KR20210129565A - Composition for preventing, improving or treating benign prostatic hyperplasia or androgen alopecia - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating or treating benign prostatic hyperplasia or androgenetic alopecia containing a Centella asiatica extract as an active component. By the same, the composition is a natural material and is harmless to the human body, can minimize side effects, and in particular, has an effect of suppressing the expression of androgen signaling related factors.

Description

Composition for preventing, improving or treating benign prostatic hyperplasia or androgen alopecia

The present invention relates to a composition for preventing, improving or treating benign prostatic hyperplasia or androgenetic alopecia.

BPH is a common chronic disease of the urinary tract in men over the age of 50 (Berry S.J. et al., 1984). BPH is also associated with decreased urinary tract symptoms (LUTS), including intermittent increase in the urinary tract, increased urinary frequency, urinary emergencies, weakened urinary flow, and incomplete bladder emptying, which leads to poorer quality of life and negative impact on daily activities in older adults. (Sarma, AV et al., 2012).

Although the underlying cause of BPH is unknown, it is well known that the prostate in aging men is affected by androgens (Kim S.K. et al., 2015). During prostatic hyperplasia, androgens promote proliferation of epithelial or stromal cells in the prostate in an autocrine or paracrine manner, resulting in an imbalance in prostate cell proliferation and apoptosis. It has been considered an important cause of BPH (Choi, H.M. et al., 2016).

In particular, dihydrotestosterone (DHT) is well known to be associated with the development of benign prostatic hyperplasia. As men age, the male sex hormone testosterone begins to be converted at a high rate to dihydrotestosterone (DHT) in the prostate, which is primarily due to the concentration of the enzyme reductase, an enzyme that converts testosterone to DHT. is caused by an increase in DHT is a more potent androgen compared to TST because of its high binding ability to the androgen receptor (AR). 5α reductase type-2 (5AR2) converts TST to DHT in the prostate, which binds to AR, increases transcription of androgen-dependent genes, and ultimately induces stimulation of protein synthesis associated with prostate proliferation. -Improve specific antigen (PSA) levels. On the other hand, PSA levels increase during BPH and prostate cancer progression, which is why PSA is widely used in the diagnosis of BPH (Chen, Y. et al., 1996).

The cell cycle occurs in prostate stromal and epithelial cells leading to their division and replication. G1/S progression is highly regulated by cyclin D1. In addition, proliferating cell nuclear antigen (PCNA) is an acidic nuclear protein recognized as a histological marker for the G1/S phase in the cell cycle. Thus, expression of PCNA and cyclin D1 may reflect the proliferative state of prostate cells during BPH (Wang, W., et al., 2004).

Conversely, prostatic epithelial apoptosis occurs more frequently in the prostate in the normal state than in prostatic hyperplasia. Bcl-2, which inhibits apoptosis, is also found in the prostate epithelium, leading to proliferation of prostate tissue (Cardillo, M., et al., 1997).

Another symptom caused by male hormones such as dihydrotestosterone (DHT) is male pattern baldness. Causes of hair loss include poor blood circulation, excessive male hormone activity, excessive sebum secretion, decreased scalp function due to dandruff and other bacteria, genetic factors, and aging stress. The cause of androgenic alopecia, which is the most common type of hair loss directly related to

In the presence of androgenetic alopecia, healthy hair gradually becomes thinner and shorter, and the hair becomes weaker and breaks easily. This phenomenon is called miniaturization. Hair follicles that shrink are eventually thin, invisible, and short fluff, leading to hair loss. Accordingly, many studies have been reported recently for the prevention and treatment of hair loss through the inhibition of male hormone activity.

Testosterone is converted to dihydrotestosterone (DHT), an active male hormone, by 5α-reductase, and the activated dihydrotestosterone binds to androgen receptors to promote protein synthesis in hair follicle cells. It delays the growth period of hair follicles and causes hair loss by atrophying the hair follicles. In addition, excess sebum is produced in the process of androgenetic alopecia, and as a result, hair loss accompanied by inflammation appears on the scalp (Dennis A. Holt, et. al, 1990).

