Hair growth stimulant, hair papilla cell proliferation promoter, and biomolecule expression promoter

Abstract

To provide a hair tonic, a hair papilla cell proliferation promoter and a biomolecule expression promoter.SOLUTION: Provided are a hair tonic, a hair papilla cell proliferation promoter, a WINT5A expression promoter, a vascular endothelial growth factor (VEGF) expression promoter, a fibroblast growth factor-7 (FGF-7) expression promoter, a tissue non-specific alkaline phosphatase (ALPL) expression promoter, a versican expression promoter, a tenascin C expression promoter, a chondroitin sulfate proteoglycan 4 (CSPG4) expression promoter, and a fibronectin expression promoter, which contain a fermentation product of extract from Calendula, extract from Fallopia and / or a fermentation product of extract from Fallopia as an active component. A hair restoration effect can be obtained, and symptoms such as thinning hair and hair loss can be prevented, improved, or treated.SELECTED DRAWING: Figure 1

Description

【Technical Field】 【0001】 The present invention relates to a hair growth agent, a hair papilla cell growth promoter, and a biomolecule expression promoter. More specifically, it relates to a hair growth agent, a hair papilla cell growth promoter, a WINT5A expression promoter, a vascular endothelial growth factor (VEGF) expression promoter, a fibroblast growth factor-7 (FGF-7) expression promoter, a tissue non-specific alkaline phosphatase (ALPL) expression promoter, a versican expression promoter, a tenascin C expression promoter, a chondroitin sulfate proteoglycan 4 (CSPG4) expression promoter, and a fibronectin expression promoter, which contain as an active ingredient a fermented product of an extract of the genus Calendula, an extract of the genus Fallopia, and / or a fermented product of an extract of the genus Fallopia. 【Background Art】 【0002】 Hair plays an important role in maintaining life, such as maintaining body temperature and protecting the body surface. In humans, it is distributed over the entire skin except for the palms, soles, and part of the genital area. Hair grows in cycles consisting of growth, regression, and resting phases (for human scalp hair, one cycle is 2 to 6 years). The average number of scalp hairs in an adult human is 100,000 to 150,000 per person. If there are no symptoms of thinning or hair loss, 85 to 90% are in the growth phase, and 50 to 100 scalp hairs fall out per day during the resting phase. However, hair growth maintains the density almost constant. 【0003】 Hair is produced in skin appendages called hair follicles. The structure of a hair follicle is complex, with the hair shaft (the part commonly referred to as hair) at its center, surrounded by the inner root sheath (IRS), and then enclosed on the outermost edge by the outer root sheath (ORS). In the growth phase, the lower part of the hair follicle is a swollen, spherical shape called the hair bulb. The hair bulb contains the dermal papilla, a mesenchymal tissue, at its center. The dermal papilla is composed of fibroblast-like dermal papilla cells, capillaries, and intercellular matrix. The rapidly dividing epithelial cell area adjacent to the dermal papilla is called the hair matrix matrix (hair matrix base), and the cells that make it up are called hair matrix cells. In the growth phase, hair matrix cells proliferate and differentiate, causing the hair to elongate. In the regression phase, apoptosis occurs in the lower tissue of the hair follicle, including the hair matrix, stopping hair growth, and the hair follicle, which had extended deep into the dermis, begins to regress. During the resting phase, the hair follicle shortens to near the epidermis and takes on a club-like shape called a club hair. Macrophages in the dermal papilla engulf melanin pigment and cell fragments during this period. When the growth phase begins again, the hair matrix cells begin to divide, producing new hair, which pushes the club hair out of its place. Generally, hair thickness is proportional to the size of the hair follicle, and hair length is proportional to the duration of the growth phase. Close interaction between the hair matrix and the dermal papilla cells that support it is essential for the hair cycle, and if there is an abnormality in this regulation, problems will arise with hair thickness, length, shape (such as wavy hair), and color. 【0004】 On the other hand, in recent years, due to various factors such as increased stress and changes in diet, the number of men and women suffering from thinning hair (a condition in which hair becomes thinner and shorter) and hair loss (hair loss) has been increasing, and the demand for hair growth products is on the rise. In response to such social demands, various hair growth products have been developed. For example, Patent Document 1 discloses a hair growth product in which one or more plant extracts selected from the group consisting of Phoenixwood, White Eyebrow Grass, and False Hawk's Claw are used as active ingredients. [Prior art documents] [Patent Documents] 【0005】 [Patent Document 1] Patent No. 5676837 [Overview of the Initiative] [Problems that the invention aims to solve] 【0006】 However, it cannot be said that there is currently a supply of hair growth products that fully satisfy the demands of consumers. The present invention has been made to solve this problem and aims to provide a hair growth product, a hair papilla cell proliferation promoter, a WINT5A expression promoter, a VEGF expression promoter, an FGF-7 expression promoter, an ALPL expression promoter, a versican expression promoter, a tenascin C expression promoter, a CSPG4 expression promoter, and a fibronectin expression promoter, all of which contain a fermented extract of Calendula, an extract of Freckles, and / or a fermented extract of Freckles as active ingredients. [Means for solving the problem] 【0007】 As a result of diligent research, the inventors have discovered that fermented extracts of Calendula, Freckles, and Freckles promote the proliferation of hair papilla cells. Furthermore, they have found that fermented extracts of Calendula, Freckles, and Freckles promote the expression of a wide range of biomolecules involved in hair growth. Based on these findings, the inventors have completed the following inventions. 【0008】 (1) The hair growth agent according to the present invention comprises one or more of the following (a) to (c) as an active ingredient: (a) a fermented extract of Calendula, (b) an extract of Freckles, (c) a fermented extract of Freckles. 【0009】 (2) The hair papilla cell proliferation promoter according to the present invention comprises one or more of the following (a) to (c) as an active ingredient: (a) a fermented extract of Calendula, (b) an extract of Freckles, (c) a fermented extract of Freckles. 【0010】 (3) The WINT5A expression promoter according to the present invention comprises one or more of the following (a) to (c) as an active ingredient: (a) a fermented extract of Calendula, (b) an extract of Frostyle, (c) a fermented extract of Frostyle. 【0011】 (4) The VEGF expression promoter according to the present invention comprises one or more of the following (a) to (c) as an active ingredient: (a) a fermented extract of Calendula, (b) an extract of Frostyle, (c) a fermented extract of Frostyle. 【0012】 (5) The FGF-7 expression promoter according to the present invention comprises one or more of the following (a) to (c) as an active ingredient: (a) a fermented extract of Calendula, (b) an extract of Ilex serrata, (c) a fermented extract of Ilex serrata. 【0013】 (6) The ALPL expression promoter according to the present invention comprises the following as an active ingredient: (a) a fermented product of Calendula extract, or (b) an extract of Freckles. 【0014】 (7) The versican expression promoter according to the present invention comprises the following as an active ingredient: (a) a fermented product of Calendula extract, or (b) an extract of Freckles. 【0015】 (8) The tenascin C expression promoter according to the present invention comprises one or more of the following (a) to (c) as an active ingredient: (a) a fermented extract of Calendula, (b) an extract of Frostyle, (c) a fermented extract of Frostyle. 【0016】 (9) The CSPG4 expression promoter according to the present invention comprises the following as an active ingredient: (a) a fermented product of Calendula extract, or (b) an extract of Freckles. 【0017】 (10) The fibronectin expression promoter according to the present invention comprises the following as an active ingredient: (a) a fermented product of Calendula extract, or (b) an extract of Freckles. 