Heat shock protein gene expression regulator, pharmaceutical product, cosmetic product, and method for producing a heat shock protein gene expression regulator.

Abstract

Heat shock protein genes that use naturally derived ingredients as active ingredients and exhibit a wide range of effects. Methods for producing gene expression regulators, pharmaceuticals, cosmetics, and heat shock protein gene expression regulators. The purpose is to provide. [Solution] Lactobacillus genus derived from mugwort or angelica tree A heat shock protein gene expression regulator comprising the heat shock protein gene expression Pharmaceuticals containing a regulator. Cosmetics containing the heat shock protein gene expression regulator. This includes obtaining the genus Lactobacillus from mogi or angelica tree. A method for producing a heat shock protein gene expression regulator.

Description

Technical Field

[0001] The present invention relates to a heat shock protein gene expression regulator, a pharmaceutical, a cosmetic, and a method for producing a heat shock protein gene expression regulator.

Background Art

[0002] In recent years, as research on the structure of human skin and its metabolic mechanisms has advanced, the causes and mechanisms of changes such as wrinkles, fine lines, spots, and sagging that appear in human skin with aging are gradually becoming clear. Skin is composed of an outer thin epidermis (epithelial tissue) and a thick dermis (connective tissue) beneath it. The epidermis, as the outermost layer of the body, protects the body from the outside world and prevents internal moisture and nutrients from leaking out. The dermis is a connective tissue mainly composed of fibroblasts, collagen fibers (collagen), elastic fibers (elastin), and proteoglycans, which has a complex three-dimensional structure extending in a three-dimensional manner, and plays a role in providing strength, extensibility, and elasticity to the skin. As the skin ages, the amount of sebum and moisture in the skin decreases, the moisturizing ability of the stratum corneum on the skin surface is lost, and fine lines and roughness of the skin due to dryness are likely to occur. On the other hand, it has been proposed to improve skin function using fermented products (see, for example, Patent Documents 1 to 7). In addition, it has been proposed to induce the expression of heat shock proteins by administering extracts such as arnica and bring about a whitening effect (see, for example, Patent Document 8). <00000()24> (For example, see Patent Documents 1 to 7.) In addition, it has been proposed to induce the expression of heat shock proteins by administering extracts such as arnica and bring about a whitening effect (see, for example, Patent Document 8). (For example, see Patent Document 8.)

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

[0004] This invention utilizes naturally derived ingredients as active ingredients and exhibits a wide range of effects, including those of heat shock proteins. Method for manufacturing gene expression regulators, pharmaceuticals, cosmetics, and heat shock protein gene expression regulators The purpose is to provide legal information. [Means for solving the problem]

[0005] The heat shock protein gene expression regulator according to one aspect of the present invention is derived from mugwort or Angelica keiskei. It comprises the genus Lactobacillus. This relates to one aspect of the present invention. The pharmaceutical product contains Lactobacillus species derived from mugwort or Angelica keiskei. To be equipped. Cosmetics relating to one aspect of the present invention include Lactobacillus (La) derived from mugwort or Angelica keiskei. It comprises the genus *Ctobacillus*. Heat shock protein genetics related to one aspect of the present invention. A method for producing a gene expression regulator is to use Lactobacillus (Lactobacillus) from mugwort or angelica tree. This includes obtaining the genus (llus). [Effect of the Invention]

[0006] According to the present invention, a heat shock protein gene expression regulator, a pharmaceutical product, a cosmetic, and a method for producing a heat shock protein gene expression regulator, which have a natural-derived component as an active ingredient and exhibit a wide range of effects, can be provided. [Brief Description of the Drawings]

[0007] [Figure 1] It is a graph and a table showing the analysis results of the bacteria contained in the fermentation broth according to Example 1. [Figure 2] It is a graph and a table showing the analysis results of the bacteria contained in the fermentation broth according to Example 2. [Figure 3] It is a table showing the analysis results of gene expression according to Example 4. [Figure 4] It is a table showing the analysis results of gene expression according to Example 4. [Figure 5] It is a table showing the analysis results of gene expression according to Example 4. [Figure 6] It is a table showing the analysis results of gene expression according to Example 4. [Figure 7] It is a table showing the analysis results of gene expression according to Example 4. [Figure 8] It is a table showing the analysis results of gene expression according to Example 4. [Figure 9] It is a photograph of a human administered with the fermentation broth according to Example 5. [Figure 10] It is a graph showing the antibacterial effect of the fermentation broth according to Example 6. [Figure 11] It is a graph showing the antifungal effect of the fermentation broth according to Example 7. [Figure 12] It is a graph showing the antiviral effect of the fermentation broth according to Example 8. [Figure 13] It is a graph showing the antiviral effect of the fermentation broth according to Example 8. [Figure 14] It is a graph showing the anti-dermatophyte effect of the fermentation broth according to Example 9. [Figure 15] This table shows the amount of type I collagen produced in Example 10. [Figure 16] This table shows the production amount of HSP47 in Example 10. [Figure 17] This is a microscopic image of SA-β-Gal stained cells according to Example 11. [Figure 18] This is a microscopic image of SA-β-Gal stained cells according to Example 11. [Figure 19] This table shows the degree of SA-β-Gal staining in Example 11. [Figure 20] This table shows the cell viability rate for Example 12. [Figure 21] This table shows the production amount of HSP70 according to Example 12. [Modes for carrying out the invention]

[0008] The embodiments of the present invention will be described in detail below. This provides examples of devices and methods for embodying the technical concept of the invention, and this invention The technical concept does not limit the combination of constituent elements, etc., to the following. The technical concept may be modified in various ways within the scope of the patent claims.

[0009] The heat shock protein (HSP) gene expression regulator according to this embodiment is derived from mugwort or asparagus. It contains the genus Lactobacillus derived from leaves. Heat according to the embodiment Shock protein gene expression regulators, in particular, enhance the anti-aging function of heat shock proteins. It promotes the expression of the protein (HSP) 70 gene. Lactobacillus is a type of lactic acid bacillus. It is a Gram-positive, facultative anaerobic bacterium. Lactobacillus species produce lactic acid by fermenting sugars. Lactobacillus species also inhabit the bodies of animals, including humans, but according to the embodiment... The genus Lactobacillus is derived from Artemisia princeps or Angelica keiskei.

[0010] For example, the Lactobacillus species according to this embodiment is extracted by fermenting mugwort or angelica tree. The heat shock protein gene expression regulator according to the embodiment is derived from mugwort or angelica tree. It may also be good to have an additional fermentation solution.

[0011] Examples of Lactobacillus species derived from Artemisia are the species parafarraginis, and par This includes species such as *Abuchneri*, *Buchneri*, and *Harbinensis*. Lactobacillus species derived from Angelica keiskei include, for example, the species vini and nagelii. The heat shock protein gene expression regulator according to this embodiment is used for multiple species of the genus Lactobacillus. It may include.

[0012] The heat shock protein gene expression regulator according to this embodiment is a heat shock protein gene expression regulator. It promotes the expression of offspring. An example of a heat shock protein gene is the one encoding HSP70. Examples include the HSPA1A gene and the HSPB1 gene, which encodes HSP27. P70 has whitening-promoting, anti-spot, anti-wrinkle, anti-stress, anti-cell death, and anti- It possesses inflammatory, cytoprotective, gastric mucosal protective, and anti-DNA damage functions. (HSP27) It has anti-stress function and wound healing function. Heat shock protein gene according to the embodiment The gene expression regulator contains Lactobacillus species derived from Angelica keiskei. It promotes the production of HSP47. HSP47 is a molecule involved in collagen biosynthesis. It is perone. Therefore, the heat shock protein gene expression regulator according to this embodiment is For example, anti-stress function, anti-cell death function, anti-inflammatory function, cell protection function, gastric mucosal protection function, It is possible to improve anti-DNA damage function and wound healing function. Heat according to the embodiment Shock protein gene expression regulators include, for example, heat shock protein expression promotion and skin whitening. Enhanced promotion function, enhanced anti-spot function, enhanced anti-wrinkle function, enhanced anti-stress function, enhanced anti-cell death function 1. Improved anti-inflammatory function, improved cell protection function, improved gastric mucosal protection function, improved anti-DNA damage function, Pharmaceuticals, cosmetics, and at least one use selected from the group consisting of wound healing. It can be used as food. Note that wrinkles include fine lines.

[0013] The heat shock protein gene expression regulator according to this embodiment is a heat shock protein gene expression regulator. The expression of genes other than offspring is also regulated. For example, the regulation of heat shock protein gene expression according to the embodiment. The agent suppresses the expression of the acid ceramide-degrading enzyme (ceramidase) gene. An example of a gene that suppresses the expression of acid ceramidase is the ASAH1 gene. Therefore, the heat shock protein gene expression regulator according to this embodiment is, for example, ceramide It is possible to promote biosynthesis and improve the skin's barrier function. (According to this embodiment, the thermotherapy...) Shock protein gene expression regulators include, for example, those that suppress ceramidase expression and ceramide biosynthesis. A pharmaceutical product for at least one use selected from the group consisting of promotion and improvement of barrier function. It can be used as a product, cosmetic, and / or food.

