WO2018124002A1 - Composition pour l'activation de la protéine l-isoaspartate méthyltransférase - Google Patents

Composition pour l'activation de la protéine l-isoaspartate méthyltransférase Download PDF

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Publication number
WO2018124002A1
WO2018124002A1 PCT/JP2017/046510 JP2017046510W WO2018124002A1 WO 2018124002 A1 WO2018124002 A1 WO 2018124002A1 JP 2017046510 W JP2017046510 W JP 2017046510W WO 2018124002 A1 WO2018124002 A1 WO 2018124002A1
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skin
plant
pimt
protein
activity
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PCT/JP2017/046510
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English (en)
Japanese (ja)
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小百合 北川
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サントリーホールディングス株式会社
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Priority to JP2018559479A priority Critical patent/JP6944957B2/ja
Priority to CN201780074469.1A priority patent/CN110022853B/zh
Publication of WO2018124002A1 publication Critical patent/WO2018124002A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/535—Perilla (beefsteak plant)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/882—Acoraceae (Calamus family), e.g. sweetflag or Acorus calamus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the present invention relates to a composition for activating protein L-isoaspartate methyltransferase (PIMT).
  • PIMT protein L-isoaspartate methyltransferase
  • the present invention also relates to a composition for promoting restoration or repair of a protein containing an isomerized amino acid.
  • the present invention further relates to a method for activating PIMT and a method for promoting restoration or repair of a protein containing an isomerized amino acid.
  • the present invention also relates to a method for evaluating skin restoration or repair activity, a method for evaluating skin anti-aging activity, and a method for screening an active ingredient for activation of PIMT present in the skin.
  • Non-Patent Document 1 describes that D-Asp is detected from tissues such as the skin of the elderly, the crystalline lens of the eye, bones, and teeth, and that D-Asp is detected from the UV-exposed part of the skin tissue. ing.
  • PIMT Protein L-isoaspartate methyltransferase
  • An object of the present invention is to provide a composition for activating PIMT, which can activate protein L-isoaspartate methyltransferase (PIMT).
  • Another object of the present invention is to provide a new index for evaluating skin restoration or repair activity and a new index for evaluating skin anti-aging activity, and the use of this index for skin restoration or repair activity. It is to provide an evaluation method and a method for evaluating the anti-aging activity of the skin.
  • PIMT protein L-isoaspartate methyltransferase
  • the expression of PIMT in skin cells is the first finding found by the present inventors. Further, the present inventor has also found that when skin-derived protein is irradiated with ultraviolet rays, Asp isomerization in the protein is induced and the isomerized protein increases. Furthermore, the present inventor has found that the expression of PIMT in skin cells decreases due to factors such as aging and exposure to ultraviolet rays.
  • the present inventor has also conceived that skin restoration or repair activity and skin anti-aging activity can be evaluated using the expression level or activity of PIMT in the skin as an index. Furthermore, it has been conceived that by using the expression level or activity of PIMT in skin cells as an index, it is possible to screen for substances effective for PIMT activation, skin restoration or repair, and skin anti-aging which are present in the skin.
  • the present invention includes the following composition for PIMT activation, method for evaluating skin restoration or repair activity, and the like.
  • the composition for activating protein L-isoaspartate methyltransferase (PIMT) of the present invention comprises a birch plant, a birch plant, a grape plant, a leguminous soybean plant, a buckwheat plant, a perilla plant, a mandarin orange
  • the plant extract has an effect of activating PIMT.
  • the PIMT activation composition of the present invention is preferably a PIMT activation composition present in the skin.
  • the plant extract is useful for PIMT activation (in the skin) present in the skin.
  • the plant extract is preferably an extract of one or more plants selected from the group consisting of birch, grape, soybean, hop, lavender, sage, enmiso, yuzu, perilla, shobu, arnica and peach. . These plant extracts are preferred because they have a high effect of activating PIMT. Since the action of activating PIMT is particularly high, the plant extract is more preferably an extract of one or more kinds of plants selected from the group consisting of birch, grape, soybean, lavender, sage and enamel. preferable.
  • composition for activating PIMT of the present invention is preferably an external preparation for skin, and more preferably a cosmetic.
  • the composition for PIMT activation is food-drinks.
  • the composition for promoting the restoration or restoration of a protein containing an isomerized amino acid comprises a birch family, birch plant, grapevine grape plant, legume soybean plant, Asaaceae plant, Lamiaceae plant, Citrus family An extract of one or more kinds of plants selected from the group consisting of mandarin orange plants, rosaceae genus plants, asteraceae arnica plants and rose peach plants is included.
  • the composition for promoting restoration or repair of a protein containing an isomerized amino acid of the present invention is preferably a composition for promoting restoration or repair of a protein containing an isomerized amino acid in the skin.
  • the plant extract is preferably an extract of one or more kinds of plants selected from the group consisting of birch, grape, soybean, hop, lavender, sage, enamel, yuzu, perilla, shobu, arnica and peach. More preferred is an extract of one or more plants selected from the group consisting of vine, soybean, lavender, sage and enamel. Since these plant extracts have a high effect of activating PIMT, they have a high effect of promoting restoration or repair of proteins containing isomerized amino acids.
  • the composition for promoting restoration or repair of protein of the present invention is preferably an external preparation for skin, and more preferably a cosmetic. Moreover, as an example of another preferable aspect in this invention, it is also preferable that the composition for protein restoration
  • the present invention includes birch family birch plant, grape family grape plant, leguminous soybean plant, Asaaceae caladium plant, Lamiaceae plant, citrus family mandarin plant, Dermatoaceae genus plant, asteraceae Arnica plant and Also included is a method for activating protein L-isoaspartate methyltransferase (PIMT), wherein an extract of one or more plants selected from the group consisting of Rosaceae peaches is applied to animals.
  • PIMT protein L-isoaspartate methyltransferase
  • the present invention includes birch family birch plant, grape family grape plant, leguminous soybean plant, Asaaceae caladium plant, Lamiaceae plant, citrus family mandarin plant, Dermatoaceae genus plant, asteraceae Arnica plant and Also included is a method for promoting restoration or repair of a protein containing an isomerized amino acid, wherein an extract of one or more plants selected from the group consisting of Rosaceae peaches is applied to animals.
  • the present invention also includes a method for accelerating the restoration or repair of a protein containing an isomerized amino acid in the skin, which activates protein L-isoaspartate methyltransferase (PIMT) present in human skin.
  • PIMT protein L-isoaspartate methyltransferase
  • the method for evaluating skin restoration or repair activity of the present invention uses the expression level or activity of protein L-isoaspartate methyltransferase (PIMT) in skin cells as an index.
  • the skin cells are preferably epidermal cells and / or dermal cells.
  • Examples of the skin restoration or repair activity include skin restoration or repair activity against ultraviolet and / or aging-induced skin aging.
  • the evaluation method of the present invention is preferably used for evaluating skin restoration or repair activity against amino acid isomerization due to ultraviolet rays and / or aging.
  • the skin anti-aging evaluation method of the present invention uses the expression level or activity of protein L-isoaspartate methyltransferase (PIMT) in skin cells as an index.
  • PIMT protein L-isoaspartate methyltransferase
  • it is preferable that the anti-aging activity is anti-aging activity against skin aging caused by ultraviolet rays and / or aging.
  • the method for evaluating the anti-aging activity of the skin of the present invention is preferably used for evaluating the anti-aging activity against ultraviolet aging and / or aging of the skin.
  • the present invention relates to activation of PIMT present in skin, promotion of restoration or repair of skin, or anti-aging of skin, based on the expression level or activity of protein L-isoaspartate methyltransferase (PIMT) in skin cells
  • PIMT protein L-isoaspartate methyltransferase
  • the screening method of the active ingredient for this is also included.
  • the screening method of the present invention uses the expression level or activity of PIMT in skin cells as an index, whereby a substance having an activation action of PIMT present in the skin, a substance having a skin restoration or repair promoting action, or skin It is possible to screen for a substance having an anti-aging action.
  • the screening method of the present invention comprises a step of contacting a test substance with the skin cells and measuring the expression level or activity of PIMT in the skin cells, and When the expression level or activity of PIMT in skin cells contacted with the test substance is larger than the expression level or activity of PIMT in skin cells not contacted with the test substance, the test substance is used as an active ingredient. It is preferable to include a step of selecting.
  • the skin cells are preferably cultured skin cells.
  • PIMT protein L-isoaspartate methyltransferase
  • the present invention also includes the following uses.
  • PIMT protein L-isoaspartate methyltransferase
  • birch family birch plant
  • grapevine grape plant legume family soybean plant
  • Asaaceae plant Labiatae plant
  • citrus family mandarin orange Use of an extract of one or more kinds of plants selected from the group consisting of plants, Camelliaaceae plants, Compositae plants Arnica plants and Rosaceae peach plants.
  • Birch family Birch plant, Grapevine plant, Legume family, Soybean plant, Lamiaceae plant, Lamiaceae plant, Citrus mandarin plant for restoring or repairing proteins containing isomerized amino acids, Use of an extract of one or more kinds of plants selected from the group consisting of the family Chrysaceae, the family Chrysanthemum, Arnica, and the family Rosaceae.