【0018】 (11) In the agent according to the present invention, the fermented product may be a fermented product obtained by fermenting with lactic acid bacteria or yeast. 【0019】 (12) In the agent according to the present invention, the lactic acid bacteria may be Lactobacillus plantarum. 【0020】 (13) In the agent according to the present invention, the genus Crocus may be saffron crocus. 【0021】 (14) In the agent according to the present invention, the genus Campanula may be Japanese bellflower. 【Advantages of the Invention】 【0022】 According to the present invention, hair growth effects such as increasing hair length, increasing hair density, or thickening hair can be obtained. Therefore, symptoms of hair loss or thinning can be prevented, improved, or treated. 【0023】 Hair papilla cells produce many cell growth factors (such as insulin-like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), VEGF, FGF, etc.) and are deeply involved in the division and differentiation of hair matrix cells. In addition, the signal for the transition from the telogen phase to the anagen phase of the hair cycle is also emitted from hair papilla cells (Norio Katsura, The main role in hair growth induction is hair papilla cells? hair follicle stem cells?, [online], broadcast on August 25, 2011, Radio Nikkei, Maruho Dermatology Seminar, [searched on May 18, 2020], Internet <URL: http: / / medical.radionikkei.jp / maruho_hifuka_pdf / maruho_hifuka-110825.pdf>). As is clear from these facts, hair papilla cells play an important role in hair growth. According to the present invention, the proliferation of such hair papilla cells can be promoted, and thereby a hair growth effect can be obtained. 【0024】 WINT5A (Wnt5A) is a protein belonging to the Wnt family. The Wnt family consists of secretory signaling molecules involved in intercellular communication, comprising 300-400 lipid-modified amino acids. In addition to being involved in morphogenesis during embryonic development, WINT5A is known to promote insulin secretion (Japanese Patent Publication No. 2005-220022) and suppress apoptosis of dermal papilla cells (Japanese Patent Publication No. 2008-133233). Therefore, if WINT5A expression can be promoted in vivo, it is thought to be effective in the prevention and treatment of diabetes, impaired glucose tolerance, insulin resistance, etc., as well as in hair growth. According to the present invention, it is possible to promote the expression of such useful WINT5A. The present invention can be used in all applications where promoting WINT5A production is significant. 【0025】 VEGF is a 34-46 kDa glycoprotein that promotes the proliferation, migration, and differentiation of vascular endothelial cells, enhances the permeability of microvessels, and is also involved in the activation of monocytes and macrophages. VEGF is produced in various cells in the body (e.g., pituitary cells, smooth muscle cells, macrophages, alveolar epithelial cells, hepatocytes, hair follicle ORS cells, and dermal papilla cells). Inhibition of VEGF production in hair follicles leads to a delay in the growth phase of the hair cycle and a reduction in hair follicle size (J. Clin. Invest., 2001, Vol. 107, p. 409-411), indicating that VEGF plays an important role in hair follicle regeneration and development (Patent No. 5676837). Furthermore, in addition to its angiogenesis effect, VEGF has also been reported to autocrinely proliferate dermal papilla cells (Lachger S, Moukadiri H, Jonca F, Charveron M, Bouhaddioui N, Vascular endothelial growth factor is an autocrine growth factor for hair dermal papilla cells. J Invest Dermatol 106, 17-23, 1996). Therefore, it is believed that promoting VEGF expression in vivo would be effective in promoting angiogenesis, hair follicle regeneration and development, and thus promoting hair growth. According to the present invention, the expression of such useful VEGF can be promoted. The present invention can be used in all applications where promoting VEGF production is significant. 【0026】 FGF-7 is a 17-30 kDa protein belonging to the fibroblast growth factor (FGF) family and is also called keratinocyte growth factor (KGF). FGF-7 mainly exhibits a growth-promoting effect specifically on epithelial cells (keratinocytes) and is involved in morphogenesis, angiogenesis, and wound healing. Also, studies using mouse and rat homologs have reported its involvement in epithelial tissue morphogenesis, re-epithelialization of wounds, angiogenesis, hair growth, etc. (NCBI, GenBank, Homo sapiens fibroblast growth factor 7 (FGF7), mRNA, NCBI Reference Sequence: NM_002009.4, Summary, [online], [searched on May 18, 2020], Internet <URL: https: / / www.ncbi.nlm.nih.gov / nuccore / NM_002009>). From these facts, if the expression of FGF-7 can be promoted in a living body, it is considered effective for the proliferation of desired epithelial cells, tissue repair, and the promotion of hair follicle cell proliferation, i.e., hair growth. According to the present invention, the expression of such a useful FGF-7 can be promoted. The present invention can be used for all applications that are meaningful in promoting the production of FGF-7. 【0027】 Alkaline phosphatase (ALP; EC 3.1.3.1) is an enzyme that hydrolyzes phosphate monoester bonds in alkaline conditions (pH 9-11) and consists of approximately 500 amino acids. Four types of alkaline phosphatases are known: liver / kidney / bone type (tissue-nonspecific), small intestine type, placental type, and germ cell type (placental-like type). Of these, tissue-nonspecific ALP (ALPL) is expressed in a wide range of tissues and cells, including the liver, bone, kidney, testes, fibroblasts, and macrophages (Yoko Ishida et al., Structure and Function of Alkaline Phosphatases, Clinical Chemistry 33, 36-44, 2004). ALPL is involved in the calcification of hard tissues (bone and teeth) and is also considered a dermal papilla marker, known to be specifically expressed in dermal papilla cells during the growth phase. Furthermore, there are reports that dermal papilla cells with high ALPL activity have high hair follicle induction ability. Based on these findings, it is believed that promoting ALPL expression in living organisms would be effective in promoting the calcification of hard tissues such as bones and teeth, and activating hair papilla cells, i.e., promoting hair growth. According to the present invention, it is possible to promote the expression of such useful ALPL. The present invention can be used in all applications where promoting ALPL production is significant. 【0028】 Versican is a large chondroitin sulfate proteoglycan with a magnitude of over 1000 kDa, a component of the extracellular matrix, and is relatively widely distributed in tissues such as blood vessels, brain, skin, and cartilage. Versican is involved in cell adhesion, cell proliferation, migration, and angiogenesis, and plays a major role in tissue morphogenesis and maintenance. Furthermore, versican is specifically expressed in dermal papillae (Kishimoto et al., PNAS, 96, 7336-7341), and it has been reported that adding its metabolite, versicin (DPEAAE), to cultured dermal papilla cells promotes proliferation (Keiko Takada et al., Grant-in-Aid for Scientific Research Research Results Report (2014), Project Number: 25861705, 2015). From these findings, it is thought that promoting versican expression in vivo would be effective in regenerative medicine, wound healing, and promoting the proliferation of dermal papilla cells, i.e., hair growth. According to the present invention, it is possible to promote the expression of such useful versican. This invention can be used in all applications where promoting versican production is significant. 【0029】 Tenascin C is an extracellular matrix glycoprotein. Its monomer has a weight of 200-400 kKa and it is usually found in tissues as a hexamer. During fetal development, tenascin C is expressed in the nervous, muscular, and vascular systems and is involved in morphogenesis. In adults, however, it is transiently expressed in limited areas during wound (inflammation) healing and tissue regeneration. It is also observed in hair follicles during the growth phase (International Publication No. 2016 / 079912). Therefore, promoting tenascin C expression in vivo is considered effective for regenerative medicine, wound healing, and promoting hair follicle growth, i.e., hair growth. According to the present invention, the expression of such useful tenascin C can be promoted. The present invention can be used in all applications where promoting tenascin C production is significant. 