CN115089717A

CN115089717A - Application of transcription factor AP-1 inhibitor in preparation of anti-hair loss medicine

Info

Publication number: CN115089717A
Application number: CN202210852081.2A
Authority: CN
Inventors: 乐志操
Original assignee: Shenzhen University
Current assignee: Shenzhen University
Priority date: 2022-07-20
Filing date: 2022-07-20
Publication date: 2022-09-23
Anticipated expiration: 2042-07-20
Also published as: CN115089717B

Abstract

The application relates to the technical field of biology, in particular to application of a transcription factor AP-1 inhibitor in preparation of a medicine for preventing alopecia and promoting hair growth. The transcription factor AP-1 inhibitor can inhibit the activity of the transcription factor AP-1, further promote the expression of SHH gene, and realize the effects of preventing alopecia and promoting hair growth. When the provided transcription factor AP-1 inhibitor is used for chemotherapy of alopecia mice, the effect of relieving chemotherapy alopecia can be effectively realized; can be used for promoting hair growth of aged mice. The transcription factor AP-1 inhibitor is expected to become a new medicine for preventing alopecia and promoting hair growth.

Description

Application of transcription factor AP-1 inhibitor in preparation of anti-alopecia drugs

Technical Field

The application belongs to the technical field of biology, and particularly relates to an application of a transcription factor AP-1 inhibitor in preparation of a medicine for preventing alopecia and promoting hair growth.

Background

The SHH signal is important for hair growth and is one of the major factors that promote hair growth. Activation of SHH signaling promotes hair growth (PMID 10510326, 16185261), while inhibition of SHH signaling induces apoptosis of hair follicle cells, leading to hair growth deficiency (PMID 10771469, 32682910). Thus, hair growth quality is affected by the SHH signal. Other related signals such as WNT, BMP, etc. also affect hair growth, and related molecules such as R-Spondin (EP-3242724-A4/WO-2016112343-A1), Noggin (PCT/KR2009/006930) have been used to promote hair growth.

Chemotherapy alopecia is a common side effect in the treatment of tumors. The currently reported chemotherapy alopecia prevention and treatment method comprises an ice cap, and has certain clinical effect; in animal experiments, growth factors EGF, KGF and SHH have certain effects; the cytokine IL-1b has certain effects; although 1,25 dihydroxy vitamin D3 was somewhat effective, it was not ideal in practice (PMID 23369683). The principle of chemotherapy alopecia is complex, and it is previously thought that toxicity of chemotherapy drugs causes hair follicle cell death; we have found that SHH signaling pathways play a major role in chemotherapy alopecia and that direct subcutaneous injection of SHH proteins, or subcutaneous injection of inhibitors of MAPK/ERK2, can partially rescue chemotherapy alopecia (PMID 25233072; 32682910), but these approaches have limitations because SHH proteins or signal activators, as well as inhibitors of MAPK/ERK2, can affect numerous cellular behaviors (PMID 21814234, 32576977), produce a broad range of responses, affect tumor therapy, and even induce tumorigenesis.

The cause of the decreased SHH gene expression caused by chemotherapeutic drugs has not been known before. We found that the inhibition of SHH gene expression by chemotherapeutic drugs requires activation by AP-1 transcription factor (JUN/FOS), EGR1, etc., and includes active oxygen, and that it acts through a specific enhancer upstream of SHH gene; if the activity of the transcription factor AP-1 is inhibited, for example by using the small chemical molecule SR11302 or T-5224, the chemotherapeutic drug cannot inhibit the expression of the SHH gene. Therefore, by inhibiting the activity of AP-1, significant expression of the SHH gene can be maintained. These results provide a new concept for the rescue of chemotherapy alopecia.