  • the composition for PIMT activation which can activate PIMT can be provided.
  • activating PIMT present in the skin according to the present invention restoration or repair of proteins containing amino acids isomerized in the skin can be promoted.
  • a new index for evaluating skin restoration or repair activity and a new index for evaluating skin anti-aging activity can be provided.
  • a substance having an activation action of PIMT present in the skin a substance having a skin restoration or repair promoting action, and a substance having an anti-aging action of skin can be screened.
  • FIG. 1 is a graph showing the expression level of PIMT in skin cells.
  • FIG. 2 is a graph showing the amount of SAH produced per protein amount by ultraviolet B wave (UVB) irradiation.
  • FIG. 3 is a graph showing PIMT expression levels in skin fibroblasts having different passage numbers.
  • FIG. 4 is a graph showing changes in PIMT expression level of dermal fibroblasts due to stress loading.
  • an isomerized amino acid (also referred to as an isomerized amino acid) is an isomer of L-aspartic acid produced by isomerization of L-aspartic acid (L-Asp) or L-asparagine (L-Asn). (Isomerized aspartic acid). More specifically, isomerized aspartic acid (isomerized Asp) is D-aspartic acid (D-Asp), D-type or L-type isoaspartic acid (D- or L-isoAsp), preferably D-Asp and L-isoAsp. D-isoAsp and L-isoAsp are also called D- ⁇ -Asp and L- ⁇ -Asp, respectively.
  • isomerization of amino acids means that L-Asp or L-Asn becomes isomerized aspartic acid.
  • a protein containing an isomerized amino acid (amino acid residue) is also referred to as an isomerized protein.
  • the number of isomerized amino acids (isomerized amino acid residues) in the isomerized protein may be one, or two or more.
  • the isomerized protein can be said to be a protein denatured by amino acid isomerization.
  • This isomerization of amino acids in proteins is considered to be related to various aging phenomena.
  • L-Asp converting the isomerized amino acid in the isomerized protein to L-Asp (restoration or repair)
  • the protein denatured by isomerization is restored to the original state (the state before isomerization, the state before denaturation), or , It can be restored to a state close to the original state.
  • the restoration or repair of the isomerized protein in the present invention is performed by converting the isomerized Asp in the isomerized protein into L-Asp, or the protein denatured by the isomerization of amino acids (the state before the isomerization). State, state before denaturation), or restoration to a state close to the original state.
  • the conversion of isomerized Asp in isomerized protein to L-Asp means that at least a part of isomerized Asp in isomerized protein is converted to L-Asp, and all isomerized Asp is converted to L-Asp. -Not limited to conversion to Asp.
  • PIMT has an action of promoting the conversion (restoration or repair) of isomerized amino acids in proteins to normal L-amino acids. More specifically, PIMT has an action of promoting the conversion of isomerized Asp, L-isoAsp and D-Asp, into L-Asp. Therefore, activation of PIMT can promote restoration or repair of isomerized proteins. For example, activation of PIMT present in the skin can promote restoration or repair of isomerized proteins in the skin. As a result, the function of the skin protein impaired by the isomerization of L-Asp and / or L-Asn can be restored to the original state or a state close to the original state.
  • Activation of PIMT is any action that enhances or promotes the action of PIMT, such as enhanced expression of PIMT, promotion of expression of PIMT, suppression of decrease in expression of PIMT, recovery of expression of PIMT, etc., any action that suppresses reduction of the action Is included.
  • composition for activating PIMT comprises a birch family, birch plant, grapevine grape plant, leguminous soybean plant, Asaaceae plant, scorpionaceae plant, citrus family mandarin plant, ginger family An extract of one or more plants selected from the group consisting of Archiaceae Arnica plants and Rosaceae peach plants.
  • the plant extract has an effect of activating PIMT. Therefore, these plant extracts are preferably used as active ingredients in the PIMT activation composition.
  • the plant extract is also effective for the restoration or restoration promotion of a protein containing an isomerized amino acid, and can be used as an active ingredient of a composition for promoting the restoration or restoration of a protein containing the isomerized amino acid.
  • a composition for promoting restoration or repair of a protein containing an isomerized amino acid (hereinafter also referred to as a composition for promoting restoration or repair of an isomerized protein) containing the extract of one or more kinds of plants described above is also 1 of the present invention.
  • the composition for activating PIMT and the composition for promoting restoration or repair of isomerized protein of the present invention usually contain the above plant extract as an active ingredient.
  • the PIMT activation composition is suitable as a PIMT activation composition present in the skin.
  • the composition for promoting restoration or repair of isomerized proteins is suitable as a composition for promoting restoration or repair of proteins containing isomerized amino acids in the skin.
  • the above-mentioned one or two or more kinds of plant extracts can be used.
  • the composition for activating PIMT and the composition for promoting restoration or restoration of isomerized protein of the present invention include extracts of two or more kinds of plants, they may belong to the same genus, and may belong to different genera. It may be a plant to which it belongs.
  • the birch family (Betula pendula or Betula alba) include birch (Betula pendula or Betula alba).
  • the Vitaceae Vitis plant include grape (Vitis spp.).
  • Grape varieties are not particularly limited, and examples include black grapes such as Cabernet Sauvignon, Concord, Merlot, Muscat Berry A; white grapes such as Chardonnay and Koshu. Among them, black grapes are preferable, and Cabernet Sauvignon, Merlot and the like are more preferable.
  • leguminous soybean (Fabaceae Glycine) plant examples include soybean (Glycine max).
  • Examples of the Cannabaceae Humulus plant include hops (Humulus lupulus).
  • Lamiaceae plants include Lavandula (Lavandula angustifolia), Lavandula; Salvia officinalis, Salvia; Rabdosia japonica (Isodon japonicus) or Rabdosia trichocarpa (Isodon) ) And other Perilla plants such as Perilla frutescens var. Crispa.
  • Citrus junos is an example of the Rutaceae Citrus plant.
  • Examples of the plant belonging to the genus Acoraceae Acorus include alum (Acorus calamus).
  • An example of the Asteroideae Arnica plant is Arnica montana.
  • a peach (Amygdalus persica) is mentioned as a Rosaceae peach genus (Rosaceae Amygdalus) plant.
  • birch family birch plant, grape family, leguminous soybean plant, Asaaceae plant, Paramecium plant (preferably a plant belonging to the genus Lavandra, Akigiri or Hyundai) Extracts of one or more kinds of citrus, citrus, rosaceae, and peach genus plants are preferred, birch, birch, vine, vine, soybean, genus More preferred are extracts of the plant of the genus Calamander and Lamiaceae, and the extract of the plant of Birchaceae, Birch, Grapevine, Leguminosae, and Lamiaceae is more preferred.
  • the birch, grape, soybean, hop, lavender, sage, enmiso, yuzu, perilla, shobu, arnica, peach extract is preferable because of its high effect of activating PIMT present in the skin, birch, More preferred is an extract of grape, soybean, hop, lavender, sage, enamel, and ginger, more preferred is an extract of birch, grape, soybean, hop, lavender, sage, and enamel, and birch, grape, soybean, lavender, sage, An extract of enamel is more preferred, and an extract of birch, grape, soybean, and lavender is even more preferred.
  • birch extract, grape extract and soybean extract are particularly preferable as the plant extract, and birch extract and grape extract are most preferable. It is preferable to use the extract of these 1 type, or 2 or more types of plants.
  • any part of the above plant for example, root, rhizome, stem, leaf, branch, bark, flower, seed (including seed coat, embryo, endosperm, hypocotyl, cotyledon, etc.), fruit (Including pulp, peel), or a combination of these.
  • a plant extract can be produced by extracting any part of the plant with a solvent.
  • part for producing the extract of a plant the following site
  • an extract of the following site of a plant is preferable.
  • the birch of the birch family Birch is preferably bark.
  • Grapes belonging to the genus Grapeaceae are preferably fruits, seed coats and / or seeds, more preferably fruit peels and seeds.
  • the soybean of the leguminous soybean genus preferably uses seeds, more preferably germ (soybean bud).
  • flowers are preferred.
  • Lamiaceae plants it is preferable to use flowers of Lavandula lavender, flowers of Akigiri sage and Perilla of Leaves, and leaves and / or stems of Prunus genus. It is preferable to use a fruit for the Citrus citrus genus. It is preferable to use roots for the alum of the genus Aceraceae.
  • Arnica belonging to the genus Arnica preferably uses flowers. It is preferable to use seeds for peaches belonging to the family Rosaceae.
  • the plant part may be subjected to the extraction step as it is, or may be subjected to the extraction step after being pulverized, cut or dried.
  • the extraction method of a plant is not specifically limited, It can obtain by the normal extraction method used for extraction of a plant component.
  • the extraction method can be set as appropriate, and the extraction conditions are not particularly limited. For example, it is preferable to obtain by extracting each part of the plant at room temperature or under heating. At the time of extraction, operations such as stirring may be appropriately performed.
  • the solvent (extraction solvent) used for the plant extraction can be appropriately selected, and those usually used for the extraction of plant components can be used.