【0030】 Chondroitin sulfate proteoglycan 4 (CSPG4), also known as NG2 (Neuron-gial angigen 2), is a transmembrane proteoglycan and a large molecule consisting of a core protein of approximately 300 kDa to which chondroitin sulfate is bound. It is expressed in a wide range of cells in the body, including tumor cells, central nervous system progenitor cells (NG2 glia), pericytes, mesenchymal stem cells, pigment cells, smooth muscle cells, and macrophages, and has been reported to be involved in cell survival, cell migration, and angiogenesis (Ampofo et al., Cellular & Molecular Biology Letters, 2017, 22, 4, DOI 10.1186 / s11658-017-0035-3). It is also expressed in the bulge of hair follicles and in the area where hair matrix cells are located at the base of the hair follicle. Its expression decreases during the regression phase of the hair cycle, remains unchanged during the resting phase, and then increases to a peak during the growth phase. In other words, there is a correlation between hair regeneration or growth and the expression level of CSPG4 (Yasuhisa Tamura, Kumi Takata, Asami Eguchi, Yosky Kataoka, "In vivo monitoring of hair cycle stages via bioluminescence imaging of hair follicle NG2 cells", Scientific Reports, doi: 10.1038 / s41598-017-18763-3). Therefore, it is considered that promoting CSPG4 expression in vivo would be effective in regenerative medicine and for hair regeneration or growth, i.e., hair restoration. According to the present invention, it is possible to promote the expression of such useful CSPG4. The present invention can be used in all applications where promoting CSPG4 production is significant. 【0031】 Fibronectin is a large glycoprotein whose monomer consists of 2146 to 2325 amino acids. Although there is only one gene, alternative splicing generates dozens of protein isoforms, resulting in four types: plasma fibronectin (present in plasma), cellular fibronectin (present on the cell surface and in the extracellular matrix), fetal fibronectin (present in amniotic fluid), and single-chain fibronectin (existing as a single chain without multimerization). In vitro studies have shown that fibronectin promotes cell adhesion, growth, migration, and differentiation. In vivo, it is thought to play many roles in supporting life functions, including cell adhesion to the extracellular matrix, formation and maintenance of connective tissue, wound healing, and formation and maintenance of tissue and organ morphology and compartments during embryonic development. Fibroblasts and hepatocytes are typical synthetic cells, but almost all cells, including undifferentiated chondrocytes, muscle cells, neutrophils, macrophages, Schwann cells, keratinocytes, and epithelial cells, synthesize and secrete fibronectin. Furthermore, fibronectin is present in body fluids and in the connective tissue and basement membrane of almost all organs, including the kidneys, brain, muscles, and cartilage. In hair follicles, it is distributed throughout the connective tissue root sheath, but fibronectin in the dermal papilla disappears during the regression and resting phases and is strongly expressed in the lower part of the hair tissue during the early growth phase (Masaaki Ito, Histochemistry of Hair Tissue, Juntendo Medical Journal 37(4), 523-534, 1992). From these findings, it is thought that promoting fibronectin expression in the body would be effective in regenerative medicine, wound healing, and promoting the hair follicle growth phase, i.e., hair growth. According to the present invention, it is possible to promote the expression of such useful fibronectin. The present invention can be used in all applications where promoting fibronectin production is significant. [Brief explanation of the drawing] 【0032】 [Figure 1] This bar graph shows the rate of cell proliferation promotion in hair papilla cells cultured in the presence of various plant extracts. [Figure 2] This bar graph shows the rate of cell proliferation promotion in hair papilla cells cultured in the presence of various plant extracts. [Figure 3]This figure shows the expression ratio of Wint5A in hair papilla cells cultured in the presence of various plant extracts. [Figure 4] This figure shows the expression ratio of Wint5A in dermal papilla cells cultured in the presence of calendula extract ferment or adenosine. [Figure 5] This figure shows the expression ratio of the VEGF gene in hair papilla cells cultured in the presence of various plant extracts. [Figure 6] This figure shows the expression ratio of the VEGF gene in dermal papilla cells cultured in the presence of calendula extract ferment or ginseng root extract. [Figure 7] This figure shows the expression ratio of the FGF-7 gene in hair papilla cells cultured in the presence of various plant extracts. [Figure 8] This figure shows the expression ratio of the FGF-7 gene in dermal papilla cells cultured in the presence of fermented or unfermented calendula extract. [Figure 9] This figure shows the expression ratio of the ALPL gene in hair papilla cells cultured in the presence of Japanese knotweed extract. [Figure 10] This figure shows the expression ratio of the ALPL gene in dermal papilla cells cultured in the presence of fermented calendula extract, unfermented calendula extract, ginseng root extract, or adenosine. [Figure 11] This figure shows the expression ratio of the versican gene in hair papilla cells cultured in the presence of various plant extracts. [Figure 12] This figure shows the expression ratio of the versican gene in dermal papilla cells cultured in the presence of calendula extract ferment or adenosine. [Figure 13] This figure shows the expression ratio of the tenascin C gene in hair papilla cells cultured in the presence of various plant extracts. [Figure 14] This figure shows the expression ratio of the tenascin C gene in dermal papilla cells cultured in the presence of fermented calendula extract, unfermented calendula extract, ginseng root extract, or adenosine. [Figure 15] This figure shows the expression ratio of the CSPG4 gene in hair papilla cells cultured in the presence of various plant extracts. [Figure 16] This figure shows the expression ratio of the CSPG4 gene in dermal papilla cells cultured in the presence of fermented calendula extract, unfermented calendula extract, ginseng root extract, or adenosine. [Figure 17] This figure shows the expression ratio of the fibronectin gene in hair papilla cells cultured in the presence of various plant extracts. [Figure 18] This figure shows the expression ratio of the fibronectin gene in dermal papilla cells cultured in the presence of fermented or unfermented calendula extract. [Modes for carrying out the invention] 【0033】 The present invention will be described in detail below. The hair growth agent, dermal papilla cell proliferation promoter, WINT5A expression promoter, vascular endothelial growth factor (VEGF) expression promoter, fibroblast growth factor-7 (FGF-7) expression promoter, tissue-nonspecific alkaline phosphatase (ALPL) expression promoter, versican expression promoter, tenascin C expression promoter, chondroitin sulfate proteoglycan 4 (CSPG4) expression promoter, and fibronectin expression promoter (hereinafter, these agents may be collectively referred to as "the agent" or any one of them) contains one or more of the following (a) to (c) as active ingredients; (a) Fermented extract of Calendula species, (i) Extract of the genus *Cardamine*, (c) A fermented extract of the genus Pyrus. 【0034】 In this invention, "hair growth" refers to increasing the length of hair, increasing hair density (increasing the amount of hair), making hair thicker, or making hair stronger, and is interchangeable with terms such as "hair regeneration" and "hair nourishment." 【0035】 In the present invention, "promoting the expression" of biomolecules such as WINT5A, VEGF, FGF-7, ALPL, versican, tenascin C, CSPG4, and fibronectin means increasing the transcription level of a gene encoding all or part of the biomolecule, increasing the amount of the biomolecule, or increasing the activity of the biomolecule in any cell, tissue, or organ of a living organism. 【0036】 The genus Calendula refers to plants belonging to the Calendula genus of the Asteraceae family. Examples of plants in the Calendula genus include the common marigold (Calendula officinalis, also known as pot marigold or calendula) and the dwarf marigold (Calendula arvensis, also known as winter marigold or winter marigold). 