In the case of prostatic hyperplasia treatment used as an alpha-1 adrenergic blocker such as terazosin, doxazosin, tamsulasin, and alfuzosin, which have been developed, it relieves symptoms of urethral obstruction by relaxing prostate smooth muscle. Side effects such as headache have been reported.

The 5α reductase inhibitors finasteride (Fi) and dutasteride inhibit the conversion of testosterone to dihydrotestosterone (DHT), an active metabolite, by 5α reductase, thereby reducing prostate size and being effective for BPH and alopecia. However (Park, ES, et al., 2018), these drugs are known to cause side effects such as erectile dysfunction, decreased libido, and decreased semen volume in ejaculation. As such, although the currently used drug treatment is somewhat effective, its side effects are a problem, and in fact, an enlarged prostate is one of the continuous aging phenomena, and there is a problem that it is difficult to fundamentally treat it.

Therefore, researchers looking for effective treatment strategies with fewer side effects are increasingly interested in alternative medicine, including drugs made from natural ingredients. Currently, only saw palmetto extract among natural ingredients is widely known as a functional food having an effect on enlarged prostate (Marks, L.S., et al., 2000).

Korean Patent Registration No. 10-1881417 Korean Patent Registration No. 10-2017187

It is an object of the present invention to provide a pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia, which contains, as an active ingredient, an extract of Centella asiatica, which is harmless to the human body as a natural material and can minimize side effects.

It is an object of the present invention to provide a food composition for preventing or improving prostatic hyperplasia or androgenetic alopecia, which contains an extract of Centella asiatica as an active ingredient, which is harmless to the human body as a natural material and can minimize side effects.

According to one aspect of the invention,

Centella asiatica is provided a pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia comprising an extract as an active ingredient.

The Centella asiatica extract may be extracted with water, an alcohol having 1-4 carbon atoms, or a mixed solvent thereof.

The pharmaceutical composition may be for inhibiting the expression of androgen signaling related factors.

The androgen signaling-related factor may be any one selected from a steroid receptor coactivator (SRC-1), an androgen receptor (AR), 5alpha reductase (5AR2), and a prostate specific antigen (PSA).

The pharmaceutical composition may be for inhibiting the expression of growth factors in the prostate.

The growth factor in the prostate may be any one selected from epidermal growth factor (EGF), insulin like growth factor I (IGF-1), transforming growth factor beta 1 (TGF-1β), and vascular endothelial growth factor (VEGF). .

The pharmaceutical composition may be for inhibiting the expression of factors related to PI3K/Akt and HIF-1 signaling.

The PI3K/Akt and HIF-1 signaling-related factors may be any one selected from phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), and hypoxia-inducible factors (HIF-1).

The pharmaceutical composition may be for inhibiting the expression of cell proliferation-related factors in prostate tissue.

The cell proliferation-related factor in the prostate tissue may be PCNA (Proliferating Cell Nuclear Antigen) or Cyclin D1.

According to another aspect of the present invention,

Centella asiatica is provided a food composition for preventing or improving prostate enlargement or androgenetic alopecia comprising an extract as an active ingredient.

According to another aspect of the present invention,

Centella asiatica ( Centella asiatica ) A health functional food for preventing or improving prostatic hyperplasia or androgenetic alopecia comprising a food composition comprising an extract as an active ingredient is provided.

The pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia comprising the Centella asiatica extract of the present invention as an active ingredient is a natural material that is harmless to the human body and minimizes side effects, and particularly inhibits the expression of androgen signaling related factors There is an effect that can be done.

The food composition for preventing or improving prostatic hyperplasia or androgenetic alopecia comprising the Centella asiatica extract of the present invention as an active ingredient is a natural material that is harmless to the human body and minimizes side effects, and in particular, inhibits the expression of androgen signaling related factors. There is an effect that can be done.

