Agent for modulating expression of heat shock protein gene, pharmaceutical, cosmetic, and method for producing agent for modulating expression of heat shock protein gene

Abstract

To provide an agent for modulating expression of a heat shock protein gene, a pharmaceutical, a cosmetic, and a method for producing the agent for modulating expression of a heat shock protein gene, each of which uses a component derived from a natural source as an active ingredient and produces a wide range of effects.SOLUTION: The present invention provides an agent for modulating expression of a heat shock protein gene, comprising a Lactobacillus sp. derived from Artemisia indica var. maximowiczii or Angelica keiskei. The present invention provides a pharmaceutical comprising the agent for modulating expression of a heat shock protein gene. The present invention provides a cosmetic comprising the agent for modulating expression of a heat shock protein gene. The present invention provides a method for producing the agent for modulating expression of a heat shock protein gene, comprising obtaining a Lactobacillus sp. derived from Artemisia indica var. maximowiczii or Angelica keiskei.SELECTED DRAWING: Figure 1

Description

[Technical field]

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

[0002] In recent years, as research into the structure of human skin and its metabolic mechanisms progresses, The cause of age-related changes in human skin, such as wrinkles, fine lines, age spots, and sagging skin The skin is made up of a thin outer epidermis (epithelial tissue) and an underlying layer The epidermis is the outermost layer of the body and is made up of a thick layer of connective tissue called the dermis. It protects the body and prevents internal moisture and nutrients from leaking out to the outside world. Fibroblasts, collagen, elastic fibers, and proteoglycans It is a connective tissue with a complex three-dimensional structure that gives the skin strength, elasticity, and It plays a role in providing elasticity. As we age, the amount of sebum and moisture in the skin decreases. When this happens, the stratum corneum on the surface of the skin loses its moisturizing power, causing fine wrinkles and dry skin. In response to this, it has been proposed to use fermented products to improve skin function. (For example, see Patent Documents 1 to 7.) In addition, the administration of extracts such as Arnica It has been proposed that it induces the expression of heat shock proteins and thus leads to a whitening effect (e.g. For example, see Patent Document 8. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2018 / 123828 [Patent Document 2] Patent No. 5468183 [Patent Document 3] JP 2015-156832 A [Patent Document 4] Patent No. 5467106 [Patent Document 5] Patent No. 4990297 [Patent Document 6] JP 2009-249366 A [Patent Document 7] JP 2009-249365 A [Patent Document 8] Patent No. 5697879 Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention relates to a heat shock protein gene that uses naturally occurring ingredients as active ingredients and has a wide range of effects. Gene expression regulator, medicine, cosmetic, and method for producing heat shock protein gene expression regulator The purpose of this document is to provide a method for [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. The present invention relates to a method for producing lactobacillus bacteria. The medicine contains Lactobacillus bacteria derived from mugwort or angelica. The cosmetic product according to one aspect of the present invention contains Lactobacillus (La The heat shock protein gene according to one aspect of the present invention is a genus of ctobacillus. The method for producing the gene expression regulator is to extract lactobacillus from mugwort or angelica. This includes obtaining the genus llus. Effect of the Invention

[0006] According to the present invention, a heat shock protein having a wide range of effects and containing naturally occurring components as active ingredients is provided. Heat shock protein gene expression regulators, pharmaceuticals, cosmetics, and heat shock protein gene expression regulators It is possible to provide a manufacturing method. [Brief description of the drawings]

[0007] [Figure 1] 1 shows graphs and a table illustrating the analysis results of bacteria contained in the fermentation broth of Example 1. [Diagram 2] 1 shows graphs and a table illustrating the analysis results of bacteria contained in the fermentation broth of Example 2. [Diagram 3] 1 is a table showing the results of gene expression analysis in Example 4. [Figure 4] 1 is a table showing the results of gene expression analysis in Example 4. [Diagram 5] 1 is a table showing the results of gene expression analysis in Example 4. [Figure 6] 1 is a table showing the results of gene expression analysis in Example 4. [Figure 7] 1 is a table showing the results of gene expression analysis in Example 4. [Figure 8] 1 is a table showing the results of gene expression analysis in Example 4. [Figure 9] 1 is a photograph of a person administered with the fermentation liquid of Example 5. [Figure 10] 1 is a graph showing the antibacterial effect of the fermentation liquid of Example 6. [Figure 11] 1 is a graph showing the antifungal effect of the fermentation liquid of Example 7. [Figure 12] 1 is a graph showing the antiviral effect of the fermentation liquid of Example 8. [Figure 13] 1 is a graph showing the antiviral effect of the fermentation liquid of Example 8. [Figure 14] 1 is a graph showing the anti-tinea fungus effect of the fermentation liquid of Example 9. [Figure 15] 1 is a table showing the amount of type I collagen produced in Example 10. [Figure 16] 1 is a table showing the amount of HSP47 produced in Example 10. [Figure 17] 13 is a microscopic image of SA-β-Gal stained cells according to Example 11. [Figure 18] 13 is a microscopic image of SA-β-Gal stained cells according to Example 11. [Figure 19] 1 is a table showing the degree of SA-β-Gal staining in Example 11. [Figure 20] 1 is a table showing cell viability according to Example 12. [Figure 21] 1 is a table showing the amount of HSP70 produced in Example 12. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] Hereinafter, the embodiments of the present invention will be described in detail. The present invention is not limited to the above, but may be modified in various ways. The technical concept of the present invention does not limit the combination of components to those described below. The technical idea can be modified in various ways within the scope of the claims.

[0009] The heat shock protein (HSP) gene expression regulator according to the embodiment is a mugwort or agarwood. The Lactobacillus genus is derived from the leaves of the The heat shock protein gene expression regulator is particularly effective in treating heat shock proteins, which improve anti-aging functions. It promotes the expression of the heat stress protein (HSP) 70 gene. Lactobacillus is a type of lactic acid bacteria. Lactobacillus fermentation produces lactic acid by fermenting sugars. The genus Lactobacillus also lives in the bodies of animals, including humans. The Lactobacillus genus is a lactobacillus genus derived from mugwort or angelica.

[0010] For example, the Lactobacillus genus according to the embodiment is extracted by fermenting mugwort or angelica. The heat shock protein gene expression regulator according to the embodiment is a heat shock protein gene expression regulator for mugwort or angelica. The apparatus may further comprise a fermentation liquid.

[0011] Lactobacillus species from mugwort include, for example, parafarraginis species, par abuchneri species, buchneri species, and harbinensis species, etc. Lactobacillus spp. from Angelica keiskei includes, for example, species vini and nagelii. The heat shock protein gene expression regulator according to the embodiment is a compound comprising a plurality of species of the genus Lactobacillus. may also include

[0012] The heat shock protein gene expression regulator according to the embodiment is a heat shock protein gene An example of a heat shock protein gene is the gene encoding HSP70. Examples of genes encoding HSP1A, HSP27, and HSP27 are the HSPA1A gene, which encodes HSP1A, and the HSPB1 gene, which encodes HSP27. P70 has functions of promoting whitening, anti-spots, anti-wrinkles, anti-stress, anti-cell death, and anti It has anti-inflammatory, cell-protective, gastric mucosal protective, and DNA-damaging functions. The heat shock protein gene according to the embodiment has an anti-stress function and a wound healing function. The gene expression regulator is a strain of the Lactobacillus genus derived from Angelica keiskei. It also promotes the production of HSP47, a molecular signaling molecule involved in collagen biosynthesis. Therefore, the heat shock protein gene expression regulator according to the embodiment is For example, anti-stress function, anti-cell death function, anti-inflammatory function, cell protection function, gastric mucosa protection function, It is possible to improve the anti-DNA damage function and wound healing function. The heat shock protein gene expression regulator is, for example, a heat shock protein expression promoter, a skin whitening agent, etc. Improved anti-aging function, improved anti-spot function, improved anti-wrinkle function, improved anti-stress function, improved anti-cell death function 1. Improved anti-inflammatory function, improved cell protection function, improved gastric mucosal protection function, improved anti-DNA damage function, and wound healing, And / or can be used as food. Note that wrinkles include fine lines.