【0037】 The genus Follopia refers to plants belonging to the genus Follopia in the family Polygonaceae. Examples of plants in the genus Follopia include Japanese knotweed (Follopia sachalinensis, Polygonum sachalinense, Reynoutria sachalinense), Japanese knotweed (Follopia japonica), creeping knotweed (Follopia dumetora), and large-flowered knotweed (Follopia dentatoalata). Some theories also place these plants within the genus Polygonum. Furthermore, the genera Follopia and Japanese knotweed were formerly classified under the genus Polygonum. In other words, in this invention, the genus Follopia is interchangeable with the genera Polygonum and Polygonum. 【0038】 In the present invention, "extract" refers to an extract obtained from all or part of the tissue of a plant (hereinafter sometimes referred to as "plant extract"). The extract can be prepared by immersing the plant in a solvent and dissolving the components contained in the plant into the solvent. Here, the solvent and extraction method can be appropriately selected and used depending on the type and part of the plant, the desired functionality, etc. 【0039】 To illustrate the method of preparing the extract in more detail, one or more parts of a plant selected from the roots, stems, leaves, flower heads, and petals are immersed in a solvent for a certain period of time to prepare an extract. Here, the plant may be used as is, or it may be dried or pulverized. Examples of solvents include water, lower alcohols (ethanol, propanol, etc.), glycols (glycerin, 1,3-butylene glycol, propylene glycol, 1,3-propanediol, etc.), and mixtures of water, lower alcohols, and / or glycols, but there are no particular restrictions as long as the solvent can extract the components contained in the plant. The amount of solvent can be exemplified by 5 to 20 parts by weight of solvent per 1 part by weight of plant. The extraction temperature can be exemplified by 4 to 90°C, and the extraction time can be exemplified by 1 hour to 2 weeks. 【0040】 Calendula extracts can be prepared using the procedure described above, or commercially available products can be used. Examples of commercially available products include Calendula Extract-J (Maruzen Pharmaceutical), Calendula Extract BG-J (Maruzen Pharmaceutical), Falcorex Calendula (Ichimaru Falcos), and Marigold Herbasol Extract BG (Lipoid Kosmetik AG). 【0041】 The extract of the genus Veraherbline can be prepared using the procedure described above, or a commercially available product can be used. Examples of commercially available products include Veraherbline (Unial). 【0042】 In the present invention, a fermented plant extract refers to a culture obtained by culturing microorganisms in a culture medium containing a plant extract, or using the plant extract itself as a culture medium. Examples of microorganisms used to obtain the fermented product include fungi such as yeast, Aspergillus (Aspergillus genus), Acremonium, Trichoderma, Rhizopus, and Monascus, as well as bacteria such as lactic acid bacteria, Penicillium, Bacillus, Acetobacter, and Gluconobacter. 【0043】 Yeast refers to fungi that spend most of their life cycle as single cells and reproduce by budding or fission. Commonly used yeasts such as baker's yeast, sake yeast, wine yeast, and beer yeast can be used. More specifically, examples include the genera Saccharomyces, Shizosaccharomyces, Pichia, Candida, Kluyveromyces, Williopsis, Debaryomyces, Galactomyces, Torulaspora, Rhodotorula, Yarrowia, and Zygosaccharomyces. Examples of the genus Saccharomyces include Saccharomyces cerevisiae, Saccharomyces sake, and Saccharomyces beticus. Examples of the genus Candida include Candida tropicalis, Candida lypolitica, Candida utilis, and Candida sake. 【0044】 Yeast such as baker's yeast, sake yeast, wine yeast, and beer yeast are commercially available and can be used in this invention. In addition, yeast that can be stored for a long period and distributed, such as the standard strain of Saccharomyces cerevisiae (NBRC 10217), can also be used. Furthermore, yeast may be isolated from readily available food products according to known methods (for example, Atsuko Kono et al., Identification and bread-making properties of yeast isolated from raisins, Seinan Jogakuin University Bulletin Vol. 14, pp. 77-82, 2010). 【0045】 Lactic acid bacteria are bacteria that produce lactic acid through metabolism. Examples of lactic acid bacteria include Lactobacillus species such as Lactobacillus plantarum (NBRC 101975), Lactobacillus delbrueckii (NBRC 13953), Lactobacillus brevis (NBRC 3345), and Lactobacillus casei (NBRC 15883); Leuconostoc species such as Leuconostoc mesenteroides (NBRC 110676) and Leuconostoc citreum (NBRC 102476); and Streptococcus faecalis (NBRC 102476). Streptococcus genus lactic acid bacteria such as Streptococcus pyogenes (3989); Enterococcus genus lactic acid bacteria such as Enterococcus casseliflavus (NBRC 3531) and Enterococcus sulfreus (NBRC 100680); Lactococcus genus lactic acid bacteria such as Lactococcus plantarum (NBRC 100936) and Lactococcus rafinolactis (NBRC 100932); Pediococcus damnosus (NBRC 3889), Pediococcus Examples of lactic acid bacteria include those of the genus Pediococcus, such as Pediococcus pentosaceus (NBRC 3182). Among these lactic acid bacteria, Lactobacillus species are preferred from the viewpoint of the effectiveness of the resulting fermented product and ease of handling due to their non-extreme anaerobic nature, with Lactobacillus plantarum and Lactobacillus delbrookii being more preferred. 【0046】 Furthermore, species of the Aspergillus genus that can be used include, for example, Aspergillus oryzae, Aspergillus sojae, Aspergillus awamori, and Aspergillus glaucus, which are commercially available as koji mold. Examples of species that can be used include Acremonium sp. (NBRC 30052) from the genus Acremonium, Penicillium pinophilum (NBRC 33285) from the genus Penicillium, Trichoderma reesei (NBRC 31328) from the genus Trichoderma, and Gluconobacter sp., Gluconobacter frateurii, Gluconobacter cerinus, Gluconobacter oxydans (NBRC 3292) and Gluconobacter albidus from the genus Gluconobacter. 【0047】 Fermented plant extracts can be obtained, for example, by the following method: A plant extract prepared by the above method is inoculated with pre-cultured microorganisms, and a culture is produced by culturing it under conditions favorable for microbial fermentation, with or without the addition of a culture medium. When a culture medium is added, there are no particular restrictions on the medium as long as it can cultivate the microorganisms. 【0048】 For example, when obtaining a fermented product using yeast, the culture medium used for preliminary cultivation or obtaining the fermented product can be appropriately set according to the yeast species and strain used. For example, for Saccharomyces cerevisiae, examples include YM liquid medium (10g glucose, 5g peptone, 3g yeast extract, 3g malt extract, 1L purified water, pH 5.4), YEP medium (20g peptone, 10g yeast extract, 1L purified water, pH 6.5), and YPD medium (20g glucose, 20g peptone, 10g yeast extract, 1L purified water, pH 6.5). The culture temperature depends on the bacterial species and strain used, but examples include approximately 20-40°C and a culture period of 12-14 days. Cultivation is carried out under aerobic conditions, either by standing still or by aeration and / or stirring as needed. The aeration rate can be exemplified by blowing sterile air into the bottom of the fermentation tank at a rate of approximately 1 / 4 to 1 / 2 of the volume of fermentation liquid per minute. The stirring conditions can be exemplified by 100 to 400 revolutions per minute (rpm). 【0049】 For example, when obtaining a fermented product using lactic acid bacteria, the culture medium used for preliminary cultivation or obtaining the fermented product can be MRS medium (10g peptone, 10g beef extract, 5g yeast extract, 20g glucose, 1g Tween80, 2g K2HPO4, 5g sodium acetate, 2g diammonium citrate, 0.2g MgSO4·7H2O, 0.05g MnSO4·nH2O, 1L purified water), which was developed as a medium that shows good growth of all lactic acid bacteria, or a synthetic medium. The composition of the synthetic medium should include a minimum amount of carbon, nitrogen, and phosphorus sources, but vitamin and mineral sources may be added. The culture temperature can be approximately 25-40°C, and the culture period can be approximately 3-50 days. Culturing can be done statically, but shaking culture or aerated culture may be used to shorten the fermentation time, etc. 