JP6529119B2 - Nrf2-related gene expression promoter - Google Patents

Description

  The present invention relates to an Nrf2 gene expression promoter.

    It is known that the increase of free radicals and reactive oxygen species (ROS; oxidative stress factor) in vivo causes cancer, arteriosclerosis, myocardial infarction, cerebral infarction, liver dysfunction, diabetes and the like. Known oxidative stress factors are hydroxy radical, superoxide, hydrogen peroxide, hydroperoxy radical, alkoxyl radical, alkylperoxy radical, nitrogen monoxide, peroxynitrite, lipid peroxide, hypochlorous acid, ozone, etc. . Oxidative stress factors tend to react with proteins, nucleic acids, lipids, etc. When reacted with these, protein denaturation, enzyme inactivation, DNA translational abnormalities, DNA degradation, lipid peroxide formation, unsaturated fatty acid It causes oxidative degeneration and the like, which causes the above-mentioned diseases.

The organism inherently has a defense mechanism against such oxidative stress factors, and in recent years, it has been reported that Nrf2 (NF-E2 related factor-2) as a transcription factor plays a major role (for example, , Patent Document 1). Nrf2 normally exists in the cytoplasm in a state of being bound to actin via Keap1 (Kelch like ECH associated protein 1). On the other hand, in the nucleus, there is an antioxidant gene encoding a second phase foreign body metabolic enzyme, an antioxidant protein and the like. When cells are exposed to oxidative stress, Keap1 senses this and Nrf2 translocates into the nucleus. Nrf2 translocated to the nucleus forms a complex with small Maf and binds to the ARE region (antioxidant response element; antioxidant response element) of the antioxidant gene, and various second-phase foreign body metabolic enzymes and antioxidant proteins Enhance the expression of

Examples of antioxidant proteins whose expression is enhanced by Nrf2 include glutathione-S-transferase (GST), heme oxygenase (HO-1), NAD (P) H: quinone oxidoreductase-1 (NQO1), thioredoxin reductase 1 ( TXNRD1), glutamate-cysteine ligase (GCLM; glutathione synthetase), superoxide dismutase (SOD), glutathione reductase, catalase and the like are known. These antioxidant proteins directly reduce oxidative stress factors or produce proteins that reduce, and protect cells from damage by oxidative stress factors.

Among the above-mentioned antioxidant enzymes and foreign body metabolism type 2 phase enzymes, GCLM, NQO-1 and TRX will be described in detail.
Glutathione (5-L-glutamyl-L-cysteinylglycine) is known as a peptide that maintains the thiol group of intracellular proteins in an appropriate oxidation / reduction state and exerts a detoxification function by reacting with peroxide. It is done. As a first reaction of the biosynthesis of glutathione, L-glutamic acid and L-cysteine are reacted to synthesize γ-L-glutamyl-L-cysteine, and GCLM is an enzyme catalyzing the reaction.
The quinone compounds contained in automobile exhaust gas, tobacco smoke, atmospheric particulates and the like easily undergo one electron or two electron reduction. NQO-1 is a detoxifying enzyme that detoxifies such quinone compounds by two-electron reduction.
TRX catalyzes the reaction of reducing ribonucleotides to deoxyribonucleotides. TRX has strong reducing activity via a pair of thiol groups of cysteine residues in the active center, and is known to be one of the antioxidant factors involved in intracellular redox control. Furthermore, it is also believed that the secretion of TRX is induced as an anti-stress response, because the extracellular release of TRX is enhanced during oxidative stress loading.

  As described above, Nrf2 and a gene cluster whose expression is controlled by Nrf2 play a very important role as a protective function against endogenous and exogenous environmental stress and aging. Therefore, activating Nrf2 with a highly safe drug for the living body and promoting the expression of a gene whose expression is controlled by this transcription factor are active oxygen, chemicals, and diseases caused by aging. Very useful for prevention and treatment.

In addition, it is also known to activate GCLC (Glutamate-cysteine Ligase, Catalytic subunit), which is a synthetic enzyme of glutathione which is an antioxidant substance, by expression of Nrf2. Glutathione has the function of reducing and eliminating active oxygen and peroxides in cells, and it is believed that this function can suppress cell damage and maintain a youthful body. Even on the skin, active oxygen causes melanin pigmentation, but it is said that the antioxidant action of glutathione suppresses stains and pigmentation.
On the other hand, there are two types of melanin pigments, black melanin (yumelanin) and yellow melanin (pheomelanin), and human skin color is determined by these two melanins. Black melanin is a melanin that darkens the skin, causes staining and pigmentation, and increases mainly when exposed to a large amount of ultraviolet light. On the other hand, yellow melanin is a melanin that brings out the natural whiteness to the skin, and it can be said that natural white skin can be brought out by suppressing the black melanin and increasing the yellow melanin, but glutathione leads to the formation of yellow melanin It is said that there is work.

JP 2008-208038 A

  Under such circumstances, the present inventors have found that plants of the genus Nadesico and their extracts have an action to promote the expression of the Nrf2 gene and the GCLM gene, and completed the present invention.

That is, an object of the present invention is to provide an Nrf2 gene expression promoter and a GCLM gene expression promoter, which comprise a novel component as an active ingredient.