[0013] The heat shock protein gene expression regulator according to the embodiment is a heat shock protein gene For example, the expression of heat shock protein genes according to the embodiment of the present invention is regulated. The agent suppresses the expression of the acid ceramide decomposing enzyme (ceramidase) gene. An example of an enzyme gene is the ASAH1 gene. It suppresses the expression of acid ceramidase. In order to achieve this, the heat shock protein gene expression regulator according to the embodiment is, for example, ceramide. It is possible to promote biosynthesis and improve the barrier function of the skin. The inhibitor of the gene expression of a shock protein is, for example, an inhibitor of ceramidase expression, an inhibitor of ceramide biosynthesis, and improving barrier function. It can be used as a cosmetic, a cosmetic, and / or a food product.

[0014] The heat shock protein gene expression regulator according to the embodiment regulates the expression of lipid synthesis enzyme genes. An example of a lipid synthesis enzyme gene is the DGAT1 gene. T1 (Diacylglycerol O-acyltransferase 1) Synthesizes triglycerides (TAG) from diacylglycerol (DAG). In the case of rheumatoid arthritis, the barrier function of the skin is abnormal. Protein gene expression regulators, for example, promote lipid synthesis and improve the barrier function of the skin. The heat shock protein gene expression regulator according to the embodiment can be, for example, For at least one purpose selected from the group consisting of promoting lipid synthesis and improving barrier function. It may be used as a medicine, cosmetic, and / or food for the treatment of

[0015] The heat shock protein gene expression regulator according to the embodiment is a lysosomal hydrolase Promotes gene expression. Lysosomes break down carbohydrates and glycolipids in cells. Lysosomal hydrolases are necessary for the functioning of lysosomes. An example of a hydrolase gene is the acid β-glucosidase (GBA) gene. In patients with lysosomal storage disorders, GBA activity is reduced or absent. Activation of BA improves the barrier function of the skin. The regulator of gene expression of a lysosomal protein is useful for preventing and treating lysosomal diseases and for treating skin blemishes. The heat shock protein gene expression according to the embodiment can improve the rear function. Current regulators include, for example, lysosomal hydrolase expression promotion, lysosomal function improvement, and lysosomal A small amount selected from the group consisting of prevention of lysosomal disease, treatment of lysosomal disease, and improvement of barrier function. It can be used as a medicine, cosmetic, and / or food for at least one application.

[0016] The heat shock protein gene expression regulator according to the embodiment of the present invention is a heat shock protein gene expression regulator that regulates tight junction biosynthesis. It promotes the expression of genes involved in the biogenesis of tight junctions. Examples of genes involved in the biogenesis of tight junctions include: These include the claudin 1 (CLDN1) gene and the occludin (OCLN) gene. Claudins and occludin are components of tight junctions. The heat shock protein gene expression regulator according to the embodiment is, for example, a tight junction It is possible to promote the biosynthesis of collagen and improve the barrier function of the skin. The heat shock protein gene expression regulator is, for example, a tight junction biogenesis factor. Enhancement of expression, enhancement of claudin expression, enhancement of occludin expression, tight junction biogenesis and improving barrier function. It can be used as a cosmetic, a cosmetic, and / or a food product.

[0017] The regulator of heat shock protein gene expression according to the embodiment regulates the expression of an intercellular adhesion molecule gene. An example of an intercellular adhesion molecule gene is the integrin α2 (ITGA2) gene. gene, E-cadherin (CDH1) gene, and hyaluronan receptor (CD44) gene. Integrins, cadherins, and CD44 contribute to cell-cell adhesion. Therefore, the heat shock protein gene expression regulator according to the embodiment is, for example, an intercellular adhesion factor. It is possible to promote the biosynthesis of stimuli and improve the barrier function of the skin. The heat shock protein gene expression regulator is, for example, a regulator of intercellular adhesion factor biosynthesis, Promotes expression of hyaluronic acid receptors, cadherin, and hyaluronan, and improves barrier function Pharmaceuticals, cosmetics, and / or pharmaceutical compositions for at least one application selected from the group consisting of the above. It can be used as food.

[0018] The heat shock protein gene expression regulator according to the embodiment is a temperature-sensitive TRP (Tra Promotes expression of nsient receptor potential channel genes An example of a TRP channel gene is the TRPV3 gene. It is involved in the proliferation and differentiation of keratinocytes that maintain the epidermal barrier function. The heat shock protein gene expression regulator according to the embodiment may, for example, regulate the biosynthesis of keratinocytes. The thermal shock absorbing agent according to the embodiment can promote the formation of keratinocytes and improve the barrier function of the skin. The protein gene expression regulator is, for example, capable of promoting TRP channel expression and keratinocyte biosynthesis. For at least one use selected from the group consisting of promoting synthesis and improving barrier function. It can be used as a medicine, cosmetic and / or food.

[0019] The heat shock protein gene expression regulator according to the embodiment regulates the expression of antimicrobial molecule genes. 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 the D The EFB103A gene is one of the 5'-terminal ... The FB103A gene encodes the antimicrobial peptides DEFB1, DEFB2, and DEFB 103. Thus, the heat shock protein according to the embodiment Regulators of protein gene expression can, for example, improve antimicrobial function. The heat shock protein gene expression regulator according to the present invention is, for example, a regulator of Toll-like receptor expression. At least one selected from the group consisting of promoting the expression of β-defensin and improving antimicrobial function. Both can be used as medicines, cosmetics, and / or foods for a single purpose.

[0020] The heat shock protein gene expression regulator according to the embodiment regulates the expression of sirtuin genes. An example of a sirtuin gene is the SIRT4 gene. The activity of the tyrosine kinase enhances the anti-aging function. The protein gene expression regulator can, for example, improve anti-aging function. The heat shock protein gene expression regulator according to the embodiment is, for example, a sirtuin expression regulator. A pharmaceutical product for at least one purpose selected from the group consisting of anti-aging and anti-aging function improvement; It can be used as a cosmetic and / or food product.

[0021] The heat shock protein gene expression regulator according to the embodiment regulates the expression of the telomerase gene. Examples of telomerase genes include the TERT gene and the TERC gene. Promoting telomerase activity increases cell life span. The heat shock protein gene expression regulator according to the present invention can, for example, improve anti-aging function. The heat shock protein gene expression regulator according to the embodiment is a telomerase. For at least one use selected from the group consisting of promoting enzyme expression and improving anti-aging function. can be used as medicines, cosmetics, and / or foods.

[0022] The heat shock protein gene expression regulator according to the embodiment is an energy metabolism factor gene An example of an energy metabolism factor gene is the PPARGC1A gene. The PPARGC1A gene is involved in the regulation of the peroxisome proliferator-activated receptor 1 (PGC-1). iferator-activated receptor gamma coacti PGC-1 encodes the gene encoding the β-peptide activator 1 (PGC-1), which promotes energy metabolism. In the embodiment, the heat shock protein gene expression regulator can be, for example, The present invention relates to a method for regulating the expression of heat shock protein genes. The agent promotes the expression of energy metabolism factors, promotes the expression of PGC-1, and improves energy metabolism function. A pharmaceutical, cosmetic, and / or food product for at least one application selected from the group consisting of It can be used as a product.

[0023] The heat shock protein gene expression regulator according to the embodiment of the present invention is a hyaluronic acid biosynthesis factor gene. The expression of hyaluronan biosynthesis factor genes is an example of hyaluronan biosynthesis factor gene. The hyaluronan synthase 1 (HAS1) gene, the hyaluronan synthase 2 (HAS2) gene, and the hyaluronan synthase Examples include the HAs3 gene, which is involved in the regulation of mitochondrial function.

[0024] In addition, the heat shock protein gene expression regulator according to the embodiment is a hyaluronic acid decomposition factor. The expression of hyaluronan decomposition factor genes is an example of hyaluronan decomposition factor genes. Hyalolytic enzyme 2 (HYAL2) gene and cell migration-inducing and hyaluronan-binding protein (CEMIP, KIA A1199) genes.

[0025] Therefore, the heat shock protein gene expression regulator according to the embodiment can be, for example, Hyaluronic acid is a key component in the prevention of osteoarthritis. It is effective in preventing and treating the skin, improving the moisturizing function, eliminating sagging skin, and reducing wrinkles. The heat shock protein gene expression regulator according to the embodiment is effective in preventing and treating osteoarthritis, for example. It is possible to treat and improve the moisturizing function, and reduce sagging and wrinkles. The heat shock protein gene expression regulator according to the present invention is, for example, a hyaluronic acid synthase gene expression regulator. Promotes osteoarthritis, inhibits expression of hyaluronic acid decomposition factors, promotes hyaluronic acid synthesis, prevents osteoarthritis, and From the group consisting of osteoarthritis treatment, moisturizing function improvement, anti-sagging function improvement, and anti-wrinkle function improvement Usable as a medicine, cosmetic, and / or food for at least one selected application It is Noh.