  • an extraction solvent for example, water; lower monohydric alcohol having 1 to 5 carbon atoms such as methanol, ethanol, propanol, butanol, pentanol; ethylene glycol, propylene glycol, 1,2-butylene glycol, 1,3-butylene glycol
  • Polyhydric alcohols such as 1,4-butylene glycol and 2,3-butylene glycol; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate and ethyl acetate; chain and cyclic ethers such as tetrahydrofuran and diethyl ether; polyethylene glycol And polyethers such as squalane.
  • the lower monohydric alcohol is preferably a monohydric alcohol having 1 to 4 carbon atoms, more preferably having 2 to 4 carbon atoms, and even more preferably ethanol.
  • the polyhydric alcohol is preferably a divalent or trivalent alcohol, and more preferably a divalent alcohol.
  • the polyhydric alcohol is preferably a polyhydric alcohol having 2 to 4 carbon atoms, and more preferably 1,3-butylene glycol.
  • the extraction solvent water, lower monohydric alcohol, polyhydric alcohol, squalane, or a mixed solvent of two or more of these is preferable, and water, lower monohydric alcohol, polyhydric alcohol, or a mixed solvent of two or more of these is used. More preferred. In one embodiment, for example, water, lower monohydric alcohol or an aqueous solution thereof, polyhydric alcohol or an aqueous solution thereof, squalane and the like are more preferable as the extraction solvent, such as water, ethanol, an aqueous ethanol solution, 1,3-butylene glycol, , 3-butylene glycol aqueous solution, squalane and the like are more preferable.
  • the lower monohydric alcohol aqueous solution preferably ethanol aqueous solution
  • the polyhydric alcohol aqueous solution preferably have an alcohol concentration of 10 to 98% by volume, more preferably 30 to 95% by volume, and still more preferably 50 to 95% by volume.
  • the above solvent extract is preferable.
  • Birch family Birch plant Grapevine plant, Asaaceae genus plant, Lamiaceae plant (preferably a plant belonging to the genus Lavandra, Akigiri genus or Dermatophaceae), Rutaceae mandarin plant, Drosophila
  • the extract of the genus Camellia and the genus Rosaceae is preferably an extract of a lower monohydric alcohol aqueous solution.
  • the extract of the leguminous soybean genus plant is preferably a water extract.
  • the Labiatae plant is preferably an extract of an aqueous polyhydric alcohol solution.
  • An acid or alkali may be added during extraction to adjust the pH of the extraction solvent. After the extraction, it is preferable to remove the plant residue (the plant body after extraction or its part) from the extract.
  • a method for removing the plant residue from the extract is not particularly limited, and examples thereof include known separation means such as filtration and centrifugation.
  • a plant extraction method for example, the following method can be used.
  • the plant material or dried product is pulverized, and the extraction solvent is added in an amount of 5 to 20 times by mass, and at normal pressure and room temperature, preferably 10 minutes to 15 days, more preferably 30 minutes to 10 days, more preferably 1 hour Extract for about 7 days, or extract for about 10 minutes to 1 day (more preferably about 10 minutes to 2 hours) near the boiling point of the extraction solvent, and then filter to obtain a filtrate.
  • the obtained filtrate plant extract
  • a plant extract obtained by extraction can be used as a plant extract as it is.
  • the plant extract may be diluted with an appropriate solvent to obtain a plant extract, or may be concentrated or dried to obtain a concentrate or a dry powder, or may be used as a paste.
  • concentration method and the drying method are not particularly limited, and known methods such as freeze drying and spray drying can be used.
  • the dry powder can also be used by dissolving or suspending it in a solvent.
  • the above-described plant extract, its concentrate, and dry powder may be further purified by deodorization, decolorization, etc., if necessary, as long as the effects of the present invention are not impaired. Such a purification method may be carried out by arbitrarily selecting ordinary means.
  • filtration a method using various chromatographies such as column chromatography using a support such as ion exchange resin, synthetic adsorption resin, activated carbon, etc.
  • carriers used for chromatography include Diaion HP-20 15L (product name, manufactured by Mitsubishi Chemical Corporation), Sephadex LH-20 (product name, manufactured by GE Healthcare), and the like.
  • the plant extract in the present invention includes various solvent extracts obtained by the extraction method as described above, dilutions thereof, concentrates thereof or dry powders thereof, and purified products thereof. Moreover, a commercial item can also be used as said plant extract.
  • the plant extract can be used for activation of PIMT, restoration of proteins containing isomerized amino acids, or promotion of repair.
  • the plant extract may be used for cosmetics (cosmetic composition), pharmaceuticals (pharmaceutical compositions), quasi-drugs (PIMT) used to activate PIMT, restore isomerized proteins, or promote restoration. (Quasi-drug composition), food / beverage products (food / beverage product compositions), etc.
  • the plant extract is blended in cosmetics, pharmaceuticals, quasi drugs, foods and drinks, and the like, and may be an active ingredient for activating PIMT, restoring isomerized proteins, or promoting restoration.
  • the activation of PIMT is preferably activation of PIMT present in the skin.
  • the restoration or repair of the isomerized protein is preferably the restoration or repair of the isomerized protein in the skin.
  • PIMT When the plant extract is used, PIMT can be activated as compared with the case where the plant extract is not used. For example, when the plant extract is used, the expression level of PIMT in the skin can be increased. In addition, for example, it is possible to suppress a decrease in PIMT expression in the skin due to factors such as exposure to ultraviolet rays.
  • the plant extract can restore PIMT expression in the skin that has been reduced by factors such as UV exposure.
  • the plant extract may have a decreased PIMT in the skin in order to promote the expression of PIMT in the skin and to suppress the decrease in the expression of PIMT in the skin (for example, the decrease in expression due to UV exposure or aging). It can be used as an active ingredient for the recovery of expression.
  • the skin-derived protein when the skin-derived protein is irradiated with ultraviolet rays, the isomerized protein increases.
  • the expression level of PIMT in the skin decreases due to factors such as aging and ultraviolet rays. From these findings, it is presumed that accumulation of isomerized proteins in the skin is promoted by factors such as aging and ultraviolet rays. Skin protein denaturation due to amino acid isomerization is thought to be associated with skin aging.
  • the activation of PIMT present in the skin promotes the restoration or repair of isomerized proteins in the skin. For example, it is effective in promoting the recovery of aging skin (skin state or skin function), preventing or improving skin aging, etc. It is thought that.
  • Aging includes one or both of aging due to aging (physiological aging accompanying aging) and aging due to ultraviolet light (photoaging due to exposure to ultraviolet light). Prevention includes prevention and delay of the onset of symptoms. Improvement includes amelioration of symptoms, suppression of progression of symptoms and complete improvement.
  • the composition for activating PIMT and the composition for promoting restoration or restoration of isomerized protein of the present invention comprising the plant extract are effective for activating PIMT existing in skin, restoring isomerized protein in skin, or promoting restoration. It is.
  • the above plant extract is applied to, for example, people who are concerned about skin aging, or who wants to prevent or improve skin aging symptoms, etc., for promoting skin recovery, preventing or improving skin aging, etc. It can be preferably used.
  • the use of the plant extract for the purpose may be therapeutic or non-therapeutic. “Non-therapeutic” is a concept that does not involve medical practice, that is, a concept that does not include methods for surgery, treatment or diagnosis of humans.
  • the form of the composition for activating PIMT and the composition for promoting restoration or restoration of isomerized protein of the present invention is not particularly limited, and may be powder, granule, paste, solid, etc. It may be selected as appropriate.
  • the above plant extract alone is a composition for PIMT activation (also referred to as PIMT activator), a composition for restoring or restoring isomerized protein (referred to as a restoration or repair accelerator for isomerized protein) Can also be used.
  • a composition for activating PIMT activation also referred to as PIMT activator
  • a composition for restoring or restoring isomerized protein referred to as a restoration or repair accelerator for isomerized protein
  • other components may be blended to provide a composition for activating PIMT and a composition for promoting restoration or restoration of isomerized proteins.
  • compositions for PIMT activation and the composition for promoting restoration or restoration of isomerized protein of the present invention can be provided in the form of an agent as an example, but is not limited to this form.
  • the agent can be provided as it is as a composition or as a composition containing the agent.
  • the composition for activating PIMT and the composition for promoting restoration or restoration of isomerized protein of the present invention can be used for various applications such as pharmaceuticals, quasi drugs, cosmetics, and foods and drinks.
  • the composition for activating PIMT and the composition for promoting the restoration or repair of isomerized protein of the present invention are itself a pharmaceutical, pharmaceutical for activating PIMT, restoring or repairing a protein containing an isomerized amino acid It may be a quasi-drug, a cosmetic or a food or drink, or may be a material or a formulation used by blending with the pharmaceutical, a quasi-drug, a cosmetic or a food or drink.
  • composition for activating PIMT and the composition for promoting restoration or restoration of isomerized protein of the present invention are suitably used, for example, as an external preparation for skin.
  • the external preparation for skin includes pharmaceuticals, quasi drugs, and cosmetics (cosmetics), preferably cosmetics.