1 is a Western blot result according to Experimental Example 1.
2 is a measurement result of AR protein expression according to Experimental Example 1.
3 is a result of measuring the expression level of 5AR2 protein according to Experimental Example 1.
4 is a result of measuring the expression level of PSA protein according to Experimental Example 1.
5 is a photograph of the prostate of each experimental group separated according to Experimental Example 2 and the result of measuring and comparing the weight of the prostate.
6 is a measurement result of the prostate index according to Experimental Example 2.
7 is a micrograph of prostate epithelial cells according to Experimental Example 2 and results of measuring epithelial cell thickness.
8 is an analysis result of androgen signaling-related factor expression inhibitory ability according to Experimental Example 3.
9 is a representative view of the reference of Experimental Example 4.
10 is a result of the analysis of the growth factor (Grow factor) expression inhibitory ability according to Experimental Example 4.
11 is a schematic diagram of the PI3K/Akt and HIF 1 signaling pathways.
12 is a western blot test result according to Experimental Example 5.
13 is an analysis result of cell proliferation-related factor expression inhibition in prostate tissue according to Experimental Example 6.

Hereinafter, the present invention will be described in detail.

The pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia of the present invention includes Centella asiatica extract as an active ingredient.

Centella asiatica is a plant of the buttercup family with white or lavender flowers on small fan-shaped leaves with serrated edges. In India, it has been used as a medicine for a long time, calling it tiger grass after seeing a wounded tiger roll around in a place where there are many centella asiatica plants.

The extraction solvent for extracting the Centella asiatica extract is water, a lower alcohol having 1 to 4 carbon atoms, ethylene glycol, ethyl ether, or a mixed solvent thereof. The lower alcohol may include 20 to 80% methanol, ethanol, butanol or propanol.

The extraction solvent is not particularly limited, but an extract extracted with an aqueous solution of 60 to 80% ethanol is preferable.

As used herein, the term 'extract' used while referring to the Centella asiatica extract includes not only the crude extract obtained by treating the extraction solvent, but also the processed product of the Centella asiatica extract. For example, Centella asiatica extract may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze-drying or spray-drying.

In addition, the Centella asiatica extract of the present invention is broadly meant to include a Centella asiatica processed product formulated to be administered to animals, for example, Centella asiatica powder. Although the experiment was conducted with Centella asiatica in the present invention, it will be expected by those skilled in the art that the desired effect can be achieved even in the same form as Centella asiatica processed products.

Meanwhile, in the present specification, the term 'comprising as an active ingredient' means including an amount sufficient to achieve efficacy or activity of the Centella asiatica extract or a fraction thereof. For example, the Centella asiatica extract or a fraction thereof is used at a concentration of 10 to 1500 μg/ml, preferably 100 to 1000 μg/ml. Centella asiatica extract or a fraction thereof is a natural product, and since there is no side effect to the human body even when administered in excess, the upper limit of the quantitative amount of the Centella asiatica extract or its fraction contained in the composition of the present invention can be selected and implemented by those skilled in the art within an appropriate range.

In addition, the present invention provides a pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia comprising an extract of Centella asiatica as an active ingredient.

The pharmaceutical composition may be used for inhibiting the expression of androgen signaling related factors.

The androgen signaling-related factor may be any one selected from a steroid receptor coactivator (SRC-1), an androgen receptor (AR), 5alpha reductase (5AR2), and a prostate specific antigen (PSA).

The pharmaceutical composition may be used for inhibiting the expression of growth factors in the prostate.

The growth factor in the prostate may be any one selected from epidermal growth factor (EGF), insulin like growth factor I (IGF-1), transforming growth factor beta 1 (TGF-1β), and vascular endothelial growth factor (VEGF). .

The pharmaceutical composition may be used for inhibiting the expression of factors related to PI3K/Akt and HIF-1 signaling.

The PI3K/Akt and HIF-1 signaling-related factors may be any one selected from phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), and hypoxia-inducible factors (HIF-1).