[0026] The heat shock protein gene expression regulator according to the embodiment is a heat shock protein gene expression regulator that regulates the expression of a basement membrane biosynthesis factor gene. An example of a basement membrane biosynthesis factor gene is the laminin α1 (LAMA1) gene. Gene, laminin α5 (LAMA5) gene, type IV collagen α1 (COL4A1) gene and type VII collagen α1 (COL7A1). Regulators of gene expression of cytokines, such as those that promote the biosynthesis of laminin and collagen, In this case, it is possible to promote the biosynthesis of the basement membrane. Examples of gene expression regulators include those that promote the expression of basement membrane biosynthesis factors, promote the expression of laminin, and promote collagen. For at least one use selected from the group consisting of promoting expression and promoting basement membrane biosynthesis. can be used as medicines, cosmetics, and / or foods.

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

[0028] The heat shock protein gene expression regulator according to the embodiment is a matrix metalloproteinase. Promotes expression of matrix metalloproteinase inhibitor genes. An example of this is the TIMP1 gene. 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 can be used, for example, in cells. The heat shock protein gene of the present invention is capable of suppressing the degradation of the extracellular matrix. The expression regulator is, for example, a matrix metalloproteinase inhibitor expression promoter and an extracellular matrix metalloproteinase inhibitor. and inhibition of the degradation of ribozymes. It can be used as a cosmetic and / or food product.

[0029] The heat shock protein gene expression regulator according to the embodiment of the present invention inhibits the expression of antioxidant genes. An example of an antioxidant gene is superoxide dismutase 3 (SOD 3) Genes, catalase (CAT) gene, glutathione reductase (GSR) gene, glutathione Glutathione peroxidase 1 (GPX1) gene, metallothionein 1F (MT1F) gene SOD is an enzyme that breaks down reactive oxygen species. CAT is an enzyme that breaks down hydrogen peroxide. GPX1 is an enzyme that breaks down oxidized glutathione. GSR is an enzyme that reduces oxidized glutathione. is an enzyme that breaks down hydrogen peroxide. MT1F is an antioxidant protein. Therefore, The heat shock protein gene expression regulator according to the embodiment has, for example, an antioxidative function. The heat shock protein gene expression regulator according to the embodiment can be, for example, an antioxidant. Promotion of factor gene expression, promotion of SOD expression, promotion of CAT expression, promotion of GSR expression, promotion of GPX1 expression At least one selected from the group consisting of promotion of mitochondrial function, promotion of MT1F expression, and improvement of antioxidant function. The composition may be used as a pharmaceutical, cosmetic, and / or food product for the purposes described above.

[0030] The heat shock protein gene expression regulator according to the embodiment is an interleukin 1 receptor Promotes expression of the interleukin 1 receptor antagonist (IL1RN) gene. Its deficiency results in Interleukin-1 Receptor Deficiency (DIRA). The heat shock protein gene expression regulator according to the embodiment can prevent and treat DIRA. The heat shock protein gene expression regulator according to the embodiment can be used, for example, For example, promoting expression of interleukin 1 receptor antagonist molecules, preventing DIRA, and treating DIRA. and It can be used as such.

[0031] The heat shock protein gene expression regulator according to the embodiment is a semaphorin gene regulator. An example of a semaphorin gene is the SEMA3A gene. Semaphorins are repulsive guidance factors that exert a repulsive effect on axonal elongation. Semaphorins suppress angiogenesis. Semaphorins control bone mass. Semaphorin suppresses itching. Semaphorin prevents and treats atopic dermatitis. Therefore, the heat shock protein gene expression regulator according to the embodiment is, for example, For example, they act to repulsively guide axonal elongation, inhibit angiogenesis, and regulate bone mass. It is possible to suppress itching and prevent and treat atopic dermatitis. The heat shock protein gene expression regulator according to the embodiment is, for example, a semaphorin gene expression regulator. promotion, inhibition of axonal elongation, inhibition of angiogenesis, bone mass control, suppression of itching, prevention of atopic dermatitis, and a medicine for at least one use selected from the group consisting of treatment of atopic dermatitis. It can be used as a cosmetic, a cosmetic, and / or a food product.

[0032] The heat shock protein gene expression regulator according to the embodiment of the present invention is a gene that regulates the expression of a heat shock protein gene. It promotes the expression of the gene and nerve growth factor receptor (NGFR). Nerve growth factor promotes neural growth. Promotes the growth and maintenance of the nervous system, promotes the recovery of brain function, and prevents Alzheimer's disease and dementia. Nerve growth factor exerts its action via nerve growth factor receptors. Therefore, the heat shock protein gene expression regulator according to the embodiment can be used to, for example, regulate neurodevelopment. It promotes the expression of growth factors, promotes the growth and maintenance of nerves, promotes the recovery of brain nerve functions, and It is possible to prevent and treat Zheimer's disease and dementia. The regulator of the expression of a neurotrophic protein gene is, for example, a regulator of the expression of a neurotrophic protein gene, which is capable of promoting the expression of a neurotrophic protein gene and maintaining the neurotrophic protein gene. Promotes recovery of brain and nerve functions; prevents Alzheimer's disease; treats Alzheimer's disease; prevents dementia A pharmaceutical for at least one use selected from the group consisting of prevention, treatment of dementia, 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 the embodiment is a heat shock protein gene expression regulator that regulates nuclear factor κB (NFκB). It promotes the expression of NFκB inhibitor genes. IA genes are examples of NFκB inhibitors such as IκBα, which inhibit the activity of NFκB. Thus, the heat shock protein gene expression according to the embodiment of the present invention can be used to prevent and treat cancer. The current regulator can, for example, prevent and treat cancer. The regulator of gene expression of a NFκB inhibitor is, for example, capable of promoting expression of the NFκB inhibitor, preventing cancer, and and cancer treatment. and / or may be used as food.

[0034] The heat shock protein gene expression regulator according to the embodiment is a calpain (CAPN) inhibitor. It promotes the expression of the calpastatin (CAST) gene, a protein that damages senescent cells. In this case, CAPN is activated and CAST disappears. The regulator of the expression of a gene for a cellular aging protein can, for example, inhibit aging. The heat shock protein gene expression regulator according to the present invention is capable of promoting the expression of CAPN inhibitory protein, and improving anti-aging functions. It can be used as food.

[0035] The heat shock protein gene expression regulator according to the embodiment of the present invention is capable of regulating citrullinated protein activity. It promotes the expression of citrullinated protein activator genes. Examples include peptidylarginine deiminase 3 (PAD3). PAD is a citrulline The present invention is therefore directed to the activation of keratinization proteins and the progression of normal epidermal keratinization. Such heat shock protein gene expression regulators, for example, promote normal skin keratinization. The heat shock protein gene expression regulator according to the embodiment can be, for example, From the group consisting of enhanced expression of citrullinated protein activator and normal skin keratinization progression It can be used as a medicine, cosmetic, and / or food for selected applications.

[0036] The heat shock protein gene expression regulator according to the embodiment is a transglutaminase gene. An example of a transglutaminase gene is the TGM1 gene. Transglutaminase increases the physical strength of the skin surface and enhances its moisturizing function. Therefore, the heat shock protein gene expression regulator according to the embodiment of the present invention is For example, it is possible to increase the strength of the skin surface and improve the skin's moisturizing function. The heat shock protein gene expression regulator according to the embodiment is, for example, a transglutaminase inhibitor. It promotes the expression of stimulants, improves the strength of the skin surface, improves the elasticity of the skin, and improves the skin's moisturizing function. As a pharmaceutical, cosmetic, and / or food for at least one use selected from the group consisting of: It can be used.

[0037] The heat shock protein gene expression regulator according to the embodiment is involucrin (IVL). IVL promotes the maturation of the cornified envelope and protects the skin. Therefore, the present invention relates to a method for controlling the expression of heat shock protein genes. The agent, for example, promotes maturation of the cornified envelope and improves the skin's moisturizing function. The heat shock protein gene expression regulator according to the embodiment can be, for example, By promoting IVL expression, promoting maturation of the cornified envelope, and improving the skin's moisturizing function and It can be used as such.

