a cyclic AMP phosphodiesterase inhibitory action and / or a lipolysis promoting action.   A whitening agent characterized by containing, as an active ingredient, an extract from one or more kinds of plants selected from the group consisting of gold incongruent, himehagi and kotohana.   The whitening agent according to claim 11, wherein the extract has an SCF mRNA expression-inhibiting action and / or a bFGF mRNA expression-inhibiting action.   A skin cosmetic comprising an extract from one or two or more plants selected from the group consisting of gold inversion, himehagi, and hanahana.   A food or drink comprising an extract from one or two or more plants selected from the group consisting of gold incongruity, himehagi and kotohana.