The pharmaceutical composition may be used for inhibiting the expression of cell proliferation-related factors in prostate tissue.

The cell proliferation-related factor in the prostate tissue may be PCNA (Proliferating Cell Nuclear Antigen) or Cyclin D1.

The pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant includes an excipient, a disintegrant, a sweetener, a binder, a coating agent, a swelling agent, a lubricant, and a lubricant. agent or flavoring agent, etc. may be used.

The pharmaceutical composition may be preferably formulated as a pharmaceutical composition by including one or more pharmaceutically acceptable carriers in addition to the active ingredients described above for administration.

Formulations of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops or injectable solutions. For formulation in the form of, for example, tablets or capsules, the active ingredient may be combined with an orally, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or required, suitable binders, lubricants, disintegrants and color-developers may also be included in the mixture. Suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.

In the composition formulated as a liquid solution, acceptable pharmaceutical carriers are sterile and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostats may be added as needed. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to form an injectable formulation such as an aqueous solution, suspension, emulsion, etc., pills, capsules, granules or tablets.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration.

A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration mode, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity of the patient, usually Thus, a skilled physician can easily determine and prescribe an effective dosage for the desired treatment or prevention. According to a preferred embodiment of the present invention, the daily dose of the pharmaceutical composition of the present invention is 0.001-10 g/kg.

The pharmaceutical composition of the present invention may be prepared in a unit dose form by formulation using a pharmaceutically acceptable carrier and/or excipient, or may be prepared by internalizing in a multi-dose container. In this case, the formulation may be in the form of a solution, suspension, or emulsion in oil or an aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant or stabilizer.

In addition, the present invention provides a food composition for preventing or improving prostatic hyperplasia or androgenetic alopecia comprising an extract of Centella asiatica as an active ingredient.

The food composition according to the present invention may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, sweets, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, gums, ice cream, vitamin complexes, health supplements etc.

The food composition of the present invention may include not only Centella asiatica extract or a fraction thereof as an active ingredient, but also ingredients commonly added during food production, for example, protein, carbohydrate, fat, nutrients, seasonings and flavoring agents. include Examples of the above-mentioned carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose, oligosaccharides and the like; and polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatine, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared as a drink or beverage, citric acid, high fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts in addition to the Centella asiatica extract or fractions thereof of the present invention may be additionally included. can

The present invention provides a health functional food comprising a food composition for preventing or improving prostatic hyperplasia or androgenetic alopecia comprising Centella asiatica extract as an active ingredient. A health functional food is a food prepared by adding Centella asiatica extract or its fractions to food materials such as beverages, teas, spices, gum, and confectionery, or by encapsulating, powdering, or suspension, etc. It means to bring it, but unlike general drugs, it has the advantage that there are no side effects that may occur when taking the drug for a long time because it uses food as a raw material. The health functional food of the present invention obtained in this way is very useful because it can be ingested on a daily basis. The amount of Centella asiatica extract added in such a health functional food varies depending on the type of health functional food and cannot be uniformly defined. to 50% by weight, preferably 0.1 to 20% by weight. In addition, in the case of a health functional food in the form of pills, granules, tablets or capsules, it is usually added in an amount of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.

In addition, the present invention provides the use of Centella asiatica extract for the manufacture of a medicament or food for preventing, treating or improving prostatic hyperplasia or androgenetic alopecia.

In addition, the present invention provides a method for improving, preventing or treating atopy comprising administering an effective amount of Centella asiatica extract to a mammal.

As used herein, the term "mammal" refers to a mammal that is the subject of treatment, observation or experimentation, preferably a human.