[0038] The heat shock protein gene expression regulator according to the embodiment regulates the expression of aquaporin genes. An example of an aquaporin gene is the AQP3 gene. Phosphorus is involved in keratinocyte migration and improves the skin's moisturizing function. The heat shock protein gene expression regulator according to the embodiment is, for example, a keratinocyte migration mechanism. The thermal shock absorber according to the embodiment can improve the function of the skin and improve the moisturizing function of the skin. The protein gene expression regulator may, for example, promote aquaporin expression, keratinocyte migration, and improving the moisturizing function of the skin. It may be used as a medicine, cosmetic, and / or food for the treatment of

[0039] In addition, the heat shock protein gene expression regulator according to the embodiment reduces fungi (mold). The regulator of heat shock protein gene expression according to the embodiment can be, for example, , fungus within 24 hours, 80% or more, 85% or more, 90% or more, or 95% or more The fungi include tinea, candida, cryptococcus, and aspergillus. Examples of heat shock protein genes according to the present invention include, but are not limited to, The expression regulator also has a therapeutic effect on fungal diseases, such as tinea, candidiasis, cryptococcosis, and psoriasis. These include, but are not limited to, tococcosis and aspergillosis.

[0040] The heat shock protein gene expression regulator according to the embodiment is capable of inhibiting gram-negative bacteria and gram-positive bacteria. The present invention also has a function of reducing the number of virulent bacteria. For example, the method is to reduce gram-negative and gram-positive bacteria by 80% or more and 85% or more within 24 hours. The number of gram-negative bacteria is reduced by more than 90% or more than 95%. These include, but are not limited to, Monella, Vibrio parahaemolyticus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Gram-positive bacteria include methicillin-resistant Staphylococcus aureus (MRSA), spore-forming Staphylococcus aureus (S. aureus), and Examples of suitable bactericidal bacteria include, but are not limited to, Bacillus cereus and Bacillus subtilis.

[0041] The heat shock protein gene expression regulator according to the embodiment has the function of reducing viruses. The heat shock protein gene expression regulator according to the embodiment may also be used to regulate, for example, a virus. within 24 hours, reduced by 80%, 85%, 90%, or 95% or more. Viruses are classified into enveloped viruses, which are viruses that have an envelope, and This includes non-enveloped viruses, which are viruses that do not have an envelope. includes DNA viruses and RNA viruses.

[0042] Enveloped DNA viruses include human herpesviruses, vaccinia virus, and Viruses and hepatitis B virus, and the like.

[0043] Enveloped RNA viruses include influenza viruses, SARS-CoV-2 viruses, and Ronavirus, RS virus, Mumps virus, Lassa virus, Dengue virus, Rabies virus, human immunodeficiency virus, measles virus, hepatitis C virus, Ebola virus , yellow fever virus, and Japanese encephalitis virus, among others.

[0044] Non-enveloped DNA viruses include adenoviruses, B19 viruses, papovavirus, human papillomavirus, and the like, but are not limited to these. .

[0045] Non-enveloped RNA viruses include norovirus, poliovirus, and Covirus, Hepatitis A virus, Hepatitis E virus, Rhinovirus, Astrovirus Examples include rotavirus, coxsackievirus, enterovirus, and sapovirus. Examples include, but are not limited to:

[0046] The heat shock protein gene expression regulator according to the embodiment comprises an effective amount of Lactobacillus sp. The heat shock protein gene expression regulator according to the embodiment includes a Lactobacillus sp. The plant may be contained in a solvent such as water, or in a fermentation liquid of the plant. Plants that can be used for this purpose include Artemisia princeps and Angelica keiskei, as well as Lactobacillus spp.

[0047] An effective amount is the amount necessary to exert a gene expression regulating effect, and is determined based on the target gene. Generally, the concentration of Lactobacillus is high and the solvent is a fermentation liquid of a plant. For example, if the target gene is the GBA gene, In the case of lactobacillus, the lower the concentration, the greater the effect of regulating gene expression. In the case of the target gene being the TLR2 gene, the solvent should not contain the fermentation liquid of the plant, so that the target gene can be detected more efficiently. The effect of regulating gene expression is achieved.

[0048] The Lactobacillus genus contained in the heat shock protein gene expression regulator according to the embodiment is The bacteria may be live bacteria or may be killed bacteria, for example, by heat treatment. The heat shock protein gene expression regulator according to the present invention comprises killed bacteria of the genus Lactobacillus. The Lactobacillus genus may be in the form of a dried cell mass. Killed cells of the Lactobacillus genus Alternatively, the dried bacterial cell product also exerts a gene expression regulating effect and an antibacterial and antiviral effect. Killed Lactobacillus bacteria or dried cells are easy to transport and store for long periods of time. do.

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

[0050] The heat shock protein gene expression regulator according to the embodiment is, for example, a cosmetic for skin conditioning. Examples of skin conditioning cosmetics include lotions, beauty essences, and packs. The heat shock protein gene expression regulator according to the embodiment is, for example, a protective cosmetic. Examples of protective cosmetics include protective lotions and protective creams. The heat shock protein gene expression regulator according to the present invention may be, for example, a base makeup cosmetic. Examples of base makeup cosmetics include foundations, face powders, and a makeup base. For example, it may be a point makeup cosmetic. Examples include lipstick, eye make-up, blusher, and nail polish.

[0051] In addition, the heat shock protein gene expression regulator according to the embodiment can be used as, for example, a disinfectant, a paint, or the like. The heat shot according to the embodiment can be used as a skin treatment, eye drops, or an oral medication. The protein gene expression regulator can be applied to, for example, the skin, hair, oral cavity, and eye of the human body, including the fingers and toes. It is administered into a ball, etc.

[0052] In addition to the Lactobacillus genus, the heat shock protein gene expression regulator according to the embodiment includes Liquid fats and oils, solid fats and oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicones Ane, anionic surfactant, cationic surfactant, amphoteric surfactant, nonionic surfactant agents, moisturizers, water-soluble polymers, thickeners, film-forming agents, sequestering agents, lower alcohols, polyhydric Alcohol, sugar, amino acids, organic amines, pH adjusters, skin nutrients, vitamins, Antioxidants, fragrances, powders, coloring materials, water, and other cosmetic and pharmaceutical ingredients are mixed according to purpose. It may be included as appropriate.

[0053] When the heat shock protein gene expression regulator according to the embodiment contains an oil component, The concentration of the oil component in the heat shock protein gene expression regulator according to the present invention is not particularly limited. However, for example, 0.1% by mass or more and 90% by mass or less, or 0.5% by mass or more and 90% by mass or less, The heat shock protein gene expression regulator according to the embodiment contains an aqueous component. When the heat shock protein gene expression regulator according to the embodiment contains The concentration is not particularly limited, but may be, for example, 0.1% by mass or more and 90% by mass or less, or 0. The heat shock protein gene expression meter according to the embodiment is 5% by mass or more and 90% by mass or less. The ratio of the oily component to the aqueous component in the preparation is determined based on the heat shock protein gene expression according to the embodiment. Is the current conditioner 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 When a surfactant is included, the heat shock protein gene expression regulator according to the embodiment The concentration of the surfactant is not particularly limited, but is, for example, from 2% by mass to 10% by mass.

[0054] In addition to the Lactobacillus genus, the heat shock protein gene expression regulator according to the embodiment includes Antibacterial or antiviral substances may be appropriately contained depending on the purpose.

[0055] The heat shock protein gene expression regulator according to the embodiment is a lactobacillus acidophilus (lactobacco) extract obtained by fermenting a plant. It is produced by obtaining a fermentation liquid containing the genus Shirasu. When fermenting the plant, salt and Sugar such as molasses is added to the plant. The fermentation temperature is, for example, 30°C. The resulting fermented liquid is The pH is around 4.0. It may be extracted.

[0056] The resulting fermentation liquid may be heated to kill the Lactobacillus bacteria contained in the fermentation liquid. The fermentation liquid may be spray-dried to obtain a dried Lactobacillus cell product. It can also be prepared by freeze-drying or hot air drying.

[0057] Furthermore, the obtained fermentation liquid, Lactobacillus bacteria, or Lactobacillus bacteria The dried product may be added to soy milk, and the soy milk may be fermented to obtain a fermented soy milk broth. It has the effect of regulating child expression.

[0058] As described above, the heat shock protein gene expression regulators according to the embodiments of the present invention are The configurations and effects of the following examples using any one or a combination of the above are as follows: Yes.

