• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 추계학술대회
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• pp.31-31
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• 2018

Benign prostatic hyperplasia (BPH), which is the most common disorder in elderly men, involves androgenic hormone imbalance with chronic inflammation that causes imbalance between cell apoptosis and cell proliferation. As the root cause of the BPH remains unclear and synthetic drugs for treatment of BPH have undesirable side effects, the development of effective alternative medicines has been considered. Chinese Skullcap has been considered natural remedy to treat pyrexia, micturition disorder and inflammation. Although skullcap has effective properties on various diseases, the effects and molecular mechanism of Skullcap on BPH are not fully understood. Therefore, in this study, we evaluated the efficacy of Chinese Skullcap root extract (SRE) in testosterone-induced BPH rats. Compared with the untreated group, the SRE treatment group suppressed pathological alterations, such as prostate growth and increase in serum dihydrotestosterone and $5{\alpha}$-reductase levels. Furthermore, SRE significantly decreased the expression of androgen receptor and proliferating cell nuclear antigen. SRE also restored Bax/Bcl-2 balance. These effect of SRE was more prevalent than commercial $5{\alpha}$-reductase inhibitor, finasteride. Taken together, we propose that SRE suppresses abnormal androgen events in prostate tissue and inhibits the development of BPH by targeting inflammation- and apoptosis-related markers. These finding strengthens that SRE could be used as plant-based $5{\alpha}$-reductase inhibitory alternative.

• 약학회지
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• 제54권6호
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• pp.466-473
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• 2010

A series of $3{\beta}$-substituted 5-androstene-$17{\beta}$-carboxamides were synthesized from analogs of $3{\beta}$-hydroxy-5-androstene-$17{\beta}$-carboxylic acid (1) with tert-butylamine, N,N-diethylamine and 3-aminopyridine and some compounds were epoxidized with mCPBA. A rat prostate testosterone $5{\alpha}$-reductase inhibitory activity of synthesized compounds was assessed by radioimmunoassay using [1,2,6,7-3H]-testosterone as substrate. All synthesized compounds showed lower activity than finasteride and the N-(3-pyridino)-$3{\beta}$-carboxycarbonyloxy-5-androstene-$17{\beta}$-carboxamide (12) showed weak inhibitory activity ($IC_{50}$: $2.4{\times}10^{-7}M$).

• 한국식품영양과학회지
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• 제43권2호
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• pp.318-322
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• 2014

본 연구에서는 울금(Curcuma longa L.)의 다양한 추출물을 대상으로 5-alpha reductase의 활성 저해 정도를 측정하였다. 5-Alpha reductase는 T에서 활성형 남성호르몬인 DHT로 전환을 담당하며, 전립선비대에서는 혈액에서 DHT 농도가 높다. Rat의 전립선조직 균질액과 5-alpha reductase를 과발현시킨 LNCaP 세포 균질액을 대상으로 측정한 결과, $100{\mu}g/mL$의 농도에서 울금의 열수추출물(CL-HW)과 20% 에탄올추출물(CL-E20)이 5-alpha reductase 활성을 효과적으로 저해하였다. 특히 CL-HW는 $100{\mu}g/mL$의 농도에서 80% 이상의 유의적 억제효과를 보였으며, CL-E20은 $50{\mu}g/mL$의 농도부터 80% 이상의 감소효과를 보였다. 이 같은 결과에서 CL-HW 및 CL-E20은 5-alpha reductase의 억제활성이 있으며, 이는 전립선비대 치료소재로 개발될 수 있는 가능성이 있음을 제안한다.

• 생약학회지
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• 제36권1호통권140호
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• pp.9-16
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• 2005

Twenty eight compounds were isolated from the whole plant of Euphorbia jolkinii and evaluated for inhibitory effect on $5{\alpha}-reductase$ activity. Among the tested compounds, 1-desgalloyl eugeniin, hippomanin A, euphorbin D, exocoecarianin, rugosin E, and pentagalloyl glucose showed potent inhibitory effect on the enzyme activity. The inhibitory potency of rugosin E and euphorbin D, which are dimeric ellagitannins on $5{\alpha}-reductase$ activity, was 7-to 8-fold stronger than that of ${\gamma}-linolenic$ acid.

