• BMB Reports
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• 제52권9호
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• pp.560-565
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• 2019

Benign prostatic hyperplasia (BPH), a common disease in elderly males, is accompanied by non-malignant growth of prostate tissues, subsequently causing hypoxia and angiogenesis. Although VEGF-related angiogenesis is one of the therapeutic targets of prostate cancer, there is no previous study targeting angiogenesis for treatment of BPH. Dihydrotestosterone (DHT)-induced expressions of vascular endothelial growth factor (VEGF) in prostate epithelial RWPE-1 cells and human umbilical vascular endothelial cells (HUVECs). Conditioned media (CM) from DHT-treated RWPE-1 cells were transferred to HUVECs. Then, 6SL inhibited proliferation, VEGFR-2 activation, and tube formation of HUVECs transferred with CM from DHT-treated RWPE-1 cells. In the rat BPH model, 6SL reduced prostate weight, size, and thickness of the prostate tissue. Formation of vessels in prostatic tissues were also reduced with 6SL treatment. We found that 6SL has an ameliorative effect on in vitro and in vivo the BPH model via inhibition of VEGFR-2 activation and subsequent angiogenesis. These results suggest that 6SL might be a candidate for development of novel BPH drugs.

• BMB Reports
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• 제43권10호
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• pp.688-692
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• 2010

In a previous study, we recently claimed that dihydrotestosterone (DHT)-inducible dickkopf-1 (DKK-1) expression is one of the key factors involved in androgen-potentiated balding. We also demonstrated that L-ascorbic acid 2-phosphate (Asc 2-P) represses DHT-induced DKK-1 expression in cultured dermal papilla cells (DPCs). Here, we investigated whether or not L-threonate could attenuate DHT-induced DKK-1 expression. We observed via RT-PCR analysis and enzyme-linked immunosorbent assay that DHT-induced DKK-1 expression was attenuated in the presence of L-threonate. We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co-culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9841-9846
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• 2014

Objectives: To compare the metabolic indices, lipid profile, androgens, and prostate specific antigen between prostate cancer and BPH and between grades of prostate cancer in a cross-sectional study. Materials and Methods: The study enrolled 95 cases of prostate cancer and 95 cases of benign prostatic hyperplasia (BPH). Prostate gland volume was measured using transrectal ultrasound. We compared insulin, testosterone, dihydrotestosterone, prostate specific antigen levels and lipid profile between prostate cancer of different grades and BPH. Further, prostate cancer patients were classified into low grade and high grade. Unpaired t-test for normally distributed variables and Man-Whitney U test for non-normal variables were used to assess differences. Results: We found that prostate cancer patients had significantly higher levels of insulin, testosterone, PSA, cholesterol, triglycerides, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) in comparison to their BPH counterparts. Higher levels of these parameters also correlated with a higher grade of the disease. Conclusions: We conclude that higher levels of insulin, testosterone, PSA, and cholesterol correlate with a higher risk of prostate cancer, and also with a higher grade of the disease.

• Mass Spectrometry Letters
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• 제3권1호
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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.

• 대한한방내과학회지
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• 제30권2호
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• pp.327-337
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• 2009

Objective : In benign prostatic hyperplasia, dihydrotestosterone acts as a potent cellular androgen and promotes prostate growth. Inhibiting enzyme 5${\alpha}$-reductase, which is involved in the conversion of testosterone to the active form dihydrotestosterone, reduces excessive prostate growth. Recently Scutellaria baicalensis has been related reports about the effect of baicalein on anti-proliferation of the prostate gland. In this study, we investigated the effects of Scutellaria baicalensis on cytopathological alterations and expression of 5${\alpha}$-reductase in the rat model of benign prostatic hyperplasia induced by castration and testosterone treatment. Methods : Sprague-Dawley rat were treated with testosterone after castration for induction of experimental benign prostatic hyperplasia, which is similar to human benign prostatic hyperplasia in histopathological profiles. Scutellaria baicalensis as an experimental specimen, and finasteride as a positive control, were administered orally. The prostates were evaluated by histopathological changes, testosterone levels, 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 Scutellaria baicalensis showed a diminished range of tissue damage. In the reverse transcription-polymerase chain reaction(RT-PCR) of 5${\alpha}$-reductase genes. Scutellaria baicalensis inhibited the expression of 5${\alpha}$-reductase genes. Conclusions : These findings suggest that Scutellaria baicalensis may protect glandular epithelial cells and also inhibit stromal proliferation in association with the suppression of 5${\alpha}$-reductase. From theses results, we suggest that Scutellaria baicalensis could be a useful remedy agent for treating benign prostatic hyperplasia.