[0059] The heat shock protein gene expression regulator, drug, or cosmetic according to this embodiment is It contains the genus Lactobacillus derived from mogi or angelica. The heat shock protein gene expression regulator, drug, or cosmetic according to the embodiment is made of mugwort or The pharmaceutical composition may further comprise a fermentation liquid derived from Angelica keiskei. The cosmetic may be an anti-wrinkle cosmetic or an anti-aging cosmetic. .

[0060] The present embodiment relates to a method for the regulation of heat shock protein gene expression using mugwort or Angelica keiskei. The present embodiment includes the genus Lactobacillus, which is a member of the Lactobacillus sp. family. The lactobacillus species derived from mugwort or angelica and the fermented liquid derived from mugwort or angelica are used. include.

[0061] The present embodiment is a method for producing a heat shock protein gene of the genus Lactobacillus derived from mugwort or angelica. The present embodiment includes the use of the present invention for producing a gene expression regulator, a pharmaceutical, or a cosmetic. Heat shock of Lactobacillus sp. derived from mugwort or angelica leaf and fermented liquid derived from mugwort or angelica leaf This includes use for producing a protein gene expression regulator, a pharmaceutical, or a cosmetic.

[0062] In this embodiment, Lactobacillus spp. derived from Artemisia anguicida or Angelica keiskei is administered to humans or non-human animals. A method for modulating heat shock protein gene expression, a therapeutic method, or a cosmetic method, comprising: The present embodiment includes administering to humans or non-human animals Lactobacillus sp. derived from Artemisia anguicida or Angelica keiskei. and administering a fermented liquid derived from mugwort or angelica to the mice. The treatment method includes a treatment for improving anti-wrinkle function. The cosmetic method may be a method for treating or improving an anti-aging function. The present invention may be a cosmetic method for improving the above-mentioned functions or a cosmetic method for improving anti-aging functions.

[0063] Is the heat shock protein gene a group consisting of the HSPA1A gene and the HSPB1 gene? The present embodiment may be characterized by the use of at least one selected from the group consisting of mugwort and angelica. The genus Lactobacillus is selected from the group consisting of the HSPA1A gene and the HSPB1 gene. The expression of at least one of the following genes may be promoted:

[0064] The Lactobacillus genus derived from mugwort or angelica according to this embodiment is a heat shock protein It is possible to regulate the expression of genes other than the gene. The genes whose expression is regulated in the Lactobacillus genus derived from Japanese leaves are ceramidase gene, lipid synthesis gene, and Synthase genes, lysosomal hydrolase genes, tight junction biosynthesis factor genes and intercellular adhesion factor genes. .

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

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

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

[0068] Tight junction biogenesis factor genes are derived from the CLDN1 and OCLN genes The mugwort or sunflower seed according to the present embodiment may be at least one selected from the group consisting of: The leaf-derived Lactobacillus sp. is selected from the group consisting of the CLDN1 gene and the OCLN gene. The expression of at least one of the genes involved in the transcriptional regulation may be promoted.

[0069] The intercellular adhesion molecule genes are ITGA2, CDH1, and CD44. The mugwort or clear according to the present embodiment may be at least one selected from the group consisting of: Lactobacillus sp. derived from Japanese leaves expresses ITGA2 gene, CDH1 gene, and CD44 gene. The expression of at least one selected from the group consisting of:

[0070] Genes whose expression is regulated in the genus Lactobacillus derived from Artemisia or Angelica keiskei according to this embodiment The antimicrobial molecule gene may be a TLR2 gene, a DE FB1 gene, DEFB4A gene, and DEFB103A gene. The lactobacillus acidophilus extract derived from mugwort or angelica tree according to the present embodiment may be at least one of the lactobacillus acidophilus extract derived from mugwort or angelica tree according to the present embodiment. The genus Shirasu 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 the genus Lactobacillus derived from Artemisia or Angelica keiskei according to this embodiment At least one gene selected from the group consisting of sirtuin genes and telomerase genes It may be one of them.

[0072] The sirtuin gene may be a SIRT4 gene. Lactobacillus 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 of the lactobacillus acidifiers may be used. The genus S. cerevisiae has at least one gene selected from the group consisting of the TERT gene and the TERC gene. Expression may be enhanced.

[0074] Genes whose expression is regulated in the genus Lactobacillus derived from Artemisia or Angelica keiskei according to this embodiment However, the energy metabolism factor gene may be PPARG. The Lactobacillus derived from Artemisia anguicida or Angelica keiskei according to the present embodiment may be a C1A gene. The genus may promote expression of the PPARGC1A gene.

[0075] Genes whose expression is regulated in the genus Lactobacillus derived from Artemisia or Angelica keiskei according to this embodiment is selected from the group consisting of hyaluronic acid biosynthesis factor genes and hyaluronic acid degradation factor genes At least one of them may be performed.

[0076] The hyaluronan biosynthesis factor genes are HAS1, HAS2, and HAS3. The present invention may be applicable to at least one selected from the group consisting of the following genes: Or, the Lactobacillus sp. derived from Angelica keiskei has the HAS1 gene, the HAS2 gene, and the HAS3 gene. The expression of at least one selected from the group consisting of genes may be promoted.

[0077] The hyaluronan decomposition factor gene is a group consisting of the HYAL2 gene and the CEMIP gene. The present embodiment may be characterized by the use of at least one selected from the group consisting of mugwort and angelica. The Lactobacillus genus is selected from the group consisting of the HYAL2 gene and the CEMIP gene. The expression of at least one may be inhibited.

[0078] Genes whose expression is regulated in the genus Lactobacillus derived from Artemisia or Angelica keiskei according to this embodiment The basement membrane biosynthesis factor gene may be a LAMA1 gene. a gene selected from the group consisting of a gene, a LAMA5 gene, a COL4A1 gene, and a COL7A1 gene. At least one of the above may be selected. The genus Actobacillus contains the LAMA1 gene, the LAMA5 gene, the COL4A1 gene, and C The expression of at least one gene selected from the group consisting of the OL7A1 gene may be promoted.

[0079] The heat shock protein gene expression regulator, drug, or cosmetic according to this embodiment is The type I collagen production promoter according to this embodiment is Artemisia anguicidae. The present invention relates to the production of type I collagen. The promoter is a mixture of Lactobacillus spp. derived from mugwort or angelica leaf and a fermented liquid derived from mugwort or angelica leaf. Prepare.

[0080] The present embodiment relates to a lactobacillus acidophilus derived from mugwort or angelica tree, which is used to promote the production of type I collagen. The present embodiment includes mugwort or bromeliad for use in promoting the production of type I collagen. It contains Lactobacillus derived from Japanese yomogi leaf and fermented liquid derived from yoshino cherry or angelica leaf.

[0081] The present embodiment is a method for promoting the production of type I collagen by the lactobacillus genus derived from mugwort or angelica. The present embodiment includes the use of lactobacillus acidophilus derived from mugwort or angelica tree leaf for the manufacture of a lactic acid accelerator. To produce a type I collagen production promoter from the fermentation liquid of the genus Rus and mugwort or angelica. This includes use for

[0082] In this embodiment, Lactobacillus spp. derived from Artemisia anguicida or Angelica keiskei is administered to humans or non-human animals. The present embodiment includes a method for promoting the production of type I collagen, comprising: The animals were given Lactobacillus sp. derived from mugwort or angelica and a fermented liquid derived from mugwort or angelica. The present invention also includes a method for promoting the production of type I collagen, comprising administering

[0083] The heat shock protein gene expression regulator, drug, or cosmetic according to this embodiment is The HSP47 production promoter according to this embodiment is derived from Angelica keiskei The HSP47 production promoter according to this embodiment is derived from Angelica keiskei (Heart Ginger) It contains a fermented liquid derived from Lactobacillus and Hashimoto leaf.

[0084] This embodiment includes a lactobacillus genus derived from Angelica keiskei (Heartroots Lactobacillus or Lactobacillus keiskei) used to promote the production of HSP47. This embodiment relates to a lactobacillus species derived from Angelica keiskei that is used to promote the production of HSP47. Contains fermented liquid derived from angelica leaf.

[0085] In this embodiment, a method for producing an HSP47 production promoter of the genus Lactobacillus derived from Angelica keiskei The present embodiment includes the use of Lactobacillus sp. derived from Angelica keiskei and fermented Angelica keiskei. The present invention also includes use of the liquid for producing an agent for promoting HSP47 production.

