• Title/Summary/Keyword: Finasteride

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Pharmacological Comparison of Timosaponin A III on the 5-beta Reductase and Androgen Receptor via In Silico Molecular Docking Approach (In silico 약리학적 분석을 통한 티모사포닌 A III의 5-베타 리덕타아제 단백질 및 안드로겐 수용체 단백질 활성 부위에 대한 결합 친화도 비교 연구)

  • Kim, Dong-Chan
    • Journal of Life Science
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    • v.28 no.3
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    • pp.307-313
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    • 2018
  • Alopecia cause psychological stress due to their effect on appearance. Thus, the global market size of the alopecia treatment products are growing quickly. Timosaponin A III is the well known active ingredient of Anemarrhenae Rhizoma. In this study, we investigated and compared the binding affinity of timosaponin A III with finasteride (5-beta reductase antagonist) and minoxidil (androgen receptor antagonist) on the target protein active site by in silico computational docking studies. The three dimensional crystallographic structure of 5-beta reductase (PDB ID : 3G1R) and androgen receptor (PDB ID: 4K7A) was obtained from PDB database. In silico computational autodocking analysis was performed using PyRx, Autodock Vina, Discovery Studio Version 4.5, and NX-QuickPharm option based on scoring functions. The timosaponin A III showed optimum binding affinity (docking energy) with 5-beta reductase as -12.20 kcal/mol as compared to the finasteride (-11.70 kcal/mol) and with androgen receptor as -9.00 kcal/mol as compared to the minoxidil (-7.40 kcal/mol). The centroid X, Y, Z grid position of the timosaponin A III on the 5-beta reductase was similar (overlap) to the finasteride, but the X, Y, Z centroid grid of the timosaponin A III on the androgen receptor was significantly far from the minoxidil centroid position. These results significantly indicated that timosaponin A III could be more potent antagonist to the 5-beta reductase and androgen receptor. Therefore, the extract of Anemarrhenae Rhizoma or timosaponin A III containing biomaterials can substitute the finasteride and minoxidil and can be applied to the alopecia protecting product and related industrial fields.

Four Cases of Androgenetic Alopecia Patient using Korean Medicine Treatment and Western Treatment (한양방 치료를 병행한 남성형 탈모 환자 4례 증례 보고)

  • Yoon, Young-Joon;Kwon, Na-Hyun;Shin, Hyun-Jin;Jang, Jin-Young
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.30 no.2
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    • pp.170-177
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    • 2017
  • Objectives : The purpose of this study is to report the effectiveness of the combination of herbal medicine and western medicine in androgenetic alopecia patients. Methods : This case study was conducted for four androgenetic alopecia patients who have visited Korean medicine clinic. Gagamcheongyoung-tang($Ji{\bar{a}}ji{\check{a}}nq{\bar{i}}ngy{\acute{i}}ng-t{\bar{a}}ng$) was prescribed to all four patients who were already taking finasteride over 1 year. Improvements of patients were evaluated through photographs. Results : As a result of examining photographs, symptoms of alopecia in four cases were improved. Conclusions : Gagamcheongyoung-tang($Ji{\bar{a}}ji{\check{a}}nq\;{\bar{i}}ngy{\acute{i}}ng-t{\bar{a}}ng$) has advantages of treating a androgenetic alopecia patients who are taking finasteride longer than 1 year.