The technical features of the present invention for solving the above problems are as follows.
(1) An Nrf2 gene expression promoter comprising as its active ingredient the Nadeshiko species Naanthus (Dianthus) and / or its extract.
(2) An agent for promoting expression of GCLM gene, which comprises, as an active ingredient, the genus Nadeshiko (Danthus) and / or an extract thereof.

It is a graph which shows the evaluation result of the Nrf2 gene expression effect | action of Kawara Nadesico extract. It is a graph which shows the evaluation result of the GCLM gene expression effect | action of Kawara Nadesico extract.

Hereinafter, the present invention will be described in detail.
The Nrf2 gene expression promoting agent and the GCLM gene gene expression promoting agent of the present invention (hereinafter simply referred to as "Nrf2-related gene expression promoting agent") use the Nadeshiko species Dianthus (Dianthus) and / or an extract thereof as an active ingredient It is characterized by

The above-mentioned family of the family Nadeshiko (Danthus) is not particularly limited as long as it belongs to this genus, and, for example, D. superbus L. var. Longicalycinus, D. superbus L. var. Superbus, D. superbus L. var. (D. superbus L. var. Speciosus Reichb.), Hymeno alderus (D. kiusianus Makino), Alminus lavifolia (D. japonicus Thunb.), Laminaria (D. shinanensis (Yatabe) Makino), Dianthus alpinus, Dianthus amurensis Jacques, Dianthus anatolicus Boiss., Dianthus arenarius L., Dianthus armeria L. (Noharanashiko Deptford Pink), Dianthus banaticus (Heuffel) Borbas, Dianthus barbatus L. (American couscous) or Sweet William
Dianthus biflorus Sm., Dianthus brevicaulis Fenzl, Dianthus callizonus Schott et Kotschy, Dianthus campestris M. Bieb, Dianthus capitatus Balb. Ex DC. Dianthus chinensis L. (Sequicular), Dianthus collinus W. et K., Dianthus cruentus Griseb., Dianthus deltoides L.-Maiden Pink
Dianthus erinaceus Boiss., Dianthus freynii Vandas, Dianthus fruticosus L.
Dianthus furcatus Balb., Dianthus gallicus Pers.-French Pink or Jersey Pink
Dianthus giganteus d'Urv, Dianthus glacialis Haenke, Dianthus gracilis Sm.
Dianthus graniticus Jord., Dianthus gratianopolitanus Vill.-Cheddar Pink
Et Heldr., Dianthus hungaricus Pers., Dianthus imereticus (Rupr.) Schischk., Dianthus integer Vis., Dianthus knappii Asch. Et Kanitz ex Borbas, Dianthus lunitzeri Wiesb.
Dianthus litanitus Brot., Dianthus microlepsis Boiss., Dianthus monspessulanus L.
Dianthus myrtinervius Griseb., Dianthus nardiformis Janka, Dianthus nitidus Waldst. Et Kit., Dianthus pavonius Tausch, Dianthus petraeus Waldst. Et Kit. Dianthus pyrenaicus Pourr., Dianthus repens Willd.-Boreal Carnation
Dianthus scardicus Wettst., Dianthus seguieri Vill., Dianthus serotinus Waldst. Et Kit.
, Dianthus spiculifolius Schur., Dianthus squarrosus Bieb., Dianthus subacaulis Vill., Dianthus superbus L. (Large Pink), Dianthus sylvestris Wulfen, Dianthus viscidus Bory et Chaubi
Non-limiting examples include Dianthus zonatus Fenzl and the like. These may be used alone or in combination of two or more.

Furthermore, it is because a higher concentration of active ingredient can be obtained, which is preferably D. superbus L. var.

In the present invention, the site is not particularly limited. For example, fruits, seeds, leaves and the like can be used, but seeds are preferably used.

The method for obtaining the extract from Kawara Nadesico (D. superbus L. var. Longicalycinus) is not particularly limited, and examples thereof include polar solvent extraction and supercritical extraction. Note that only one of them may be performed, or both of them may be performed. Also, this extraction may be performed only once or twice or more.

Here, when extracting by polar solvent extraction, the polar solvent to be used is not particularly limited. For example, water, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin and the like And alcohols of acetic acid, ethyl acetate, ether and the like. Among these, water and alcohol are preferable. At this time, the alcohol is preferably methanol, ethanol, 1,3-butylene glycol, or propylene glycol. It is because an active ingredient can be extracted efficiently. These may be used alone or in combination of two or more.

When water is used as the polar solvent, the extraction temperature may be 20 to 100 ° C, preferably about 40 to 70 ° C. This is because when the extraction temperature is too low, it is difficult to extract the active ingredient. The type of water for extraction is not particularly limited, and tap water, distilled water, mineral water, alkali ion water, etc. can be used.

When a water-containing alcohol is used as the polar solvent, the alcohol concentration is preferably 10 wt% or more, preferably 30 wt% or more. This is to make it possible to obtain a high extraction amount of the active ingredient. The extraction temperature may be about 0 to 95 ° C., preferably about 20 to 80 ° C. The water-containing alcohol extraction may be repeated at various concentrations in order to improve the content of the active ingredient.