[0086] The present embodiment relates to administering Lactobacillus derived from Angelica keiskei to humans or non-human animals. The present embodiment includes a method for promoting the production of HSP47, comprising administering Angelica keiskei to a human or non-human animal. The production of HSP47, including administering fermentation liquid derived from Lactobacillus sp. and Angelica keiskei This includes methods for promoting

[0087] The Lactobacillus species derived from Artemisia or Angelica keiskei according to this embodiment is parafarr aginis sp., parabuchneri sp., buchneri sp., harbinen At least one selected from the group consisting of sis species, vini species, and nagelii species may be also possible.

[0088] The Lactobacillus genus derived from Artemisia princeps or Angelica keiskei according to this embodiment may be killed bacteria. The Lactobacillus genus derived from Artemisia anguicida or Angelica keiskei according to the present embodiment may be heat-treated. The lactobacillus derived from mugwort or angelica according to this embodiment is a dried cell product. Good too.

[0089] Production of heat shock protein gene expression regulator, pharmaceutical, or cosmetic according to the present embodiment The method involves obtaining Lactobacillus from mugwort or angelica. The heat shock protein gene expression regulator, pharmaceutical, or chemical The cosmetic manufacturing method may further include fermenting mugwort or angelica tree to obtain a fermented liquid. The heat shock protein gene expression regulator, pharmaceutical, or cosmetic according to this embodiment The method may further comprise killing the obtained Lactobacillus. Method for producing a heat shock protein gene expression regulator, a medicine, or a cosmetic according to the embodiment However, the method may further include heat treating the obtained Lactobacillus. The present invention relates to a method for producing a heat shock protein gene expression regulator, a pharmaceutical product, or a cosmetic product. The method may further comprise drying the isolated Lactobacillus. EXAMPLES

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

[0091] (Example 1: Lactobacillus from Artemisia) For mugwort leaves, the temperature is between 1 hour before and 1 hour after sunrise, for a total of 2 hours. It is said that the number of lactic acid bacteria is at its highest during this time period. It is said that the number of photosynthetic bacteria increases slightly. Therefore, during these two hours, About 20 cm of the tip was collected. The collected 6.3 kg of mugwort leaves were immediately Place in the first pickle barrel with a plastic bag inside, add 3.2 kg of molasses and 0. After sprinkling 6 kg of coarse salt on the fish, the plastic bag was closed and sealed. A weight was placed on top and the mugwort leaves were soaked in it.

[0092] A few days later, when the pickling liquid had risen to the top of the mugwort leaves, the weights were removed. Next, the second barrel was filled with pickles. Add 10L of chlorine-free water for rinsing, and add mugwort leaf pickles and 10 kg of pickling juice was poured into the third pickling barrel. A mesh filter was placed on the second barrel. The mugwort leaves were picked little by little from the second barrel, while being washed by hand. Then, press the mugwort leaves lightly with your palm onto the wire mesh filter above the opening of the third pickling barrel, and pour the pickling liquid into it. was narrowed down.

[0093] After squeezing out all the mugwort leaves, the remaining pickling liquid in the second pickling liquid is passed through a wire mesh filter. Next, molasses (Hateruma brown sugar) was added to the pickling liquid in the third pickling barrel to a final concentration of 10% by weight. % and crude salt was dissolved in the mixture so that the final concentration was 3% by weight. Fermentation was started by bringing the ambient temperature of the barrel to about 30°C. The foam gradually turned into fine bubbles, and finally subsided. After about a week When the foaming stopped, the pH was around 3.8. A part of the obtained mugwort fermentation liquid was heated at 70°C for 30 minutes to kill the bacteria. A mugwort fermentation liquid was obtained.

[0094] The unheat-treated mugwort fermentation liquid was analyzed using next-generation sequencers (MiSeq, Illumina As shown in Figure 1, the mugwort fermentation liquid was found to be capable of inhibiting the Lactobacillus spp. afarraginis spp., parabuchneri spp., buchneri spp., and h arbinensis species. Also called a sequencer. The numbers in the table in Figure 1 indicate the number of bacteria contained in the mugwort fermentation liquid. This reflects the number of bacteria in the culture.

[0095] (Example 2: Lactobacillus from Angelica keiskei) In the case of Angelica keiskei, milk is released during a total of two hours, one hour before and one hour after sunrise. The number of lactic acid bacteria is said to be at its highest during this time period. During these two hours, the number of photosynthetic bacteria increases. The stems were harvested. The harvested 6.3 kg of angelica leaves were immediately placed in a plastic bag and placed in a storage container. Put them in the pickle barrel in step 1, sprinkle 3.2 kg of molasses and 0.6 kg of coarse salt on the leaves, and then pour them into the pot. The opening of the plastic bag was closed and sealed. A weight was placed on top of the plastic bag and the angelica leaves were soaked. .

[0096] A few days after the pickling liquid had risen to the top of the angelica leaves, the weight was removed. Next, the second pickling barrel was filled with soot. Pour 10L of chlorine-free water for washing, and add 10kg of pickled angelica leaves and In addition, a third pickle barrel was prepared and a wire mesh filter was placed on the opening of the third pickle barrel. From the second barrel, the angelica leaves were taken out little by little while being washed by hand, and then placed in the third barrel. The angelica leaves were lightly pressed with the palm of the hand onto a wire mesh filter placed over the opening of the pickle barrel to squeeze out the pickling liquid.

[0097] After squeezing out all the ashitaba leaves, filter the remaining pickling liquid in the second pickling liquid through a wire mesh filter. Next, molasses was added to the pickling liquid in the third pickling barrel to a final concentration of 10% by weight. Crude salt was dissolved in the third pickle barrel to a final concentration of 3% by weight. Fermentation was started by heating the temperature to 30°C. First, large bubbles were observed, and gradually The foam turned into fine bubbles, and finally subsided. After about a week, when the foaming subsided, The pH of the soaking liquid was about 4.0. The resulting soaking liquid was used as the fermented Angelica keiskei liquid. A part of the fermented liquid of Angelica keiskei was heated at 70℃ for 30 minutes to kill the bacteria, and a heat-treated Angelica keiskei fermented liquid was obtained. .

[0098] The unheated fermented solution of Angelica keiskei was analyzed using a next-generation sequencer (MiSeq, Illumina) ) and, as shown in Figure 2, the fermented liquid of Angelica keiskei was found to be The numbers in the table in Figure 2 indicate the number of species of bacteria contained in the Angelica keiskei fermentation liquid. Reflects the number of bacteria.

[0099] (Example 3: Fermented soy milk using Lactobacillus sp.) The soy milk was heated to 70°C and sterilized for about 30 minutes. The non-heat-treated mugwort fermentation liquid prepared in Example 1 was added to the flask so that the final concentration was about 10 wt%. After that, the soy milk to which the non-heat-treated mugwort fermented liquid had been added was heated at 37°C. After fermentation, the solids were removed by filtration and Lactobacillus sp. Thus, a fermented soy milk broth containing the above was obtained.

[0100] Example 4: Gene Expression Testing Live Lactobacillus was isolated from the mugwort fermentation liquid obtained in Example 1, and The isolated live lactobacillus was dispersed in pure water at a concentration of 0.5 g / L and used as sample 1. The genus Shirasu was dispersed in pure water at a concentration of 5.0 g / L and used as sample 2. The mugwort fermentation liquid containing Bacillus at a concentration of 5.0 g / L was designated sample 3.

[0101] Growth medium (Growth Medium: 18 SGM 082, EPISKIN) Using this, a three-dimensional cultured epidermal model (SkinEtchic RHE:18 RHE 09 8, EPISKIN) overnight. Then, the cells were placed in a 6-well plate with growth medium. The 3D cultured epidermal model was transferred to a Transwell insert (Corning) and placed in the well. 50 μL of any of Samples 1 to 3 was applied to the stratum corneum side of the three-dimensional cultured epidermis model. After 4 hours, the medium containing the samples was removed from the wells and calcium and magnesium were added. The three-dimensional cultured epidermal model was washed with phosphate buffered saline (PBS(-)) that does not contain erythrocytes.