[0014] The heat shock protein gene expression regulator according to this embodiment is used for the expression of lipid synthesis enzyme genes. It promotes [something]. An example of a lipid synthesis enzyme gene is the DGAT1 gene. T1 (Diacylglycerol O-acyltransferase 1) is Diacylglycerol (DAG) is used to synthesize triglycerides (TAG). DGAT1 deficiency This causes abnormalities in the skin's barrier function. Therefore, according to this embodiment, heat shock tan Protein gene expression regulators, for example, promote lipid synthesis and improve skin barrier function. This is possible. The heat shock protein gene expression regulator according to this embodiment is, for example, For at least one application selected from the group consisting of promoting lipid synthesis and improving barrier function. It can be used as a medicine, cosmetic, and / or food.

[0015] The heat shock protein gene expression regulator according to this embodiment is a lysosomal hydrolase. It promotes gene expression. Lysosomes break down carbohydrates and glycolipids within cells. Lysosomes require lysosomal hydrolases to function properly. An example of a hydrolytic enzyme gene is the acid β-glucosidase (GBA) gene. In patients with lysosomal storage diseases, GBA activity is reduced or absent. Also, G Activation of BA improves the skin's barrier function. Therefore, according to this embodiment, Protein gene expression regulators, for example, prevent and treat lysosomal storage diseases and skin conditions. It is possible to improve rear function. Heat shock protein gene generation according to the embodiment Current regulators include, for example, promoting lysosomal hydrolase expression, improving lysosomal function, and A small number of options are selected from the group consisting of prevention of sososomal storage diseases, treatment of lysosomal storage diseases, and improvement of barrier function. It can be used as a pharmaceutical, cosmetic, and / or food product for at least one purpose.

[0016] The heat shock protein gene expression regulator according to this embodiment is tight junction biosynthesis It promotes the expression of growth factor genes. Examples of tight junction biosynthesis factor genes include: Examples include the claudin 1 (CLDN1) gene and the occludin (OCLN) gene. Claudines and occludines are components of tight junctions. Therefore The heat shock protein gene expression regulator according to this embodiment is, for example, tight junction It is possible to promote the biosynthesis of ions and improve the skin's barrier function. Examples of heat shock protein gene expression regulators include tight junction biosynthesis factors. Expression enhancement, claudin expression enhancement, occludin expression enhancement, tight junction biosynthesis A pharmaceutical product for at least one use selected from the group consisting of promotion and improvement of barrier function. It can be used as a product, cosmetic, and / or food.

[0017] The heat shock protein gene expression regulator according to this embodiment modifies the expression of intercellular adhesion factor genes. It promotes cell adhesion. An example of an intercellular adhesion factor gene is integrin α2 (ITGA2) gene. The genes, E-cadherin (CDH1) gene, and hyaluronic acid receptor (CD44) gene Integrins, cadherins, and CD44 contribute to cell-cell adhesion. Therefore, the heat shock protein gene expression regulator according to this embodiment is, for example, a cell adhesion molecule. It is possible to promote the biosynthesis of this substance and improve the skin's barrier function. Heat shock protein gene expression regulators include, for example, those that promote the biosynthesis of intercellular adhesion factors, and integrating Promotes glycin expression, promotes cadherin expression, promotes hyaluronic acid receptor expression, and improves barrier function. Pharmaceuticals, cosmetics, and / or for at least one use selected from the group consisting of the above. It can be used as food.

[0018] The heat shock protein gene expression regulator according to this embodiment is a temperature-sensitive TRP (Tra Promotes the expression of (insient receptor potential) channel genes. An example of a TRP channel gene is the TRPV3 gene. TRPV3 is It is involved in the proliferation and differentiation of keratinocytes, which maintain the epidermal barrier function. Heat shock protein gene expression regulators related to the application method include, for example, keratinocyte biosynthesis It is possible to promote growth and improve the skin's barrier function. The thermal shock according to this embodiment Protein gene expression regulators include, for example, those that promote TRP channel expression and keratinocyte expression. For at least one application selected from the group consisting of synthesis promotion and barrier function improvement It can be used as a pharmaceutical, cosmetic, and / or food product.

[0019] The heat shock protein gene expression regulator according to this embodiment is used for the expression of antimicrobial molecule genes. It promotes [something]. An example of an antimicrobial molecule gene is the Toll-like receptor 2 (TLR2) gene. Toll-like receptors have the function of detecting microorganisms and activating the immune system. Examples of antimicrobial molecule genes include the DEFB1 gene, the DEFB4A gene, and D Examples include the EFB103A gene, the DEFB1 gene, the DEFB4A gene, and DE The FB103A gene is responsible for the antimicrobial peptides DEFB1, DEFB2, and DEFB It encodes β-defensins such as 103. Therefore, the heat shock tank according to the embodiment Protein gene expression regulators can, for example, improve antimicrobial function. Examples of heat shock protein gene expression regulators related to morphology include, for example, those that promote Toll-like receptor expression. Selected from the group consisting of promotion of β-defensin expression and enhancement of antimicrobial function, It can be used as a pharmaceutical, cosmetic, and / or food product for a single purpose.

[0020] The heat shock protein gene expression regulator according to this embodiment is used for sirtuin gene expression It promotes. An example of a sirtuin gene is the SIRT4 gene. The activity of the yuin gene enhances anti-aging function. Therefore, according to this embodiment, Protein gene expression regulators can, for example, enhance anti-aging functions. The heat shock protein gene expression regulator according to this embodiment is, for example, a sirtuin expression promoter. A pharmaceutical product for at least one use selected from the group consisting of promoting and improving anti-aging functions. It can be used as a cosmetic and / or food product.

[0021] The heat shock protein gene expression regulator according to this embodiment is used for telomerase gene expression It promotes [something]. Examples of telomerase genes include the TERT gene and the TERC gene. It can be done. Promoting telomerase activity extends the lifespan of cells. Therefore, Morphological heat shock protein gene expression regulators, for example, enhance anti-aging functions. This is possible. The heat shock protein gene expression regulator according to this embodiment is telomer For at least one use selected from the group consisting of promoting enzyme expression and improving anti-aging function It can be used as a pharmaceutical, cosmetic, and / or food product.

[0022] The heat shock protein gene expression regulator according to this embodiment is an energy metabolism factor gene It promotes the expression of energy metabolism factor genes. An example of an energy metabolism factor gene is the PPARGC1A gene. It can be listed. The PPARGC1A gene is PGC-1 (Peroxisome prol iferator-activated receptor gamma coacti It encodes vator 1). PGC-1 promotes energy metabolism. Therefore The heat shock protein gene expression regulator according to the embodiment is, for example, an energy metabolite. It is possible to improve performance. Heat shock protein gene expression regulation according to the embodiment The agent promotes the expression of energy metabolism factors, promotes PGC-1 expression, and improves energy metabolic function. Pharmaceuticals, cosmetics, and / or food products selected from the group consisting of at least one use. It is usable as a product.

[0023] The heat shock protein gene expression regulator according to this embodiment is a hyaluronic acid biosynthesis factor gene It promotes gene expression. An example of a hyaluronic acid biosynthesis factor gene is hyaluronic acid synthesis. The enzyme 1 (HAS1) gene, the hyaluronic acid synthase 2 (HAS2) gene, and hyaluronic acid One example is the phosphate synthase 3 (HAS3) gene.

[0024] Furthermore, the heat shock protein gene expression regulator according to this embodiment is a hyaluronic acid degradation agent. It suppresses the expression of subgenes. An example of a hyaluronic acid degradation factor gene is hyaluronic acid The HYAL2 gene and cell migration-inducing and hyaluronan-binding protein (CEMIP, KIA A1199) is one example of this gene.

[0025] Therefore, the heat shock protein gene expression regulator according to this embodiment is, for example, a It is possible to improve hyaluronic acid biosynthesis function. Hyaluronic acid is a prognosis for osteoarthritis. It is effective in prevention and treatment, improving moisturizing function, eliminating sagging, and reducing wrinkles. Therefore, Heat shock protein gene expression regulators related to the application method, for example, prevent osteoarthritis and It is possible to treat sagging, improve moisturizing function, and reduce wrinkles and sagging. Examples of heat shock protein gene expression regulators related to the state include, for example, hyaluronic acid synthase gene expression regulators. Promotion, suppression of hyaluronic acid degradation factor expression, promotion of hyaluronic acid biosynthesis, prevention of osteoarthritis, change From the group consisting of treatment for osteoarthritis, improvement of moisturizing function, improvement of anti-sagging function, and improvement of anti-wrinkle function May be used as a pharmaceutical, cosmetic, and / or food product for at least one selected use. It is Noh.

[0026] The heat shock protein gene expression regulator according to this embodiment is a basement membrane biosynthesis factor gene It promotes expression. An example of a basement membrane biosynthesis factor gene is laminin α1 (LAMA1). Genetic genes, laminin α5 (LAMA5) gene, type IV collagen α1 (COL4A1) gene Examples include the sap and type VII collagen α1 (COL7A1). The heat shock according to the embodiment Protein gene expression regulators, for example, promote the biosynthesis of laminin and collagen. It is possible to promote the biosynthesis of the basement membrane. Heat shock protein gene according to the embodiment Examples of gene expression regulators include those that promote the expression of basement membrane biosynthesis factors, laminin expression, and collagen. For at least one application selected from the group consisting of expression enhancement and basement membrane biosynthesis enhancement It can be used as a pharmaceutical, cosmetic, and / or food product.

[0027] The heat shock protein gene expression regulator according to this embodiment promotes the expression of type I collagen. It progresses. Type I collagen gives elasticity to bones. Type I collagen gives strength to the skin. The heat shock protein gene expression regulator according to this embodiment modulates the expression of type I collagen. It can be used as a pharmaceutical, cosmetic, and / or food product to promote [something].