  • a composition for activating PIMT and a composition for promoting restoration or repair of isomerized protein when used for PIMT activation in skin, or for promoting restoration or repair of isomerized protein in skin
  • the product is an external preparation for skin, and cosmetics are more preferable.
  • the skin external preparation containing the plant extract is preferably used as a skin external preparation for activating PIMT existing in the skin; a skin external preparation for promoting restoration or repair of isomerized proteins in the skin.
  • the composition for activating PIMT and the composition for promoting restoration or restoration of isomerized protein of the present invention can also be used as pharmaceuticals or quasi-drugs other than external preparations for skin.
  • it is also preferable that the PIMT activation composition and the isomerized protein restoration or repair promoting composition be food or drink.
  • the food / beverage products containing the plant extract are preferably used, for example, for activating PIMT in the skin or for promoting restoration or repair of isomerized proteins in the skin.
  • the food / beverage products containing the plant extract can be used as a food / beverage product for activating PIMT existing in the skin, or a food / beverage product for promoting restoration or repair of isomerized proteins in the skin.
  • PIMT activation composition of the present invention and the composition for promoting restoration or restoration of isomerized protein are used as pharmaceuticals, quasi drugs, skin external preparations such as cosmetics, foods and drinks, etc. will be described below.
  • composition for PIMT activation and the composition for promoting restoration or restoration of isomerized protein of the present invention are used as a skin external preparation (skin external preparation for PIMT activation, skin external preparation for promoting restoration or restoration of isomerized protein)
  • skin external preparation for PIMT activation skin external preparation for promoting restoration or restoration of isomerized protein
  • the dosage form and the like are not particularly limited, and may be any form such as a solution, emulsion, cream, gel, powder, aerosol, mist, capsule, and sheet.
  • the external preparation for skin is preferably a cosmetic.
  • the product form of the cosmetic is not particularly limited.
  • skin care cosmetics such as face wash, makeup remover, lotion, cosmetic liquid, pack, milky lotion, cream, sunscreen; foundation, makeup base, lipstick, eye shadow, eye
  • Makeup cosmetics such as liner, mascara, eyebrow, blusher, nail enamel
  • hair cosmetics such as hair shampoo, hair rinse, hair styling, hair dye, hair restorer
  • detergents such as soap and body soap
  • the plant extract may be used alone.
  • components such as carriers, additives, etc. that are acceptable for cosmetics, such as water, alcohols, oils, surfactants, thickeners, in the range not impairing the effects of the present invention.
  • Metal soap, gelling agent, powder, chelating agent, water-soluble polymer, film forming agent, resin, inclusion compound, antibacterial agent, deodorant, salt, pH adjuster, ultraviolet absorber, animals and plants other than the above -One or more of microorganism-derived extracts, keratolytic agents, enzymes, hormones, other vitamins, moisturizers, bactericides, anti-inflammatory agents, fragrances and the like can be appropriately contained.
  • Cosmetics can be manufactured by a general manufacturing method. For example, it can be obtained by mixing the plant extract and the component 1 or 2 or more that can be used in the cosmetic, and then processing it into a desired form.
  • the above-mentioned plant extract may be used alone, and the plant extract and carriers, additives, etc. acceptable for the drug or quasi-drug It may be used in combination with these components.
  • examples of such components include one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants and the like, and these can be used as necessary.
  • Pharmaceutical products and quasi drugs can be produced by a general production method. For example, it can be obtained by mixing the plant extract and one or more components that can be used in a pharmaceutical or quasi-drug, and then processing the mixture into a desired form.
  • the content of the plant extract in the external preparation for skin such as cosmetics is not particularly limited.
  • the mass of the extract in terms of dry matter is preferably 0.0000001 to 100% by mass in the external preparation for skin. 0.000001 to 100% by mass is more preferable, 0.00001 to 99.9% by mass is further preferable, and 0.00001 to 10% by mass is particularly preferable.
  • the composition for activating PIMT and the composition for accelerating restoration or repair of isomerized protein of the present invention can be a pharmaceutical other than the above-mentioned external preparation for skin and quasi-drug.
  • Such pharmaceuticals or quasi drugs may be administered orally or parenterally.
  • the medicinal product or quasi-drug can be in the form of an orally administered preparation (internal use) or a parenteral preparation.
  • the dosage form of the orally administered preparation include liquids, tablets, powders, fine granules, granules, dragees, capsules, suspensions, emulsions, chewables and the like.
  • dosage forms of parenteral preparations include injections and infusions.
  • the above plant extract may be used alone, and the plant extract and components such as carriers and additives that are acceptable for the pharmaceuticals or quasi drugs. May be used in combination.
  • examples of such components include one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, corrigents, and the like, which can be used as necessary.
  • Pharmaceutical products and quasi drugs can be produced by a general production method. For example, it can be obtained by mixing the plant extract and one or more components that can be used in a pharmaceutical or quasi-drug, and then processing the mixture into a desired form.
  • the content of the plant extract in a pharmaceutical or quasi-drug other than the external preparation for skin is not particularly limited, and is, for example, 0. It is preferably from 000001 to 100 mass%, more preferably from 0.000001 to 100 mass%, further preferably from 0.00001 to 99.9 mass%, particularly preferably from 0.00001 to 10 mass%.
  • the food or drink is not particularly limited.
  • general food and drink, health food, functional indication Examples include foods and foods for specified health use.
  • the form of the food or drink is not particularly limited.
  • the above health food, functional indication food, and food for specified health use are various preparations such as liquids, tablets, powders, fine granules, granules, dragees, capsules, suspensions, emulsions, chewables, liquid foods, etc. It can also be in the form.
  • the plant extract may be used alone, and the ingredients acceptable for the food and drink, for example, other food and drink materials, additives and the like mixed in the food and drink, It is good also as food / beverage products for PIMT activation (food / beverage product composition for PIMT activation), food / beverage products for restoration
  • Such food and drink can be manufactured by a general manufacturing method. For example, what is necessary is just to mix
  • the content of the plant extract in the food or drink is not particularly limited, and for example, the weight of the extract in terms of dry matter is preferably 0.0000001 to 100% by weight, and 0.000001 to 100% in the food or drink. % By mass is more preferable, 0.00001 to 99.9% by mass is further preferable, and 0.00001 to 10% by mass is particularly preferable.
  • the usage amount of the pharmaceutical, quasi-drug, cosmetic, or food or drink is not particularly limited, and can be appropriately set according to the condition, weight, sex, age, or other factors of the subject.
  • the above-mentioned plant extract (in terms of dry matter) is, for example, 0.01 to 500 mg per day per adult (60 kg).
  • the dose when a pharmaceutical product or quasi-drug is orally administered is preferably, for example, 0.01 to 500 mg as a plant extract (in terms of dry matter) per day per adult (60 kg), for example. .
  • the intake is preferably, for example, 0.01 to 500 mg as an extract of the above plant (in terms of dry matter) per day per adult (60 kg).
  • the above amount of plant extract can be applied, ingested or administered in single or multiple doses.
  • the target of application of the above-mentioned pharmaceuticals, quasi drugs, cosmetics or foods and drinks is not particularly limited, and can be applied to humans or non-human mammals, but humans (people) are preferred.
  • an application target for example, a person who desires or requires activation of PIMT (preferably activation of PIMT in the skin), restoration of isomerized protein, or promotion of restoration (preferably restoration of isomerized protein in skin or Those who desire or need repair promotion are preferred.
  • a person who is concerned about aging of the skin a person who wants to prevent or ameliorate skin aging symptoms, a person who needs to improve, a recovery of aging skin, prevention or improvement of skin aging Those who want or who need it are preferred.
  • the body part to which the external preparation for skin such as cosmetics is applied is not particularly limited, but when used for the above purpose, for example, the skin of the part where aging is anxious, the part where prevention or improvement of aging symptoms is desired It is preferable to apply to the skin of the skin and the skin of the site
  • the method of the present invention is effective, for example, in promoting the recovery of aging skin (skin state or skin function), preventing or improving skin aging.
  • Examples of a method for activating PIMT present in human skin include a method in which the above plant extract is applied to humans.
  • a method of applying the plant extract to human skin a method of applying the plant extract by administering or ingesting it to a human, and the like can be mentioned.
  • the plant extract is applied to human skin.
  • the plant extract is as described in the above-mentioned composition for PIMT activation.
  • the plant extract can be applied in the form of the above-mentioned external preparations for skin, pharmaceuticals, quasi drugs, foods and drinks and the like.
  • Birch family Birch plant Grape family Grape plant, Legume family Soybean plant, Asaaceae Caladium plant, Lamiaceae plant, Citrus family Citrus plant, Asteraceae plant, Arnica plant and Araceae plant
  • a method for activating PIMT wherein an extract of one or more plants selected from the group consisting of plants is applied to an animal; an isomerized amino acid is applied, wherein the extract of one or more plants is applied to an animal.
  • a method for promoting protein restoration or repair is also encompassed by the present invention.
  • the animal is preferably the above-mentioned human or non-human mammal, more preferably a human.
  • the method for activating PIMT is preferably a method for activating PIMT present in the skin.
  • the method for promoting restoration or repair of a protein containing an isomerized amino acid is preferably a method for promoting restoration or repair of a protein containing an isomerized amino acid in the skin.