[0102] The 3D cultured epidermis model was cut out from the Transwell insert together with the membrane using a scalpel. The three-dimensional cultured epidermal model was then immersed in a dissolving solution (QIAzol, registered trademark, QIAGEN). After incubation, the cells were disrupted using a tissue lyser (QIAGEN). A homogenate was obtained. The homogenate was purified using an RNA purification kit (miRNeasy Mini Kit, The RNA was purified using QIAGEN (registered trademark) and the purified RNA was collected. The RNA was then sent to Mitsubishi Chemical Corporation, which provides contract analysis services, to be used for mRNA generation. Using the present analysis chip, gene expression in cells treated with the samples was analyzed. The gene expression in cells not treated with pull (control) was adjusted to 1.00. Normalized gene expression in sample-treated cells versus control The gene expression ratio was calculated. Significance tests were performed using Student t-test. Ta.

[0103] The results are shown in Figures 3 to 8. Values ​​greater than 1.00 indicate higher gene expression than the control. Values ​​less than 1.00 indicate suppression of gene expression compared to the control. This indicates that

[0104] (Example 5: Anti-wrinkle effect) A 46-year-old woman was given the Lactobacillus sp. prepared in Example 1 twice a day for five months on her face and cheeks. The mugwort fermentation liquid containing 5.0 g / L of ... A reduction in wrinkles due to aging was observed. No inflammatory reactions or tanning were observed. The mugwort fermentation liquid containing Lactobacillus spp. at a concentration of 5.0 g / L prepared in Example 1 was As shown in Example 4, the effect of promoting the expression of the HSP70 gene is extremely high, The anti-inflammatory and whitening effects of , and the expression promotion effect of inflammation-related genes and tanning-related genes It is believed that it exceeded that.

[0105] Example 6: Antibacterial effect of Lactobacillus Staphylococcus aureus and MRSA were used as gram-positive cocci, and Bacillus subtilis was used as gram-positive rods. Substances such as Bacillus subtilis and Bacillus cereus were prepared, and gram-negative cocci such as Escherichia coli, Salmonella enterica, and Vibrio parahaemolyticus were prepared. As a gram-negative bacillus, Pseudomonas aeruginosa was prepared.

[0106] In the soy milk fermentation liquid containing Lactobacillus prepared in Example 3 (10 mL), any of the above bacteria was added. Reka 10 7 0.1 mL of the bacterial solution containing 1000 cells / mL of bacteria was inoculated and incubated at 25°C for 1 h. The viable cell count of the bacteria inoculated into the medium was measured for 24 hours. 0.1 mL of the bacterial solution was inoculated into 10 mL of phosphate buffer (pH 7.2, mol / L) and incubated at 25°C. The number of live bacteria inoculated over time was measured for 24 hours. The results are shown in Figure 10. The soy milk fermentation liquid containing Lactobacillus genus killed all kinds of bacteria in the test within 24 hours. was reduced to.

[0107] Example 7: Antifungal effect of Lactobacillus sp. Trichophyton and Candida were used as fungi. Fermented soy milk containing Shirasu genus was added with 100g of Trichophyton or Candida. 7 Contains 0.1 particles / mL The bacteria solution was inoculated into the sample at 25°C and the viable cell count was measured over 24 hours. 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 the bacterial solution was inoculated into an acid buffer solution, and the viable cell count of the inoculated bacteria was measured over time at 25°C. The measurement was performed for 24 hours. As a result, as shown in FIG. 11, the soy milk fermented liquid containing Lactobacillus sp. reduced the number of tinea and candida species present within 24 hours.

[0108] Example 8: Antiviral effect of Lactobacillus The culture medium of influenza virus type A (H1N1) was used as the enveloped virus. In addition, as a non-enveloped virus, norovirus (feline calicivirus) The virus culture solution was serially diluted 10-fold with purified water. , 50% Tissue Culture Infectious Dose (TCID50:50% Tissue Culture In According to the Infectious Dose, soy milk containing Lactobacillus prepared in Example 3 was The antiviral test was carried out at room temperature using the fermentation liquid. The study was carried out in

[0109] As a result, as shown in Figure 12, the soy milk fermented liquid containing Lactobacillus was able to In addition, as shown in FIG. 13, lactobacillus casei was found to reduce the infectivity of influenza virus. Fermented soy milk containing Russus spp. reduced the infectivity of norovirus within 24 hours.

[0110] Example 9: Anti-Trichophyton Effect of Lactobacillus sp. The non-heat-treated mugwort fermentation liquid obtained in Example 1 was spray-dried to obtain Lactobacillus sp. The dried cells were mixed with water and diluted with water so that the dried cells amounted to 10 parts by weight. The Lactobacillus suspension according to Example 9 was obtained by suspending the Lactobacillus in lycerol. The suspension was added to the tinea fungus and the colony forming units (CFU) of the tinea fungus were counted. 14, a suspension of Lactobacillus killed Trichophyton fungi within 24 hours.

[0111] (Example 10: Effect of Lactobacillus on promoting type I collagen and HSP47 production) Normal human dermal fibroblasts were cultured in a culture vessel until confluency using DMEM medium (+5% FBS). After reaching confluence, the medium was removed from the incubator and the cells were incubated until they reached a confluent state. , culture in DMEM (0% FBS) containing 600 μmol / L hydrogen peroxide (HO). The cells were then cultured at 37°C for 1 hour. After 1 hour of culture, the cells were then cultured in H2O2-containing DMEM (0 % FBS) was removed from the culture vessel, and DMEM medium (+10% FBS) was added to the culture vessel. This procedure was repeated for four days, after which the cells were cultured in DMEM (10% FBS) for an additional three days. The resulting cells were used as senescence-inducing treated cells.

[0112] The induction of senescence in cells was confirmed by the senescence marker senescence-associated Confirmed by ciated beta-galactosidase (SA-β-Gal) staining. I acknowledged.

[0113] Senescence-inducing cells were cultured at 5.0 × 10 4 cel The cells were seeded in a 48-well plate at a cell density of 1 1 / well. 24 hours after seeding, the medium was The mugwort fermentation liquid prepared in Example 1 was used at concentrations of 0.0% and 10.0% without heat treatment. DMEM medium (+0.5% FBS), prepared in Example 2 at concentrations of 1.0% and 10.0% DMEM medium (+0.5% FBS) containing unheat-treated Angelica keiskei fermentation liquid, 25 μl DMEM medium (+0.5% FBS) containing vitamin C magnesium phosphate in mol / L, DMEM medium (+0.5% FBS) containing 25 μmol / L vitamin C, and DME After culturing the cells for 48 hours, the medium was replaced with M medium (+0.5% FBS). The medium was then collected. After washing the cells with PBS(-), the cells were trypsinized and The cells were then collected from the plate. The collected cells were disrupted by ultrasonication 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 collected medium was measured by ELISA (Anti-Human Collagen Immunosorbent Assay). The results were quantified using a direct method using agen Type I antibody (Rabbit). As shown in FIG. 15, the medium containing vitamin C magnesium phosphate or vitamin C (positive control) It was shown that culturing cells in the presence of acetylcholine (control) promoted the production of type I collagen. In addition, when cells were cultured in a medium containing mugwort fermentation liquid and Angelica keiskei fermentation liquid, It was also shown that type I collagen production was promoted.

[0115] In addition, HSP47 in the supernatant of the cell lysate was measured using a commercially available ELISA kit (Abcam). As a result, as shown in FIG. 16, the cells were cultured in a medium containing the fermented solution of Angelica keiskei. It was shown that when the cells were cultured, the production of HSP47 was promoted.

[0116] Example 11: Anti-aging effects of Lactobacillus Normal human dermal fibroblasts were cultured in DMEM medium (+5% FBS) at 5.0 × 10 5 c The cells were seeded onto a 6-well plate at a cell density of 1000 cells / well, and cultured for 24 hours.

[0117] Remove the medium from each well and replace with DM containing 600 μmol / L hydrogen peroxide (HO). EM (0% FBS) was added to the wells, and the cells were cultured at 37°C for 1 hour to induce senescence in the cells. After 1 hour of culture, the H2O2-containing DMEM (0% FBS) was removed from the wells, and the Contains 1.0% mugwort fermentation liquid containing Lactobacillus spp. prepared in 1 at a concentration of 5.0 g / L DMEM medium (+10% FBS) for the preparation of Lactobacillus sp. DMEM medium (+10% FBS) containing 1.0% of the fermented solution of Angelica keiskei (Angelica keiskei) at a concentration of / L, As a control, we used D containing 10 μmol / L of resveratrol, which has antioxidant properties. MEM medium (+10% FBS) and DMEM medium (+10% FBS) as a negative control. BS) was added to the wells. These operations were repeated for 4 days.