Determination of finasteride in human serum by LC-MS/MS (LC-MS/MS를 이용한 혈청 중 finasteride 분석)

  • Nam, Hye-Seon;Nam, Kyong-Hee;Jung, Su-Hee;Lee, Jang-Woo;Kang, Jin-Yeong;Hong, Soon-Keun;Kim, Tae-Sung;Kang, Tae-Seok;Yoon, Hae-Jung;Lee, Kwang-Ho;Rhee, Gyu-Seek
    • Analytical Science and Technology
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    • v.24 no.5
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    • pp.345-351
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    • 2011
  • A liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) method was developed and validated for the determination of finasteride in human serum. Beclomethasone was used as internal standard (IS) and liquid-liquid extraction (LLE) using methyl tert-butyl ether (MTBE) was carried out to isolate analyte. The mass transitions monitored in multiple reaction monitoring (MRM) in positive ion mode were m/z 373.2${\rightarrow}$305.2 for finasteride and m/z 409.3${\rightarrow}$391.2 for IS. Retention times of finasteride and IS were 5.81 and 5.46 min, respectively. The limit of quantitation (LOQ) was 0.1 ng/mL and the calibration curve showed good linearity in the range of 0.1~20.0 ng/mL ($R^2$=0.9997). The intra-day assay precision and accuracy were in the range 6.3~10.6% and 97.3~103.6%, respectively, and the inter-day assay precision and accuracy were in the range 0.8~5.2% and 99.8~102.5%, respectively. The sample extract recovery of the method was 80~83%.

The Antihyperplastic Effect of Oral Curcuma longa Ingestion in a Rat Model of Benign Prostatic Hyperplasia (강황(薑黃)이 고환절제술 및 testosterone으로 유발된 rat의 전립선비대증에 미치는 영향)

  • Lee, Sang-Hun;Ahn, Young-Min;Ahn, Se-Young;Kim, Young-Ock;Lee, Byung-Cheol
    • The Journal of Internal Korean Medicine
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    • v.30 no.2
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    • pp.355-364
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    • 2009
  • Objectives : Benign prostatic hyperplasia (BPH) is one of the most common diseases among elderly men. Though medicines such as 5${\alpha}$-reductase inhibitor (finasteride) have recently been developed for treating BPH, their adverse effects and low efficacy should not be overlooked. Curcuma longa has a long history of use in traditional medicines of Asian countries. Many reports conclude the component curcumin in Curcuma lonfa, has the potential to treat various diseases including prostate cancer. In this study, we investigated the therapeutic effects and action mechanism of Curcuma longa with a BPH rat model. Methods : Sprague-Dawley rats were used with subcutaneous injection of testosterone after castration, which were histologically similar to human BPH. A total of 30 rats were equally divided into five groups: Group 1 served as control (sham-operated group): Group 2 was the model group: Group 3 and Group 4 animals were administered Curcuma longa at dose levels of 0.5g/kg and 1.0g/kg: Group 5 served as a positive control group and was treated with finasteride at a dose of 1 mg/kg. The drugs were administered orally once a day for 30 days consecutively. After 31 days, the prostates were removed, and analyzed for their prostatic weight and histological examination. Results : The oral Curcuma longa ingestion group showed statistically significant decreases in their prostatic weights compared with the BPH-induced group and the oral finasteride ingestion group (p<0.05). Curcuma longa is also very safe in liver and kidney up to a dose of lg/kg. Injected testosterone histologically led to prostatic hyperplasia in rats, but oral Curcuma longa ingestion decreased this change. Conclusions : These results suggest that Curcuma longa has a definite inhibitory effect on BPH and might be an alternative medicine for treatment and prevention of human BPH.

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Effect of Oral Administration of Houttuynia Cordata Extract on Benign Prostatic Hyperplasia (전립선비대증의 어성초추출물에 의한 경구투여 효과)