[0028] The heat shock protein gene expression regulator according to this embodiment is a matrix metalloprotein It promotes the expression of matrix metalloproteinase inhibitor genes. An example of this is the TIMP1 gene, which inhibits matrix metalloproteinases. The factor inhibits matrix metalloproteinases and suppresses the degradation of the extracellular matrix. Therefore, the heat shock protein gene expression regulator according to the embodiment is, for example, a fine The degradation of the extracellular matrix can be suppressed. Heat shock protein gene according to this embodiment Expression regulators include, for example, those that promote the expression of matrix metalloproteinase inhibitors and extracellular matrix A pharmaceutical product for at least one use selected from the group consisting of inhibition of trichlear degradation. It can be used as a cosmetic and / or food product.

[0029] The heat shock protein gene expression regulator according to this embodiment modulates the expression of antioxidant factor genes. To promote. An example of an antioxidant factor gene is superoxide dismutase 3 (SOD). 3) Genes, catalase (CAT) gene, glutathione reductase (GSR) gene, Lutathione peroxidase 1 (GPX1) gene, metallothionein 1F (MT1F) Genes are one example. SOD is an enzyme that breaks down reactive oxygen species. CAT is hydrogen peroxide. It is an enzyme that breaks down [something]. GSR is an enzyme that reduces oxidized glutathione. GPX1 It is an enzyme that breaks down hydrogen peroxide. MT1F is an antioxidant protein. Therefore The heat shock protein gene expression regulator according to this embodiment improves, for example, antioxidant function. It is possible. The heat shock protein gene expression regulator according to the embodiment is, for example, an antioxidant Factor gene expression promotion, SOD expression promotion, CAT expression promotion, GSR expression promotion, GPX1 expression At least one selected from the group consisting of promotion, MT1F expression promotion, and improved antioxidant function. It can be used as a pharmaceutical, cosmetic, and / or food product for the following purposes.

[0030] The heat shock protein gene expression regulator according to this embodiment is the interleukin-1 receptor It promotes the expression of the antagonist molecule (IL1RN) gene. Interleukin-1 receptor antagonist molecules A deficiency in this molecule leads to interleukin-1 receptor antagonist deficiency (DIRA). Therefore, Therefore, the heat shock protein gene expression regulator according to this embodiment prevents and treats DIRA. It is possible to do so. The heat shock protein gene expression regulator according to the embodiment is, for example, Furthermore, from promoting the expression of interleukin-1 receptor antagonist molecules, preventing DIRA, and treating DIRA Pharmaceuticals, cosmetics, and / or food products for at least one use selected from the group It can be used as is.

[0031] The heat shock protein gene expression regulator according to this embodiment is the semaphorin gene It promotes expression. An example of a semaphorin gene is the SEMA3A gene. Semaphorinin is a repulsive guidance factor that exhibits a repulsive effect on nerve axon extension. Yes. Semaphorin inhibits angiogenesis. Semaphorin controls bone mass. Also, Maphorin suppresses itching. Semaphorin is used for the prevention and treatment of atopic dermatitis. It is effective. Therefore, the heat shock protein gene expression regulator according to the embodiment is, for example, For example, they can repulsively guide nerve axon extension, suppress angiogenesis, and control bone mass. It can suppress itching and prevent and treat atopic dermatitis. Examples of heat shock protein gene expression regulators related to the application method include, for example, semaphorin expression regulators. Promotion, inhibition of nerve axon elongation, inhibition of angiogenesis, control of bone mass, suppression of itching, prevention of atopic dermatitis, A pharmaceutical product for at least one use selected from the group consisting of the treatment of atopic dermatitis and the treatment of atopic dermatitis. It can be used as a product, cosmetic, and / or food.

[0032] The heat shock protein gene expression regulator according to this embodiment is a nerve growth factor (NGF) gene expression regulator. It promotes the expression of genes and nerve growth factor receptors (NGFRs). Nerve growth factors are essential for nerve growth. Promotes growth and maintenance, accelerates the recovery of brain nerve function, and prevents Alzheimer's disease and dementia. It is effective in treatment. Nerve growth factor exerts its effects via nerve growth factor receptors. Therefore, the heat shock protein gene expression regulator according to this embodiment is, for example, a neurological It promotes the expression of growth factors, promotes nerve growth and maintenance, and promotes the functional recovery of cranial nerves. It is possible to prevent and treat Zheimer's disease and dementia. (Thermal shock according to the embodiment) Protein gene expression regulators include, for example, those that promote nerve growth factor expression, nerve growth, and maintenance. Promotion, promotion of brain nerve function recovery, prevention of Alzheimer's disease, treatment of Alzheimer's disease, dementia prevention A pharmaceutical product for at least one use selected from the group consisting of prevention and treatment of dementia. It can be used as a cosmetic and / or food product.

[0033] The heat shock protein gene expression regulator according to this embodiment is nuclear factor κB (NFκB) It promotes the expression of inhibitory genes for NFκB. An example of an inhibitory gene for NFκB is NFKB. The IA gene is one example. NFκB inhibitors such as IκBα inhibit NFκB activity. , to prevent and treat cancer. Therefore, the heat shock protein gene development according to the embodiment The current regulator can, for example, prevent and treat cancer. Protein gene expression regulators include, for example, those that promote NFκB inhibitor expression, cancer prevention, and Pharmaceuticals, cosmetics, and for at least one use selected from the group consisting of cancer treatment. It can be used as a beverage or food.

[0034] The heat shock protein gene expression regulator according to this embodiment is a calpain (CAPN) inhibitor. It promotes the expression of the harmful protein calpastatin (CAST) gene. In this case, CAPN is activated and CAST disappears. Therefore, the thermal shock according to the embodiment Protein gene expression regulators can, for example, suppress aging. Heat shock protein gene expression regulators related to the state promote CAPN inhibitor protein expression, Pharmaceuticals, cosmetics, and / or pharmaceuticals for uses selected from the group consisting of and improved anti-aging function. It can be used as food.

[0035] The heat shock protein gene expression regulator according to this embodiment is citrullinated protein activity It promotes the expression of sexation factor genes. An example of a citrullinated protein activator gene is... One example is peptidylarginine deiminase 3 (PAD3). PAD stands for citrulline It activates keratinized proteins and promotes normal epidermal keratinization. Therefore, in the embodiment Such heat shock protein gene expression regulators, for example, promote the keratinization of normal skin. This is possible. The heat shock protein gene expression regulator according to this embodiment is, for example, From the group consisting of the promotion of citrullinated protein activator expression and the progression of normal skin keratinization It can be used as a pharmaceutical, cosmetic, and / or food product for selected applications.

[0036] The heat shock protein gene expression regulator according to this embodiment is transglutaminase gene It promotes gene expression. An example of a transglutaminase gene is the TGM1 gene. Transglutaminase can increase the physical strength of the skin surface and improve moisturizing function. To increase or enhance. Therefore, the heat shock protein gene expression regulator according to the embodiment is For example, it can increase the strength of the skin surface and improve the skin's moisturizing function. The heat shock protein gene expression regulator according to this embodiment is, for example, transglutamyl This is due to the promotion of minase expression, improvement of skin surface strength, improvement of skin firmness, and improvement of skin moisturizing function. A pharmaceutical, cosmetic, and / or food product selected from the group for at least one use. It is usable.

[0037] The heat shock protein gene expression regulator according to this embodiment is involucrin (IVL). It promotes gene expression. IVL promotes the maturation of the cornified envelope and maintains skin integrity. To improve humidity control. Therefore, the heat shock protein gene expression regulation according to this embodiment. The agent, for example, promotes the maturation of the cornified envelope and improves the skin's moisturizing function. This is possible. The heat shock protein gene expression regulator according to this embodiment is, for example, From promoting IVL expression, accelerating cornified envelope maturation, and improving skin moisturizing function Pharmaceuticals, cosmetics, and / or food products for at least one use selected from the group It can be used as is.

[0038] The heat shock protein gene expression regulator according to this embodiment is used for aquaporin gene expression It promotes. An example of an aquaporin gene is the AQP3 gene. Phosphorus is involved in the migration of keratinocytes and improves the moisturizing function of the skin. Therefore, Examples of heat shock protein gene expression regulators related to the application method include keratinocyte migratory mechanisms. It is possible to improve the function and enhance the moisturizing function of the skin. The thermal shock according to the embodiment Protein gene expression regulators include, for example, those that promote aquaporin expression and keratinocyte migration. For at least one application selected from the group consisting of functional improvement and improved skin moisturizing function. It can be used as a medicine, cosmetic, and / or food.

[0039] Furthermore, the heat shock protein gene expression regulator according to this embodiment reduces fungi (mold). It also has the function of causing [something]. The heat shock protein gene expression regulator according to the embodiment is, for example, , fungi, within 24 hours, 80% or more, 85% or more, 90% or more, or 95% or more To reduce. Examples of fungi include dermatophytes, Candida, Cryptococcus, and Aspergillus. Examples include, but are not limited to, the heat shock protein gene according to this embodiment. Expression regulators also have therapeutic effects on fungal infections. These include tinea, candidiasis, and cryptid infections. Examples include, but are not limited to, tococcosis and aspergillosis.