  • the plant extract is preferably brought into contact with the skin.
  • the plant extract is applied to animal skin.
  • a skin external preparation containing the plant extract to the skin of an animal such as a human, the plant extract can be brought into contact with the skin cells.
  • the plant extract, preferred embodiments thereof, preferred use amounts and the like are as described above.
  • the external preparation for skin is also as described above.
  • the method is preferably a non-therapeutic method (a method that does not involve medical practice).
  • ⁇ Method for evaluating skin restoration or repair activity and method for evaluating skin anti-aging activity Using the expression level or activity of PIMT present in the skin as an index, skin restoration or repair activity and skin anti-aging activity can be evaluated.
  • the method for evaluating skin restoration or repair activity of the present invention uses the expression level or activity of PIMT in skin cells as an index.
  • the evaluation method of skin anti-aging activity of the present invention uses the expression level or activity of PIMT in skin cells as an index.
  • the method for evaluating skin restoration or repair activity of the present invention and the method for evaluating skin anti-aging activity of the present invention are also referred to as the evaluation method of the present invention.
  • the skin restoration or repair activity in the present invention is usually caused by isomerization (conversion to L-isoAsp or D-Asp) of amino acids (specifically, L-Asp or L-Asn) in skin proteins. It refers to the activity of restoring or repairing denatured protein (isomerized protein) and the activity of promoting the restoration or repair of isomerized protein in the skin.
  • the activity of promoting the restoration or repair of isomerized protein in the skin includes the activity of suppressing the reduction of the restoration or repair activity of isomerized protein in the skin due to factors such as ultraviolet rays and aging.
  • the expression level or activity of PIMT in skin cells is useful as an index for evaluating the skin restoration or repair activity.
  • Skin restoring or repairing activity can also be restated as skin restoring or repairing power, skin restoring or repairing action. Skin restoration or repair activity may also contribute to skin recovery.
  • skin protein denaturation due to amino acid isomerization is also considered to be related to skin aging. By restoring or repairing the isomerized protein in the skin, for example, it is considered that the function of the aged skin is restored. Therefore, the expression level or activity of PIMT in skin cells is also useful as an index of skin anti-aging activity.
  • Anti-aging in the present invention is prevention or improvement of aging, preferably skin aging.
  • Aging includes one or both of aging by aging and aging by ultraviolet rays.
  • the expression of PIMT in skin cells is reduced by ultraviolet light and / or aging, but in skin where the decrease in PIMT expression by ultraviolet light and / or aging is small, the protein of the skin protein by ultraviolet light and / or aging is reduced. High activity to restore or repair isomerization. Using the expression level or activity of PIMT in skin cells as an index, the skin restoration against ultraviolet and / or aging-induced skin aging is suppressed. Alternatively, the repair activity can be evaluated.
  • the method for evaluating skin restoration or repair activity of the present invention can be used as a method for evaluating skin restoration or repair activity against skin aging due to ultraviolet rays and / or aging.
  • the method for evaluating anti-aging activity of skin of the present invention can be used as an evaluation method of anti-aging activity against skin aging due to ultraviolet rays and / or aging.
  • the expression level or activity of PIMT in skin cells is used as an index. More specifically, using the expression level or activity level of PIMT as an index, the degree or change of skin restoration or repair activity, or the degree or change of skin anti-aging activity is evaluated. For example, when the expression level or activity of PIMT in skin cells is high, the activity of converting isomerized Asp in protein into L-Asp is high. That is, the activity to restore or repair the isomerized protein is high. In addition, when the expression level or activity of PIMT in skin cells is high, the activity of suppressing reduction of various functions of the skin due to amino acid isomerization is high. Therefore, when the expression level or activity of PIMT in skin cells is high, the activity (action) for restoring or repairing the skin is high, and the activity (action) for preventing or improving skin aging is high.
  • Skin with a high expression level or activity of PIMT has a high restoration or repair activity of isomerized proteins, and therefore can be said to have a high skin restoration or repair activity and skin anti-aging activity.
  • skin with high expression level or activity of PIMT has a low degree of aging of skin cells (aging has not progressed).
  • the skin where the expression level or activity of PIMT is low has low skin restoration or repair activity and skin anti-aging activity.
  • the expression or activity of PIMT when the expression or activity of PIMT is low, it can be said that the skin is aged. Therefore, by using the expression level or activity of PIMT in skin cells as an index, it is possible to objectively evaluate skin restoration or repair activity and skin anti-aging activity.
  • the expression level or activity of PIMT in skin cells can also be used as an index for evaluating the degree of progress of skin aging.
  • the skin restoration or repair activity of the subject or the anti-aging activity of the skin is compared with, for example, the activity of standard skin, or the skin by skin care. It is also possible to evaluate the restoration or repair activity of the skin, or the change in the anti-aging activity of the skin. For this reason, based on said evaluation, the appropriate treatment with respect to the symptom relevant to skin aging can be selected, for example.
  • the skin cells used in the evaluation method of the present invention may be the skin cells of the subject who needs the evaluation or the subject who desires the evaluation, and include human or non-human mammal skin cells. Skin cells are preferred. Skin cells are usually skin cells collected from a subject. As skin cells, epidermal cells and / or dermal cells are preferred. The expression level or activity of PIMT in epidermal cells and / or dermal cells is preferable as an index for evaluating skin restoration or repair activity and skin anti-aging activity. Of these, dermal cells are more preferred.
  • dermal tissue accumulates damage due to aging, ultraviolet rays, etc.
  • the skin restoration or repair activity of the subject and the anti-aging activity of the skin are more appropriate Can be evaluated.
  • epidermal cells are preferable from the viewpoint of easy collection.
  • the method for collecting skin cells is not particularly limited.
  • Epidermal cells can be collected by, for example, tape stripping.
  • Dermal cells can be collected with an injection needle or the like. Further, for example, when a part of skin is collected for the purpose of regenerative medicine or the like, cells from the skin that are redundant during fat excision can be used.
  • the site of the skin is not particularly limited.
  • a site where the skin restoration or repair activity or the evaluation of the anti-aging activity of the skin is required or desired is preferable.
  • skins such as the face (forehead, cheek, around eyes, around mouth, chin), behind ears, neck, arms, hands, feet, buttocks, etc. can be mentioned.
  • skin cells of an exposed part are preferable, and examples of the skin of the exposed part include a face (particularly a cheek part), a neck part, an upper arm part, and a back of a hand.
  • the skin cells in the exposed part are suitably used for evaluation of skin restoration or repair activity against skin aging caused by ultraviolet rays, and evaluation of anti-aging activity against skin aging caused by ultraviolet rays.
  • evaluation is preferably performed using facial skin cells, for which evaluation of skin restoration or repair activity and anti-aging activity is considered important.
  • the evaluation method of the present invention preferably includes a step of measuring the expression level of PIMT or the activity of PIMT in skin cells.
  • the expression level of PIMT can be measured by measuring the amount of PIMT (protein amount) in skin cells or the amount of mRNA encoding PIMT. Since the operation is simple, it is preferable to measure the amount of PIMT as the expression level of PIMT.
  • a sample is prepared by extracting a protein from the collected skin cells, and the amount of PIMT in the sample may be measured.
  • the protein extraction method and the PIMT amount measurement method are not particularly limited.
  • a commercially available protein extraction solvent for example, M-PER (registered trademark) Mammalian Protein Extraction Reagent manufactured by Thermo or product name Mammalian Cell Lysis Buffer manufactured by GE Healthcare, etc.
  • M-PER registered trademark
  • Mammalian Protein Extraction Reagent manufactured by Thermo or product name Mammalian Cell Lysis Buffer manufactured by GE Healthcare, etc.
  • M-PER registered trademark
  • M-PER Mammalian Protein Extraction Reagent manufactured by Thermo or product name Mammalian Cell Lysis Buffer manufactured by GE Healthcare, etc.
  • the amount of PIMT can be measured by a known method such as an immunoassay method using an antibody specific for PIMT (for example, an ELISA method using an enzyme reaction or a Western blot method).
  • ELISA Kit for Homo sapiens (Human) Protein L-Isopartate-O-Methyltransferase (PCMT1), manufactured by CLOUD-CLONE) can be used.
  • the extraction of mRNA and the method for measuring the amount may be performed by a known method.
  • the measurement of mRNA can be performed by a method such as a PCR method.
  • the DNA sequence of human PIMT is known (NCBI Accession No. NM_005389).
  • a person skilled in the art can easily design and synthesize primers for measuring the amount of mRNA encoding PIMT, amplify DNA, and the like.
  • Primers that can be used for quantification of the human PIMT gene are commercially available (OriGene, product numbers HK25454, HK205453, etc.). Such a commercially available primer can be obtained to measure the amount of mRNA encoding PIMT.
  • Measurement of PIMT activity in skin cells can be performed quantitatively or qualitatively according to any method capable of measuring PIMT enzyme activity. Specifically, a protein is extracted from skin cells, and the amount of S-adenosylhomocysteine (SAH) generated from S-adenosyl-L-methionine (SAM) by PIMT reaction is measured by HPLC, which serves as a substrate
  • SAH S-adenosylhomocysteine
  • SAM S-adenosyl-L-methionine
  • the activity of PIMT can be measured.