The AP-1 transcription factor can affect tumorigenesis, tumor angiogenesis, skin differentiation, skin inflammatory response, skin wound healing and the like. Therefore, the downstream genes of AP-1 are also very complex, including EGFR, FAS, FASL, DNMT1, MMP1, MMP3, CCND, K1, K5, K8, K14, K18, SPRR1, SPRR3, KGF, IL-1, EGF, PDGF, IL-6, IL-8, GM-CSF, etc. (PMID 11402337). Known molecules that can affect SHH gene expression include: MAPK has previously been reported to inhibit SHH gene expression, including growth factors such as EGF, FGF2, etc. (PMID 23123965); growth factor FGF8 has also been reported to inhibit SHH gene expression by transcription factors Etv4, Etv5 (PMID 19386268); however, there has been no report on the rescue of the expression of SHH gene by inhibiting the activity of AP-1 transcription factor. It has been reported that AP-1 can induce/promote the expression of SHH gene (PMID 22641094) in liver diseases, contrary to our findings, that inhibition of the activity of AP-1 can promote the expression of SHH gene. Therefore, our results provide a new way to regulate the expression of the SHH gene, including under the action of chemotherapeutic drugs, as well as under the action of reactive oxygen species.

Obesity has been reported to cause defects in hair growth and regrowth, leading to hair loss; this includes the increase in reactive oxygen species levels and the resulting suppression of SHH gene expression (PMID 34163066). We found that an AP-1 transcription factor inhibitor can maintain the expression of the SHH gene in the presence of active oxygen. Other reports indicate that under stress, inflammation or injury conditions, intracellular AP-1 transcription factors (PMID 9436645, PMID 11402337) may be activated and thus also have the potential to inhibit SHH gene expression; the AP-1 inhibitor can possibly rescue SHH gene expression, thereby saving related alopecia.

As people age, hair growth slows. This was also shown in mouse models: the hair growth and regeneration rate of aged mice was decreased, and the expression level of SHH gene was also significantly decreased. By inhibiting the activity of AP-1 transcription factor, the hair growth and regeneration of aged mice can be promoted. Similarly, if the SHH protein is added, or an activator of SHH signal such as SAG (smoothened aginst), it should theoretically also promote hair growth in aged rats.

The types of inhibitors of AP-1 transcription factor are many and are described in the PMID 24831826, 31774677 paper, and research and development of new molecules is continuing. Theoretically, any drug which can inhibit the activity of the AP-1 transcription factor, including a drug which interferes with the combination of the AP-1 transcription factor and the target DNA, a drug which interferes with the dimer formation (JUN/FOS) of the AP-1 transcription factor and a drug with an AP-1 transcription activation function, can save/promote the expression of the SHH gene, thereby realizing the functions of saving chemotherapy alopecia and promoting hair growth.

Disclosure of Invention

The application aims to provide application of a transcription factor AP-1 inhibitor in preparation of a medicament for preventing chemotherapy alopecia and promoting hair growth, and aims to solve the problem that no better medicament is used for alopecia in the prior art.

In order to achieve the purpose of the application, the technical scheme adopted by the application is as follows:

in a first aspect, the present application provides the use of a transcription factor AP-1 inhibitor in a medicament for preventing hair loss and promoting hair growth.

Further, the transcription factor AP-1 inhibitor comprises at least one of SR11302, T-5224, BJC005, NDGA and respective derivatives thereof.

Furthermore, the transcription factor AP-1 inhibitor can promote the expression of SHH gene by inhibiting AP-1 transcription factor, and the generated SHH protein can prevent alopecia caused by chemotherapy.

Further, the alopecia prevention includes at least one of alopecia prevention caused by chemotherapy, alopecia prevention caused by obesity, alopecia prevention caused by mental stress, and alopecia prevention caused by malnutrition.

Further, the promoting hair growth includes at least one of promoting hair growth affected by aging, promoting hair growth in which hair growth is slow, and promoting hair growth affected by a regeneration disorder.

Furthermore, the drug concentration of the transcription factor AP-1 inhibitor is 1-100 mu M.

Furthermore, the alopecia prevention medicine also comprises at least one of cytokines with the alopecia prevention effect and cell cycle inhibitors.

Further, the drug for promoting hair growth further includes at least one of a drug having a function as a WNT signal activator and a drug having a function as a BMP inhibitor.

Further, the cytokine having the alopecia preventing effect includes at least one of EGF, KGF, and IL-1 b.

Further, the cell cycle inhibitor comprises at least one of Abelide, palbociclib, Ribociclib, and 1, 25-dihydroxy vitamin D3.