[0040] The heat shock protein gene expression regulator according to this embodiment is Gram-negative bacteria and Gram-positive bacteria. It also has the function of reducing sexually transmitted bacteria. Heat shock protein gene expression regulator according to the embodiment For example, Gram-negative bacteria and Gram-positive bacteria are reduced by more than 80% and less than 85% within 24 hours. The goal is to reduce the levels by 90% or more, or by 95% or more. Gram-negative bacteria include E. coli and monkey bacteria. Examples include Monella, Vibrio parahaemolyticus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, but are not limited to these. No. Gram-positive bacteria include methicillin-resistant Staphylococcus aureus (MRSA), which forms spores. Examples include, but are not limited to, Bacillus cereus and Bacillus subtilis.

[0041] The heat shock protein gene expression regulator according to this embodiment has the function of reducing the virus. It also has. The heat shock protein gene expression regulator according to the embodiment is, for example, a virus If the amount decreases by more than 80%, 85%, 90%, or 95% within 24 hours Viruses are enveloped viruses, which are viruses that have an envelope, and This includes non-enveloped viruses, which are viruses that do not have an envelope. This includes DNA viruses and RNA viruses.

[0042] Examples of enveloped DNA viruses include human herpesviruses and vaccinia. Examples include, but are not limited to, viruses and hepatitis B virus.

[0043] Examples of enveloped RNA viruses include influenza virus and SARS-CoV-2. Ronavirus, RSV, mumps virus, lassa virus, dengue virus, cold Measles virus, human immunodeficiency virus, measles virus, hepatitis C virus, Ebola virus Examples include, but are not limited to, yellow fever virus and Japanese encephalitis virus.

[0044] Examples of DNA viruses that do not have an envelope include adenoviruses and B19 virus. Examples include, but are not limited to, papovavirus and human papillomavirus. .

[0045] RNA viruses that do not have an envelope include norovirus, poliovirus, and erythrocytes. Covirus, Hepatitis A virus, Hepatitis E virus, Rhinovirus, Astrovirus Examples include rotavirus, coxsackievirus, enterovirus, and sapovirus. These are some examples, but they are not limited to these.

[0046] The heat shock protein gene expression regulator according to the embodiment contains an effective amount of Lactobacillus genus The heat shock protein gene expression regulator according to this embodiment includes Lactobacillus species. It may be contained in a solvent such as water, or it may be contained in a plant fermentation liquid. Plants used for this purpose include mugwort and angelica tree, as well as Lactobacillus.

[0047] The effective dose is the amount necessary to produce a gene expression regulatory effect, and is applied to the target gene. Therefore, it is determined as appropriate. Generally, the concentration of Lactobacillus is high, and the solvent is a plant fermentation liquid. Including it will have a gene expression regulatory effect, for example, if the target gene is the GBA gene. A lower concentration of Lactobacillus species is more effective in regulating gene expression. Also, for example... If the target gene is a TLR2 gene, it is preferable that the solvent does not contain plant fermentation liquid. A gene expression regulation effect is achieved.

[0048] The Lactobacillus genus included in the heat shock protein gene expression regulator according to this embodiment is These may be live bacteria, or, for example, dead bacteria that have been heat-treated. Therefore, implementation The heat shock protein gene expression regulator related to morphology contains dead bacteria of the Lactobacillus genus. It may be present. Lactobacillus species may also be present as dried bacterial cells. Dead Lactobacillus species. Furthermore, dried bacterial cells also exhibit gene expression regulatory and antibacterial / antiviral effects. Dead or dried Lactobacillus bacteria are easy to transport and store for long periods. ru.

[0049] The heat shock protein gene expression regulator according to this embodiment is, for example, a liquid, a cream, It may be an ointment, plaster, gel, wax, or spray.

[0050] The heat shock protein gene expression regulator according to this embodiment is, for example, a skin-conditioning cosmetic. It is also acceptable to use them. Examples of skin-conditioning cosmetics include lotions, serums, and face masks. Examples of heat shock protein gene expression regulators related to application methods include protective cosmetics. This is also acceptable. Examples of protective cosmetics include protective lotions and protective creams. Examples of heat shock protein gene expression regulators related to morphology include those used in base makeup cosmetics. It can also be a product. Examples of base makeup cosmetics include foundation, face powder, and a makeup base are examples. The heat shock protein gene expression regulator according to the embodiment is For example, it could be point makeup cosmetics. Example of point makeup cosmetics Examples include lipstick, eye makeup, blush, and nail polish.

[0051] Furthermore, the heat shock protein gene expression regulator according to the embodiment is, for example, a disinfectant, a coating agent. It is used as a topical skin medication such as a cloth treatment, eye drops, and oral medication. The embodiment of the thermal shock... Protein gene expression regulators are used, for example, in the skin, hair, mouth, and eyes of the human body, including the fingers and toes. It is administered to spheres, etc.

[0052] The heat shock protein gene expression regulator according to this embodiment includes, in addition to Lactobacillus species, Liquid oils and fats, solid oils and fats, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silica Anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants Agents, humectants, water-soluble polymers, thickeners, coating agents, metal ion chelating agents, lower alcohols, polyvalents Alcohol, sugars, amino acids, organic amines, pH adjusters, skin nutrients, vitamins, Antioxidants, fragrances, powders, colorants, and water are used as ingredients in cosmetics and pharmaceuticals, according to their purpose. It may be included as appropriate.

[0053] When the heat shock protein gene expression regulator according to the embodiment contains an oily component, The concentration of the oily component in the heat shock protein gene expression regulator related to the state is not particularly limited. However, for example, 0.1% by mass or more and 90% by mass or 0.5% by mass or more and 90% It is less than or equal to mass%. The heat shock protein gene expression regulator according to the embodiment contains an aqueous component If included, the concentration of the aqueous component in the heat shock protein gene expression regulator according to the embodiment The degree is not particularly limited, but for example, 0.1% by mass or more and 90% by mass or less, or 0. The amount is 5% by mass or more and 90% by mass or less. Heat shock protein gene expression according to the embodiment The ratio of oily components to aqueous components in the conditioning agent is determined by the heat shock protein gene generation according to the embodiment. Is the current regulator an oil-in-water (O / W) type or a water-in-oil (W / O) type? The heat shock protein gene expression regulator according to the embodiment is set appropriately. When containing a surfactant, the neural network of the heat shock protein gene expression regulator according to the embodiment The concentration of the surfactant is not particularly limited, but is, for example, 2% by mass or more and 10% by mass or less.

[0054] The heat shock protein gene expression regulator according to this embodiment includes, in addition to Lactobacillus species, Antimicrobial or antiviral substances may be included as appropriate, depending on the purpose.

[0055] The heat shock protein gene expression regulator according to this embodiment ferments plants and lactobacilli It is produced by obtaining a fermented liquid containing the genus *Cirrhizus*. When fermenting the plants, salt and Sugars such as molasses are added to the plants. The fermentation temperature is, for example, 30°C. The water in the resulting fermentation liquid... The pH is around 4.0. From the fermentation liquid, secretions of Lactobacillus species are extracted. Extraction is permitted.

[0056] The resulting fermentation liquid may be heated to kill the Lactobacillus species present in it. Alternatively, the fermentation liquid may be spray-dried to obtain dried Lactobacillus cells. The dried cells are It can also be produced by freeze-drying and hot-air drying methods.

[0057] Furthermore, the obtained fermentation liquid, Lactobacillus cells, or Lactobacillus cells Dried ingredients can be added to soy milk, and the soy milk can be fermented to obtain fermented soy milk liquid. Fermented soy milk liquid is also genetically inherited. It exerts a regulatory effect on offspring expression.

[0058] As described above, the heat shock protein gene expression regulators, etc., according to each embodiment of the present invention are The configuration and effects described below, based on one or more of the above-mentioned combinations, are as follows: To possess.

[0059] The heat shock protein gene expression regulator, pharmaceutical, or cosmetic according to this embodiment is It contains the Lactobacillus genus, derived from Mogi or Ashitaba. Heat shock protein gene expression regulators, pharmaceuticals, or cosmetics related to application methods may contain mugwort or It may further comprise a fermented liquid derived from Angelica keiskei. The pharmaceutical is an anti-wrinkle drug or an anti-aging drug. It may be a pharmaceutical product. The cosmetic product may be an anti-wrinkle cosmetic or an anti-aging cosmetic. .

[0060] This embodiment uses mugwort or Angelica keiskei for regulating heat shock protein gene expression. This includes the Lactobacillus genus. This embodiment is for the regulation of heat shock protein gene expression. The fermented liquid used contains Lactobacillus genus derived from mugwort or Angelica keiskei and mugwort or Angelica keiskei. include.

[0061] This embodiment relates to heat shock protein genes of the Lactobacillus genus derived from Artemisia princeps or Angelica keiskei. This includes use for manufacturing gene expression regulators, pharmaceuticals, or cosmetics. This embodiment is a Y Heat shock of Lactobacillus species derived from Artemisia princeps or Angelica keiskei and fermented liquid derived from Artemisia princeps or Angelica keiskei. This includes use in the manufacture of protein gene expression regulators, pharmaceuticals, or cosmetics.