  In the case of extraction with a polar solvent, the extraction method is not particularly limited. For example, any method such as continuous extraction, immersion extraction, countercurrent extraction can be adopted, and any device under heating from room temperature to reflux Can be used. In addition, when extracting by the method mentioned above, only one of these may be performed and you may combine these methods. Moreover, these extractions may be performed only once, and may be performed twice or more.

As a specific method, an extraction raw material (seed of kawara nadesico) is put into a treatment tank filled with an extraction solvent, and the active ingredient is eluted while stirring. For example, when using water or water-containing alcohol as an extraction solvent, a polar solvent of about 5 to 100 times the amount (weight ratio) of the extraction raw material is used for extraction for about 1 minute to 150 hours. After eluting the active ingredient in the solvent, the extract is obtained by filtering and removing the extraction residue. Thereafter, the extract is subjected to treatments such as dilution, concentration, drying, purification and the like according to a conventional method to obtain an extract containing an active ingredient such as high concentration polyphenol.
Examples of the purification method include methods such as activated carbon treatment, resin adsorption treatment, ion exchange resin, liquid-liquid countercurrent distribution, and membrane separation.

Furthermore, when extraction is performed by supercritical extraction, the supercritical fluid used at this time is not particularly limited, and examples thereof include carbon dioxide and nitrogen. In addition, these may use only 1 type and may use 2 or more types together. Among these, carbon dioxide is particularly preferred.
It is because an active ingredient can be extracted more easily. In addition, the extraction method at this time may be performed by a known method. Thereafter, the extract is subjected to treatments such as dilution, concentration, drying, purification and the like according to a conventional method to obtain an extract containing an active ingredient such as high concentration polyphenol.

  The present invention provides a food comprising the Nrf2-related gene expression promoter. This food may contain the extract as an active ingredient, for example, in an amount of 100 to 1,000 mg, preferably 250 to 500 mg, per single dose for adults. In the Nrf2-related gene expression promoter of the present invention, the content of the active ingredient may change depending on the age and the like.

  The Nrf2-related gene expression promoter of the present invention can be used as a material of various food and drink. Examples of food and drink include food oil (salad oil), confectionery (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummi, tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products Milk, ice cream, yoghurt etc.) Boiled indigo fish (Konbu seaweed boiled with seaweed, seaweed boiled in soy sauce, etc.), seasoning (miso, soy sauce etc.), soups, beverages (juice, coffee, black tea, tea, carbonated drinks, sports And foods such as beverages, health foods (tablets, capsules, etc.), and nutritional supplements (nutritive drinks, etc.). The Nrf2-related gene expression promoter of the present invention may be appropriately blended in these food and drink.

  In these food and drink, various components can be blended according to the kind, and for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid Acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, Food materials such as carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, flavors, preservatives and the like can be used. In addition, the present Nrf2-related gene expression promoter having a health maintenance function includes distribution agents such as other antioxidants and health food materials (eg, antioxidant, reduced ascorbic acid (vitamin C), vitamin E, Reduced glutatin, tocotrienol, vitamin A derivative, lycopene, β-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sesamin, lignans, catechin, isoflavone, chalcone, tannin , Flavonoids, coumarin, isocoumarins, blueberry extract, arbutin, tannin, tannin, anthocyanin, apple polyphenol, grape seed extract, elladiic acid, kojic acid, surge extract health food material, V. (vitamin) A, V. B1, V.B2, V.B6, V.B12, VC, VD, VE, VP, choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharide, dietary fiber, squalene, soya lecithin, taurine, donariella, protein, octacosanol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, magnesium , Zinc, chromium, selenium, potassium, heme iron, oyster meat extract, chitosan, chitin oligosaccharides, collagen, chondroitin, turmeric, licorice, kukoshi, kishi, hawthorn, ginger, ganoderma, licorice extract, snail extract, psyllium, chamomile, Chamomile, Dandelion, Hibiscus, Honey, Boren, Royal Jelly, Lime, Lavender, Rosehip, Rosemary, Sage, Bifidobacterium, Faecalis, Lacris, Wheat Germ Oil, Sesame Oil, Sesame Oil, Soy Oil, Mid-Chain Fatty Acid, Agari Ssu, Ginkgo biloba extract, turmeric, chondroitin, brown rice germ extract, lychee, onion, DHA, EPA, DPA, mochi tea, Cordyceps, garlic, bee cub, papaya, poual, propolis, megsuri tree, yabusitake, royal jelly, saw palmetto Hyaluronic acid, collagen, gumba, harp seal oil, shark cartilage, glucosamine, lecithin, phosphatidylserine, rice bran carrot, mulberry leaf, soy bean extract, echinacea, licorice, barley extract, olive leaf, olive seed, gymnema, banaba , Salacia, Garcinia, Chitosan, St. John's Wort, Jujube, Carrot, Passion Flower, Placental, Hathokii, Grape Seed, Peanut Seed Coat, Bilberry, Black Cohosh, Milk Thistle, Laurels, Sage, Rosemary , Rahma, black vinegar, bitter gourd, maca, safflower, flax, oolong tea, flower buds, caffeine, capsaicin, xylooligosaccharides, glucosamine, buckwheat, citrus, dietary fiber, protein, prune, spirulina, barley young leaf, nucleic acid, yeast, shiitake , Plum meat, amino acid, deep-seaweed extract, noni, oyster meat, soppong, champignon, plantain, acerola, pineapple, banana, peach, apricot, melon, strawberry, raspberry, orange, fucoidan, mesima cob, cranberry, chondroitin sulfate, zinc , Iron, ceramide, silk peptide, glycine, niacin, chest tree, ceramide, L-cysteine, L-carnitine, red wine leaf, millet, horsetail, biotin, centela asiatica, lotus cup, pycnogenol, oyster, rhubarb, clove, The Zumary, catechin, puial, citric acid, brewer's yeast, mellowroth, black zinger, ginger, guageuts, nattokinase, bilberry, tocotrienol, lactoferrin, cinnamon, persimmon buckwheat, cocoa, yuzu seed extract, perilla extract, litchi seed extract, evening primrose Extract, black rice extract, α-lipoic acid, gaba, fresh coffee bean extract, Japanese persimmon extract, kiwi seed extract, Wenzhou orange extract, red ginger extract, astaxanthin, walnut extract, mandarin orange extract, mung bean polysaccharide, lingonberry extract, fucoxanthin, loin Veratrol, strawberry seed extract, cherry blossom extract, swallow nest extract, black ginger extract, maki berry extract, junisai extract, purple tea extract, chrysanthemum flower extract, etc. can also be blended.

