Application of cibotium barometz extract and medicament for inhibiting prostatic hyperplasia

Abstract

The invention discloses an application of a rhizoma cibotii extract and a medicament for inhibiting prostatic hyperplasia. According to the present invention, the prostatic hypertrophy inhibition effect is provided, and the new practical value of the cibotium barometz is increased.

Description

Technical Field

[0001] The present invention relates to a use of a Pteris chinensis extract and a medicament, in particular to a use of the Pteris chinensis extract in inhibiting prostatic hypertrophy and a medicament. The present invention belongs to the field of medical technology. Background Art

[0002] At present, prostate hypertrophy is common in middle-aged and elderly men, mainly due to prostate hyperplasia leading to lower urinary tract syndrome, whose symptoms include frequent urination and nocturia, seriously affecting the quality of life. Causes of prostate hyperplasia include metabolic diseases, obesity, hypertension, hyperlipidemia, diabetes, etc., which are related to cell growth regulated by dihydrotestosterone (DHT). Dihydrotestosterone is a metabolite of testosterone via 5α-reductase. Dihydrotestosterone binds to androgen receptors in the cell nucleus and stimulates the proliferation of prostate epithelial cells and stromal cells, thus causing prostate hypertrophy.

[0003] At present, adrenaline inhibitors α1-blockers include terazosin, doxazosin, tamsulosin, alfuzosin and silodosin and 5α-reductase inhibitors, which are the most commonly used drugs for the treatment of prostate hypertrophy. Among them, 5α-reductase inhibitors include finasteride and dutasteride, which have the effect of inhibiting the production of dihydrotestosterone and downstream prostate-specific antigen (PSA). In the testosterone-induced prostate hypertrophy animal model, the expression of Nrf2 in prostate tissue sections is inversely proportional to inflammatory precursors. Nrf2 is a transcription factor that resists oxidative stress. By activating Nrf2 expression, the inflammatory response of prostate cells can be inhibited and the phenomenon of prostate cell hyperplasia can be slowed down.

[0004] Cibotium, belonging to the Dicksoniaceae family, is also known as the Philippine Cibotium. Among the edible ferns listed in Taiwan, China, the edible parts are the stems and young leaves. Its roots and stems are also used as traditional Chinese medicine. It has the effects of nourishing the liver and kidneys, strengthening the tendons and bones, dispelling wind and dampness, and treating arthritis and sciatica. Cibotium contains volatile oils, flavonoids, pteridin, sugars, glycosides, sterols, amino acids, phospholipids and other ingredients, and has antioxidant, anti-osteoporosis, liver protection, anti-cancer, antibacterial and antiviral effects. According to the literature, the ethyl acetate layer after extraction of Pteris crenata with methyl tert-butyl ether (MTBE) / ethanol (EtOH) (80 / 20) and methanol can promote the proliferation of LNCaP cell lines, but the compounds contained in it do not significantly affect the proliferation of LNCaP or PC-3 cell lines, so it does not have anti-androgenic or cytotoxic properties (Journal of Ethnopharmacology, 155 (2014) 721-730).

[0005] In summary, there is currently no literature showing that the extract of Pteris crenata has the effect of inhibiting prostate hypertrophy. Summary of the invention

[0006] The main purpose of the present invention is to provide a use of a Pteris chinensis extract and a medicament for inhibiting prostatic hypertrophy.

[0007] The invention provides a use of a Pteris chinensis extract for inhibiting prostatic hypertrophy.

[0008] In one embodiment of the use of the extract of Pteris chinensis of the present invention, the extract of Pteris chinensis is obtained by subjecting Pteris chinensis to water extraction.

[0009] The present invention is used to prepare a compound recipe of golden dog hair fern for treating prostatic hypertrophy, wherein the golden dog hair fern and goat teat are ground into powder and mixed before water extraction, and then extracted together, wherein the mixing weight ratio of the golden dog hair fern and goat teat is 0.8g-1.2g:0.5g-1.8g.

[0010] In one embodiment of the use of the extract of the present invention, the Pteris chinensis is an underground part of the Pteris chinensis.

[0011] In one embodiment of the use of the extract of Pteris chinensis of the present invention, the underground part is at least one of a tuber, hairs and roots.

[0012] The present invention provides a medicament for inhibiting prostatic hypertrophy, comprising: a Pteris chinensis extract.