[0062] This embodiment involves administering Lactobacillus species derived from Artemisia princeps or Angelica keiskei to humans or non-human animals. A method for regulating heat shock protein gene expression, a treatment method, or a cosmetic method, including the action of doing so. This embodiment includes Lactobacillus species derived from Artemisia princeps or Angelica keiskei in humans or non-human animals. This includes administering a fermented liquid derived from mugwort or angelica tree, which helps to induce heat shock protein gene development. This includes current adjustment methods, treatment methods, or cosmetic methods. Treatment methods include treatments for improving anti-wrinkle function. It may be a therapeutic method or a treatment method for improving anti-aging function. It may be a beauty method for the above purpose or a beauty method for improving anti-aging function.

[0063] Is the heat shock protein gene a group consisting of the HSPA1A gene and the HSPB1 gene? It may be at least one of the following selected. Artemisia or Angelica keiskei derived according to this embodiment The genus Lactobacillus was selected from a group consisting of the HSPA1A gene and the HSPB1 gene. At least one expression may be promoted.

[0064] The Lactobacillus species derived from Artemisia princeps or Angelica keiskei according to this embodiment is a heat shock protein. It is possible to regulate the expression of genes other than the gene itself. This embodiment is found in mugwort or light green. In Lactobacillus species derived from Nichiyo, the genes whose expression is regulated include the ceramidase gene and the lipid compound gene. Genetic enzyme genes, lysosomal hydrolase genes, tight junction biosynthesis factor genes At least one selected from the group consisting of offspring and intercellular adhesion factor genes. .

[0065] The ceramidase gene may be the ASAH1 gene. The mugwort or Lactobacillus species derived from Angelica keiskei may suppress the expression of the ASAH1 gene.

[0066] The lipid synthesis enzyme gene may be the DGAT1 gene. The mugwort or Lactobacillus species derived from Angelica keiskei may promote the expression of the DGAT1 gene.

[0067] The lysosomal hydrolase gene may be the GBA gene. Lactobacillus species derived from Angelica keiskei or Angelica keiskei may promote the expression of the GBA gene.

[0068] Tight junction biosynthesis factor genes are derived from the CLDN1 gene and the OCLN gene. At least one selected from the group may be: Mugwort or Tomorrow according to this embodiment. Lactobacillus species derived from leaves are selected from a group consisting of the CLDN1 gene and the OCLN gene. It may promote the expression of at least one of the following:

[0069] The intercellular adhesion factor genes are the ITGA2 gene, the CDH1 gene, and the CD44 gene. At least one selected from the group. This embodiment may include Artemisia or Akebia. Lactobacillus species derived from Nichiyo have the ITGA2 gene, CDH1 gene, and CD44 gene The expression of at least one selected from the group consisting of offspring may be promoted.

[0070] Genes whose expression is regulated in Lactobacillus species derived from Artemisia princeps or Angelica keiskei according to this embodiment However, it may also be an antimicrobial molecule gene. The antimicrobial molecule gene is the TLR2 gene, DE Selected from the group consisting of the FB1 gene, DEFB4A gene, and DEFB103A gene. There may be at least one of the following: Lactobacillus derived from mugwort or Angelica keiskei according to this embodiment. The genus *Cirrhizus* has the TLR2 gene, DEFB1 gene, DEFB4A gene, and DEFB1 The expression of at least one gene selected from the group consisting of 03A genes may be promoted.

[0071] Genes whose expression is regulated in Lactobacillus species derived from Artemisia princeps or Angelica keiskei according to this embodiment However, at least one selected from the group consisting of sirtuin genes and telomerase genes You can have any.

[0072] The sirtuin gene may be the SIRT4 gene. The mugwort or Lactobacillus species derived from Angelica keiskei may promote the expression of the SIRT4 gene.

[0073] The telomerase gene is selected from the group consisting of the TERT gene and the TERC gene. At least one may be present. Lactobacillus derived from mugwort or angelica according to this embodiment. The genus *S* is selected from the group consisting of the TERT gene and the TERC gene, at least one Expression may be promoted.

[0074] Genes whose expression is regulated in Lactobacillus species derived from Artemisia princeps or Angelica keiskei according to this embodiment However, it could also be an energy metabolism factor gene. If the energy metabolism factor gene is PPARG The C1A gene may also be used. Lactobacillus derived from Artemisia princeps or Angelica keiskei according to this embodiment. The genus may promote the expression of the PPARGC1A gene.

[0075] Genes whose expression is regulated in Lactobacillus species derived from Artemisia princeps or Angelica keiskei according to this embodiment However, selected from a group consisting of hyaluronic acid biosynthesis factor genes and hyaluronic acid degradation factor genes. It may be at least one of the following:

[0076] The hyaluronic acid biosynthesis factor genes are HAS1, HAS2, and HAS3 genes. At least one selected from the group consisting of genes. Mugwort according to this embodiment Alternatively, Lactobacillus species derived from Angelica keiskei possess the HAS1 gene, HAS2 gene, and HAS3 The expression of at least one gene selected from a group of genes may be promoted.

[0077] Is the group of hyaluronic acid degradation factor genes comprised of the HYAL2 gene and the CEMIP gene? It may be at least one of the following selected. Artemisia or Angelica keiskei derived according to this embodiment The genus Lactobacillus is selected from a group consisting of the HYAL2 gene and the CEMIP gene. The expression of at least one gene may be suppressed.

[0078] Genes whose expression is regulated in Lactobacillus species derived from Artemisia princeps or Angelica keiskei according to this embodiment However, it may also be a basement membrane biosynthesis factor gene. The basement membrane biosynthesis factor gene is LAMA1 gene From the group consisting of the gene, LAMA5 gene, COL4A1 gene, and COL7A1 gene At least one of the selected materials may be used. According to this embodiment, the larvae derived from mugwort or angelica tree are The genus Cutobacilus has the LAMA1 gene, LAMA5 gene, COL4A1 gene, and C The expression of at least one gene selected from the group consisting of OL7A1 genes may be promoted.

[0079] The heat shock protein gene expression regulator, pharmaceutical, or cosmetic according to this embodiment is I It promotes the production of type I collagen. The type I collagen production promoter according to this embodiment is yomo The present embodiment comprises Lactobacillus species derived from Gypsum or Angelica keiskei. Production of type I collagen according to this embodiment The accelerator is a fermented liquid derived from mugwort or angelica tree, containing Lactobacillus species and mugwort or angelica tree. Prepare.

[0080] This embodiment provides a lactose derived from mugwort or Angelica keiskei for use in promoting the production of type I collagen. This includes the genus Bacillus. This embodiment uses Artemisia or Aster to promote the production of type I collagen. Contains Lactobacillus genus derived from Nichiyo and fermented liquid derived from mugwort or Angelica keiskei.

[0081] This embodiment promotes the production of type I collagen by Lactobacillus species derived from mugwort or Angelica keiskei. This includes use for manufacturing a growth agent. This embodiment uses lactobacillus derived from mugwort or angelica tree. To produce a type I collagen production promoter from a fermented liquid derived from the genus Russus and Artemisia princeps or Angelica keiskei. Includes use.

[0082] This embodiment involves administering Lactobacillus species derived from Artemisia princeps or Angelica keiskei to humans or non-human animals. This embodiment includes a method for promoting the production of type I collagen, which includes the following. Animals were given Lactobacillus species derived from mugwort or Angelica keiskei and a fermented liquid derived from mugwort or Angelica keiskei. The present invention includes a method for promoting the production of type I collagen, which includes providing a substance to a substance.

[0083] The heat shock protein gene expression regulator, pharmaceutical, or cosmetic according to this embodiment is H The production of SP47 is promoted. The HSP47 production promoter according to this embodiment is derived from Angelica keiskei. It comprises the genus Lactobacillus. The HSP47 production promoter in this embodiment is derived from Angelica keiskei. It contains a fermented liquid derived from Lactobacillus and Angelica keiskei.

[0084] This embodiment includes Lactobacillus species derived from Angelica keiskei for promoting HSP47 production. This embodiment uses Lactobacillus species derived from Angelica keiskei to promote the production of HSP47. Contains fermented liquid derived from Angelica keiskei.

[0085] This embodiment provides a method for producing an HSP47 production promoter from Lactobacillus species derived from Angelica keiskei. This includes use for the following purposes. This embodiment involves Lactobacillus genus derived from Angelica keiskei and fermentation derived from Angelica keiskei. The liquid includes use for manufacturing an HSP47 production accelerator.

[0086] This embodiment involves administering Lactobacillus species derived from Angelica keiskei to humans or non-human animals. This includes a method for promoting the production of HSP47. This embodiment involves cultivating Angelica keiskei in humans or non-human animals. Production of HSP47, including administration of a fermented liquid derived from Lactobacillus and Angelica keiskei. This includes methods for promoting [the process].

[0087] In this embodiment, a species of the genus Lactobacillus derived from Artemisia princeps or Angelica keiskei is parafarr aginis sp., parabuchneri sp., buchneri sp., harbinen At least one selected from the group consisting of species sis, vini, and nagelii. That's fine.

[0088] The Lactobacillus species derived from Artemisia princeps or Angelica keiskei according to this embodiment may be dead bacteria. In this embodiment, Lactobacillus species derived from Artemisia princeps or Angelica keiskei may be present even if heat-treated. i. The Lactobacillus genus derived from mugwort or angelica in this embodiment is a dried cell product. That's good too.