Further, the drug having a function as a WNT signal activator includes R-Spondin.

Further, the drug having a function of the BMP inhibitor includes Noggin.

Furthermore, the medicine for preventing alopecia and promoting hair growth also comprises pharmaceutically acceptable auxiliary materials, wherein the auxiliary materials comprise at least one of diluents, excipients, fillers, adhesives, wetting agents, absorption promoters, surfactants, lubricants, stabilizers, flavoring agents, sweetening agents and pigments which are conventional in the pharmaceutical field.

Furthermore, the medicine for preventing alopecia and promoting hair growth can be prepared into any pharmaceutically acceptable dosage form, wherein the dosage form comprises at least one of tablets, capsules, granules, oral liquid, sustained release preparations, nano preparations, injections and external application paints.

The application of the transcription factor AP-1 inhibitor in preparing the medicine for preventing alopecia and promoting hair growth, wherein the transcription factor AP-1 inhibitor acts on cells, can inhibit the activity of the transcription factor AP-1, further promotes SHH gene expression, can prevent alopecia, can promote hair growth and improve hair quality; the provided transcription factor AP-1 inhibitor can effectively promote hair growth when being used for aged mice. The transcription factor AP-1 inhibitor is expected to become a new medicine for promoting hair growth.

Drawings

To more clearly illustrate the technical solutions in the embodiments of the present application, the drawings used in the embodiments or the prior art descriptions will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and it is obvious for those skilled in the art that other similar results can be obtained without inventive efforts.

FIG. 1 shows that in an in vitro cell culture system provided in the examples of the present application, chemotherapeutic agents and reactive oxygen species inhibit SHH gene expression, while AP-1 inhibitors rescue SHH gene expression;

FIG. 2 is a graph of the AP-1 inhibitor provided in the examples herein rescuing mice from chemotherapy alopecia;

FIG. 3 is a graph showing the promotion of hair regrowth in aged mice by an AP-1 inhibitor provided in the examples herein.

Detailed Description

In order to make the technical problems, technical solutions and advantageous effects to be solved by the present application more clearly apparent, the present application is further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are merely illustrative of and not restrictive on the broad application.

In this application, the term "and/or" describes an association relationship of associated objects, meaning that there may be three relationships, e.g., a and/or B, which may mean: a is present alone, A and B are present simultaneously, and B is present alone. Wherein A and B can be singular or plural. The character "/" generally indicates that the former and latter associated objects are in an "or" relationship.

In the present application, "at least one" means one or more, "a plurality" means two or more. "at least one of the following" or similar expressions refer to any combination of these items, including any combination of the singular or plural items. For example, "at least one (a), b, or c", or "at least one (a), b, and c", may each represent: a, b, c, a-b (i.e., a and b), a-c, b-c, or a-b-c, wherein a, b, and c may be single or plural, respectively.

It should be understood that, in various embodiments of the present application, the sequence numbers of the above-mentioned processes do not mean the execution sequence, some or all of the steps may be executed in parallel or executed sequentially, and the execution sequence of each process should be determined by its function and inherent logic, and should not constitute any limitation to the implementation process of the embodiments of the present application.

The terminology used in the embodiments of the present application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in the examples of this application and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.

The weight of the related components mentioned in the description of the embodiments of the present application may not only refer to the specific content of each component, but also represent the proportional relationship of the weight among the components, and therefore, the content of the related components is scaled up or down within the scope disclosed in the description of the embodiments of the present application as long as it is scaled up or down according to the description of the embodiments of the present application. Specifically, the mass in the description of the embodiments of the present application may be in units of mass known in the chemical industry, such as μ g, mg, g, and kg.

The terms "first" and "second" are used for descriptive purposes only and are used for distinguishing purposes such as substances from one another and are not to be construed as indicating or implying relative importance or to implicitly indicate the number of technical features indicated. For example, a first XX may also be referred to as a second XX, and similarly, a second XX may also be referred to as a first XX, without departing from the scope of embodiments of the present application. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature.

In a first aspect, the embodiments of the present application provide an application of a transcription factor AP-1 inhibitor in preparing a medicament for preventing alopecia and promoting hair growth.