【0050】 Plant extracts and their fermented products may be purified before use. Purification methods include removing microbial and plant residues by filtration or decantation, followed by heat sterilization. Heat sterilization can be performed by heating at 80-120°C, preferably 90-105°C, for approximately 30-60 minutes. Residue can be removed by filtration using a filter large enough to filter out the microbial or plant residues, or by centrifugation to settle the residue and collecting the supernatant. 【0051】 Plant extracts and their fermented products can be used as is, but may be diluted or concentrated as needed. Furthermore, the extracts and their fermented products may be in liquid form, or in solid form such as powder, granules, or solid matter. 【0052】 This product may be used as is in cosmetics, pharmaceuticals, quasi-drugs, etc., or it may be used as an ingredient in cosmetics, pharmaceuticals, quasi-drugs, etc., in combination with other ingredients. 【0053】 The present invention will be described below based on various examples. However, the technical scope of the present invention is not limited to the features shown in these examples. Furthermore, in these examples, "%" represents mass %((w / w)%) unless otherwise specified. [Examples] 【0054】 <Example 1> Preparation of various plant extracts (1) Calendula extract The flower heads of Calendula officinalis were dried and powdered. This dried powder was immersed in a 50 vol% 1,3-butylene glycol aqueous solution. The solution was then filtered to remove the residue, and the collected filtrate was identified as "Calendula extract." The liquid is yellow to yellowish-brown in color. 【0055】 (2) Fermented product of calendula extract The lactic acid bacteria (Lactobacillus plantarum: NBRC 101975) used was cultured on MRS agar medium (10g peptone, 10g beef extract, 5g yeast extract, 20g glucose, 1g Tween80, 2g K2HPO4, 5g sodium acetate, 2g diammonium citrate, 0.2g MgSO4·7H2O, 0.05g MnSO4·nH2O, 1L purified water). 【0056】 Calendula petals were powdered. 3g of the powdered petals were immersed in 100g of purified water, and hot water extraction was performed at 85°C for 1 hour, after which it was allowed to cool to 37°C. A small amount of lactic acid bacteria was added to the resulting hot water extract and cultured statically for 3 days to serve as the starter culture (no components of the storage medium were included). The starter culture was mixed with another hot water extract and cultured statically at 30°C to 37°C for 7 days. After the culture was complete, the petals were filtered out, and the collected filtrate was heat-sterilized at 85°C for 30 minutes. Subsequently, the residue was removed by filtration, and 1,3-butylene glycol was added to a concentration of 30%. The mixture was then passed through a membrane filter to obtain the "calendula extract ferment." 【0057】 (3) Japanese knotweed extract (BG) The underground parts (rhizomes and roots) of Polygonum sachalinense were dried and powdered. 100g of this dried powder was immersed in 900g of a 30% by volume 1,3-butylene glycol aqueous solution and left to stand at room temperature (approximately 20°C) for one week. Subsequently, the supernatant was transferred to a separate container and stored in a refrigerator at 4°C for one week. After that, the residue was removed by filtration, and the collected filtrate was designated as "Polygonum sachalinense extract (BG)". 【0058】 (4) Japanese knotweed extract (ET) The underground parts (rhizomes and roots) of Polygonum sachalinense were dried and powdered. 100g of this dried powder was immersed in 900g of 100% ethanol and left to stand at room temperature (approximately 20°C) for one week. Subsequently, the supernatant was transferred to a separate container and refrigerated at 4°C for one week. After that, the residue was removed by filtration, and the collected filtrate was designated as "Polygonum sachalinense extract (ET)". 【0059】 (5) Yeast fermented product of Japanese knotweed extract The yeast (Saccharomyces cerevisiae: NBRC 10217) used was cultured in YM liquid medium (10g glucose, 5g peptone, 3g yeast extract, 3g malt extract, 1L purified water), and then preserved in YM agar medium (10g glucose, 5g peptone, 3g yeast extract, 3g malt extract, 1L purified water, 15g agar). 【0060】 The underground parts (rhizomes and roots) of Polygonum sachalinense were dried and powdered. 50g of this dried powder was immersed in 950g of purified water, and hot water extraction was performed at 85°C for 1 hour, after which it was allowed to cool to 37°C. A small amount of yeast was added to the resulting aqueous extract and cultured statically for 3 days to use as a starter culture. The starter culture was mixed with another aqueous extract and cultured statically at 30°C to 37°C for 7 days. After the culture was complete, the residue was filtered off, and the collected filtrate was heat-sterilized at 85°C for 30 minutes. Subsequently, the residue was removed by filtration, and 1,3-butylene glycol was added to a concentration of 30%. The mixture was then passed through a membrane filter to obtain the "Polygonum sachalinense extract yeast ferment." 【0061】 (6) Lactic acid fermented product of Japanese knotweed extract The underground parts (rhizomes and roots) of Japanese knotweed were dried and powdered. 50g of this dried powder was immersed in 950g of purified water, and after hot water extraction at 85°C for 1 hour, it was allowed to cool to 37°C. A small amount of lactic acid bacteria (as described in Example 1(2)) was added to the resulting aqueous extract and cultured statically for 3 days to serve as the starter culture (components of the storage medium were not included). The starter culture was mixed with another aqueous extract and cultured statically at 30°C to 37°C for 7 days. After the culture was complete, the residue was filtered off, and the collected filtrate was heat-sterilized at 85°C for 30 minutes. Subsequently, the residue was removed by filtration, and 1,3-butylene glycol was added to a concentration of 30%. The mixture was then passed through a membrane filter to obtain the "Japanese knotweed extract lactic acid bacteria fermented product". 【0062】 <Example 2> Evaluation of the effect of promoting the proliferation of hair papilla cells Test media were prepared by adding the plant extracts from Examples 1(1) to (6) to DMEM (Dulbecco's modified minimal essential medium) containing 1% calf serum (FBS) at concentrations of 0.5%, 1.0%, 1.5%, 2.0%, or 3.0%. Using the 1% FBS-containing DMEM, normal human dermal papilla cells (Takara Bio Inc.) were divided into 2.0 × 10⁶ cells. 4 The cells were seeded in a 96-well plate to a cell density of one cell per well and cultured for 24 hours. Then, the culture medium was replaced with 1% FBS-containing DMEM (control medium) without the test medium or plant extract, and cultured for a further 48 hours. 【0063】 The cell proliferation-promoting effect was measured using the MTT assay. After the culture period, the culture medium was replaced with 1% FBS-containing DMEM containing 0.4 mg / mL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and the cells were cultured for another 2 hours. The medium was removed, and 2-propanol was added to extract the generated formazan. The absorbance of the extract at 550 nm was measured and this was defined as the amount of formazan produced. 【0064】 In general, the amount of formazan produced is considered to have a positive correlation with the number of viable cells. Therefore, the ratio of the amount of formazan produced in cells cultured in the test medium (A) to the amount of formazan produced in cells cultured in the control medium (B) can be used as an indicator of the change in the number of cells due to the action of the test medium. Based on the measurement results, the cell proliferation promotion rate (%) was calculated using the following formula 1. That is, if the cell proliferation promotion rate is significantly greater than 100%, it can be concluded that the proliferation of hair papilla cells was promoted by the action of the plant extract added to the test medium. Equation 1: Cell proliferation promotion rate (%) = A / B × 100 A; Amount of formazan produced in cells cultured in test medium B; Amount of formazan produced in cells cultured in control medium The cell proliferation promotion rate was calculated by taking four similar tests and determining the average value. Furthermore, a Student's t-test was used to determine the significance of the results compared to the control medium sample, with a p-value < 0.05 indicating a statistically significant difference. 