As a specific production method, the Nrf2-related gene expression promoter of the present invention is spray-dried or freeze-dried as it is, in the case of an extract, together with powdered dextrin, and is easily made into powder, granules, tableting or solution It can be contained in food (instant food etc.). Moreover, it is also possible to mix with binders, such as gum arabic, to make it a powder form or a granular form, and to add to solid foodstuffs as needed. In the case of the extract, it is also possible to add it to the beverage as it is or, for example, dispersed and dissolved in water, ethanol, glycerin or a mixture thereof.

The Nrf2-related gene expression promoter of the present invention may be used as a material of medicines (including medicines and quasi-drugs). The Nrf2-related gene expression promoting agent of the present invention can be appropriately blended with a raw material for pharmaceutical preparation to produce. The above drug may be used for humans or mammals other than humans. Examples of drug substances that can be added to the Nrf2-related gene expression promoter of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cocoa butter, hydrogenated vegetable oil, kaolin) , Talc etc., binders (distilled water, saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinyl pyrrolidone etc.), disintegrants (sodium alginate, agarten, Sodium hydrogen carbonate, calcium carbonate, sodium lauryl sulfate, monoglyceride stearic acid, starch, lactose, gum arabic powder, gelatin, ethanol etc., disintegration inhibitor (sucrose, stearin, cocoa butter, hydrogenated oil etc), absorption accelerator Quaternary ammonium base, lauryl sulfate Sodium, etc.), adsorbents (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, and the like) and the like.

The method of administering the Nrf2-related gene expression promoter according to the present invention can generally be orally administered in the form of tablets, pills, soft and hard capsules, fine granules, powders, granules and the like. In addition, the water-soluble preparation can be orally administered as a solution. Furthermore, parenteral administration may be performed. When administered as a parenteral agent, the agent for promoting expression of Nrf2 gene of the present invention is dispersed in a suitable solubilizer such as ethanol or water, and then a patch, lotion, ointment, tincture, cream, etc. It can be applied in dosage form. In addition, the water-soluble preparation of the present Nrf2-related gene expression promoter is, as it is, or in the state where a dispersing agent, a suspending agent, a stabilizer and the like are added, such as a patch, lotion, ointment, tincture, cream It can be applied in dosage form.

The dose may vary depending on the administration method, medical condition, age of the patient, etc. However, in adults, it can be administered usually 5 to 200 mg as an active ingredient per day, and usually 0.5 to 100 mg in children.

Although the compounding ratio at the time of using the Nrf2-related gene expression promoter of the present invention as a drug can be appropriately changed depending on the dosage form, it is usually about 0.0001 to about 200 when administered orally or by mucosal absorption. It is recommended that the concentration be about 30 wt%, or about 0.0001 to 30 wt% in the case of parenteral administration.
In addition, since the dose varies depending on various conditions, a smaller amount than the dose may be sufficient, or it may be necessary to administer beyond the range. The pharmaceutical composition may include, in addition to the above-mentioned Nrf2-related gene expression promoting agent, other known compounds commonly used in the pharmaceutical field and compounds necessary for shaping into a form suitable for oral administration. Such compounds include, for example, lactose, starch, hydroxypropyl cellulose, kaolin, talc, calcium carbonate and the like.

The Nrf2-related gene expression promoter of the present invention can be expected to have an Nrf2-related gene expression promoting action even when used as a skin external preparation (including cosmetics, medicines and quasi-drugs).
The form of the external preparation for skin to which the Nrf2-related gene expression promoter of the present invention can be incorporated is, for example, milk, soap, face wash, bath powder, cream, milk, lotion, eau de cologne, shave cream, shave Lotion, cosmetic oil, suntan / suntan lotion, powder, foundation, perfume, pack, nail cream, enamel, enamel remover, black ink, blusher, eye cream, eye shadow, mascara, eye liner, lipstick, lip balm, shampoo , Rinse, hair dye, dispersion liquid, cleaning agent and the like. Moreover, as a form of the pharmaceuticals or quasi-drugs which can mix | blend the Nrf2-related gene expression promoter of this invention, an ointment, a cream agent, the liquid for external use etc. are mentioned.