[0089] Manufacturing of heat shock protein gene expression regulators, pharmaceuticals, or cosmetics according to this embodiment The method involves obtaining the Lactobacillus genus from mugwort or Angelica keiskei. This includes the following: a heat shock protein gene expression regulator, pharmaceutical, or chemical according to this embodiment. Even if the method for manufacturing cosmetics further includes fermenting mugwort or angelica tree to obtain a fermented liquid, Good. The heat shock protein gene expression regulator, pharmaceutical, or cosmetic according to this embodiment The manufacturing method may further include killing the obtained Lactobacillus species. Method for producing a heat shock protein gene expression regulator, pharmaceutical, or cosmetic according to the embodiment However, this method may further include heat treatment of the obtained Lactobacillus species. A method for producing heat shock protein gene expression regulators, pharmaceuticals, or cosmetics related to the state of heat shock protein is obtained. The process may further include drying the Lactobacillus species. [Examples]

[0090] Examples of the present invention are described below. However, the present invention is not limited to the following examples. Of course.

[0091] (Example 1: Lactobacillus species derived from Artemisia princeps) For mugwort leaves, during the 2-hour period of the day, one hour before and one hour after sunrise. It is believed that the number of lactic acid bacteria is maximized during this time. Also, outside of this time period, the number of lactic acid bacteria decreases. It is believed that photosynthetic bacteria increase slightly. Therefore, during these two hours, the mugwort leaves Approximately 20 cm from the tip was collected. The 6.3 kg of mugwort leaves that were collected were immediately processed. Place it in the first pickling barrel lined with a plastic bag, and wrap it in mugwort leaves with 3.2 kg of molasses and 0. After sprinkling 6 kg of coarse salt, the opening of the plastic bag was closed and sealed. A weight was placed on top, and the mugwort leaves were pickled.

[0092] A few days after the pickling liquid had risen to the top of the mugwort leaves, the weight was removed. Next, into the second pickling barrel, Add 10 liters of chlorine-free water for rinsing, and put the pickled mugwort leaves into the water. I added 10 kg of pickling liquid. Furthermore, I prepared a third pickling barrel and placed a metal slab over the opening of the third pickling barrel. I placed a mesh filter on top. I took mugwort leaves little by little from the second pickling barrel, washing them by hand. Then, place the mugwort leaves on the wire mesh filter at the opening of the third pickling barrel, lightly pressing them down with your palm, and add the pickling liquid. I narrowed it down.

[0093] After squeezing all the mugwort leaves, pass the remaining pickling liquid from the second batch through a wire mesh filter. It was filtered. Next, molasses (Hateruma brown sugar) was added to the pickling liquid in the third pickling barrel until it reached a final concentration of 10 by weight. The coarse salt was dissolved in the mixture so that the final concentration was 3% by weight. Then, the third pickling process was carried out. Fermentation was initiated by raising the ambient temperature of the storage vat to approximately 30°C. Initially, large bubbles formed. The foaming was observed, gradually changing to fine bubbles, and finally subsiding. Approximately one week later The pH was around 3.8 when the fizzing subsided. The pickling liquid at this time was used as a mugwort fermentation liquid. The obtained mugwort fermentation liquid was then heated at 70°C for 30 minutes to kill the bacteria. We obtained a fermented mugwort liquid.

[0094] Unheat-treated mugwort fermented liquid is used with next-generation sequencers (MiSeq, Illumina Analysis conducted by the company revealed, as shown in Figure 1, that the mugwort fermentation liquid contains Lactobacillus parenchyma. afarraginis species, parabuchneri species, buchneri species, and h It included species such as *arbinensis*. Furthermore, next-generation sequencers are high-throughput. Also called a sequencer. The numbers in the table in Figure 1 represent the bacterial species contained in the mugwort fermentation liquid. This reflects the number of bacteria.

[0095] (Example 2: Lactobacillus genus derived from Angelica keiskei) In the case of Ashitaba, the milk is released during the 2-hour period around sunrise, one hour before and one hour after. It is believed that the number of acid-producing bacteria is maximized during this time. Also, outside of this time period, the number of lactic acid bacteria decreases. It is believed that photosynthetic bacteria increase during this two-hour period. The stems were harvested. The 6.3 kg of harvested Angelica keiskei were immediately placed in a plastic bag. Place in pickling barrel 1, sprinkle 3.2 kg of molasses and 0.6 kg of coarse salt over the Angelica keiskei, then... I closed the opening of the plastic bag and sealed it. I placed a weight on top of the plastic bag and pickled the Angelica keiskei inside. .

[0096] A few days later, when the pickling liquid had risen to the top of the Angelica leaves, the weight was removed. Next, in the second pickling barrel, Add 10 liters of chlorine-free water for rinsing, and then add the pickled Angelica keiskei and 10 kg of other ingredients to the water. The pickling liquid was added. Furthermore, a third pickling barrel was prepared, and a wire mesh filter was placed over the opening of the third pickling barrel. I put the ta on. From the second pickling barrel, I took out the angelica little by little, rubbing and washing it by hand, and the third I lightly pressed the angelica leaves with my palms against the wire mesh filter on the opening of the pickling barrel and squeezed out the pickling liquid.

[0097] After squeezing all the Angelica keiskei, the remaining pickling liquid in the second batch was filtered through a wire mesh filter. Next, molasses was added to the pickling liquid in the third pickling barrel so that the final concentration was 10% by weight. Coarse salt was dissolved in the mixture to a final concentration of 3% by weight. Then, the ambient temperature of the third pickling barrel was adjusted to approximately Fermentation was initiated by raising the temperature to 30°C. Initially, large bubbles were observed, and gradually... The foaming gradually changed to fine bubbles, and finally subsided. About a week later, when the foaming had stopped. The pH was around 4.0. The pickling liquid at this time was used as the Angelica keiskei fermentation liquid. A portion of the Angelica keiskei fermentation liquid was heated at 70°C for 30 minutes to kill the bacteria, resulting in a heat-treated Angelica keiskei fermentation liquid. .

[0098] Unheat-treated Angelica keiskei fermented liquid is processed using a next-generation sequencer (MiSeq, Illumina). Analysis using the following method revealed, as shown in Figure 2, that the Angelica keiskei fermented liquid contains vini species and nagel species. It contained species ii, etc. The numbers in the table in Figure 2 represent the bacterial species contained in the Angelica keiskei fermentation liquid. This reflects the number of bacteria.

[0099] (Example 3: Soy milk fermented liquid using Lactobacillus genus) The soy milk was heated to 70°C and sterilized by heat for approximately 30 minutes. The unheat-treated mugwort fermented liquid prepared in Example 1 was processed to a final concentration of approximately 10 wt%. In addition, it was thoroughly stirred. Then, the soy milk to which the unheated mugwort fermented liquid had been added was heated to 37°C. It was fermented for 24 hours. After fermentation, the solids were removed by filtration, and the Lactobacillus genus was extracted. A fermented soy milk liquid containing the following was obtained.

[0100] (Example 4: Gene expression test) Live Lactobacillus species were isolated from the mugwort fermentation liquid obtained in Example 1, and 0.05 The solution was dispersed in pure water at a concentration of g / L and designated as Sample 1. In addition, isolated living lactobacilli were also used. A genus of *Cirrhizus* was dispersed in pure water at a concentration of 5.0 g / L to create Sample 2. Sample 3 was a fermented mugwort solution containing Bacillus species at a concentration of 5.0 g / L.

[0101] Growth medium (18 SGM 082, EPISKIN) Using a three-dimensional cultured epidermal model (SkinEtchic RHE:18 RHE 09), 8. The EPISKIN (stock) was allowed to acclimate overnight. Then, the growth medium was dispensed into a 6-well plate. Transfer the three-dimensional cultured epidermal model to a Transwell insert (Corning), and Apply 50 μL of any one of Samples 1 to 3 to the stratum corneum side of the three-dimensional cultured epidermal model. 2 After 4 hours, remove the medium to which the sample was added from the well, and wash the three-dimensional cultured epidermal model with phosphate-buffered saline without calcium and magnesium (PBS(-)).

[0102] Cut out the three-dimensional cultured epidermal model together with the membrane from the Transwell insert with a scalpel and immerse the three-dimensional cultured epidermal model in a lysing solution (QIAzol, registered trademark, QIAGEN). After that, disrupt the cells using a disruption device (Tissue Lyser, QIAGEN) to obtain a disrupted solution. Purify RNA from the disrupted solution using an RNA purification kit (miRNeasy Mini Kit, registered trademark, QIAGEN), and recover the purified RNA. Send the recovered RNA to Mitsubishi Chemical Corporation, which provides a commissioned analysis service, and analyze the gene expression in the cells treated with the sample using an mRNA expression analysis chip. Normalize the gene expression in the cells not treated with the sample (control) to 1.00, and calculate the ratio of the gene expression in the cells treated with the sample to the gene expression in the control. Also, perform a significance test using the Student t-test (Example 5: Anti-wrinkle effect) (Example 5: Anti-wrinkle effect) (Example 5: Anti-wrinkle effect) (Example 5: Anti-wrinkle effect)

[0103] The results are shown in FIGS. 3 to 8. Values greater than 1.00 indicate that gene expression was promoted compared to the control. Values less than 1.00 indicate that gene expression was suppressed compared to the control. (Example 5: Anti-wrinkle effect) (Example 5: Anti-wrinkle effect)

[0104] (Example 5: Anti-wrinkle effect) On the cheeks of a 46-year-old woman, the mugwort fermentation broth containing Lactobacillus prepared in Example 1 was applied twice a day for 5 months. As a result, as shown in Fig. 9, a decrease in wrinkles associated with aging was confirmed. In addition, no inflammatory reaction or tanning was confirmed. The mugwort fermentation broth containing Lactobacillus prepared in Example 1 at a concentration of 5.0 g / L has a very high effect of promoting the expression of the HSP70 gene as shown in Example 4. Therefore, the anti-inflammatory effect and whitening effect of HSP70 are considered to exceed the effect of promoting the expression of inflammation-related genes and tanning-related genes.