• Nutrition Research and Practice
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• 제7권3호
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• pp.172-177
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• 2013

Benign prostatic hyperplasia (BPH) is one of the most common diseases among elderly men. As the old-age population is increasing recently, it is to our interest to observe the growing BPH within them. In BPH, the dihydrotestosterone (DHT) acts as promotes prostate growth. It inhibits enzyme $5{\alpha}$-reductase that is involved in the conversion of testosterone to the DHT activity which reduces the excessive prostate growth. Through experiments, the effects of Phellius linteus water extract performed on the BPH rats were induced by testosterone treatments. For 12 weeks, Sprague-Dawley rats were treated with testosterone for the induction of BPH. Rats were divided into four experimental groups: the not treated group (N), the testosterone injection and D.W treatment group (TN), the testosterone injection and Phellinus linteus treatment group (TP) and testosterone injection and finasteride treatment group (TF). Prostate weight, volume and weight ratio in the TP group and the TF group were significantly lower than the TN group. Testosterone and DHT levels in the TN group were significantly higher than that of the N group. And the TP group was significantly decreased than that of the TN group. While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation; the TP and TF groups showed trophic symptoms and were lined by flattened epithelial cells, thus, the stromal proliferation is relatively low as compared to the TN group. These suggest that Phellinus linteus water extracts may be an useful remedy for treating the benign prostatic hyperplasia.

• 대한한방내과학회지
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• 제31권3호
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• pp.457-466
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• 2010

Objective : In benign prostatic hyperplasia, dihydrotestosterone acts as a potent cellular androgen and promotes prostate growth. Inhibiting enzyme $5{\alpha}$-reductase that is involved in the conversion of testosterone to the active form dihydrotestosterone reduces this excessive prostate growth. The mechanism on benign prostatic hyperplasia is substantiating evidence to support the clinical value in the evaluation of therapeutic efficacy. In this study, we investigated the effects of Lygodium japonicum on cyto-pathological alterations and expression of $5{\alpha}$-reductase in the rat model of benign prostatic hyperplasia 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. Lygodium japonicum as an experimental specimen, and finasteride as a positive control, were administered orally. The prostates were evaluated by histopathological changes and testosterone levels. Also, the prostates were observed by hematological alterations of AST, ALT, ${\gamma}$-GTP, BUN and creatinine. Results : The rats treated with Lygodium japonicum showed a diminished range of luminal cell and duct epithelial cell damage. The stromal elements and connective tissue proliferation of Lygodium japonicum treated group as compared to the control group decreased. Conclusions : These findings suggest that Lygodium japonicum may protect the glandular epithelial cells. We concluded that Lygodium japonicum could be a useful remedy agent for treating the benign prostatic hyperplasia.

• Natural Product Sciences
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• 제29권1호
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• pp.31-37
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• 2023