In addition to the Nrf2-related gene expression promoter according to the present invention, the external skin preparation of the above embodiment is a component to be blended in a skin external agent such as cosmetics and quasi-drugs to the extent that its Nrf2-related gene expression promoting action is not impaired Oil, higher alcohol, fatty acid, UV absorber, powder, pigment, surfactant, polyhydric alcohol / sugar, polymer, physiologically active ingredient, solvent, antioxidant, perfume, preservative, etc. it can.
Examples are listed below, but the invention is not limited to these examples.

(1) Example of oil: Oil component of ester type: glyceryl tri 2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearic acid Isocetyl, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine Diisopropylate, Isoarakyl neopentanoate, Glyceryl tri (caprylic capric acid), Trimethylolpropane tri-2-ethylhexanoate, Trimethylol triisostearate Propane, pentaerythritol tetra 2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl licinoleate, iso laurate Stearyl, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyl dodecyl oleate, octyl dodecyl linoleate, isopropyl isostearate, Setoaryl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate Ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di (caprylic capric acid) propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctoate, glyceryl tricaprylate, glyceryl triundecylate, triisopalmitin Glyceryl acid, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleate Ester, polyglycerin isostearic acid ester, dipropyl carbonate, charcoal Dialkyl (C12-18), triisocetyl citrate, triisoalkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyl decyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, Trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, 2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, olein Cholesteryl acid, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, 12-stearoyl hydroxystearate Cetyl, 12-stearoyl-hydroxystearic acid stearyl 12-stearoyl-hydroxystearic acid isostearate, and the like.
Hydrocarbon oil phase components: squalane, liquid paraffin, α-olefin oligomers, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, vaseline and the like.
Animal and vegetable oils and their hardened oils, and naturally derived waxes: beef oils, hardened beef fat, pork fat, hardened pork fat, horse oil, hardened horse oil, mink oil, orange raffine oil, fish oil, hardened fish oil, egg yolk oil etc. and other animal oils The hydrogenated oil, avocado oil, almond oil, olive oil, cacao butter, kiwi seed oil, sesame seed oil, kucunut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, safflower oil, shea butter, soybean oil, evening primrose oil , Perilla oil, tea seed oil, camel oil, corn oil, rapeseed oil, hardened rapeseed oil, palm kernel oil, hardened palm kernel oil, palm oil, hardened palm oil, peanut oil, hardened peanut oil, castor oil, hardened castor oil , Sunflower oil, grape seed oil, jojoba oil, hardened jojoba oil, macadamia nut oil, medium oil, cottonseed oil, hardened cottonseed oil, coconut oil, vegetable oil such as hardened coconut oil and its hardening , Beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax and montan wax.
Silicone oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether modified organopolysiloxane, dimethyl Siloxane / methyl cetyloxy siloxane copolymer, dimethylsiloxane / methyl stearoxy siloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic Examples thereof include silicone, trimethylsiloxysilicate, silicone RTV rubber and the like.
Fluorine-based oil phase components: perfluoropolyethers, fluorine-modified organopolysiloxanes, fluorinated pitches, fluorocarbons, fluoroalcohols, fluoroalkyl-polyoxyalkylene co-modified organopolysiloxanes and the like.

(2) Examples of higher alcohols Lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, octyl dodecanol and the like.

(3) Examples of fatty acids caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linoleic acid, arachidic acid, arachidonic acid, behenic acid , Erucic acid, 2-ethylhexanoic acid and the like.

(4) Examples of UV absorbers paraaminobenzoic acid, amyl paraaminobenzoate, ethyldihydroxypropyl paraaminobenzoate, glyceryl paraaminobenzoate, ethyl paraaminobenzoate, octyl paraaminobenzoate, octyl dimethyl paraaminobenzoate, ethylene glycol salicylate, salicylic acid Octyl, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl paramethoxycinnamate, 2-ethylhexyl paramethoxycinnamate, monodiparamethoxycinnamic acid 2- Glyceryl ethylhexanoate, Isopropyl paramethoxycinnamate, Diethanolamine salt of paramethoxyhydrocinnamic acid, Diisopropyl and diisopropylcinnamic acid Stel mixture, urocanic acid, ethyl eurocanic acid, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, dihydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenone disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, Butylmethoxydibenzoylmethane, 2,4,6-trianilino-p- (carbo-2-ethylhexyl-1-oxy) -1,3,5-triazine, 2- (2-hydroxy-5-methylphenyl) benzotriazole , Methyl-O-aminobenzoate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate, phenylbenzimidazole sulfuric acid, 3- (4-methylbenzylidene) can Le, isopropyl dibenzoylmethane, 4- (3,4-dimethoxyphenyl methylene) 2-ethylhexyl-2,5-dioxo-1-imidazolidin propionate,, and polymer derivatives and silane derivatives thereof.