[0013] In one embodiment of the medicament for inhibiting prostatic hypertrophy with Pteris crenata, the Pteris crenata extract is mixed with goat teat, ground into powder, and then subjected to water extraction.

[0014] In order to enable a further understanding of the purpose, features and effects of the present invention, embodiments are listed and described in detail with reference to the accompanying drawings as follows: BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 This is the concentration of extracts from various parts of Pteris crenata that can inhibit the growth of human prostate cell line LNCaP by 50%.

[0016] Figure 2 The expression levels of 5-α reductase SDA1 and prostate-specific antigen PSA, which are the targets of prostate hypertrophy drugs.

[0017] Figure 3 is the expression level of oxidative stress proteins related to prostate hypertrophy.

[0018] Figure 4 The water extract of Pteris crenata inhibits the expression of prostate-specific antigen PSA by activating Nrf2.

[0019] Figure 5 The mixed extract of golden dog hair fern and goat milk teat can enhance the inhibition of the expression of prostate-specific antigen PSA and 5-α reductase SRD5A2. DETAILED DESCRIPTION

[0020] Please refer to Figures 1 to 5 The experimental results will illustrate the use of the golden dog hair fern extract of the present invention, which is used to prepare a drug for inhibiting prostatic hypertrophy, and the medicament for inhibiting prostatic hypertrophy of the present invention.

[0021] Please refer to Figure 1 , Figure 1 The concentration of extracts from various parts of Pteris chinensis that inhibits the growth of human prostate cell line LNCaP by 50%, and the unit of concentration is μg / mL. This experiment selected the prostate cell line LNCaP expressing androgen receptors as the test for the effect of extracts from various parts of Pteris chinensis on the growth of prostate cell line LNCaP. This experiment added different concentrations of extracts from various parts of Pteris chinensis to the prostate cell line LNCaP for 24 hours, and then added presto blue reagent to detect the survival rate of the prostate cell line LNCaP. Among them, 40μg / mL of Pteris chinensis water extract inhibited the growth of prostate cell line LNCaP by 30%±2.55. In addition, Figure 1The concentration of the water extract of golden dog fern hair that inhibits the growth of 50% of the human prostate cell line LNCaP is 54.9μg / mL. The water extracts or wine extracts of the tubers, roots, leaves and phial of other parts of golden dog fern require higher concentrations to inhibit the growth of 50% of the human prostate cell line LNCaP. This shows that the water extracts or wine extracts of the tubers, roots, leaves and phial of parts of golden dog fern are not as effective as the water extract of golden dog fern hair in inhibiting the human prostate cell line LNCaP.

[0022] Figure 2 M is culture medium; D1 means adding 1 nM dihydrotestosterone (DHT); D10 means adding 10 nM dihydrotestosterone; CBH is water extract of golden dogtail fern hair; CBS is water extract of golden dogtail fern tuber; CBR is water extract of golden dogtail fern root; the numbers after CBH, CBS and CBR are the concentrations used, in μg / mL; FIN2 is 2 μM finasteride, a 5-α reductase inhibitor; GAPDH is glyceraldehyde-3-phosphate dehydrogenase gene; PSA is prostate-specific antigen; and SDA1 is 5-α reductase gene.

[0023] Figure 2 The experiment was to add extracts of golden dog fern, including golden dog fern hair water extract CBH, golden dog fern tuber water extract CBS, golden dog fern root water extract CBR, to detect the expression of 5-α reductase gene SDA1 and prostate specific antigen PSA in LNCaP cells. The experiment showed that FIN2 as a positive control group inhibited the expression of 5-α reductase gene SDA1, golden dog fern tuber water extract CBS inhibited the expression of 5-α reductase gene SDA1, and golden dog fern root water extract CBR inhibited the expression of prostate specific antigen PSA.

[0024] Figure 3 is the expression level of oxidative stress proteins related to prostate hypertrophy, where M is culture medium; DHT is dihydrotestosterone; CBH is water extract of golden dog fern hair; CBR is water extract of golden dog fern root; CBS is water extract of golden dog fern tuber; the numbers after CBH, CBR and CBS are the usage concentrations, in μg / mL; FIN2 is 2μM finasteride's 5α-reductase inhibitor, PSA is prostate-specific antigen; HO-1 is hemosiderin oxidase-1; keap-1 is kelchlike ECH associated protein 1, which is a linker protein responsible for regulating intracellular redox; GAPDH is glyceraldehyde-3-phosphate dehydrogenase.