【0065】 Table 1 and Figure 1 show the results for the following concentrations of plant extracts in the test medium: calendula extract 1.0% and 2.0%, calendula extract ferment, Japanese knotweed extract (BG), Japanese knotweed extract yeast ferment, and Japanese knotweed extract lactic acid bacteria ferment, and Japanese knotweed extract (ET) 1.5%, respectively. Table 2 and Figure 2 show the results for the following concentrations in the test medium: calendula extract 1.0% and 2.0%, calendula extract ferment, Japanese knotweed extract (BG), Japanese knotweed extract (ET), Japanese knotweed extract yeast ferment, and Japanese knotweed extract lactic acid bacteria ferment, and Japanese knotweed extract (ET) 1.0%, respectively. [Table 1] 【0066】 [Table 2] 【0067】 As shown in Table 1 and Figure 1, calendula extract did not show a significant increase in cell proliferation at either 1.0% or 2.0% concentrations in the test medium. In contrast, calendula extract ferment, Japanese knotweed extract (BG), Japanese knotweed extract yeast ferment, and Japanese knotweed extract lactic acid bacteria ferment showed a significant increase in cell proliferation at a concentration of 1.5% in the test medium. Japanese knotweed extract (ET) also showed a significant increase in cell proliferation at a concentration of 0.5% in the test medium. 【0068】 Similarly, as shown in Table 2 and Figure 2, calendula extract ferment, Japanese knotweed extract (BG), and Japanese knotweed extract yeast ferment showed a significant increase in cell proliferation even at a concentration of 3.0% in the test medium. Japanese knotweed extract (ET) also showed a significant increase in cell proliferation even at a concentration of 1.0% in the test medium. 【0069】 These results revealed that fermented calendula extract, knotweed extract, and fermented knotweed extract can promote the proliferation of hair papilla cells. 【0070】 <Example 3> Evaluation of the WINT5A expression-promoting effect (1) Evaluation of various plant extracts The plant extracts from Examples 1(2) to 1(6) were evaluated by real-time PCR to determine whether they altered the expression level of Wint5A (NM_003392.4; Homo sapiens Wnt family member 5A (WINT5A), transcript variant 1, mRNA). 【0071】 First, human dermal papilla cells (Takara Bio Inc.) were pre-cultured for 18 hours at 37°C under 5% CO2 conditions using dermal papilla cell basic medium (Takara Bio Inc.). Subsequently, plant extracts from Examples 1(2) to (6) were added at concentrations of 3.125 μg / mL, 12.5 μg / mL, 50 μg / mL, or 200 μg / mL, and cultured for 24 hours to serve as the test group. Similarly, cells were cultured for 24 hours without the addition of plant extracts to serve as the control group. 【0072】 After culturing, the cells were thoroughly washed with PBS(-). Total RNA was extracted using NucleoSpin® RNA (Takara Bio Inc.). A portion of the obtained RNA sample was diluted 50-fold, and the RNA concentration (ng / μL) was calculated by measuring the absorbance at 260 nm. cDNA was prepared by reverse transcription reaction by PCR using PrimeScript® RT Master Mix (Takara Bio Inc.) (37°C for 15 minutes, 85°C for 5 seconds). 【0073】 The prepared cDNA was used as a template, and real-time PCR was performed under the following reaction conditions to measure the Ct value (Threshold Cycle value) of the target nucleic acid. Reaction mixture composition: 12.5 μL of SYBRR Premix Ex Taq II (Tli RNaseH Plus) (2X), 1 μL each of forward and reverse primers (10 μM), 1 μL or 2 μL of cDNA, and RNase-free water to make a total volume of 25 μL. Reaction cycle: 1 cycle at 95°C for 10 seconds (initial denaturation), 45 cycles of 5 seconds at 95°C and 30 seconds at 60-65°C, and 1 cycle at 60-95°C at 0.2°C / second. Primer sequence: 《Wint5A》 Forward; 5'-AGCAGCATCAGTCCACAAACACTTA-3' (Sequence ID 1) Reverse; 5'-AGACCTGTGCCTTCGTGCCTA-3'(Sequence ID 2) Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (internal standard) Forward; 5'-TGTGTCCGTCGTGGATCTGA-3' (Sequence ID 3) Reverse; 5'-TTGCTGTTGAAGTCGCAGGAG-3'(Sequence ID 4) 【0074】 The measurement results were corrected using an internal standard Ct value, and then quantified using the ΔΔCt method. The ratio was calculated by setting the expression level of the control group to 1.0, and this was taken as the expression ratio of the target gene (Wint5A). The results are shown in Figure 3. If the expression ratio was 1.1 or higher, it was determined that the expression level of the target gene was higher in the test group than in the control group. 【0075】 As shown in Figure 3, Wint5A expression was higher in the groups treated with calendula extract ferment at concentrations of 3.125 and 12.5 μg / mL, the groups treated with Japanese knotweed extract (ET) at concentrations of 3.125, 12.5, and 50 μg / mL, and the group treated with Japanese knotweed extract yeast ferment at a concentration of 200 μg / mL. In other words, Wint5A expression was higher in cells in the presence of calendula extract ferment, Japanese knotweed extract, or Japanese knotweed extract ferment. From these results, it is clear that calendula extract ferment, Japanese knotweed extract, and Japanese knotweed extract ferment can promote WINT5A expression. 【0076】 (2) Comparative evaluation of calendula extract ferment The WINT5A expression-promoting effect of calendula extract ferment was compared with that of adenosine, a substance known to have hair growth-promoting properties. Specifically, the expression level of Wint5A was evaluated using the calendula extract ferment from Example 1(2) and adenosine (Fujifilm Wako Pure Chemical Industries) instead of the plant extract, using the real-time PCR method described in Example 3(1). However, the concentrations of the test substances added were 3.125 and 12.5 μg / mL. The results are shown in Figure 4. 【0077】 As shown in Figure 4, the expression ratio of Wint5A was higher in the group treated with calendula extract ferment than in the group treated with adenosine, at both concentrations of 3.125 and 12.5 μg / mL. This result clearly indicates that calendula extract ferment is superior to adenosine, a known hair growth ingredient, in promoting WINT5A expression. 【0078】 <Example 4> Evaluation of the effect of promoting the expression of vascular endothelial growth factor (VEGF) (1) Evaluation of various plant extracts The plant extracts from Examples 1(2) to 1(6) were evaluated by real-time PCR as described in Example 3(1) to determine whether they altered the expression level of the VEGF gene (NM_001025366.2; Homo sapiens vascular endothelial growth factor A (VEGFA), transcript variant 1, mRNA). However, instead of the primers used to amplify Wint5A, the VEGF gene amplification primers shown below were used. The results are shown in Figure 5. 《VEGF gene》 Forward; 5'-TCACAGGTACAGGGATGAGGACAC-3' (Sequence No. 5) Reverse; 5'-CAAAGCACAGCAATGTCCTGAAG-3' (Sequence ID 6) 【0079】 As shown in Figure 5, the expression ratio of the VEGF gene was higher in the test groups treated with calendula extract ferment at concentrations of 3.125, 12.5, 50, and 200 μg / mL, Japanese knotweed extract (BG) at concentrations of 3.125, 12.5, and 50 μg / mL, Japanese knotweed extract (ET) at concentrations of 12.5, 50, and 200 μg / mL, and Japanese knotweed extract lactic acid bacteria ferment at concentrations of 3.125 and 12.5 μg / mL. In other words, the expression level of the VEGF gene in cells was higher in the presence of calendula extract ferment, Japanese knotweed extract, or Japanese knotweed extract ferment. From these results, it is clear that calendula extract ferment, Japanese knotweed extract, and Japanese knotweed extract ferment can promote VEGF expression. 【0080】 (2) Comparative evaluation of calendula extract ferment The VEGF expression-promoting effect of calendula extract ferment was compared with that of ginseng root extract, a substance known to have hair growth-promoting properties. Specifically, the calendula extract ferment from Example 1(2) and ginseng root extract (commercially available) were used instead of the plant extract, and the expression level of the VEGF gene was evaluated by the real-time PCR method described in Example 4(1). However, the concentration of the test substance added was set to 50 and 200 μg / mL. The results are shown in Figure 6. 