(5) Examples of powder and pigment Dyes such as red No. 104, red No. 201, yellow No. 4, blue No. 1, black No. 401, yellow No. 4 AL lake, yellow No. 203 BA lake etc., nylon powder, nylon powder , Silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polymers such as polyethylene powder, yellow iron oxide, red iron oxide, black Colored pigments such as iron oxide, chromium oxide, carbon black, ultramarine blue and bitumen, white pigments such as zinc oxide, titanium oxide and cerium oxide, extender pigments such as talc, mica, sericite, kaolin and barium barium sulfate, mica titanium Pearl pigments such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, metal salts such as magnesium silicate, Inorganic powders such as silica and alumina; metal soaps such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate and zinc undecylenate; bentonite; smectite; boron nitride etc. Be There are no particular limitations on the shape (spherical, rod-like, needle-like, plate-like, irregularly-shaped, scaly, fusiform, etc.) and particle diameter of these powders. These powders may be subjected to conventionally known surface treatment such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine treatment, It may or may not be surface-treated in advance by polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment or the like.

(6) Examples of surfactants: anionic surfactants: fatty acid soaps, α-acyl sulfonates, alkyl sulfonates, alkyl allyl sulfonates, alkyl naphthalene sulfonates, alkyl sulfates, POE alkyl ether sulfates , Alkyl amide sulfate, alkyl phosphate, POE alkyl phosphate, alkyl amide phosphate, alkyloyl alkyl taurine salt, N-acyl amino acid salt, POE alkyl ether carboxylate, alkyl sulfo succinate, alkyl sulfo acetic acid Sodium, acylated hydrolysed collagen peptide salt, perfluoroalkyl phosphate ester and the like can be mentioned.
Cationic surfactants: alkyl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, stearyl trimethyl ammonium bromide, cetostearyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, behenyl trimethyl ammonium bromide, benzalkonium chloride And behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide stearic acid, lanolin derivative quaternary ammonium salt and the like.
Amphoteric surfactants: carboxybetaine type, amidobetaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amidoamine type and the like.
Nonionic surfactants: Propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbite fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE cured castor Oil, POE castor oil, POE • POP copolymer, POE • POP alkyl ether, polyether modified silicone lauric acid alkanolamide, alkyl amine oxide, hydrogenated soybean phospholipid etc. may be mentioned.
Natural surfactants: lecithin, saponin, sugar surfactants and the like.

(7) Examples of polyhydric alcohols and sugars ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1, 3 And butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltose, maltose, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan and the like. In addition, these chemically modified products can also be used.

(8) Examples of polymers Acrylic acid ester / methacrylic acid ester copolymer (plus size, manufactured by Chemochemicals Co., Ltd.), vinyl acetate / crotonic acid copolymer (resin 28-1310, manufactured by NSC), vinyl acetate / crotone Acid / vinyl neodecanate copolymer (28-2930, manufactured by NSC), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP), T-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (rubomer) Manufactured by BASF, vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer (Lubiscol VAP, manufactured by BASF), vinyl acetate / crotonic acid copolymer (Lubiset CA, manufactured by BASF), vinyl acetate / croton Acid / vinyl pyrrolidone copolymer (Rubiset CAP, manufactured by BASF), vinyl pyrrolidone / acrylate copolymer (Rubiflex, BAS Company F), acrylate / acrylamide copolymer (Ultrahold, made by BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer (advantage, made by ISP), carboxyvinyl polymer (Carbopol, Anionic polymer compound such as BF Goodrich), acrylic acid / alkyl methacrylate copolymer (Pemulene, BF Goodrich), etc., and an acetic acid amphipathic compound of dialkylaminoethyl methacrylate polymer (Yuka Former, manufactured by Mitsubishi Chemical Corporation), Amphoteric polymer compounds such as octyl acrylate / hydroxypropyl acrylate / butyl aminoethyl methacrylate copolymer (AMPHOMER, manufactured by NSC), vinyl pyrrolidone / quaternized dimethylaminoethyl methacrylate (GAFQUAT, manufactured by ISP) , Methyl vinyl imidazolium chlori / Cationic polymer compounds such as vinyl pyrrolidone copolymer (rubicoat, manufactured by BASF), polyvinyl pyrrolidone (Lubiscol K, manufactured by BASF), vinyl pyrrolidone / vinyl acetate copolymer (Lubiscol, manufactured by BASF) Nonionic polymer compounds such as vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer 937, manufactured by ISP), vinylcaprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer VC713, manufactured by ISP), etc. is there. Also, cellulose or derivatives thereof, keratin and collagen or derivatives thereof, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, xanthan gum, carrageenan, high methoxyl pectin, lomethoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabino Naturally occurring high molecular compounds such as galactan, karaya gum, tragacanth gum, alginic acid, albumin, casein, curdlan, gellan gum, dextran and the like can also be suitably used.