[0025] Figure 3In the experiment, after adding 10nM dihydrotestosterone DHT to stimulate prostate cells, it can be observed that the expression of PSA increased. The water extract of the root of golden dog fern CBR and the water extract of the tuber of golden dog fern CBS inhibited the expression of PSA protein induced by DHT, while the water extract of the hair of golden dog fern CBH had no effect on inhibiting PSA. In addition, 2μM Finasteride can also effectively inhibit the expression of PSA. The expression levels of HO-1 and Keap-1 related to the reactive oxygen species (ROS) pathway induced by DHT were further confirmed. The results showed that the water extract of the root of CBR and the water extract of the tuber of CBS could promote the expression of HO-1 and Keap-1, but finasteride had no effect on the promotion of the expression of HO-1 and Keap-1. It can be inferred that the water extract of the root of CBR and the water extract of CBS inhibit the expression of the PSA protein, a downstream gene of dihydrotestosterone DHT, by inducing the ROS pathway.

[0026] Figure 4 The water extract of Pteris cretica inhibits the expression of prostate-specific antigen by activating Nrf2, wherein M is culture medium; DHT is dihydrotestosterone; CBS is the water extract of Pteris cretica tuber; CBW is the water extract of the edible parts of Pteris cretica, which includes the water extract of tuber, root and hair; the numbers after CBS and CBW are the usage concentrations in μg / mL; GAPDH is glyceraldehyde-3-phosphate dehydrogenase; PSA is prostate-specific antigen; Nrf2 is NF-E2-related factor2, which is an antioxidant transcription factor.

[0027] Please refer to Figure 4 Among them, 800μg / mL water extract of the tubers of Pteris cretica (CBS800) and 200μg / m and 400μg / m water extracts of the edible parts of Pteris cretica (CBW200 and CBW400) induced Nrf2 expression in prostate cells and inhibited the expression of PSA protein. This proves that the water extract of the tubers of Pteris cretica CBS and the water extract of the edible parts of Pteris cretica (including water extracts of tubers, roots and hairs) CBW both have the effect of activating Nrf2 transcription factor and inhibiting the excessive oxidation of dihydrotestosterone (DHT) in prostate cells.

[0028] The extract of golden dog hair fern is obtained by extracting golden dog hair fern, which is carried out by water extraction in this embodiment. Furthermore, the present invention provides another embodiment that before water extraction, the golden dog hair fern can be mixed with the Chinese herbal medicine of goat teat and extracted together. Among them, in addition to the aforementioned goat teat having the effect of inhibiting prostate hypertrophy, a Chinese herbal compound with the effect of inhibiting prostate hypertrophy can also be used, and these Chinese herbal compound prescriptions are described as follows.

[0029] The Chinese herbal medicine for assisting in inhibiting prostatic hypertrophy can be the ten common medicinal materials for prostatic hypertrophy summarized in the literature of clinical treatment of Chinese herbal medicine of the University of Hong Kong (Asian J Androl. 2013 Jul; 15 (4): 471-482.), including: cinnamon (Cortex Cinnamomi), astragalus (Radix Astragali), pangolin (Manispentadactyla Linnaeus), radix rehmanniae perparata (Radix Rehmanniae Perparata), cornus officinalis (Fructus Corni), tuckahoe (Poria), zedoaria (Rhizoma Curcumae), phellodendri (Cortx Phellodendri), rhizoma alismatis (Rhizoma Alismatis) and semen vaccrriae (Wang Bu Liu Xing).

[0030] In the embodiment, one of the extraction methods is as follows: take a Chinese herbal medicine of golden dog hair fern or golden dog hair fern and goat milk head (mixed weight ratio is 0.8g~1.2g:0.5g~1.8g), wash and grind into a powder (size is about: 100-300 microns), extract for 1~2 hours by hot reflux method, filter the residue, and concentrate the filtrate to dryness under reduced pressure to obtain the extract of the golden dog hair fern compound. Among them, the golden dog hair fern can be an underground part of golden dog hair fern (including tubers, hairs and roots, so the underground part can be at least one of tubers, hairs and roots), leaves or tissue culture seedlings, and the other Chinese herbal medicine can be goat milk head, and at least one of the stems and roots of the goat milk head can be used for the aforementioned mixed use. In addition, the above extraction method is only one of the extraction methods, and the present invention is not limited to the extraction method described in this embodiment.