As used herein, the term "effective amount" refers to the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human as conceived by a researcher, veterinarian, physician, or other clinician, which is the disease in question. or an amount that induces alleviation of the symptoms of the disorder. The effective amount and frequency of administration for the active ingredient of the present invention may vary depending on the desired effect. Therefore, the optimal dosage to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the content of the active ingredient and other components contained in the composition, the type of formulation, and the age, weight, and general health of the patient It can be adjusted according to various factors including condition, sex and diet, administration time, administration route and secretion rate of the composition, treatment period, and concurrently used drugs. In the prevention, treatment or improvement method of the present invention, it is preferable to administer the extract at a dose of 0.001 g/kg to 10 g/kg when the extract is administered once to several times a day for adults.

In the treatment method of the present invention, the composition comprising Centella asiatica extract as an active ingredient is administered via oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, or intradermal routes. method can be administered.

Hereinafter, preferred examples are presented to aid the understanding of the present invention, but the following examples are merely illustrative of the present invention and it will be apparent to those skilled in the art that various changes and modifications are possible within the scope and spirit of the present invention, It goes without saying that such variations and modifications fall within the scope of the appended claims.

[Example]

Example 1: Preparation of Centella asiatica extract

Commercially sold dried centella asiatica ( Centella asiatica ) was purchased and 1L of DW was added to 100 g of a sample, followed by extraction at 100° C. for 1 hour in a constant temperature water bath. The extract was filtered with a filter paper and then concentrated under reduced pressure using a vacuum rotary concentrator. After that, it was cooled in a deep freezer for one day and freeze-dried. The freeze-dried Centella asiatica hot-water extract was dissolved in DMSO (dimethyl sulfoxide) solvent at a concentration of 1 g/ml, used for cell experiments, and dissolved in DW to be used for animal experiments.

[Experimental Example: In vitro experiment]

Experimental Example 1: Androgen signaling-related factor expression inhibitory ability analysis

LNCaP cells are treated with testosterone propionate (TP) to induce cell proliferation, and after treatment with the Centella asiatica extract of Example 1, AR (androgen receptor), 5AR2 (5 alpha reductase), PSA (prostate specific antigen) ) was confirmed for the expression inhibitory effect.

Specifically, the inhibitory ability of androgen signaling related factors of Centella asiatica in LNCaP cells was confirmed. ^{After seeding 2 x 10 6} LNCaP cells in a 6-well plate, 100 nM testosterone (testosterone propionate, TP) and Centella asiatica extract (CA) of Example 1 were added to each concentration at 250, 500 or 1000 μg/ml. 24 hours treatment. At this time, the androgen inhibitory drug, finasteride (Fi) 1㎍ / ㎖ treatment group was used as a positive control group.

After the cells were treated, the expression levels of androgen signaling-related factors AR, 5AR2 and PSA were measured using Western blot, and the band intensity was determined using image J (NIH ver. 1.48, USA) to determine the area of each sample. Afterwards, the area of the relative β-Actin was set in the same way and quantified by dividing the value. Accordingly, the result of the Western blot experiment is shown in FIG. 1 , the measurement result of the AR protein expression level is shown in FIG. 2 , the 5AR2 protein expression level measurement result is shown in FIG. 3 , and the PSA protein expression level measurement result is shown in FIG. 4 . It was.

According to this, according to the treatment of Centella asiatica extract of Example 1, the expression levels of AR, 5AR2 and PSA proteins tended to decrease in a concentration-dependent manner. and the 1000 μg/ml treatment group showed a very high expression level inhibition ability at a slightly higher level than the finasteride drug treatment group.

[Experimental example: in vivo experiment]