The application of the transcription factor AP-1 inhibitor provided by the embodiment of the application in preparing the medicine for preventing alopecia and promoting hair growth, wherein the transcription factor AP-1 inhibitor acts on cells, can inhibit the activity of the transcription factor AP-1, further promotes the expression of SHH gene, can prevent alopecia, can promote hair growth and improve hair quality; the provided transcription factor AP-1 inhibitor can effectively promote hair growth when being used for aged mice. The transcription factor AP-1 inhibitor is expected to become a new medicine for promoting hair growth.

In some embodiments, the preventing hair loss comprises at least one of preventing hair loss due to chemotherapy, preventing hair loss due to obesity, preventing hair loss due to mental stress, preventing hair loss due to malnutrition.

In some embodiments, the promoting hair growth comprises at least one of promoting hair growth affected by aging, promoting slow hair growth, promoting hair growth affected by a regrowth disorder.

In some embodiments, the transcription factor AP-1 inhibitor can inhibit the AP-1 transcription factor to promote SHH gene expression, thereby preventing alopecia and promoting hair growth.

In some embodiments, the transcription factor AP-1 inhibitor comprises at least one of SR11302, T-5224, BJC005, NDGA, and their respective derivatives.

In some embodiments, the transcription factor AP-1 inhibitor is preferentially selected from at least one of SR11302, T-5224. The two small molecules have been used for tumor therapy and inflammation control before, and the safety is proved. As targets downstream, they have a small range of possible actions, that is to say a low probability of causing other reactions. SR11302 or T-5224 acts on cells, can effectively inhibit AP-1 transcription factors, thereby mediating MAPK/ERK2 signal pathway to promote SHH gene expression SHH protein to play the role of preventing alopecia.

In some embodiments, the protective effect of hair on chemical damage can be seen with subcutaneous injections of SR11302 or T-5224, resulting in white hair.

In some embodiments, the drug concentration of the transcription factor AP-1 inhibitor is 1-100 μ M. In some embodiments, the drug concentration of the transcription factor AP-1 inhibitor includes, but is not limited to, 1. mu.M, 5. mu.M, 10. mu.M, 15. mu.M, 20. mu.M, 25. mu.M, 30. mu.M, 35. mu.M, 40. mu.M, 45. mu.M, 50. mu.M, 55. mu.M, 60. mu.M, 65. mu.M, 70. mu.M, 75. mu.M, 80. mu.M, 85. mu.M, 90. mu.M, 95. mu.M, 100. mu.M. The drug concentration of the transcription factor AP-1 inhibitor is limited to be 1-100 mu M, so that the transcription factor AP-1 inhibitor can be ensured. The concentrations of the inhibitors SR11302, T-5224, etc. should be determined according to the specific application mode/administration route and species, including from the beginning of IC50 to the occurrence of obvious toxic and side effects.

In some embodiments, the alopecia preventing drug further comprises at least one of a cytokine and a cell cycle inhibitor having an alopecia preventing effect. The provided anti-alopecia medicine also comprises a cell factor or a cell cycle inhibitor with an anti-alopecia effect to perform a synergistic effect, and is more favorable for the anti-alopecia effect.

In some embodiments, the anti-alopecia cytokine comprises at least one of EGF, KGF, IL-1 b.

In some embodiments, the cell cycle inhibitor comprises at least one of Abelix, palbociclib, Ribociclib, 1, 25-dihydroxy vitamin D3.

In some embodiments, the medicament for promoting hair growth further comprises at least one of a medicament having a function of a WNT signaling activator, a medicament having a function of a BMP inhibitor.

In some embodiments, the drug that functions as an activator of WNT signaling comprises R-Spondin.

In some embodiments, the agent that functions as a BMP inhibitor includes Noggin.

In some embodiments, the anti-hair loss agent further comprises pharmaceutically acceptable excipients, wherein the excipients comprise at least one of diluents, excipients, fillers, binders, humectants, absorption enhancers, surfactants, lubricants, stabilizers, flavoring agents, sweeteners, pigments, which are conventional in the pharmaceutical field.