  • the measured values of the expression level of PIMT and the activity of PIMT may be values that are easy to use depending on the measurement method.
  • the measured value of the PIMT expression level can be a value converted into the PIMT amount per protein amount.
  • the level of PIMT expression or the measured value of PIMT activity can be used to evaluate the degree of skin restoration or repair activity, the degree of skin anti-aging activity, and the change in the activity.
  • the step of measuring the expression level or activity of PIMT in the skin cells of a subject the population (for example, the same generation) in which the expression level or activity of PIMT in the skin cells of the subject is measured in advance
  • the distribution of the expression level or activity distribution in the skin cells of the population For example, if the expression level or activity of PIMT in a skin cell of a subject is higher than the distribution of the expression level or activity of PIMT in a previously measured population of skin cells, the subject may restore or repair the skin. It is evaluated (determined) that the activity and the anti-aging activity of the skin are high.
  • the expression level of PIMT in the skin cells of the exposed area and the unexposed area or The activity can also be evaluated by comparing the activity.
  • the step of measuring the expression level or activity of PIMT in the skin cells of the exposed and non-exposed areas of the same subject, and the expression level of PIMT in the skin cells of the exposed and non-exposed areas or the evaluation method including the process of comparing activity is mentioned.
  • UV light decreases PIMT expression or activity in skin cells.
  • the expression or activity of PIMT is usually lower in the exposed skin than in the non-exposed skin. For this reason, comparing the expression level or activity of PIMT in the skin cells of the exposed area and the unexposed area, if the difference is small, it is evaluated that the skin restoration or repair activity of the subject and the anti-aging activity of the skin are high.
  • the Examples of the skin of the exposed portion include the skin such as the face described above. Although it does not specifically limit as a non-exposure part, For example, a collar part etc. are mentioned.
  • Comparing the expression level or activity of exposed and unexposed PIMTs in the same subject can be used to evaluate skin restoration or repair activity against UV-induced skin aging, and anti-aging activity against UV-induced skin aging. Suitable for evaluation. The smaller the difference between the PIMT expression level or activity in the non-exposed skin cells and the PIMT expression level or activity in the exposed skin cells, the skin restoration or repair activity against skin aging due to ultraviolet rays, and It is evaluated as having high anti-aging activity against aging.
  • the step of measuring the expression level or activity of PIMT in the skin cells of the subject the step of irradiating the skin cells of the subject with ultraviolet light, the expression level or activity of PIMT in the skin cells of the subject after ultraviolet irradiation
  • a step of measuring and a step of comparing the expression level or activity of PIMT before and after UV irradiation it is preferable to include a step of measuring and a step of comparing the expression level or activity of PIMT before and after UV irradiation.
  • Comparing the expression level or activity of PIMT before and after UV irradiation is suitable for evaluating the skin restoration or repair activity against skin aging caused by UV light and the anti-aging activity against skin aging caused by UV light. It is evaluated that the lower the decrease in PIMT expression level or activity after irradiation, the higher the skin restoration or repair activity against skin aging caused by ultraviolet light and the anti-aging activity against skin aging caused by ultraviolet light compared to before UV irradiation. Is done.
  • the PIMT expression level or activity in skin cells when predetermined skin care is performed on the skin can be compared with the PIMT expression level or activity when skin care is not performed.
  • This comparison may be a comparison of PIMT expression level or activity before and after skin care. This makes it possible to evaluate changes in skin restoration or repair activity by skin care or changes in skin anti-aging activity. For example, when the expression level or activity of PIMT is increased by a certain skin care compared with the case where the care is not performed, the skin restoration or repair activity and the anti-aging activity of the skin are enhanced by the skin care. Can be evaluated.
  • the PIMT expression level or activity in skin cells when a certain food or ingredient is ingested can also be compared with the PIMT expression level or activity when the food or ingredient is not ingested.
  • the change of the skin restoration or repair activity or the change of the anti-aging activity of the skin due to the food or ingredient can be evaluated.
  • skin ingestion or restoration activity by ingestion of the food or ingredient and It can be evaluated that the anti-aging activity of the skin was enhanced.
  • Substances having an action of activating PIMT present in the skin, substances having an action of promoting restoration or repair of skin, and substances having an anti-aging action of skin can be screened by the method described later.
  • the screening method of the present invention is a method for screening an active ingredient for activation of PIMT present in the skin, promotion of restoration or repair of the skin, or anti-aging of the skin.
  • the expression level or activity of PIMT in skin cells is used as an index.
  • PIMT expression level or activity in skin cells as an indicator, activation of PIMT present in skin, promotion of restoration or repair of skin, or active ingredient for anti-aging of skin, in other words, PIMT present in skin
  • a substance having an activating action, a substance having a skin restoration or repair promoting action, or a substance having a skin anti-aging action can be screened.
  • the screening method of the present invention is usually a method performed in vitro (in vitro screening method).
  • Skin cells used in the screening method of the present invention include human or non-human mammal skin cells.
  • the skin cell may be a cell collected from the above-mentioned subject, but preferably a cultured skin cell is used.
  • cultured skin cells such as human epidermal keratinocytes and human dermal fibroblasts can be used.
  • the skin cells used are preferably grown to confluence.
  • the culture conditions for growing the cells are not particularly limited, and known conditions may be employed depending on the cells.
  • the screening method of the present invention comprises a step of contacting a test substance with the skin cells and measuring the expression level or activity of PIMT in the skin cells, and When the expression level or activity of PIMT in skin cells contacted with the test substance is larger than the expression level or activity of PIMT in skin cells not contacted with the test substance, the test substance is used as an active ingredient. It is preferable to include a step of selecting.
  • the test substance is not particularly limited, and examples thereof include plant extracts, cell extracts, fermentation products, proteins, peptides, vitamins, and synthetic compounds. These may be known substances or new substances.
  • the method for bringing the test substance into contact with the skin cells is not particularly limited as long as the test substance can contact the cell.
  • the test substance may be added to a medium for culturing the skin cells. In this case, it is preferable to measure the expression level or activity of PIMT in the cells after culturing the skin cells for a predetermined time in a medium to which a test substance is added.
  • the culture medium, culture conditions, and the like can be appropriately set according to the type of cells.
  • the culture time is not particularly limited, and may be appropriately set depending on the culture conditions.
  • skin cells may be cultured in a medium to which a test substance is added, preferably for 5 to 72 hours, more preferably for 12 to 48 hours.
  • An example of the medium is ⁇ -MEM medium.
  • Serum for example, fetal calf serum
  • a commercially available product may be used as the medium.
  • the expression level or activity of PIMT in skin cells can be measured by the method described above. As described above, since the expression level or activity of PIMT in skin cells is reduced by ultraviolet rays, for example, the skin cells may be irradiated with ultraviolet rays before or after contacting the skin cells with a test substance.
  • the test substance When the expression level or activity of PIMT in the skin cells contacted with the test substance is greater than the expression level or activity of PIMT in the skin cells not contacted with the test substance when irradiated with ultraviolet rays, the test It can be said that the substance has a high PIMT activation action existing in the skin.
  • the test substance is considered to have a high effect of suppressing the restoration of isomerized protein in the skin due to ultraviolet rays or a reduction in the repair activity, that is, the skin restoration or restoration effect against skin aging caused by ultraviolet rays.
  • the test substance is considered to have a high anti-aging effect against skin aging caused by ultraviolet rays.
  • Skin cells not contacted with the test substance are controls.
  • skin cells contacted with an active ingredient of a known anti-aging agent or the like instead of the test substance can be used.
  • a test substance having a higher PIMT activating action than the known active ingredient a test having a higher skin restoring or repairing action A substance or a test substance having a high anti-aging effect on the skin can be selected.
  • the active ingredient obtained by the screening method of the present invention can activate PIMT present in the skin. Thereby, restoration or repair of the skin can be promoted. Moreover, the active ingredient obtained by the screening method of the present invention can prevent or improve the above-mentioned skin aging. More specifically, skin aging can be prevented or improved based on the activity of promoting the conversion of isomerized Asp to L-Asp in skin cells.
  • the present invention also encompasses the use of the expression level or activity of protein L-isoaspartate methyltransferase (PIMT) in skin cells as an indicator of skin restoration or repair activity or skin anti-aging activity. More specifically, the expression level or activity level of PIMT in skin cells can be used as an index of the activity level.
  • the expression level or activity of PIMT in skin cells is preferably used as an index of skin restoration or repair activity.
  • the expression level or activity of PIMT in skin cells is preferably used as an index of skin anti-aging activity.
  • the present invention includes the following uses. To activate protein L-isoaspartate methyltransferase (PIMT), birch family, birch plant, grapevine grape plant, legume family soybean plant, Asaaceae plant, Labiatae plant, citrus family mandarin orange Use of an extract of one or more kinds of plants selected from the group consisting of plants, Camelliaaceae plants, Compositae plants Arnica plants and Rosaceae peach plants.