8-week-old male SD rats (weight 200±5 g) experimental animals were divided into 5 groups as summarized in Table 1 below, and then, the BPH-induced group was intraperitoneally administered 50 mg/kg of phenobarbital after 1 week of rest. After injection and anesthesia, the testes and epididymis were removed and the surgical site was sutured using a suture thread. All experiments were conducted in a sterile environment. After 3 days of surgical stabilization, the benign prostatic hyperplasia induced group (BPH) induced BPH by dissolving testosterone in corn oil and subcutaneously injecting it daily at a concentration of 3 mg/kg. Centella asiatica administration group (BPH+CA200) was orally administered by dissolving the Centella asiatica extract of Example 1 in sterile distilled water and using a weekly sonde at 200 mg/k. The positive control group (BPH+Saw) administered saw palmetto dissolved saw palmetto in sterile distilled water and administered 100mg/kg, and the finasteride-administered group (BPH+Fi) was orally administered with 1mg/kg of saw palmetto daily for 4 weeks using a sonde. . After completion of the experiment, mice were sacrificed using zoletil, blood was collected through a heart puncture, and serum was separated and stored at -80°C. After separating the prostate with a surgical instrument from which RNAse has been removed, it was stored at -80°C, and then a Western blot experiment was performed.

group number of individuals Dosage substance and concentration Con 6 - BPH 6 Testosterone (3 mg/kg) BPH+CA200 6 Centella asiatica extract (200 mg/kg) BPH+Saw 6 Saw Palmetto (100 mg/kg) BPH+Fi 6 Finasteride (1 mg/kg)

Experimental Example 2: Measurement of prostate size and epithelial cell thickness

A photograph of the prostate of each separated experimental group and the result of measuring and comparing the weight of the prostate are shown in FIG. 5 , and the measurement result of the prostate index is shown in FIG. 6 .

According to this, it was confirmed that the prostate enlargement inducing group (BPH) significantly increased the size of the prostate compared to the control group. On the other hand, the size (weight) of the prostate and the prostate index were significantly decreased in the group treated with Centella asiatica (BPH+CA200) compared to the hypertrophy-inducing group (BPH).

On the other hand, the micrograph of the prostate epithelial cells of each experimental group and the results of measuring the thickness of the epithelial cells are shown in FIG. 7 .

According to this, it was confirmed that the prostate hyperplasia inducing group (BPH) significantly increased the thickness of prostate epithelial cells compared to the control group. On the other hand, it was confirmed that the epithelial cell thickness of the prostate was significantly decreased in the group treated with Centella asiatica (BPH+CA200) compared to the hypertrophy-inducing group (BPH).

Experimental Example 3: Androgen signaling-related factor expression inhibitory ability analysis

Western blot experiments detailing the protein expression of androgen signaling related factors SRC-1 (steroid receptor coactivator), AR (androgen receptor), 5AR2 (5alpha reductase), and PSA (prostate specific antigen) for the animal test groups The results of the analysis are shown in FIG. 8 .

According to this, the expression of androgen signaling-related factors in the Centella asiatica administration group (BPH+CA200) showed a significant overall decrease compared to the BPH inducing group, and in particular, the AR expression amount was significantly reduced.

Experimental Example 4: Growth factor (Grow factor) expression inhibitory ability analysis

According to the British Journal of Cancer, 101(12), 1949-1956, it is known that epidermal growth factor plays a role in releasing androgen control in prostate cancer. 9 is shown. Growth factors are transcribed in the androgen response element (ARE) due to androgen signaling, and thus the expression level tends to increase. Growth factors can be seen as a major factor inducing BPH.

(Transforming growth factor beta 1), VEGF(Vascular endothelial growth factor)의 발현량이 전립선 비대증 유발군(BPH)에 비해 유의적으로 감소한 것을 확인할 수 있었다.Accordingly, in order to confirm whether the administration of Centella asiatica extract in this experimental example reduces the expression of growth factors in the prostate in mice induced by prostatic hyperplasia, a Western blot experiment was performed as described above for the experimental groups, and the results are shown in FIG. shown in According to this, prostatic hyperplasia was the growth factors EGF (Epidermal growth factor), IGF-1 (Insulin like growth factor I), TGF-1 in the Centella asiatica administration group (BPH+CA200).

(Transforming growth factor beta 1), it was confirmed that the expression levels of VEGF (Vascular endothelial growth factor) significantly decreased compared to the BPH-induced group.