【0081】 As shown in Figure 6, the VEGF gene expression ratio was higher in the test group treated with calendula extract ferment than in the test group treated with ginseng root extract, at both concentrations of 50 and 200 μg / mL. This result clearly indicates that calendula extract ferment is superior to ginseng root extract, a known hair growth ingredient, in promoting VEGF expression. 【0082】 <Example 5> Evaluation of the expression-promoting effect of fibroblast growth factor-7 (FGF-7) (1) Evaluation of various plant extracts The plant extracts from Examples 1(2) to 1(6) were evaluated using the real-time PCR method described in Example 3 to determine whether they altered the expression level of the FGF-7 gene (NM_002009.4; Homo sapiens fibloblast growth factor 7 (FGF7), mRNA). However, instead of the primers used to amplify Wint5A, the following FGF-7 gene amplification primers were used. The results are shown in Figure 7. 《FGF-7 gene》 Forward; 5'-GGATGCAGGCCACTATGACTAAC-3' (Sequence ID 7) Reverse; 5'-AGAGTAGCTGACAACAATGCTGAA-3' (Sequence ID 8) 【0083】 As shown in Figure 7, the expression ratio of the FGF-7 gene was higher in the test groups treated with calendula extract ferment at concentrations of 3.125, 12.5, 50, and 200 μg / mL, Japanese knotweed extract (BG) at concentrations of 3.125, 12.5, 50, and 200 μg / mL, Japanese knotweed extract (ET) at concentrations of 3.125, 12.5, 50, and 200 μg / mL, Japanese knotweed extract yeast ferment at concentrations of 3.125 and 12.5 μg / mL, and Japanese knotweed extract lactic acid bacteria ferment at concentrations of 3.125, 12.5, 50, and 200 μg / mL. In other words, the expression level of the FGF-7 gene in cells was higher in the presence of calendula extract ferment, Japanese knotweed extract, or Japanese knotweed extract ferment. These results revealed that fermented calendula extract, knotweed extract, and fermented knotweed extract can promote FGF-7 expression. 【0084】 (2) Comparative evaluation of calendula extract ferment The FGF-7 expression-promoting effect of fermented calendula extract was compared with that of unfermented calendula extract. Specifically, the expression levels of the FGF-7 gene were evaluated using the real-time PCR method described in Example 5(1) with the calendula extract from Example 1(1) and the fermented calendula extract from Example 1(2). The concentrations of the test substance added were 12.5 and 200 μg / mL. The results are shown in Figure 8. 【0085】 As shown in Figure 8, the expression ratio of the FGF-7 gene was higher in the group treated with calendula extract ferment than in the group treated with calendula extract alone, at both concentrations of 12.5 and 200 μg / mL. This result clearly indicates that calendula extract ferment is superior to unfermented calendula extract in promoting FGF-7 expression. 【0086】 <Example 6> Evaluation of the effect of promoting the expression of tissue-nonspecific alkaline phosphatase (ALPL) (1) Evaluation of Japanese knotweed extract The real-time PCR method described in Example 3 was used to evaluate whether the Japanese knotweed extract (ET) from Example 1(4) altered the expression level of the ALPL gene (NM_000478.6; Homo sapiens alkaline phosphatase, biomineralization associated (ALPL), transcript variant 1, mRNA). However, instead of the primers used to amplify Wint5A, the ALPL gene amplification primers shown below were used. The results are shown in Figure 9. 《ALPL gene》 Forward; 5'-GGACCATTCCCACGTCTTCA-3' (Sequence ID 9) Reverse; 5'-CAGGCCCATTGCCATACA-3' (Sequence ID 10) 【0087】 As shown in Figure 9, the expression ratio of the ALPL gene was higher in the test groups to which Japanese knotweed extract (ET) was added at concentrations of 3.125, 12.5, 50, and 200 μg / mL. In other words, the expression level of the ALPL gene in cells was higher in the presence of Japanese knotweed extract. From these results, it was clear that Japanese knotweed extract can promote the expression of tissue-nonspecific alkaline phosphatase (ALPL). 【0088】 (2) Comparative evaluation of calendula extract ferment The ALPL expression-promoting effect of fermented calendula extract was compared with that of unfermented calendula extract, ginseng root extract, and adenosine. Specifically, the calendula extract from Example 1(1) and the fermented calendula extract from Example 1(2), as well as ginseng root extract (commercially available) and adenosine (Fujifilm Wako Pure Chemical Industries) instead of plant extract, were used to evaluate the expression level of the ALPL gene using the real-time PCR method described in Example 6(1). However, the concentration of the test substance added was 50 μg / mL. The results are shown in Figure 10. 【0089】 As shown in Figure 10, the expression ratio of the ALPL gene was highest in the test group to which calendula extract ferment was added. From these results, it was clear that calendula extract ferment was superior to unfermented calendula extract and to known hair growth ingredients such as ginseng root extract and adenosine in promoting ALPL expression. 【0090】 <Example 7> Evaluation of Versican expression-promoting effect (1) Evaluation of various plant extracts The plant extracts from Examples 1(2) to 1(6) were evaluated using the real-time PCR method described in Example 3 to determine whether they altered the expression level of the versican gene (NM_001126336.2; Homo sapiens versican (VCAN), transcript variant 2, mRNA). However, instead of the primers used to amplify Wint5A, the versican gene amplification primers shown below were used. The results are shown in Figure 11. Versican gene Forward; 5'-GCTGGAAATGGTTTCACTTGCTC-3' (Sequence ID 11) Reverse; 5'-GATCCCATTCGCAGCCTTTAG-3' (Sequence ID 12) 【0091】 As shown in Figure 11, the versican gene expression ratio was higher in the test groups treated with calendula extract ferment at concentrations of 3.125, 12.5, 50, and 200 μg / mL, the test groups treated with Japanese knotweed extract (BG) at concentrations of 12.5, 50, and 200 μg / mL, and the test groups treated with Japanese knotweed extract (ET) at concentrations of 12.5, 50, and 200 μg / mL. In other words, the expression level of the versican gene in cells was higher in the presence of calendula extract ferment or Japanese knotweed extract. From these results, it is clear that calendula extract ferment and Japanese knotweed extract can promote versican expression. 【0092】 (2) Comparative evaluation of calendula extract ferment The versican expression-promoting effect of calendula extract ferment was compared with that of adenosine. Specifically, the calendula extract ferment from Example 1(2) and adenosine (Fujifilm Wako Pure Chemical Industries) were used instead of the plant extract, and the expression level of the versican gene was evaluated by the real-time PCR method described in Example 7(1). The concentrations of the test substances added were 3.125 and 12.5 μg / mL. The results are shown in Figure 12. 【0093】 As shown in Figure 12, the expression ratio of the versican gene was higher in the test group treated with calendula extract ferment than in the test group treated with adenosine, at both concentrations of 3.125 and 12.5 μg / mL. This result clearly shows that calendula extract ferment is superior to adenosine, a known hair growth component, in promoting versican expression. 【0094】 <Example 8> Evaluation of the Tenacin C expression-promoting effect (1) Evaluation of various plant extracts The plant extracts from Examples 1(2) to 1(6) were evaluated using the real-time PCR method described in Example 3 to determine whether they altered the expression level of the tenascin C gene (NM_002160.4; Homo sapiens tenascin C (TNC), mRNA). However, instead of the primers used to amplify Wint5A, the tenascin C gene amplification primers shown below were used. The results are shown in Figure 13. Tenascin C gene Forward; 5'-CTCCCAGTGACAACATCGCAATA-3' (Sequence ID 13) Reverse; 5'-GGATGGCTTCCAATGACACATTTA-3' (Sequence ID 14) 【0095】 As shown in Figure 13, the expression ratio of the tenascin C gene was higher in the test groups treated with calendula extract ferment at a concentration of 200 μg / mL, Japanese knotweed extract (BG) at a concentration of 200 μg / mL, Japanese knotweed extract (ET) at a concentration of 200 μg / mL, and Japanese knotweed extract lactic acid bacteria ferment at a concentration of 200 μg / mL. In other words, the expression level of the tenascin C gene in cells was higher in the presence of calendula extract ferment, Japanese knotweed extract, or Japanese knotweed extract ferment. From these results, it is clear that calendula extract ferment, Japanese knotweed extract, and Japanese knotweed extract ferment can promote the expression of tenascin C. 