[0118] Then, the mugwort fermentation solution containing Lactobacillus spp. prepared in Example 1 at a concentration of 5.0 g / L was used. DMEM medium (+10% FBS) containing 1.0% of the lactobacillus acidophilus extract prepared in Example 2 DMEM medium (+1 0% FBS), and 10 μmol of resveratrol, which has antioxidant properties, was used as a positive control. l / L containing DMEM medium (+10% FBS), and DMEM as a negative control Culture medium (+10% FBS) was added to each well and the cells were cultured for 3 days.

[0119] Then, the cells cultured under each condition were diluted to 5.0 × 10 4 Cells / well The cells were seeded in a 48-well plate at 100% cell density and cultured for 24 hours. Then, the cells were incubated with 3% The wells were then fixed with PBS containing 1 mg / mL 5-methylaldehyde. bromo-4-chloro-3-indolyl-D-galactoside(X -Gal), and the mixture was left to stand for 12 to 16 hours. We performed microscopic observations and identified senescence-associated markers Beta-galactosidase (SA-β-Gal) staining was observed.

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

[0121] (Example 12: HSP70 production promoting effect of Lactobacillus genus) Three-dimensional cultured epidermal model (SkinEthic RHE:19RHE 008, EPIS KIN Co., Ltd.) and growth medium (Growth Medium: 19SGM 005, EPIS After acclimation, the epidermal cells were cultured overnight in a 6-well plate containing 1 mL of growth medium. The Lactobacillus sp. prepared in Example 1 was added to the stratum corneum side of the epidermis model at 5.0 g / ml. 50 μL of mugwort fermentation liquid containing 50 μL of Lactobacillus spp. prepared in Example 2, and 5. 50 μL of the Angelica keiskei fermentation broth containing 0 g / L of Angelica keiskei fermentation broth was applied to each of the plants.

[0122] After culturing the epidermis model for 24 hours, the fermentation liquid was removed and the epidermis model was washed with PBS(-). The viability of the epidermis model was evaluated using the Alamar Blue method. AlamarBlue Cell Viability Reagent (registered trademark) Maintenance medium containing 100% ethanol (registered trademark, Invitrogen) was dispensed into a 24-well plate. The epidermis model was transferred to a plate and cultured for 2 hours, after which the fluorescence intensity of the culture supernatant was measured. The cell viability was calculated as a function of the fluorescence intensity of the control group, in which PBS(-) was applied instead of the fermentation medium. The results were calculated as an index (%) of the number of cases. As a result, as shown in FIG. 20, the mugwort fermentation liquid or the Angelica keiskei fermentation liquid No significant decrease in cell viability was observed due to the application of

[0123] After measuring the fluorescence intensity, the epidermis model was immersed in PBS and crushed with a sample crusher (Tissue The epidermis model was disrupted using a Lyser. The cell lysate was centrifuged at 15,000 rpm. The supernatant was collected and the HSP70 in the collected solution was analyzed using a commercially available ELISA kit (Enzo The results were quantified using the Student t As a result, as shown in FIG. 21, the mugwort fermentation liquid and the light Application of fermented juice of Japanese leaves significantly increased the production of HSP70.

[0124] The above-described embodiments and examples are intended to facilitate understanding of the present invention. The present invention is not intended to be interpreted as being limited to the above. , modifications / improvements may be made, and the present invention also includes equivalents thereof. Any modifications to the embodiments and examples made by a person skilled in the art will be included as long as they include the features of the present invention. For example, the elements of each embodiment and example are included in the scope of the present invention. The present invention is not limited to the above and may be modified as appropriate. The examples are merely examples, and partial substitution or combination of the configurations shown in different embodiments is possible. Needless to say, these are also included within the scope of the present invention as long as they include the features of the present invention. .

Claims

1. The genus Lactobacillus is included, which is derived from mugwort or angelica. Heat shock protein gene expression regulator.

2. The heat shock protein gene consists of the HSPA1A gene and the HSPB1 gene. At least one selected from the group consisting of HSPA1A gene and HSPB1 gene The heat shock receptor according to claim 1, which promotes the expression of at least one gene selected from the group consisting of: Protein gene expression regulator.

3. Ceramidase gene, lipid synthesis enzyme gene, lysosomal hydrolase gene, titer junction biosynthesis factor genes, and intercellular adhesion factor genes. The expression of at least one heat shock protein gene according to claim 1 or 2 is regulated. Expression regulators.

4. The ceramidase gene is the ASAH1 gene, and the expression of the ASAH1 gene is inhibited. 、 The lipid synthesis enzyme gene is a DGAT1 gene, and the expression of the DGAT1 gene is promoted. 、 The lysosomal hydrolase gene is the GBA gene, and the expression of the GBA gene is promoted. Proceed, The tight junction biosynthesis factor gene is a CLDN1 gene and an OCLN gene. At least one selected from the group consisting of the CLDN1 gene and the OCLN gene Promoting the expression of at least one selected from the group consisting of The intercellular adhesion molecule genes are ITGA2 gene, CDH1 gene, and CD44 gene. At least one selected from the group consisting of ITGA2 gene, CDH1 gene, and CD44 gene, The heat shock protein gene expression regulator according to claim 3 .

5. The heat shock protein according to claim 1 or 2, which regulates the expression of antimicrobial molecule genes. Gene expression regulators.

6. The antimicrobial molecule gene is a TLR2 gene, a DEFB1 gene, a DEFB4A gene, and DEFB103A gene, 2 genes, DEFB1 gene, DEFB4A gene, and DEFB103A gene. The heat shock protein according to claim 5, which promotes the expression of at least one selected from the group consisting of Protein gene expression regulator.

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

8. The sirtuin gene is a SIRT4 gene, and promotes the expression of the SIRT4 gene. 、 The telomerase gene is selected from the group consisting of a TERT gene and a TERC gene. At least one of the genes is selected from the group consisting of the TERT gene and the TERC gene. and promoting the expression of at least one of The heat shock protein gene expression regulator according to claim 7 .

9. The heat shock protein according to claim 1 or 2, which regulates the expression of an energy metabolism factor gene. Protein gene expression regulator.

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

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

12. The hyaluronic acid biosynthesis factor genes are HAS1 gene, HAS2 gene, and HAS At least one selected from the group consisting of HAS1 gene, HAS2 gene, and promoting the expression of at least one gene selected from the group consisting of the HAS3 gene, The hyaluronic acid decomposition factor gene is a group consisting of HYAL2 gene and CEMIP gene. At least one selected from the group consisting of the HYAL2 gene and the CEMIP gene. suppressing the expression of at least one selected from the group The heat shock protein gene expression regulator according to claim 11.

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

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

15. The heat shock protein gene of claim 1 or 2, which promotes production of type I collagen. Child expression regulator.

16. The Lactobacillus genus derived from the angelica tree is included, and the heat shock resistance The heat shock protein gene of claim 1 or 2, which promotes the production of protein 47. Child expression regulator.

17. 17. The method according to claim 1, further comprising the step of providing a fermented liquid derived from said mugwort or angelica. A heat shock protein gene expression regulator as described in claim 1.

18. The Lactobacillus species is eri species, buchneri species, harbinensis species, vini species, and nage Any one of claims 1 to 17, which is at least one selected from the group consisting of lii species. A heat shock protein gene expression regulator according to claim 1.

19. The heat treatment method according to any one of claims 1 to 18, wherein the Lactobacillus spp. is killed. Regulator of protein gene expression.

20. 20. The method of claim 1, wherein the Lactobacillus is heat treated. Regulators of heat shock protein gene expression.

21. The lactobacillus strain according to any one of claims 1 to 20, wherein the lactobacillus strain is a dried cell product. Heat shock protein gene expression regulator.

22. The heat shock protein gene expression regulator according to any one of claims 1 to 21, A medicine that can be used.

23. 23. A pharmaceutical product according to claim 22 which is an anti-wrinkle pharmaceutical product.

24. 23. The pharmaceutical product of claim 22 which is an anti-aging pharmaceutical product.

25. The heat shock protein gene expression regulator according to any one of claims 1 to 21, Cosmetics that can be used.

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

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

28. Obtaining Lactobacillus from mugwort or angelica A method for producing a heat shock protein gene expression regulator comprising the steps of:

29. The method according to claim 28, further comprising fermenting the mugwort or Angelica keiskei to obtain a fermented liquid. A method for producing a regulator of heat shock protein gene expression.

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