• 한국한의학연구원논문집
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• 제16권2호
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• pp.131-141
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• 2010

Objective : Benign prostatic hyperplasia(BPH) is one of the most common diseased among elderly men. BPH can be treated with alpha-1 adrenergic blocker or $5{\alpha}$-reductase inhibitor(Finasteride) that reduces serum dihydrotestosterone(DHT). Phellodendri Cortex Ex has been broad studied on its chemical components, pharmacological activity, and clinical effects on anti-inflammation, anti-allergy, anti-tumor, immunity, antibacteria and other bioactivities. In this study, we investigated the therapeutic effects and action mechanism of Phellodendri Cortex Ex with a BPH induced by castration and testosterone treatment. Methods : Sprague-Dawley rats were treated with testosterone after castration for induction of experimental benign prostatic hyperplasia, which is similar to human benign prostatic hyperplasia in histopathological profiles. Phellodendri Cortex as an experimental specimen, and Finasteride as a positive control, were administered orally. The prostates were evaluated by histopathological changes, and the expression of $5{\alpha}$-reductase genes. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Phellodendri Cortex Ex showed a diminished range of the tissue damage. In the reverse transcription-polymerase chain reaction(RT-PCR) of $5{\alpha}$-reductase genes, Phellodendri Cortex inhibited the expression of $5{\alpha}$-reductase genes. Conclusions : These findings suggest that Phellodendri Cortex Ex may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the suppression of $5{\alpha}$-reductase. From these results, we suggest that Phellodendri Cortex Ex could be a useful agent for treating the benign prostatic hyperplasia.

• Urogenital Tract Infection
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• 제13권3호
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• pp.79-83
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• 2018

Purpose: The 5 alpha reductase inhibitor (5ARI) reduces the size of the prostate and alleviates lower urinary tract symptoms. After stopping 5ARI, the prostate quickly recovers to its pre-medication size. The purpose of this study was to investigate the factors affecting the restoration of prostate size after 5ARI discontinuation. Materials and Methods: Between March 2009 and May 2017, patients who visited an outpatient clinic and were diagnosed with benign prostatic hyperplasia were selected and start 5ARI medication. After 6 months of medication, the patients stopped medication for 1 year. Meanwhile, we measured the prostate volumes of patients 3 times (before and after medication, after discontinuation) and divide the patients into 3 groups (maintained, intermediate, and restored) with recovered prostate volume ratio. After classification, we investigated the relationship between the variable factors (age, serum prostate-specific antigen, initial volume, reduced volume after medication) between groups. Results: Among the 147 selected patients, the mean age and plasma PSA level were $61.6{\pm}7.9$ and $0.8{\pm}0.6$, respectively. The mean initial prostate volume was $32.3{\pm}4.2ml$, which reduced to $23.2{\pm}3.2ml$ after medication. After one year of discontinuation, the mean volume was $31.4{\pm}6.4ml$, with restoration to 101.5% of the reduced size. We noticed a tendency that patients with faster prostate volume recovery were generally older than those with slower recovery; however, this was not statistically significant. Other factors showed no relationship with prostate recovery. Conclusions: When using 5ARI in elderly patients, continuous treatment seems better than intermittent treatment. If discontinuation is needed, short term follow-up is recommended.

• Natural Product Sciences
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• 제5권2호
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• pp.97-103
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• 1999