[0105] (Example 6: Antibacterial effect of Lactobacillus) Staphylococcus aureus and MRSA were prepared as Gram-positive cocci, Bacillus subtilis and Bacillus cereus were prepared as Gram-positive bacilli, Escherichia coli, Salmonella, Vibrio parahaemolyticus and Klebsiella pneumoniae were prepared as Gram-negative cocci, and Pseudomonas aeruginosa was prepared as Gram-negative bacilli.

[0106] To 10 mL of the soy milk fermentation broth containing Lactobacillus prepared in Example 3, 0.1 mL of a bacterial solution containing any of the above bacteria at a concentration of 10 7 cells / mL was inoculated, and the viable cell count of the inoculated bacteria was measured over time at 25°C. Also, as a control, 0.1 mL of a bacterial solution was inoculated into 10 mL of a phosphate buffer solution with a concentration of 1 / 15 mol / L and pH 7.2, and the viable cell count of the inoculated bacteria was measured over time at about 25°C. As a result, as shown in Fig. 10, the soy milk fermentation broth containing Lactobacillus reduced all the types of bacteria prepared within 24 hours.

[0107] (Example 7: Antifungal effect of Lactobacillus) ​​​​​​​​As fungi, dermatophytes and Candida were prepared. 10 mL of lactobacilli prepared in Example 3 Soy milk fermented liquid containing the genus *Cynamomum*, infused with 10 *Trichophyton* or *Candida*. 7 Contains 0.1 at a concentration of 0.1 cells / mL mL of bacterial solution was inoculated and allowed to react at 25°C. The number of viable bacteria in the inoculated bacteria was measured over 24 hours. Additionally, as a control, 10 mL of phosphorus solution with a concentration of 1 / 15 mol / L and pH 7.2 was used. 0.1 mL of bacterial solution was inoculated into an acid buffer, and the number of viable bacteria was measured over time at 25°C. Measurements were taken for 24 hours. As a result, as shown in Figure 11, the soy milk fermented liquid contained Lactobacillus. The prepared dermatophytes and Candida were reduced within 24 hours.

[0108] (Example 8: Antiviral effect of Lactobacillus species) As an enveloped virus, a culture medium of influenza virus type A (H1N1) was used. I intended to include it. Also, as a non-enveloped virus, norovirus (feline calicivirus) A culture medium was prepared. The virus culture medium was serially diluted 10 times with purified water. , 50% Tissue Culture Infectious Dose (TCID50:50% Tissue Culture In Soy milk containing Lactobacillus genus prepared in Example 3 according to the fectious dose. Antiviral testing was conducted using the fermentation liquid at room temperature. The antiviral testing was performed by the Japan Food Research Laboratories. It was carried out at -.

[0109] As a result, as shown in Figure 12, the soy milk fermented liquid containing Lactobacillus genus was within 1 hour. It reduced the infectivity titer of the influenza virus. Also, as shown in Figure 13, lactobacilli A fermented soy milk liquid containing the genus Russ reduced the infectivity titer of norovirus within 24 hours.

[0110] (Example 9: Antifungal effect of Lactobacillus species) The non-heat-treated mugwort fermentation broth obtained in Example 1 was spray-dried to obtain dried cells of the genus Lactobacillus. The obtained dried cells were suspended in water and glycerin so that the dried cell mass became 10 parts by weight, and a suspension of the genus Lactobacillus according to Example 9 was obtained. The suspension of the genus Lactobacillus was added to Trichophyton, and when the colony forming units (CFU) of Trichophyton were measured, as shown in Fig. 14, the suspension of the genus Lactobacillus killed Trichophyton within 24 hours.

[0111] (Example 10: Promoting effect of type I collagen and HSP47 production by the genus Lactobacillus) Normal human dermal fibroblasts were maintained in a DMEM medium (+5% FBS) in an incubator until they reached a confluent state. After reaching confluence, the medium was removed from the incubator, and DMEM (0% FBS) containing 600 μmol / L of hydrogen peroxide (H2O2) was added to the incubator, and the cells were cultured at 37 °C for 1 hour. After culturing for 1 hour, the H2O2-containing DMEM (0 % FBS) was removed from the incubator, and DMEM medium (+10% FBS) was added to the incubator. After repeating this operation for 4 days, the cells were further cultured in DMEM (10% FBS) for 3 days, and the obtained cells were used as senescence-induced cells. That the cells were induced to senescence was confirmed by staining with senescence-associated beta-galactosidase (SA-β-Gal), which is a senescence marker.

[0112] ciated beta-galactosidase(SA-β-Gal) staining to confirm <000*********969> <0*********970><0*********971><0*********972>The senescence-induced cells were seeded in a 4 cel 48-well plate at a cell density of 5.0×10 The unheated mugwort fermented liquid prepared in Example 1 is contained at concentrations of 0.0% and 10.0%. DMEM medium (+0.5% FBS) was prepared in Example 2 at concentrations of 1.0% and 10.0%. DMEM medium (+0.5% FBS) containing unheated Angelica keiskei fermented liquid, 25 μg DMEM medium containing magnesium vitamin C phosphate at mol / L (+0.5% FBS), DMEM medium containing vitamin C at 25 μmol / L (+0.5% FBS), and DME Each was replaced with M medium (+0.5% FBS). After that, the cells were cultured for 48 hours. The culture medium was then collected. After washing the cells with PBS(-), the cells were treated with trypsin. The cells were then collected from the plate. The collected cells were disrupted using ultrasound to obtain a cell lysate. The mixture was centrifuged at 15,000 rpm, and the supernatant was collected.

[0114] The amount of type I collagen in the recovered culture medium was measured by ELISA (Anti-Human Collagen Quantitative analysis was performed using a direct method with agen Type I antibody (Rabbit). As a result, As shown in Figure 15, a culture medium containing magnesium vitamin C phosphate or vitamin C (positive It was shown that culturing cells with (a control) promoted the production of type I collagen. Furthermore, when cells are cultured in a culture medium to which mugwort fermentation liquid and angelica keiskei fermentation liquid have been added, Furthermore, it was shown that the production of type I collagen was promoted.

[0115] Furthermore, HSP47 in the supernatant of the cell lysate was analyzed using a commercially available ELISA kit (abcam). The results were obtained by quantification using the culture medium to which Angelica keiskei fermentation liquid was added. As a result, as shown in Figure 16, the molecules were finely divided in the culture medium to which Angelica keiskei fermentation liquid was added. When the cells were cultured, it was shown that HSP47 production was promoted.

[0116] (Example 11: Anti-aging effects of Lactobacillus species) Normal human dermal fibroblasts were cultured in DMEM medium (+5% FBS) for 5.0 × 10⁶ cells. 5 c Cells were seeded in 6-well plates at a cell density of ells / well and cultured for 24 hours.

[0117] Remove the culture medium from each well and add DM containing 600 μmol / L hydrogen peroxide (H2O2). EM (0% FBS) was added to the wells, and the cells were cultured at 37°C for 1 hour to induce cell senescence. The following steps were taken: After 1 hour of incubation, the H2O2-containing DMEM (0% FBS) was removed from the wells, and the results were obtained as shown in the example. This product contains 1.0% of the fermented mugwort liquid prepared in step 1, which contains Lactobacillus species at a concentration of 5.0 g / L. Prepare DMEM medium (+10% FBS) and 5.0 g of Lactobacillus species prepared in Example 2. DMEM medium (+10% FBS) containing 1.0% of Angelica keiskei fermented liquid at a concentration of / L, D contains 10 μmol / L of resveratrol, which has antioxidant properties, as a sex control. MEM medium (+10% FBS), and DMEM medium (+10% FBS) as a negative control. Each of the following was added to the wells. These procedures were repeated for 4 days.

[0118] Subsequently, mugwort fermentation containing Lactobacillus species prepared in Example 1 at a concentration of 5.0 g / L was performed. DMEM medium containing 1.0% of the liquid (+10% FBS), lactobacillus prepared in Example 2 DMEM medium (+1) containing 1.0% Angelica keiskei fermented liquid with a concentration of 5.0 g / L of Russ species (0% FBS), 10 μmg of resveratrol, which has antioxidant properties, as a positive control. DMEM medium containing 1 / L (+10% FBS), and DMEM as a negative control. Each well was inoculated with culture medium (+10% FBS), and the cells were cultured for 3 days.

[0119] Subsequently, the cells cultured under each condition were divided into 5.0 × 10⁶ 4 cells / well Cells were seeded at cell density into 48-well plates and cultured for 24 hours. Afterward, the cells were treated with 3% hormone solution. The samples were fixed with PBS containing mualdehyde. Next, the solution in the wells was treated with 1 mg / mL of 5- bromo-4-chloro-3-indolyl-D-galactoside(X The reaction solution was replaced with one containing -Gal at pH 6 and allowed to stand for 12 to 16 hours. Microscopic observation was performed to identify senescence-associated markers. Beta-galactosidase (SA-β-Gal) staining was observed.