(9) Example of physiologically active ingredient The physiologically active ingredient includes a substance that imparts some physiological activity to the skin when applied to the skin. For example, skin lightening ingredients, immunostimulants, anti-aging agents, ultraviolet light protective agents, slimming agents, squeezing agents, antioxidants, hair growth agents, hair growth agents, moisturizers, circulation promoters, antibacterial agents, bactericides, desiccants, A cooling agent, a warming agent, vitamins, an amino acid, a wound healing promoting agent, an irritation reducing agent, an analgesic, a cell activator, an enzyme component and the like can be mentioned. Examples of these suitable combination components include, for example, altava extract, avocado extract, amacha extract, altea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo extract, fennel extract, turmeric extract, oolong tea extract, AGEZ Extract, Echinacea leaf extract, aubergine extract, aubergium extract, aurum extract, barley extract, aubergium extract, aubergium extract, aubergium extract, callus extract, orange extract, dried sea water, seaweed extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk , Kamomira Extract, Carrot Extract, Kawara Yomogi Extract, Licorice Extract, Licorice Extract, Karkade Extract, Kakyo Extract, Kina Extract, Kukamba Extract, Guanosine, Gardenia Extract, Kumazasa Extract, Clarae Kiss, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentiana extract, black tea extract, yeast extract, burdock extract, rice bran extract, rice germ oil, rice germ oil, comfrey extract, collagen, bilberry extract, saishin extract, saiko extract , Sai Tai extract, Salvia extract, Sapon extract, Sasa extract, Halibut extract, Sansho extract, Shitake extract, Shiitake extract, Shiou extract, Shikon extract, Sesame extract, Shinoki extract, Shimokuso extract, Shiakuyaku extract, Shobu root extract, Birch extract, Suzuna extract, Sailflower extract Kirishima extract, Azalea extract, Azalea extract, Azalea extract, Azalea extract, Azalea extract, Azalea extract, Azalea extract, Azalea Yue Extract, Sensory Extract, Soy Bean Extract, Daisy Extract, Thyme Extract, Tea Extract, Chijia Extract, Chigaya Extract, Chinpi Extract, Chii Extract, Toukisenka Extract, Toinan Extract, Toenin Extract, Touhi Extract, Dokudami Extract, Tomato Extract, Natto Extract, Carrot Extract, Garlic Extract, Novara extract, Hibiscus extract, Bac mondous extract, Parsley extract, honey, Hamamellis extract, Parietalia extract, Hikiokoshi extract, Bisavolol, Loquat extract, Fukinada extract, Fukinotou extract, Bokuryou extract, Butcherbroom extract, Grape extract, Propolis, Hechima extract Safflower extract, peppermint extract, body oil extract, button extract, hop extract, pine extract, marronier extract, mizuboshi Kiss, Mukuroji extract, Melissa extract, peach extract, cornflower extract, Eucalyptus extract, Euquinia extract, Yukinoshita extract, Yoquinin extract, yomogi extract, lavender extract, lavender extract, apple extract, lettuce extract, lemon extract, Japanese apricot extract, rose extract, rosemary extract, Roman chamomile extract And royal jelly extract.
In addition, deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, biopolymer such as hydrolyzed eggshell membrane, amino acid, hydrolyzed peptide, sodium lactate, urea, sodium pyrrolidone carboxylate Moisturizing component such as betaine, whey, trimethylglycine, sphingolipid, ceramide, phytosphingosine, cholesterol, cholesterol derivative, oil component such as phospholipid, ε-aminocaproic acid, glycyrrhizinic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, Immunoactivators such as hydrocortisone, vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester Active ingredients such as allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, tocopherols, carotenoids, flavonoids, tannins, lignans, antioxidants such as saponins, α-hydroxy acids, β-hydroxy acids, etc. Cell activators, blood circulation enhancers such as γ-oryzanol and vitamin E derivatives, wound healing agents such as retinol and retinol derivatives, albutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione etc. Light-whitening agent, cephalantin, licorice extract, chili pepper tin, hinokitiol, garlic garlic extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivative, calcium pantothenate, D-pan Totenyl alcohol, acetylpantotenyl ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethynyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonyl acid vanillylamide, nonanoic acid vanillylamide, pirocton Olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcinol, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin hydrochloride, feminine hormone, cantalistinski, cyclosporin, zinc pyrithione, hydrocortisone, minoxidil, monostearic acid Hair growth agents such as polyoxyethylene sorbitan, peppermint oil, sasaniki extract and the like can be mentioned.

(10) Examples of antioxidants Sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolylbiguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxyl Examples thereof include toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignans, lignans, saponins, and plant extracts that exhibit an antioxidant effect such as apple extract and clove extract.

(11) Examples of Solvents Purified water, ethanol, lower alcohols, ethers, LPG, fluorocarbons, N-methylpyrrolidone, fluoroalcohols, volatile linear silicones, next-generation fluorocarbons and the like can be mentioned.

〔Example〕
Example 1 Preparation of Extract of Kawara Nadeshiko Kawara Nadesico seeds were extracted by immersion for 2 days or more with 4 volumes of water. Then, the extract was subjected to net filtration, and the filtrate was subjected to suction filtration using diatomaceous earth and filter paper to obtain a filtrate. The filtrate was concentrated under reduced pressure and dried to give a solid. The solid content was dissolved in a 30% aqueous solution of 1,3 propanediol, and then sterile filtered to obtain an extract of kawara nadesico.

Test Example 1: Evaluation of Nrf2 Gene Expression Promoting Action Using the human epidermal keratinocytes, the extract of the Chinese cabbage extract of the above example was added at each concentration (0.01 wt%, 0.03 wt%, 0.10 wt%). After 24 hours, mRNA was extracted and the expression level of Nrf2 gene was evaluated. The results are shown in FIG.

Test Example 2 Evaluation of GCLM Gene Expression Promoting Action Using the human epidermal keratinocytes, the extract of the Chinese cabbage extract of the above example was added at each concentration (0.01 wt%, 0.03 wt%, 0.10 wt%). The mRNA was extracted 24 hours after that, and the expression level of the GCLM gene was evaluated. The results are shown in FIG.