  • Song, Won-Yeong;Choi, Jeong-Hwa
    • Journal of Life Science
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    • v.29 no.6
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    • pp.705-711
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    • 2019
  • Benign prostatic hyperplasia (BPH) is the most common urogenital disorder in men, benign tumor and is a typical disease deteriorating the quality of old men's lives, and its prevalence increases with age. Though the molecular pathogenesis of BPH has not yet been clearly revealed, it is known that the variation and aging of the endocrine including sex hormone may cause BPH. Especially the hypertrophy of the prostate cell by the formation of the excessive dihydrotestosterone (DHT) is estimated to cause BPH. If testosterone exists excessively in blood, a lot of DHT is produced in prostate by $5{\alpha}-reductase$. Thus, in this study we tried to analyze haematological change and histopathological change by using the model rat with BPH caused by hypodermic injection of testosterone to prove the effect of Houttuynia cordata extracts on BPH. Rats were divided into four experimental groups: no treatment group (N), the testosterone injection and D.W treatment group (DO), the testosterone injection and Houttuynia cordata treatment group (HO) and testosterone injection and finasteride treatment group (FO). Prostate weight, volume and weight ratio in the HO and FO groups were significantly lower than the DO group. Testosterone and DHT levels in the HO group were significantly lower than the DO group. The HO and FO groups showed trophic symptoms and were lined by flattened epithelial cells, thus, the stromal proliferation is relatively low as compared to the DO group. These results suggest that Houttuynia cordata may control benign prostatic hyperplasia.

The Effect of the Compound of Tomato Extract to the Prostatic Cancer Cell and the Prostate of the Rat Model of Benign Prostatic Hyperplasia (토마토 추출액 복합체가 전립선 암 세포와 전립선 비대증에 미치는 영향)

  • Kang, Han-Saem;Kim, Gwang-Yun;Jung, Il;Oh, Sung-Dug;Kim, Chang-Hoon;Shim, Bong-Sup;Park, Keun-Hyung;Oh, Suk-Jung
    • Korean Journal of Pharmacognosy
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    • v.38 no.2 s.149
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    • pp.197-203
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    • 2007
  • Benign prostatic hyperplasia (BPH) is one of the common disease in elderly men. Recently old-age population is increased and we are growing more and more interested in clinical importance of BPH. In this study, the effect of PLX, which was the mixture of tomato extract (including 2% of lycopene) and chitooligosaccharide, on prostatic cancer cell and testosterone-induced BPH in adult rats of the Sprague Dawley strain was determined. The cell viability was evaluated by MTT method using L929 and LNCaP cell line, pretreated with various concentrations of PLX. The expression of prostatic specific antigen (PSA) and 5${\alpha$}$-reductase genes were evaluated by realtime PCR using LNCaP cell line and compared various concentrations of PLX with 50 ${\mu}$M of finasteride. An experimental prostatic hyperplasia was induced in male Sprague Dawley rats by giving testosterone for 8 weeks. After 2 weeks from start of giving testosterone, PLX and finasteride were administered orally once a day. The results were analyzed with prostate weight per body weight at 8 weeks. Cell viability of L929 cell line decreased specifically at the concentration of 2000 ${\mu}$g/mf of PLX. The cytotoxicity of PLX to the LNCaP cell line was shown at above 500 ${\mu}$g/ml of PLX. The inhibitory effect of PLX to the expression of PSA and 5${\alpha$}$-reductase genes in LNCaP cell line increased with the concentration of PLX. In vivo study, the results of PLX and finasteride administered group were 3.75${\pm}$0.60 and 3.49${\pm}$0.49 prostate weight ${\times}10^3$/body weight, which were lower than the result of BPH induced group (4.74${\pm}$0.58). These results suggested that PLX may be an effective material in BPH by having the role of the 5a-reductase inhibitor.

Determination of Optimal Dosage of Ethanol Extract of Houttuynia cordata Thunberg Against Benign Prostatic Hyperplasia (전립선 비대증에 대한 Houttuynia cordata Thunberg 에탄올 추출물의 최적용량 결정)