  • PIMT protein L-isoaspartate methyltransferase
  • Birch family Birch plant, Grapevine plant, Legume family, Soybean plant, Lamiaceae plant, Lamiaceae plant, Citrus mandarin plant for restoring or repairing proteins containing isomerized amino acids, Use of an extract of one or more kinds of plants selected from the group consisting of the family Chrysaceae, the family Chrysanthemum, Arnica, and the family Rosaceae.
  • the above uses are preferably used in human or non-human mammals.
  • the use may be therapeutic or non-therapeutic.
  • the use can be for non-therapeutic cosmetic purposes.
  • the preferable aspect etc. of a plant extract are as above-mentioned.
  • the plant extract may be used as it is, or may be used as a composition containing the plant extract.
  • the plant extract can be used in the form of the above-mentioned external preparation for skin, food and drink, and the like.
  • the present invention relates to the use of the above plant extract for producing a composition for activating PIMT; the use of the above plant extract for producing a composition for promoting the restoration or repair of proteins containing isomerized amino acids. Is also included.
  • the preferable aspect etc. of a plant extract are as above-mentioned.
  • the protein extraction reagent used in the following experiments is a product name M-PER (registered trademark) Mammalian Protein Extraction Reagent manufactured by Thermo.
  • M-PER registered trademark Mammalian Protein Extraction Reagent manufactured by Thermo.
  • the significant difference was tested by Student's t test.
  • PIMT protein L-isoaspartate methyltransferase in human skin
  • PIMT Protein L-Isopartate-O-Methyltransferase
  • FIG. 1 is a graph showing PIMT expression level (PIMT amount per protein amount) in skin cells. It was shown that PIMT was expressed in all skin-derived NHEK cells and NHDF cells, although it was low compared with HEK293 cells.
  • Neonatal-derived normal human dermal fibroblasts used in Test Examples 2 to 8 below are the same as NHDF-NB used in Test Example 1.
  • Cell culture was performed at 37 ° C. and a carbon dioxide concentration of 5 vol% unless otherwise specified.
  • PIMT repair action of isomerized aspartic acid in skin protein produced by ultraviolet B wave (UVB) irradiation Normal human skin fibroblasts (NHDF-NB) derived from newborns induced isomerization of aspartic acid by UVB irradiation
  • UVB ultraviolet B wave
  • NHDF-NB Normal human skin fibroblasts
  • a culture medium in which NHDF-NB cells were suspended was seeded in a culture dish and cultured at 37 ° C. in a carbon dioxide concentration of 5 vol% until it became confluent.
  • the protein After recovering the protein from the confluent cells using the protein extraction reagent, the protein is irradiated with UVB for a certain period of time, and the amount of L- ⁇ -Asp as isomerized aspartic acid is determined by ISOQUANT (registered trademark) Isoaspartate Detection Kit (Promega) Quantitative determination was performed according to the attached instructions.
  • This kit transfers the methyl group of the coenzyme S-adenosyl-L-methionine (SAM) to the ⁇ -carboxyl group of isoaspartic acid when PIMT acts on isoaspartic acid in the protein or peptide.
  • SAM coenzyme S-adenosyl-L-methionine
  • SAH demethylated product S-adenosyl homocyte
  • DSIP delta sleep-inducing peptide
  • FIG. 2 is a graph showing the amount of SAH produced per protein amount by UVB irradiation.
  • * is a significant difference with respect to 0 minutes of UVB irradiation time (*: p ⁇ 0.05). It means that the amount of isomerized aspartic acid produced increases as the amount of SAH produced increases.
  • a certain amount of SAH was also detected from the NHDF-NB cell-derived protein that had not been irradiated with UVB, but the amount of SAH increased depending on the UVB irradiation time (40 minutes, 60 minutes).
  • NHDF-NB is a dermal fibroblast. From this result, it was shown that isomerization of aspartic acid is induced by UVB irradiation in dermal fibroblast-derived protein, and PIMT acts on aspartic acid in the isomerized skin protein. It was shown that.
  • PIMT expression level in dermal fibroblasts with different passage numbers It is known that when cells are repeatedly passaged and cultured, the cells progress with aging and eventually lose their division function. For this reason, normal human dermal fibroblasts (dermal fibroblasts) derived from newborns that had been subcultured repeatedly were used as an aging model. PIMT protein expression level using normal human skin fibroblasts derived from newborns (NHDF-NB, purchased from Kurabo Corp.) with repeated passages in order to verify how the expression level of PIMT varies with aging The change of was verified.
  • NHDF-NB normal human skin fibroblasts derived from newborns
  • NHDF-NB cells (passage number (P): 3, 6, 10, 12, 15, and 17) that had been repeatedly subcultured were seeded and cultured at 37 ° C. in a carbon dioxide concentration of 5 vol% until they became confluent. .
  • Proteins soluble in the extraction reagent were recovered from the confluent cells using a protein extraction reagent, and the amount of PIMT per protein amount was measured. The amount of PIMT was measured by the same method as in Test Example 1.
  • FIG. 3 is a graph showing the PIMT expression level (PIMT amount per protein amount) in skin fibroblasts having different passage numbers.
  • PIMT expression level PIMT amount per protein amount
  • NHDF-NB cells in which subculture was repeated 6 times or more, a tendency for the PIMT expression level per protein amount to decrease was confirmed. It has been confirmed that isomerized aspartic acid accumulates in aged skin tissue, but in cells that have advanced aging, the expression of PIMT capable of repairing isomerized aspartic acid in the protein is reduced, leading to isomerization. Aspartic acid accumulation is expected to increase.
  • ⁇ Test Example 4 Changes in PIMT expression level under various stress loads
  • normal human skin fibroblasts NHDF-NB
  • UVB normal human skin fibroblasts
  • inflammation inflammation
  • nutrient depletion Then, stimulation with active oxygen or the like was given, and changes in the protein expression level of PIMT were verified.
  • the cells were seeded on a 100 mm culture dish and cultured at 37 ° C. in a carbon dioxide concentration of 5 vol%.
  • An ⁇ -MEM medium manufactured by SIGMA
  • FBS bovine serum
  • PIMT amount was measured by the same method as in Test Example 1. Further, as a control, cells exchanged with ⁇ -MEM medium containing 10% FBS without applying the above stimuli (1) to (3) were used.
  • FIG. 4 is a graph showing changes in PIMT expression level (PIMT amount per protein amount) of skin fibroblasts due to stress load.
  • the expression level of PIMT was significantly reduced in comparison with control cells under hydrogen peroxide (H 2 O 2 ) exposure, UVB exposure, and undernutrition. From these facts, the expression of PIMT decreases in skin exposed to ultraviolet rays, skin exposed to reactive oxygen species, etc., and skin whose nutritional state has decreased with aging, so that isomerized asparagine It is assumed that acid accumulation increases.
  • Plants and their parts used for the preparation and extraction of plant-derived extracts are as follows. (1) Isodon japonicus: stem and leaf (2) perilla (Perilla frutescens var. Crispa): leaf (3) birch (Betula pendula): bark (4) citrus (Citrus junos): fruit (5) sage ( Salvia officinalis): leaf (6) soybean (Glycine max): germ (soybean bud) (7) Arnica montana: Flowers (8) Prunus armeniaca: Seeds (9) Acorus calamus: Roots (10) Lavandula angustifolia: Flowers (11) Peach (Amygdalus persica): Seeds (12) Hop (Humulus lupulus): female flower ear (13) Vitis spp. (Cabernet sauvignon): skin and seed
  • Each of the plant crushed materials (1), (3) to (5) and (7) to (13) is immersed in a 30 to 90 vol% ethanol aqueous solution having a mass 10 times the mass, and once a day at room temperature.
  • the mixture was extracted with stirring for 10 minutes to 7 days. Thereafter, the residue was removed by filtration to obtain an extract.
  • the extract was concentrated and freeze-dried to obtain an extract of each plant (ethanol extract) as a powder.
  • the powdery plant extract was used in the evaluation of Test Examples 5 to 8.
  • Perilla was extracted by the above method using 1,3-butylene glycol aqueous solution instead of ethanol aqueous solution. After extraction, the residue was removed by filtration to obtain an extract (Perilla butylene glycol extract). The extract was concentrated and freeze-dried to obtain a perilla extract (butylene glycol extract) as a powder. The powdery perilla extract was used for the evaluation of Test Examples 5-6.
  • soybean germ was pulverized and extracted with 10 times the mass of hot water. Thereafter, the residue was removed by filtration to obtain an extract (soybean water extract). The extract was concentrated and freeze-dried to obtain a soybean extract (water extract) as a powder. This powdery soybean extract was used in the evaluation of Test Examples 5-6.
  • ⁇ Test Example 5 Changes in PIMT expression level in skin cells by addition of plant extract Humans when the plant extract prepared in Preparation Example 1 was added using human-derived human dermal fibroblasts (NHDF-NB: purchased from Kurabo Corporation) The protein expression level of PIMT in the skin was evaluated. Cells were seeded on a 100 mm culture dish and cultured at 37 ° C. in a carbon dioxide concentration of 5 vol% until confluence. Thereafter, each plant extract described in Table 1 or 2 was added to the obtained cells at a concentration of 10 ⁇ g / mL and cultured for 24 hours.