In this study, we investigated the efficacy of Celtis choseniana Nakai (C. choseniana) as complementary herbal medicine to ameliorate androgenic alopecia (AGA). The effects of C. choseniana on AGA were evaluated using testosterone propionate-induced AGA mouse model and dihydrotestosterone-treated human hair follicle dermal papilla cells. In vivo, C. choseniana treatment deactivated androgen signaling by reducing the concentration of serum dihydrotestosterone level and expressions of 5α-reductase 2 and androgen receptor. Next, C. choseniana treatment increased the hair regrowth rate. Histological studies demonstrated that C. choseniana induced the anagen phase in testosterone propionate-induced AGA mouse model. Cellular proliferation was promoted by C. choseniana treatment via increasing the expression of proliferation factors, such as proliferating cell nuclear antigen and cyclin D1. Furthermore, C. choseniana treatment increased the expression of proteins related to the Wnt/β-catenin signaling pathway. In addition, dickkopf-1, a Wnt inhibitor, was downregulated with C. choseniana treatment. Likewise, C. choseniana treatment promoted cellular proliferation in vitro. This study demonstrated the inhibitory effect of C. choseniana on androgen-induced AGA. Moreover, C. choseniana induced activation of Wnt/β-catenin signaling, resulting in prolonged anagen and cellular proliferation. Therefore, we suggest that C. choseniana can be used as a therapeutic agent to alleviate AGA.

• 생명과학회지
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• 제31권10호
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• pp.885-897
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• 2021

오미자와 산수유는 한국을 포함한 동아시아 지역에서 다양한 질병의 예방 및 치료에 오랫동안 사용되어 왔다. 최근에 이들 추출물에 의한 양성 전립선 비대증(BPH)의 발병 및 진행을 억제할 수 있다는 가능성에 대한 보고가 있었지만 관련 기전에 대한 연구는 여전히 부족한 실정이다. 본 연구에서는 LNCaP 전립선 세포를 사용하여 DHT 처리에 의한 in vitro BPH 모델에서 오미자 및 산수유 추출물에 의한 BPH의 개선 가능성을 조사하였다. 본 연구의 결과에 의하면, 오미자와 산수유의 열수 및 에탄올 추출물은 DHT 처리에 의해 LNCaP 세포의 증식을 유의적으로 억제하였으며, DHT로 유도된 BPH 바이오 마커와 성장인자의 발현을 현저히 감소시켰다. 그들은 또한 세포사멸 관련 인자의 발현을 조절하였고, DHT 매개 산화적 스트레스를 유의적으로 감소시켰으며, BPH 발병에 관여하는 주요 인자에 대한 보호 효과는 열수 추출물보다 에탄올 추출물 처리군에서 더 효과적이었다. 또한, BPH에 대한 보호 효과는 오미자와 산수유의 에탄올 추출물 단독 처리군보다 1:1 복합 혼합물 처리군에서 더 높았으며, 60% 에탄올 추출물이 40% 에탄올 추출물보다 더 높은 개선 효과를 보였다. 따라서 본 연구 결과는 오미자와 산수유 추출물이 항산화 활성과 연관된 androgen 신호 전달 경로의 억제를 통해 전립선 세포의 과다 증식을 방지함으로써 BPH 개선에 관여할 수 있음을 의미한다. 따라서 오미자와 산수유 추출물은 BPH의 임상 치료에 유용할 수 있으며, 이 두 추출물의 조합은 BPH 개선에 상승 효과를 낼 수 있을 것이다.

• Nutritional Sciences
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• 제1권1호
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• pp.3-7
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• 1998

The aim of the present investigation was to see whether an anabolic steroid, nandrolone phenylpropionate (NPP), exerts protienanabolic effects under such adverse nutritional conditions as protein deficiency and protein-energy malnutrition in male rats. feeding on a low-protein (8% casein) diet resulted in a marked reduction in body weight gain that was associated with reductions in body protein and protein content of gastrocnemius muscle. Administration of NPP (4 mg/kg body weight) did not alter muscle and body protein depletion induced by a low-protein diet. 50% food restriction caused reductions in body protein and in protein content of gastrocnemius muscle. These reductions were partially prevented by NPP (4 mg/kg body weight). Food restriction did not affect plasma concentration of corticosterone, insulin, or tetosterone plus dihydrotestosterone. On the other hand, neither plasma concentration of corticosterone nor insulin were affected by NPP. The present results show that anabolic steroids do not express anabolic effects under conditions of protein deficiency, but in protein-energy malnutrition, anabolic steroids exert their anabolic effects even in male rats.