  • Lee, Jin Young;Kim, Hyung Hoi;Kang, Jae Seon
    • Journal of Life Science
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    • v.31 no.7
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    • pp.631-640
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    • 2021
  • Houttuynia cordata Thunberg has been studied for a variety of pharmacological actions in traditional oriental medicine. In this study, we investigated the effects of Houttuynia cordata ethanol extract (HCE) on benign prostatic hyperplasia (BPH) models induced by castration and testosterone propionate (TP) injection. Thirty rats were divided into six groups. One group was used as a normal control, and the other groups were castrated and had intraperitoneal injections of TP for 14 days to induce BPH. A positive control group was given daily doses of finasteride (5 mg/kg) to the BPH model. Rats administered HCE (0.5, 1 or 2 mg/kg) instead of finasteride were compared with controls as experimental groups. There was no statistical significance in terms of prostate weight based on 100 g of body weight. The concentrations of 5-α reductase and dehydroxytestosteronre (DHT) were determined via ELISA tests, and there was a significant decrease in all experimental groups. The 0.5 mg/kg HCE group had the lowest level of 5-α reductase, and the 2 mg/kg HCE group had the lowest level of DHT. In the histopathological observation of prostates, the control and the 2 mg/kg HCE groups had normal cell shapes and no swelling. However, in the negative control group and the 1 mg/kg HCE group, the cells were swollen, and the gap between the cells was narrowed. In particular, in the 0.5 mg/kg HCE group, some cells were bursting. Therefore, the administration of more than 2 mg/kg of HCE is suitable to protect against BPH.

Effect of Hot Water Extract from Curcuma longa L. on Inflammatory Mediators in Prostate Tissue of BPH-Induced Rats (전립선 비대유도 쥐의 전립선 조직에서 울금 급여에 따른 염증인자의 변화)

  • Lee, Jeong Yoon;Kim, Yungjae;Jun, Woojin;Lee, Yoo-Hyun
    • Journal of the East Asian Society of Dietary Life
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    • v.25 no.5
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    • pp.806-812
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    • 2015
  • Prostatic inflammation plays a crucial role on benign prostate hyperplasia (BPH) pathogenesis and progression. In this study, BPH was induced by testosterone propinate in castrated rats for 8 weeks. Hot water extract from Curcuma longa L. (CL) was administered orally for 4 weeks along with positive controls, saw Palmetto and finasteride. CL supplementation induced histological changes, reduced expression of TNF-${\alpha}$, IL-6, IL-$1{\beta}$, COX-2, and phospo-p65 in prostate tissue compared with the BPH group. These findings suggest that suppression of pro-inflammatory cytokines could be attributed, at least partly, to the anti-inflammatory action of C. longa, and this action may be helpful to understand the inhibitory effect of Curcuma longa L. in BPH.

Comparative GC-MS Based In vitro Assays of 5α-Reductase Activity Using Rat Liver S9 Fraction

  • Lee, Su-Hyeon;Lee, Dong-Hyoung;Lee, Jeong-Ae;Lee, Won-Yong;Chung, Bong-Chul;Choi, Man-Ho
    • Mass Spectrometry Letters
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    • v.3 no.1
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    • pp.21-24
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    • 2012
  • $5{\alpha}$-Dihydrotestosterone (DHT) is the primary active metabolite of testosterone, catalyzed by $5{\alpha}$-reductase ($5{\alpha}R$) in the skin, prostate, and liver. In this study, the $5{\alpha}R$ activity in rat liver S9 fraction in the presence of a NADPH-generating system was evaluated and compared by gas chromatography-mass spectrometry (GC-MS)-based in vitro assays. Testosterone and a $5{\alpha}R$ inhibitor, finasteride, were added to the S9 fractions and incubated at $37^{\circ}C$ for 1 h. Both testosterone and DHT were quantitatively measured and compared with two different GC-MS-based steroid profiling techniques. DHT was not detected by conventional GC-MS analysis in the absence of finasteride when the concentration of testosterone in the S9 fraction was less than $0.2{\mu}M$, whereas the isotope-dilution GC-MS (GC-IDMS) system was able to evaluate the $5{\alpha}R$ activity. Because the S9 fraction contains more reactive enzymes and is easier to collect from tissues compared with a microsomal solution, the combination of the S9 fraction and GC-IDMS technique may be a promising assay for evaluating the $5{\alpha}R$ activity in large-scale clinical studies.