In some embodiments, the anti-hair loss drug can be prepared into any pharmaceutically acceptable dosage form, including at least one of tablets, capsules, granules, oral liquid, sustained release preparations, nano preparations, injections and external application paints. In particular applications, topical applications are preferred and may be combined with a regimen to promote transdermal absorption.

Correspondingly, the medicine for preventing alopecia and promoting hair growth comprises an inhibitor of the transcription factor AP-1.

The provided anti-alopecia medicine comprises transcription factor AP-1 inhibitor. The transcription factor AP-1 inhibitor acts on cells, can inhibit the activity of the transcription factor AP-1, so as to promote SHH gene expression SHH protein to play roles in preventing alopecia and promoting hair growth; and when the provided transcription factor AP-1 inhibitor is used for a baldness mouse, the effect of relieving baldness can be effectively realized. The transcription factor AP-1 inhibitor is expected to become a new anti-alopecia drug, and provides a new direction for clinical alopecia treatment.

The following description will be given with reference to specific examples.

Example 1

In vitro cell culture (HT29 cells), chemotherapy drugs such as fluorouracil (5FU), adriamycin, oxaliplatin, etc. are added, or hydrogen peroxide is used for treatment, so that SHH gene expression can be rapidly and effectively inhibited (fig. 1A-C). If the expression of the FOS or JUN gene in the cell is reduced by the RNAi method, the chemotherapeutic drug 5FU cannot inhibit the expression of the SHH gene (FIGS. 1D-E). Similarly, the AP-1 inhibitor SR11302 (SR) or T-5224 can also rescue SHH gene expression reduction caused by chemotherapeutic drugs or hydrogen peroxide (FIG. 1F-G).

Example 2

A medicine for preventing alopecia caused by chemotherapy.

The mouse is taken out 60 days after birth, the hair is regenerated by hair plucking at the back, the hair enters a rapid regeneration stage nine days later, chemotherapy medicament cyclophosphamide (150 mg/kg; administration day-day zero) is injected into the abdominal cavity to induce chemotherapy alopecia, and the hair of the mouse completely falls off in the seventh day and the fourteenth day. At the same time (or 2 hours later) as the injection of the chemotherapeutic agent, SR11302(100 μ M,100 μ L) was injected subcutaneously, and it was observed that hair was protected by the fourteenth day and white hair grew (fig. 2D).

Example 3

A medicine for preventing alopecia caused by chemotherapy.

After 60 days after the mice are taken out, the hairs on the back are plucked to induce the hairs to regenerate, the hairs enter a rapid regeneration stage after nine days, chemotherapy drugs cyclophosphamide (150 mg/kg; administration day-day zero) are injected into the abdominal cavity to induce chemotherapy alopecia, and the hairs of the mice completely fall off on the seventh day and the fourteenth day. At the same time (or 2 hours later) as the injection of the chemotherapeutic drug, T-5224 (100. mu.M, 100. mu.L) was injected subcutaneously, and it was observed that hair was protected and white hair grew on the fourteenth day (FIG. 2E).

Example 4

A medicine for promoting hair growth is provided.

The hair was regenerated by pulling hair from the back of 18-month-old mice (day zero of regeneration). On the first, third and fifth days, SR11302(100 μ M,100 μ L) was subcutaneously injected, and photographing was continuously observed, and hair regrowth was found to be promoted (fig. 3D).

Example 5

A medicine for promoting hair growth is provided.

The hair was regenerated by pulling hair from the back of 18-month-old mice (day zero of regeneration). T-5224 (100. mu.M, 100. mu.L) was subcutaneously injected on the first, third and fifth days, respectively, and photographing was continuously observed, and hair regrowth was found to be promoted (FIG. 3E).

Performance determination and results analysis

The results of the in vitro cell culture experiments provided in example 1 are shown in FIG. 1.

FIG. 1 (A) shows that fluorouracil (5 FU; 100. mu.M), a chemotherapeutic drug, inhibits the mRNA expression level of the SHH gene in HT29 cells; as can be seen from (a) of fig. 1, the SHH gene expression level was rapidly suppressed as the drug concentration increased (20 μm, 50 μm,100 μm). The gene expression level was relatively quantified by qPCR method, with ACTB gene as an internal control.