The enzyme steroid $5{\alpha}-reductase$ is responsible for the conversion of testosterone into the most potent androgen dihydrotestosterone (DHT). In man, this steroid acts on a variety of androgen-responsive target tissues to mediate such diverse endocrine processes as male sexual differentiation in the fetus and prostatic growth in men. Androgen levels in the prostate may influence carcinogenesis in this organ. The use of a $5{\alpha}-reductase$ inhibitor, finasteride, in the chemoprevention of prostate cancer is being evaluated in a clinical trial and have been used successfully for treatment of benign prostatic hyperplasia. Therefore, for the discovery of $5{\alpha}-reductase$ type 2 inhibitors, we have evaluated the inhibitory effects of solvent fractionated extracts of natural products on $5{\alpha}-reductase$ type 2 activity. We have tested approximately 80 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from 100% methanol extracts of plants. The ethyl acetate fractions of Perilla sikokiana $(seed,\;IC_{50}\;:\;6.2\;ug/ml)$, Sophora flavescens $(root,\;IC_{50}\;:\;8.9\;ug/ml)$, and Angelica tenuissima $(root,\;IC_{50}\;:\;11.7\;ug/ml)$ revealed inhibitory effects on $5{\alpha}-reductase$ 2 activity in LNCaP cells. The effective ethyl acetate fractions of Perilla sikokiana, Sophora flavescens, Hydnocarpus anthelmintica, and Angelica tenuissima were subfractionated by column chromatography and tested. The subfractions $F4\;(IC_{50}\;:\;1.1\;ug/ml),\;F5\;(IC_{50}\;:\;2.0\;ug/ml),\;and\;F6\;(IC_{50}\;:\;5.8\;ug/ml)$ of the ethyl acetate fraction of Perilla sikokiana and the subfraction $F8\;(IC_{50}\;:\;5.3\;ug/ml)$ of the ethyl acetate fraction of Sophora flavescens displayed greater inhibition of $5{\alpha}-reductase$ type 2 than did finasteride in LNCaP cells. These active fractions are under the process of further sequential fractionation to find the effective pure compounds against $5{\alpha}-reductase$ 2 activity.

• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.401-411
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• 2015

Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-${\beta}_1$, ${\alpha}$-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-${\beta}_1$, AR, ${\alpha}$-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of ${\alpha}$-SMA and collagen I induced by TGF-${\beta}_1$, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-${\beta}_1$-induced proliferation of fibroblasts, up-regulation of ${\alpha}$-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.

• Journal of Microbiology and Biotechnology
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• 제25권3호
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• pp.407-412
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• 2015

We investigated the effect of ultra-high molecular weight poly-γ-glutamic acid (UHMW γ-PGA) on hair loss in vitro and in vivo. 5-Alpha reductase is an enzyme that metabolizes the male hormone testosterone into dihydrotestosterone. By performing an in vitro experiment to analyze the inhibitory effects of UHMW γ-PGA on 5-alpha reductase activity, we determined that UHMW γ-PGA did in fact inhibit 5-alpha reductase activity, indicating the use of UHMW γ-PGA as a potential 5-alpha reductase inhibitor in the treatment of men with androgenetic alopecia. To evaluate the promotion of hair growth in vivo, we topically applied UHMW γ-PGA and minoxidil on the shaved dorsal skin of telogenic C57BL/6 mice for 4 weeks. At 4 weeks, the groups treated with UHMW γ-PGA showed hair growth on more than 50% of the shaved skin, whereas the control group showed less hair growth. To investigate the progression of hair follicles in the hair cycle, hematoxylin and eosin staining was performed. Histological observations revealed that the appearance of hair follicles was earlier in the UHMW γ-PGA-treated group than in the control group. The number of hair follicles on the relative area of shaved skin in the UHMW γ-PGA-treated group was higher than that observed on the shaved skin in the control group. These results indicate that UHMW γ-PGA can promote hair growth by effectively inducing the anagen phase in telogenic C57BL/6 mice.

• 대한화장품학회지
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• 제42권3호
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• pp.203-209
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• 2016

최근 남성성탈모증에 대한 관심이 증대되고 있으며, 이에 천연물 및 그의 활성성분을 활용한 새로운 약물 개발에 대한 연구가 증가하고 있다. 송지(Resina Pini, RP)는 Pinus sp. (Pinaceae)의 수지질로 전통의학적으로 감염, 우식증, 치주질환에 사용되어왔다. 본 연구진은 RP의 성분인 아비에트산(abietic acid, AA)이 남성성탈모기전에 중요한 효소인 $5{\alpha}$-reductase를 억제하는 효과를 세포 수준에서 입증한바 있으며, 이번 연구에서는 실제로 탈모억제 및 모발 성장에 대하여 실험동물 수준에서 입증하고자 한다. C3H/HeN 탈모마우스 모델에서 RP는 300 mg/kg에서 유의하게 탈모억제를 확인하였으며, 뿐만 아니라 AA는 30 mg/kg에서도 유의하게 탈모억제효과를 보였다. 이상의 결과로부터 RP는 그 활성성분인 AA가 $5{\alpha}$-reductase 억제하는 기전을 통해 남성성탈모억제효과를 보였다고 사료되며, 향후 탈모억제 보완치료법으로의 이용 가능성을 보였다.