【0096】 (2) Comparative evaluation of calendula extract ferment The tenascin C expression-promoting effect of calendula extract ferment was compared with that of unfermented calendula extract, ginseng root extract, and adenosine. Specifically, the expression levels of the tenascin C gene were evaluated using the real-time PCR method described in Example 8(1) with the calendula extract from Example 1(1) and the calendula extract ferment from Example 1(2), as well as ginseng root extract (commercially available) and adenosine (Fujifilm Wako Pure Chemical Industries) instead of the plant extract. The concentration of the test substance added was 3.125 μg / mL. The results are shown in Figure 14. 【0097】 As shown in Figure 14, the expression ratio of the tenascin C gene was highest in the test group to which calendula extract ferment was added. From these results, it was clear that calendula extract ferment was superior to unfermented calendula extract, as well as to known hair growth ingredients such as ginseng root extract and adenosine, in promoting tenascin C expression. 【0098】 <Example 9> Evaluation of the expression-promoting effect of chondroitin sulfate proteoglycan 4 (CSPG4) (1) Evaluation of various plant extracts The plant extracts from Examples 1(2) to 1(6) were evaluated using the real-time PCR method described in Example 3 to determine whether they altered the expression level of the CSPG4 gene (NM_001897.5; Homo sapiens chondroitin sulfate proteoglycan 4 (CSPG4), mRNA). However, instead of the primers used to amplify Wint5A, the CSPG4 gene amplification primers shown below were used. The results are shown in Figure 15. 《CSPG4 gene》 Forward; 5'-TGCTTTGGAGGCTCTGGACA-3' (Sequence ID 15) Reverse; 5'-GTATGCAAGCCGACGCAGAC-3' (Sequence ID 16) 【0099】 As shown in Figure 15, the expression ratio of the CSPG4 gene was higher in the test group treated with calendula extract ferment at a concentration of 200 μg / mL and in the test group treated with Japanese knotweed extract (BG) at a concentration of 200 μg / mL. In other words, the expression level of the CSPG4 gene in cells was higher in the presence of calendula extract ferment or Japanese knotweed extract. From these results, it became clear that calendula extract ferment and Japanese knotweed extract can promote CSPG4 expression. 【0100】 (2) Comparative evaluation of calendula extract ferment The CSPG4 expression-promoting effect of fermented calendula extract was compared with that of unfermented calendula extract, ginseng root extract, and adenosine. Specifically, the expression levels of the CSPG4 gene were evaluated using the real-time PCR method described in Example 9(1) with the calendula extract from Example 1(1) and the fermented calendula extract from Example 1(2), as well as ginseng root extract (commercially available) and adenosine (Fujifilm Wako Pure Chemical Industries) instead of the plant extract. The concentration of the test substance added was 12.5 μg / mL. The results are shown in Figure 16. 【0101】 As shown in Figure 16, the expression ratio of the CSPG4 gene was highest in the test group to which calendula extract ferment was added. From these results, it was clear that calendula extract ferment was superior to unfermented calendula extract and to known hair growth ingredients such as ginseng root extract and adenosine in promoting CSPG4 expression. 【0102】 <Example 10> Evaluation of the effect of promoting fibronectin expression (1) Evaluation of various plant extracts The plant extracts from Examples 1(2) to 1(6) were evaluated using the real-time PCR method described in Example 3 to determine whether they altered the expression level of the fibronectin gene (NM_001306129.1; Homo sapiens fibronectin 1 (FN1), transcript variant 8, mRNA). However, instead of the primers used to amplify Wint5A, the fibronectin gene amplification primers shown below were used. The results are shown in Figure 17. Fibronectin gene Forward; 5'-GCCTTGCACGATGATATGGAGA-3' (Sequence ID 17) Reverse; 5'-CTTGTGGGTGTGACCTGAGTGAA-3' (Sequence ID 18) 【0103】 As shown in Figure 17, the expression ratio of the fibronectin gene was higher in the test groups to which calendula extract ferment was added at concentrations of 3.125, 12.5, 50, and 200 μg / mL, as well as in the test group to which Japanese knotweed extract (BG) was added at a concentration of 200 μg / mL. In other words, the expression level of the fibronectin gene in cells was higher in the presence of calendula extract ferment or Japanese knotweed extract. From these results, it is clear that calendula extract ferment and Japanese knotweed extract can promote fibronectin expression. 【0104】 (2) Comparative evaluation of calendula extract ferment The fibronectin expression-promoting effect of the fermented calendula extract was compared with that of unfermented calendula extract. Specifically, the expression level of the fibronectin gene was evaluated using the real-time PCR method described in Example 10(1) with the calendula extract from Example 1(1) and the fermented calendula extract from Example 1(2). The concentrations of the test substance added were 12.5 and 200 μg / mL. The results are shown in Figure 18. 【0105】 As shown in Figure 18, the fibronectin gene expression ratio was higher in the group treated with calendula extract ferment than in the group treated with calendula extract alone, at both concentrations of 12.5 and 200 μg / mL. This result clearly indicates that calendula extract ferment is superior to unfermented calendula extract in promoting fibronectin expression.

Claims

[Claim 1] Hair growth products containing (a) and / or (c) below as active ingredients; (i) Extract from the underground part of Japanese knotweed, (c) Lactic acid fermented or yeast fermented extract of the underground part of Japanese knotweed. [Claim 2] A hair papilla cell proliferation promoter comprising (a) and / or (c) below as active ingredients; (i) Extract from the underground part of Japanese knotweed, (c) Lactic acid fermented or yeast fermented extract of the underground part of Japanese knotweed. [Claim 3] WINT5A expression promoters comprising (a) and / or (c) below as active ingredients; (i) Extract from the underground part of Japanese knotweed, (c) Lactic acid fermented or yeast fermented extract of the underground part of Japanese knotweed. [Claim 4] A vascular endothelial growth factor (VEGF) expression promoter comprising (a) and / or (c) below as active ingredients; (i) Extract from the underground part of Japanese knotweed, (c) Lactic acid fermented or yeast fermented extract of the underground part of Japanese knotweed. [Claim 5] A fibroblast growth factor-7 (FGF-7) expression promoter comprising the following (a) and / or (c) as active ingredients; (i) Extract from the underground part of Japanese knotweed, (c) Lactic acid fermented or yeast fermented extract of the underground part of Japanese knotweed. [Claim 6] An expression promoter of tissue-nonspecific alkaline phosphatase (ALPL), comprising the following (a) as the active ingredient; (i) Extract from the underground part of Japanese knotweed. [Claim 7] Versican expression promoters containing the following (a) as the active ingredient; (i) Extract from the underground part of Japanese knotweed. [Claim 8] Tenascin C expression promoters comprising (a) and / or (c) below as active ingredients; (i) Extract from the underground part of Japanese knotweed, (c) Lactic acid fermented or yeast fermented extract of the underground part of Japanese knotweed. [Claim 9] An expression promoter of chondroitin sulfate proteoglycan 4 (CSPG4), comprising the following (a) as the active ingredient; (i) Extract from the underground part of Japanese knotweed. [Claim 10] A fibronectin expression promoter containing the following (a) as the active ingredient; (i) Extract from the underground part of Japanese knotweed. [Claim 11] The agent according to any one of claims 1 to 10, wherein the lactic acid bacterium is Lactobacillus plantarum. [Claim 12] A hair growth method (excluding medical procedures for humans) that uses an extract of the underground part of Japanese knotweed, or a lactic acid fermented or yeast fermented product of the underground part of Japanese knotweed. [Claim 13] A method for promoting the proliferation of hair papilla cells using an extract of the underground part of Japanese knotweed, or a lactic acid fermented product or yeast fermented product of the underground part of Japanese knotweed (excluding medical procedures for humans).

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