[0120] As a result, as shown in Figures 17, 18, and 19, only the cells that were senescent-induced showed S The degree of A-β-Gal staining was strong. In contrast, aging was induced, and mugwort fermentation liquid or Cells treated with Angelica keiskei fermented liquid were senescent-induced, and cells treated with resveratrol were also affected. Similarly, the degree of SA-β-Gal staining was reduced. Therefore, mugwort fermentation liquid and Angelica keiskei were used. The fermented liquid has been shown to have anti-aging properties.

[0121] (Example 12: Effect of promoting HSP70 production in Lactobacillus species) Three-dimensional cultured epidermal model (SkinEthic RHE:19RHE 008, EPIS) KIN Corporation) uses the growth medium (Growth Medium: 19SGM 005, EPIS The cells were acclimatized overnight at KIN Corporation. After acclimatization, 1 mL of growth medium was dispensed into a 6-well plate, and the epidermal cells were placed on top. Transfer the Dell to the stratum corneum side of the epidermal model and add 5.0 g / of the Lactobacillus species prepared in Example 1. 50 μL of mugwort fermentation liquid containing L at a concentration of L, and 5 Lactobacillus species prepared in Example 2. Each sample was treated with 50 μL of fermented Angelica keiskei containing 0 g / L of the active ingredient.

[0122] After culturing the epidermal model for 24 hours, remove the fermentation solution and wash the epidermal model with PBS(-). The skin was cleaned. The survival rate of the epidermal model was evaluated using the Alamar blue method. 10% Alamar blue Alamar Blue Cell Viability Reagent Maintenance medium containing the registered trademark (Invitrogen Inc.) was dispensed into 24-well plates. The epidermal model was transferred to a plate and incubated for 2 hours, after which the fluorescence intensity of the culture supernatant was measured. Cell viability is compared to the fluorescence intensity of the control group to which PBS(-) was applied instead of the fermentation solution. The results were calculated as an index (%). The obtained results were analyzed using Student's t-test. A significance test was then performed. As a result, as shown in Figure 20, the difference between mugwort fermented liquid and angelica keiskei fermented liquid was observed. No significant decrease in cell viability was observed after applying the treatment.

[0123] After measuring the fluorescence intensity, the skin model was immersed in PBS and then subjected to a sample disruption device (Tissue The epidermal model was disrupted using a lyser. The cell lysate was centrifuged at 15,000 rpm. The solution was separated, and the supernatant was collected. HSP70 in the collected solution was analyzed using a commercially available ELISA kit (Enzo). The results were quantified using (lifesciences). A statistical test was performed using a statistical test. As a result, as shown in Figure 21, the mugwort fermented liquid or the light The application of the Nichiyo fermentation liquid significantly increased the production of HSP70.

[0124] The embodiments and examples described above are provided to facilitate understanding of the present invention. This invention is not intended to be interpreted as limiting. The invention will be made without departing from its spirit. The invention may be modified / improved, and equivalents thereof are also included. That is, each embodiment Even if a person skilled in the art has made appropriate design modifications to the form and embodiment, as long as it retains the features of the present invention, The present invention is encompassed within its scope. For example, each element of each embodiment and example is illustrative. It is not limited to the above and can be modified as appropriate. Furthermore, each embodiment and actual The examples are illustrative, and partial substitution or combination of the configurations shown in different embodiments is possible. Needless to say, these are also included in the scope of the present invention insofar as they include the features of the present invention. .

Claims

1. It contains the genus Lactobacillus, derived from Artemisia princeps or Angelica keiskei. A heat shock protein gene expression regulator.

2. The heat shock protein genes consist of the HSPA1A gene and the HSPB1 gene. At least one selected from the group, and derived from the HSPA1A gene and the HSPB1 gene. The heat shock treatment according to claim 1, which promotes the expression of at least one selected from the group. Protein gene expression regulator.

3. Ceramidase gene, lipid synthesis enzyme gene, lysosomal hydrolase gene, tight Selected from a group consisting of junction biosynthesis factor genes and intercellular adhesion factor genes. A heat shock protein gene according to claim 1 or 2, which modulates the expression of at least one of the genes. Expression regulator.

4. The ceramidase gene is the ASAH1 gene, and the expression of the ASAH1 gene is suppressed. 、 The aforementioned lipid synthesis enzyme gene is the DGAT1 gene, and it promotes the expression of the DGAT1 gene. 、 The aforementioned lysosomal hydrolase gene is the GBA gene, and the expression of the GBA gene is promoted. Proceed, The tight junction biosynthesis factor genes are the CLDN1 gene and the OCLN gene. At least one selected from the group consisting of the CLDN1 gene and the OCLN gene Promote the expression of at least one selected from the group consisting of, The aforementioned cell adhesion factor genes are the ITGA2 gene, the CDH1 gene, and the CD44 gene. At least one selected from the group consisting of offspring, and containing the ITGA2 gene and the CDH1 gene. , and promote the expression of at least one selected from the group consisting of the CD44 gene, The heat shock protein gene expression regulator according to claim 3.

5. A heat shock protein according to claim 1 or 2, which modulates the expression of antimicrobial molecule genes. Gene expression regulator.

6. The aforementioned antimicrobial molecule genes are the TLR2 gene, DEFB1 gene, and DEFB4A gene. At least one selected from the group consisting of the , and the DEFB103A gene, and TLR It consists of two genes: DEFB1 gene, DEFB4A gene, and DEFB103A gene. The heat shock tongue according to claim 5, which promotes the expression of at least one selected from the group. A protein gene expression regulator.

7. At least one selected from the group consisting of sirtuin genes and telomerase genes A heat shock protein gene expression regulator according to claim 1 or 2, which modulates the expression of the following.

8. The sirtuin gene is the SIRT4 gene, and it promotes the expression of the SIRT4 gene. 、 The telomerase gene is selected from the group consisting of the TERT gene and the TERC gene. It is at least one of the following, selected from the group consisting of the TERT gene and the TERC gene. To promote the expression of at least one of the following The heat shock protein gene expression regulator according to claim 7.

9. A heat shock tanning method according to claim 1 or 2, which modulates the expression of energy metabolism factor genes. A protein gene expression regulator.

10. The aforementioned energy metabolism factor gene is the PPARGC1A gene, and the PPARGC1A gene A heat shock protein gene expression regulator according to claim 9, which promotes gene expression.

11. Selected from a group consisting of hyaluronic acid biosynthesis factor genes and hyaluronic acid degradation factor genes. The heat shock protein gene according to claim 1 or 2, which modulates the expression of at least one of the heat shock proteins. Gene expression regulator.

12. The hyaluronic acid biosynthesis factor genes are HAS1 gene, HAS2 gene, and HAS It is at least one selected from a group consisting of three genes, including the HAS1 gene and the HAS2 gene. Promote the expression of at least one selected from the group consisting of genes and the HAS3 gene, The group in which the hyaluronic acid degradation factor gene consists of the HYAL2 gene and the CEMIP gene. At least one selected from the following, consisting of the HYAL2 gene and the CEMIP gene. Suppress the expression of at least one selected from the group. The heat shock protein gene expression regulator according to claim 11.

13. A heat shock protein according to claim 1 or 2, which regulates the expression of basement membrane biosynthesis factor genes. A gene expression regulator.

14. The aforementioned basement membrane biosynthesis factor genes are LAMA1 gene, LAMA5 gene, COL4A1 At least one selected from the group consisting of the gene and the COL7A1 gene, LA From the MA1 gene, LAMA5 gene, COL4A1 gene, and COL7A1 gene The heat shock treatment according to claim 13, which promotes the expression of at least one selected from the group. Protein gene expression regulator.

15. A heat shock protein gene according to claim 1 or 2 that promotes the production of type I collagen. A drug that regulates the expression of offspring.

16. The aforementioned Lactobacillus species derived from Angelica keiskei is provided, and heat shock The heat shock protein gene according to claim 1 or 2, which promotes the production of protein 47. A drug that regulates the expression of offspring.

17. Any one of claims 1 to 16 further comprises the fermented liquid derived from mugwort or angelica tree. A heat shock protein gene expression regulator as described above.

18. The aforementioned species of the genus Lactobacillus include parafarraginis and parabuchn species eri, species buchneri, species harbinensis, species vini, and nage At least one selected from the group consisting of li species, any one of claims 1 to 17 A heat shock protein gene expression regulator as described in item 1.

19. The heat treatment according to any one of claims 1 to 18, wherein the Lactobacillus species is dead. A protein gene expression regulator.

20. The Lactobacillus species is heat-treated, as described in any one of claims 1 to 19. A heat shock protein gene expression regulator.

21. The Lactobacillus genus is a dried bacterial cell product, according to any one of claims 1 to 20. A heat shock protein gene expression regulator.

22. The heat shock protein gene expression regulator according to any one of claims 1 to 21 Pharmaceuticals.

23. The pharmaceutical product according to claim 22, which is an anti-wrinkle drug.

24. The pharmaceutical product according to claim 22, which is an anti-aging drug.

25. The heat shock protein gene expression regulator according to any one of claims 1 to 21 L Cosmetics.

26. The cosmetic according to claim 25, which is an anti-wrinkle cosmetic.

27. The cosmetic according to claim 25, which is an anti-aging cosmetic.

28. To obtain the genus Lactobacillus from mugwort or Angelica keiskei. A method for producing a heat shock protein gene expression regulator, including

29. The claim 28 further comprises fermenting the mugwort or angelica tree to obtain a fermented liquid. A method for producing a heat shock protein gene expression regulator.

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