[0031] Figure 5 is the expression of prostate-specific antigen PSA and 5-α reductase SRD5A2 inhibited by the mixed extract of Pteris chinensis and Papillae ovata. M is the culture medium; TP0.1 is 0.1 mM testosterone; CB is the water extract of Pteris chinensis tubers; FF is the water extract of Papillae ovata; Mix is ​​the mixed water extract of Pteris chinensis and Papillae ovata; the numbers after CB, FF and Mix are the concentrations used, in μg / mL; GAPDH is glyceraldehyde-3-phosphate dehydrogenase; PSA is prostate-specific antigen; SRD5A2 is 5-α reductase.

[0032] like Figure 5As shown in the results, the mixed water extract of golden dog fern and goat teat, in which goat teat can enhance the effect of the water extract of the edible part of golden dog fern (including the water extract of tuber) in inhibiting the excessive oxidation of testosterone in prostate cells, thus proving that the mixed water extract of golden dog fern and goat teat has the effect of inhibiting prostate hypertrophy. Figure 5 As shown in the content, the experiment of the present invention also found that goat teat alone has the effect of inhibiting prostate hypertrophy.

[0033] According to the above experimental results, the extract of golden dog hair fern and the golden dog hair fern compound (golden dog hair fern and goat teat) of the present invention can be used to prepare drugs for inhibiting prostatic hypertrophy, such as tablets, aqueous solutions or ointments, or for preparing health foods for inhibiting prostatic hypertrophy. In addition, the medicament for inhibiting prostatic hypertrophy of the present invention includes golden dog hair fern extract, or golden dog hair fern extract is obtained by mixing with goat teat, grinding into powder, and then extracting with water. Among them, goat teat can enhance the effect of golden dog hair fern in inhibiting excessive oxidation of testosterone in prostate cells, thereby enhancing the effect of inhibiting prostatic hypertrophy.

[0034] In summary, the uses of the extract of the golden dog fern and the golden dog fern compound and the medicament for inhibiting prostatic hypertrophy of the present invention enable the golden dog fern to have the effect of inhibiting prostatic hypertrophy and increase the new practical value of the golden dog fern.

[0035] Although the present invention has been disclosed by the embodiments as above, they are not intended to limit the present invention. Any person skilled in the art should be able to make some changes and modifications without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention should be based on the definition of the appended claims.

Claims

1. A use of a Pteris chinensis extract, characterized in that: It is used for preparing a drug for inhibiting prostate hypertrophy.

2. The use of the extract of Pteris chinensis as claimed in claim 1, characterized in that: The extract of golden dog hair fern is obtained by subjecting golden dog hair fern to water extraction treatment.

3. The use of the extract of Pteris chinensis as claimed in claim 2, characterized in that: Before water extraction, the golden dog hair fern is mixed with Chinese herbal medicine and extracted together, wherein the mixing weight ratio of the golden dog hair fern and the Chinese herbal medicine is 0.8g-1.2g:0.5g-1.8g.

4. The use of the extract of Pteris chinensis as claimed in claim 3, characterized in that: The golden dog hair fern is an underground part of the golden dog hair fern.

5. The use of the extract of Pteris chinensis as claimed in claim 4, characterized in that: The underground part is at least one of a tuber, hairs and roots.

6. The use of the extract of Pteris chinensis as claimed in claim 3, characterized in that: The Chinese herbal medicine is goat's teat or a Chinese herbal medicine capable of inhibiting prostate hypertrophy.

7. The use of the extract of Pteris chinensis as claimed in claim 6, characterized in that: The method of mixing the golden dog hair fern and the goat teat is to grind them into powder and then mix them.

8. A medicament for inhibiting prostatic hypertrophy, characterized in that: Includes a golden dog hair fern extract.

9. The agent for inhibiting prostatic hypertrophy according to claim 8, characterized in that The golden dog hair fern is ground into powder and then mixed with the ground goat teat or a compound containing the goat teat, and then water extraction is performed, wherein the mixing weight ratio of the golden dog hair fern and the ground goat teat or the compound containing the goat teat is 0.8g-1.2g:0.5g-1.8g.

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