FIG. 1 (B) is the protein expression level of the chemotherapeutic drug 5FU (100. mu.M) inhibiting SHH in HT29 cells; as can be seen from fig. 1 (B), the SHH protein level significantly decreased at the current concentration. The SHH protein expression level was quantified by the WesternBlot method, and the GAPDH protein level was used as an internal control.

FIG. 1 (C) shows that the chemotherapeutic drugs adriamycin (1 μ M), oxaliplatin (1 μ M) and hydrogen peroxide (1 mM; 3mM) inhibit the mRNA expression level of the SHH gene in HT29 cells; as can be seen from (C) of FIG. 1, the commonly used chemotherapeutic drugs doxorubicin, oxaliplatin, and active oxygen molecules in hydrogen peroxide can rapidly and effectively inhibit the expression of the SHH gene.

FIG. 1 (D) shows that in HT29 cells, the expression level of FOS gene is reduced by RNAi method, and the SHH gene expression of cells is not affected by the chemotherapeutic drug 5FU (100. mu.M); as can be seen from (D) of FIG. 1, the inhibition of SHH gene expression by chemotherapeutic drugs requires passing through the FOS gene.

FIG. 1 (E) is a graph showing that in HT29 cells, when the expression level of JUN gene is decreased by RNAi method, the SHH gene expression of the cells is not affected by 5FU (100. mu.M) which is a chemotherapeutic agent; as can be seen from (E) of FIG. 1, the inhibition of the expression of the SHH gene by the chemotherapeutic drug requires passage through the JUN gene.

FIG. 1 (F) shows that the AP-1 inhibitors SR11302 (SR; 10. mu.M) and T-5224 (10. mu.M) rescue the decreased SHH gene expression in HT29 cells caused by the chemotherapeutic drug 5FU (100. mu.M); as can be seen from FIG. 1 (F), the AP-1 inhibitor is effective in preventing the decrease in SHH gene expression caused by the chemotherapeutic agent 5 FU.

FIG. 1 (G) shows that AP-1 inhibitors SR11302 (SR; 10. mu.M) and T-5224 (10. mu.M) rescue the SHH gene expression reduction caused by hydrogen peroxide (1mM) in HT29 cells; as can be seen from FIG. 1 (G), the AP-1 inhibitor is effective in preventing the decrease in the expression of the SHH gene caused by reactive oxygen species in hydrogen peroxide.

(II) the results of experiments on the rescue of chemotherapy-induced alopecia by the AP-1 inhibitor provided in examples 2 and 3 are shown in FIG. 2.

FIG. 2 (A) shows that cyclophosphamide (CYP; 150mg/kg intraperitoneal injection), a chemotherapeutic drug, inhibits the mRNA expression of the SHH gene in the skin. As can be seen from FIG. 2 (A), cyclophosphamide, a chemotherapeutic drug, rapidly and effectively suppressed the expression of the SHH gene in the skin.

Fig. 2 (B) is that two hours after intraperitoneal injection of the chemotherapeutic drug CYP (150mg/kg), subcutaneous injection of SR11302(100 μ M,100 μ L) significantly rescued the mRNA expression level of the SHH gene in the skin. As can be seen from FIG. 2 (B), the AP-1 inhibitor SR11302 can effectively rescue SHH gene expression reduction caused by cyclophosphamide as a chemotherapeutic drug.

FIG. 2 (C) shows that subcutaneous injection of T-5224 (100. mu.M, 100. mu.L) significantly increased the mRNA expression level of the SHH gene in the skin two hours after intraperitoneal injection of the chemotherapeutic drug CYP (150 mg/kg). As can be seen from (C) of FIG. 2, the AP-1 inhibitor T-5224 can effectively rescue the SHH gene expression reduction caused by the chemotherapy drug cyclophosphamide.

FIG. 2 (D), FIG. 2 (E) and FIG. 2 (F) show the SR11302, T-5224, and control mice, respectively, showing the rescue of mice chemotherapy alopecia. It can be seen that the control mice (150mg/kg CYP i.p.) had completely shed hair on the seventh/fourteenth day, while SR11302 and T-5224(100 μ M,100 μ L s.c.) saved white hair.