  • NHDF-NB human-derived human dermal fibroblasts
  • ⁇ -MEM medium without FBS was used, and the plant extract was dissolved in dimethyl sulfoxide (DMSO) and added so that the final concentration of DMSO in the medium was 0.1% by mass.
  • DMSO dimethyl sulfoxide
  • a control a medium containing 0.1% by mass DMSO was used.
  • the culture supernatant was removed, replaced with Hanks balanced salt solution (manufactured by Nacalai Tesque), and irradiated with UVB (integrated light intensity of about 5.7 mJ / cm 2 ).
  • the plant extract was replaced with a fresh 10% FBS-containing ⁇ -MEM medium (the final concentration of the plant extract was 10 ⁇ g / mL, and the final concentration of DMSO was 0.1% by mass) to which the DMSO solution of the plant extract was added.
  • the culture was further continued for 48 hours.
  • PIMT Protein L-Isopartate-O-Methyltransferase
  • Tables 1 and 2 The results are shown in Tables 1 and 2.
  • control is a control not irradiated with UVB
  • control (+ UV) is a control irradiated with UVB
  • ⁇ of UV irradiation means that UVB was not irradiated
  • + means that UV irradiation was performed.
  • “*” and “**” indicate a significant difference from “control (+ UV)” (*: p ⁇ 0.05, **: p ⁇ 0.01).
  • the quantitative results of PIMT are shown as a relative value (%) (PIMT expression level (%)) where the PIMT amount (PIMT expression level) per protein amount of the UVB-irradiated control (control (+ UV)) is 100%. Moreover, it was shown as "recovery rate (%)" how much the plant extract shows a recovery action with respect to the decrease in the expression level of PIMT by UVB irradiation.
  • ⁇ Test Example 6 Changes in PIMT expression level in skin cells by addition of plant extract The following evaluation was performed using the birch extract, sage extract, soybean extract, enamel extract, and lavender extract prepared in Preparation Example 1.
  • neonatal human dermal fibroblasts (NHDF-NB: purchased from Kurabo Corporation) were cultured until they became confluent. Thereafter, each plant extract was added to the obtained cells at a concentration of 10 ⁇ g / mL and cultured for 24 hours.
  • As the medium ⁇ -MEM medium without FBS was used, and the plant extract was dissolved in DMSO and added so that the final concentration of DMSO in the medium was 0.1% by mass.
  • a medium containing 0.1% by mass DMSO was used as a control. 24 hours after the addition of the plant extract, the culture supernatant was removed, and a fresh 10% FBS-containing ⁇ -MEM medium supplemented with the DMSO solution of the plant extract (the final concentration of the plant extract was 10 ⁇ g / mL, the final DMSO concentration). The concentration was changed to 0.1% by mass), and further cultured for 24 hours. After this culture, a sample obtained by recovering protein soluble in the protein extraction reagent from the cells was used as a sample, and the amount of PIMT per protein amount (PIMT mass / protein mass) was measured by the same method as in Test Example 5.
  • the PIMT amount was measured twice for each sample, and the average value was used as the measured value for each sample.
  • Table 3 shows the relative value (%) (PIMT expression level (%)) where the control PIMT expression level is 100% when each plant extract is added.
  • “*” indicates a significant difference from the control (*: p ⁇ 0.05).
  • NHDF-NB newborn-derived human dermal fibroblasts
  • the cells were cultured until they became confluent by the same method as in Test Example 5. Thereafter, the grape extract was added to the obtained cells at a concentration of 2.5 ⁇ g / mL, 5 ⁇ g / mL or 10 ⁇ g / mL and cultured for 24 hours.
  • the medium ⁇ -MEM medium without FBS was used, and the grape extract was dissolved in dimethyl sulfoxide (DMSO) and added so that the final concentration of DMSO in the medium was 0.1% by mass.
  • DMSO dimethyl sulfoxide
  • a sample obtained by recovering protein soluble in the protein extraction reagent from the cells was used as a sample, and the amount of PIMT per protein amount (PIMT mass / protein mass) was measured by the same method as in Test Example 5.
  • the PIMT amount was measured twice for each sample, and the average value was used as the measured value for each sample.
  • Table 4 shows the results.
  • Control is a control not irradiated with UVB
  • Control (+ UV) is a control irradiated with UVB
  • ⁇ of UV irradiation means that UVB was not irradiated
  • + means that UV irradiation was performed.
  • ** indicates a significant difference from “control (+ UV)” (**: p ⁇ 0.01).
  • the quantitative results of PIMT are shown as a relative value (%) (PIMT expression level (%)) where the PIMT amount (PIMT expression level) per protein amount of the UVB-irradiated control (control (+ UV)) is 100%.
  • the recovery rate of the grape extract against the decrease in the expression level of PIMT due to UVB irradiation was shown as “recovery rate (%)”.
  • the recovery rate (%) was determined by the same method as in Test Example 5.
  • the PIMT expression level was higher compared to the cells to which the extract was not added and UVB irradiation was performed. It was shown that the grape extract suppresses the decrease in PIMT expression level due to UVB irradiation.
  • ⁇ Test Example 8> In the same manner as in Test Example 5, neonatal human dermal fibroblasts (NHDF-NB: purchased from Kurabo Corporation) were cultured until they became confluent. Thereafter, the grape extract prepared in Preparation Example 1 was added to the obtained cells at a concentration of 2.5 ⁇ g / mL or 5 ⁇ g / mL, and cultured for 24 hours.
  • the medium ⁇ -MEM medium without FBS was used, and the grape extract was dissolved in DMSO and added so that the final concentration of DMSO in the medium was 0.1% by mass. A medium containing 0.1% by mass DMSO was used as a control.
  • Table 5 shows the relative value (%) (PIMT expression level (%)) where the control PIMT expression level is 100% when the grape extract is added.
  • “*” indicates a significant difference from the control (*: p ⁇ 0.05).
  • the expression level of PIMT was significantly increased compared to the control.
  • cosmetics and foods and drinks that contain extracts of birch, grape, soybean, hop, lavender, sage, enmiso, yuzu, perilla, shobu, arnica and peach plants are shown below.
  • These cosmetics and foods and drinks can be used as cosmetics and foods and drinks for PIMT activation, and are particularly suitable as cosmetics and foods and drinks for PIMT activation present in the skin.
  • these cosmetics and foods and drinks can also be used as cosmetics or foods and drinks for promoting restoration or restoration of isomerized proteins, and as cosmetics or foods and drinks for promoting restoration or restoration of isomerized proteins in the skin. It can be preferably used.
  • the plant extract used in Production Examples 1 to 3 was an ethanol extract of each plant (birch, grape, hop, lavender, sage, enamel, yuzu, shobu, arnica or peach) obtained in Preparation Example 1, perilla butylene.
  • a glycol extract or a soybean water extract is concentrated to a solid content concentration of 0.12% by mass / volume, respectively.
  • each plant extract obtained in Preparation Example 1 (powder obtained by freeze-drying the ethanol extract of each plant, perilla butylene glycol extract or soybean water extract) was used. .
  • Powder for dissolution at the time of use The raw materials listed in Table 9 were uniformly stirred to prepare a powder for activating PIMT.
  • the powder for dissolution at the time of use can be used, for example, by dissolving in a beverage such as water, coffee, tea or juice, or by mixing with a food such as yogurt.
  • an arbitrary test substance is used instead of the plant extract, and the PIMT expression level in the skin cells when the test substance is added is evaluated.
  • the test The substance is selected as the active ingredient.
  • the test substance selected as an active ingredient can be used as an active ingredient for activating PIMT present in the skin, promoting skin restoration or repair, or anti-aging the skin.
  • the present invention is useful in the fields of pharmaceuticals, quasi drugs, cosmetics, foods and drinks, and the like.

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Abstract

Le but de la présente invention est de fournir : une composition pour l'activation de la protéine L-isoaspartate méthyltransférase (PIMT) avec laquelle il est possible d'activer la PIMT; un nouvel indicateur pour évaluer une activité de restauration ou de réparation de la peau; un nouvel indicateur pour évaluer une activité anti-âge de la peau; et un procédé pour évaluer une activité de restauration ou de réparation de la peau et un procédé pour évaluer une activité anti-âge de la peau, etc, dans lesquels ces indicateurs sont utilisés, respectivement. Cette composition pour l'activation de la protéine L-isoaspartate méthyltransférase (PIMT) contient un extrait d'une ou de plusieurs plantes sélectionnées dans le groupe constitué par: des plantes de la famille des Betulaceae (Bétulacées), du genre Betula; des plantes de la famille des Vitaceae (Vitacées), du genre Vitis; des plantes de la famille Fabaceae (Fabacées), du genre Glycine; des plantes de la famille Cannabaceae (Cannabacées), du genre Humulus; des plantes de la famille des Labiatae (labiacées); des plantes de la famille Rutaceae (Rutacées), du genre Citrus; des plantes de la famille Acoraceae (Acoracées), du genre Acorus; des plantes de la famille des Asteraceae (Astéracées), du genre Arnica; et des plantes de la famille Rosaceae (Rosacées), du genre Prunus.
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