Results and Effects of Examples As shown in FIG. 1, it was confirmed that the expression level of the Nrf2 gene was increased in a concentration dependent manner as compared with the control. Furthermore, as shown in FIG. 2, it was confirmed that the expression of the GCLM gene was promoted.
As apparent from the above-mentioned examples, the Chinese cabbage extract exerts an expression promoting action of the Nrf2 gene to activate Nrf2. Furthermore, it exerts the expression promoting action of the GCLM gene located downstream of ARE or EpRE to which Nrf2 binds, and whose expression is controlled by Nrf2.

[Formulation example]
Although the formulation example of the Nrf2-related gene expression promoter of this invention is given to the following, the following formulation example does not limit this invention.
Formulation 1: Chewing gum sugar 53.0 wt%
Gum base 20.0
Glucose 10.0
Water tank 16.0
Fragrance 0.5
Nrf2-related gene expression promoter 0.5
100.0 wt%

Formulation example 2: Gummy reduced starch syrup 40.0 wt%
Granulated sugar 20.0
Glucose 20.0
Gelatin 4.7
Water 9.68
Grape juice 4.0
Grape Flavor 0.6
Dye 0.02
Nrf2-related gene expression promoter 1.0
100.0 wt%

Formulation example 3: candy sugar 50.0 wt%
Water tank 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
Nrf2-related gene expression promoter 0.4
100.0 wt%

Formulation example 4: Yogurt (hard / soft)
Milk 41.5 wt%
Skimmed milk powder 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Nrf2-related gene expression promoter 0.4
A small amount of perfume
Water residual
100.0 wt%

Formulation example 5: Soft drink fructose glucose liquid sugar 30.0 wt%
Emulsifier 0.5
Nrf2-related gene expression promoter 0.05
Appropriate amount of flavor
Purified water residual
100.0 wt%

Formulation example 6: Soft capsule grape seed oil 87.0 wt%
Emulsifier 12.0
Nrf2-related gene expression promoter 1.0
100.0 wt%

Formulation example 7: Tablet lactose 54.0 wt%
Crystalline cellulose 30.0
Starch degradation product 10.0
Glycerin fatty acid ester 5.0
Nrf2-related gene expression promoter 1.0
100.0 wt%

Formulation example 8: Granules internal medicine (pharmaceutical product)
Nrf2-related gene expression promoter 1.0 wt%
Lactose 30.0
Corn starch 60.0
Crystalline cellulose 8.0
Polyvinylpyrrolidone 1.0
100.0 wt%

Formulation example 9: Tablet sugar 76.4 wt%
Glucose 19.0
Sucrose fatty acid ester 0.2
Nrf2-related gene expression promoter 0.5
Purified water 3.9
100.0 wt%

Formulation example 10: Cosmetic cream squalane 20.0 wt%
Bee wax 5.0
Refined jojoba oil 5.0
Glycerin 5.0
Glycerin mono-stearate 2.0
Polyoxyethylene (20) sorbitan-
Monostearate 2.0
Nrf2-related gene expression promoter 2.0
Antiseptics appropriate amount perfume appropriate amount
Purified water residual
100.0 wt%

Formulation example 11: 5.0 wt% of toner ethanol
Glycerin 2.0
1,3-butylene glycol 2.0
Polyethylene oleyl ether 0.5
Sodium citrate 0.1
Citric acid 0.1
Nrf2-related gene expression promoter 0.1
Purified water residual
100.0 wt%

Formulation example 12: Body gel macadamia nut oil 2.0 wt%
Octyldodecyl myristate 10.0
Methyl phenyl polysiloxane 5.0
Behenyl alcohol 3.0
Stearic acid 3.0
Batil Alcohol 1.0
Glyceryl monostearate 1.0
Tetraoleate Polyoxyethylene Sorbit 2.0
Hydrogenated soybean phospholipids 1.0
Ceramide 0.1
Retinol palmitate 0.1
Antiseptics appropriate amount of Sturgea extract 1.0
Nrf2-related gene expression promoter 1.0
1,3-Butylene glycol 5.0
Purified water residual
100.0 wt%

Formulation example 13: Emulsion squalane 4.0 wt%
Vaseline 2.5
Setanol 2.0
Glycerin 2.0
Lipophilic Glyceryl Monostearate 1.0
Stearic acid 1.0
L-arginine 1.0
Nrf2-related gene expression promoter 0.5
Potassium hydroxide 0.1
A small amount of perfume
Purified water residual
100.0 wt%

Formulation example 14: bath agent (liquid)
Propylene glycol 50.0 wt%
Ethanol 20.0
Sodium sulfate 5.0
Nrf2-related gene expression promoter 0.5
Lanolin 0.5
Avocado oil 0.5
Dye 1.5
Flavoring 22.0
100.0 wt%

  As described above, the present invention provides an Nrf2-related gene expression promoter that uses a novel component as an active ingredient and is safe.

Claims (2)

An Nrf2 gene expression promoter comprising as an active ingredient a D. superbus L. var. Longicalycinus seed extract . A GCLM gene expression promoter comprising a seed extract of D. superbus L. var. Longicalycinus as an active ingredient.