Experimental Example 5: PI3K / Akt and HIF-1 signaling pathway (signaling pathway) related factor expression inhibitory ability analysis

Previously, in Experimental Example 4, it was confirmed that the Centella asiatica administration group (BPH+CA200) suppressed androgen signaling and thereby suppressed the expression of epidermal growth factor (EGF). On the other hand, PI3K/Akt and HIF-1 signaling pathway related factors, PI3K (phosphatidylinositol-3-kinase), Akt (protein kinase B), PTEN (phosphatase and tensin homologue), HIF-1 (Hypoxia- Western blot experiments were performed as described above to confirm whether the expression of inducible factors) is suppressed. For reference, a schematic diagram of the PI3K/Akt and HIF-1 signaling pathways is shown in FIG. 11 , and the western blot test results are shown in FIG. 12 .

According to this, the expression of all related factor proteins except for PTEN, which is a factor that inhibits PI3K among related factors of PI3K/Akt and HIF-1 signaling pathways derived from epidermal growth factor (EGF) in the Centella asiatica administration group (BPH+CA200) was found to be high.

Experimental Example 6: Analysis of ability to inhibit expression of cell proliferation-related factors in prostate tissue

The expression of PCNA (Proliferating Cell Nuclear Antigen) and Cyclin D1 (Cyclin D1) proteins, which are representative factors related to cell proliferation in prostate tissue, was analyzed by the above-described Western blot experiment, and the results are shown in FIG. 13 . According to this, the analysis. It was confirmed that PCNA and Cyclin D1 protein expression was decreased in the centella asiatica treated group (BPH+CA200) compared to the prostatic hyperplasia inducing group (BPH).

In the above, although embodiments of the present invention have been described, those of ordinary skill in the art can add, change, delete or add components within the scope that does not depart from the spirit of the present invention described in the claims. The present invention may be variously modified and changed by, etc., and this will also be included within the scope of the present invention.

Claims (12)

Centella asiatica A pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia comprising an extract as an active ingredient. According to claim 1,
The Centella asiatica extract is a pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia, characterized in that it is extracted with water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof. According to claim 1,
The pharmaceutical composition is a pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia, characterized in that it is for inhibiting the expression of androgen signaling related factors. 4. The method of claim 3,
The androgen signaling related factor is SRC-1 (steroid receptor coactivator), AR (androgen receptor), 5AR2 (5alpha reductase), and PSA (prostate specific antigen), characterized in that any one selected from prostate enlargement or androgenetic alopecia prevention or a therapeutic pharmaceutical composition. According to claim 1,
The pharmaceutical composition is a pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia, characterized in that it is for inhibiting the expression of growth factors in the prostate. 6. The method of claim 5,
The growth factor in the prostate is characterized in that any one selected from EGF (Epidermal growth factor), IGF-1 (Insulin like growth factor I), TGF-1β (Transforming growth factor beta 1), and VEGF (Vascular endothelial growth factor) A pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia. According to claim 1,
The pharmaceutical composition is a pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia, characterized in that it is for suppressing the expression of PI3K/Akt and HIF-1 signaling related factors. 8. The method of claim 7,
The PI3K/Akt and HIF-1 signaling-related factors are prostatic hypertrophy or A pharmaceutical composition for preventing or treating androgenetic alopecia. According to claim 1,
The pharmaceutical composition is a pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia, characterized in that it is for suppressing the expression of cell proliferation-related factors in prostate tissue. According to claim 1,
The proliferating cell proliferation-related factor in the prostate tissue is PCNA (Proliferating Cell Nuclear Antigen) or cyclin D1 (Cyclin D1), a pharmaceutical composition for preventing or treating benign prostatic hyperplasia or androgenetic alopecia. Centella asiatica ( Centella asiatica ) Food composition for preventing or improving prostatic hyperplasia or androgenetic alopecia comprising an extract as an active ingredient. Centella asiatica ( Centella asiatica ) Health functional food for preventing or improving prostatic hyperplasia or androgenetic alopecia, comprising a food composition comprising an extract as an active ingredient.

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