(III) the results of experiments in which the AP-1 inhibitor provided in examples 4 and 5 promotes hair growth in aged mice are shown in FIG. 3.

FIG. 3 (A) is a comparison of the expression levels of the SHH gene on the eighth day after the hair removal-induced regeneration of the back skin in an aged mouse (18 months) and a young mouse (3 months). It can be seen that the dorsal skin of young mice expresses more SHH gene than that of old mice.

Fig. 3 (B) shows the process of plucking the back skin to induce regeneration in young mice (3 months old). On the seventh and tenth days, it was observed that the back skin began to discolor, and on the fourteenth day, black hair was developed.

Fig. 3 (C) shows the process of hair removal-induced regeneration of the back skin of an aged mouse (18 months old). It can be seen that hair regrowth is significantly slower in older mice than in younger mice, especially on the fourteenth day.

FIG. 3 (D) and FIG. 3 (E) show the AP-1 inhibitors SR11302 and T-5224, respectively, promoting hair regeneration in aged mice. Significant promotion of hair regrowth was observed by subcutaneous injection of the AP-1 inhibitor SR11302 or T-5224 (100. mu.M, 100. mu.L subcutaneous injection) on the first, third and fifth days of the epilation-induced regrowth process, respectively.

The above description is only exemplary of the present application and should not be taken as limiting the present application, as any modification, equivalent replacement, or improvement made within the spirit and principle of the present application should be included in the protection scope of the present application.

Claims

1. Application of transcription factor AP-1 inhibitor in preparing medicine for preventing alopecia and promoting hair growth is provided.

2. The use of claim 1, wherein the transcription factor AP-1 inhibitor comprises at least one of SR11302, T-5224, BJC005, NDGA and their respective derivatives.

3. The use of claim 1, wherein the transcription factor AP-1 inhibitor can inhibit AP-1 transcription factor to promote SHH gene expression, thereby preventing alopecia and promoting hair growth.

4. The use of claim 1, wherein the preventing hair loss comprises at least one of preventing hair loss caused by chemotherapy, preventing hair loss caused by obesity, preventing hair loss caused by mental stress, and preventing hair loss caused by malnutrition.

5. The use according to claim 1, wherein said promoting hair growth comprises at least one of promoting hair growth affected by aging, promoting hair growth that is slow in hair growth, promoting hair growth affected by a regeneration disorder.

6. The use of claim 2, wherein the drug concentration of the transcription factor AP-1 inhibitor is 1-100 μ Μ.

7. The use according to any one of claims 1 to 6, wherein the alopecia preventing agent further comprises at least one of a cytokine and a cell cycle inhibitor having an alopecia preventing effect; and/or the presence of a gas in the atmosphere,

the drug for promoting hair growth further includes at least one of a drug having a function of a WNT signal activator, a drug having a function of a BMP inhibitor.

8. The use according to claim 7, wherein the cytokine having alopecia preventing effect comprises at least one of EGF, KGF, IL-1 b; and/or the presence of a gas in the gas,

the cell cycle inhibitor comprises at least one of Abelide, palbociclib, Ribociclib and 1, 25-dihydroxy vitamin D3; and/or the presence of a gas in the gas,

the drug having a function of a WNT signaling activator includes R-Spondin; and/or the presence of a gas in the gas,

the drug having a function of a BMP inhibitor includes Noggin.

9. The use according to any one of claims 1 to 6, wherein the medicament for preventing hair loss and promoting hair growth further comprises pharmaceutically acceptable excipients, wherein the excipients comprise at least one of diluents, excipients, fillers, binders, wetting agents, absorption enhancers, surfactants, lubricants, stabilizers, flavoring agents, sweeteners, pigments, which are conventional in the pharmaceutical field.

10. The use according to any one of claims 1 to 6, wherein the medicament for preventing hair loss and promoting hair growth can be prepared into any one of pharmaceutically acceptable dosage forms, and the dosage forms comprise at least one of tablets, capsules, granules, oral liquid, sustained release preparations, nano preparations, injections and external application paints.