• Nutrition Research and Practice
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• v.17 no.1
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• pp.32-47
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• 2023

BACKGROUND/OBJECTIVES: Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosterone-induced BPH. MATERIALS/METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. RESULTS: Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. CONCLUSIONS: Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.

• Journal of Life Science
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• v.28 no.10
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• pp.1147-1155
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• 2018

Agaricus blazei mycelial liquid culture extract (ABMLCE) promoted the production of testosterone (TS) in TM-3 mouse Leydig testis cells. Now, we report that ABMLCE containing eritadenine (EA) as a minor constituent (15.3 mg/100 g) reduced $5{\alpha}-reductase$ 2 ($5{\alpha}-R2$) enzyme activity and dihydrotestosterone (DHT) content which are key constituents for the benign prostatic hyperplasia (BPH) inductions. RWPE-1 prostate cells were grown in a Keratinocyte serum-free medium (K-SFM) containing ABMLCE (0~50 ppm), EA (0~10 ppm,), and finasteride (FS $10{\mu}M$: a positive control) in a 24-well plate for 24 hr. Supernatants collected from cell-cultured media were used for the assay of $5{\alpha}-R2$, superoxide dismutase (SOD), catalase (CAT) and cyclooxygenase-2 (COX-2) enzyme activities, and for TS, DHT, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and $interleukin-1{\beta}$ ($IL-1{\beta}$) contents by their assay kits. The $5{\alpha}-R2$ activity and DHT content were proportionally reduced (p<0.05) to concentrations of ABMLCE. The SOD and CAT enzyme activities were significantly (p<0.05) elevated concomitant with ABMLCE concentrations, while COX-2, $TNF-{\alpha}$ and $IL-1{\beta}$ showed reverse results (p<0.05). Similarly, the effects of EA were similar to those of ABMLCE. Efficacies of ABMLCE 50 ppm and EA 10 ppm in $5{\alpha}-R2$ and DHT reduction were similar to those of $10{\mu}M$ FS. These results suggest that ABMLCE and EA reduced $5{\alpha}-R2$ and DHT through their anti-inflammatory and anti-oxidative actions. This implies that ABMLCE containing EA could be a beneficial material in the cure of BPH in humans.

• Journal of Applied Biological Chemistry
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• v.59 no.4
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• pp.305-311
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• 2016

This study investigated the effects of a mixture of fenugreek seeds and Lespedeza cuneata extracts on testosterone synthesis in TM3 cells that were oxidatively stressed with $H_2O_2$. In order to oxidatively stress TM3 cells, the cells were treated with $50{\mu}M$ hydrogen peroxide for 4 hr in serum-free media. Yagwanmun-horopa mixture (YHM) showed neither cytotoxicity nor increment of cell proliferation in the oxidatively stressed TM3 cells in any concentration. When the cells were treated with hydrogen peroxide, testosterone levels decreased, but the testosterone level was returned to that of the control level in the presence of YHM. In order to find out the reasons for the increase of testosterone, the expression of the genes involved in the synthesis or disintegration of testosterone. On the other hand, the levels of $3{\beta}$-HSD4 and 17, 20-desmorase, which are involved in testosterone synthesis, were decreased through the use of hydrogen peroxide and were recovered through YHM treatment. Aromatase and $5{\alpha}$-reductase2, which convert testosterone to estradiol and dihydrotestosterone, respectively, were increased through the use of hydrogen peroxide, and were returned to control level through YHM treatment. These results suggest that YHM does not affect TM3 cell proliferation. However, YHM increases the expression of testosterone-synthesizing enzyme, which was decreased through oxidative stress, and decreases the expression of testosterone- converting enzyme, which was increased through oxidative stress. Therefore, it is reasonable that YHM has strong recovery activity on testosterone to normal level, even in the oxidatively stressed TM3 cells which mimics the andropause state.

• Journal of Life Science
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• v.28 no.12
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• pp.1507-1515
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• 2018

Benign prostatic hyperplasia (BPH) is characterized by prostatic hypertrophy mainly in the elderly. Corni Fructus is reportedly effective in the prevention and treatment of various diseases, but its efficacy on BPH has not been previously studied. In the present study, we investigated whether or not a Corni Fructus water extract (CF) could prevent testosterone-induced prostatic hyperplasia in rats. To induce BPH, castrated rats were subcutaneously injected with testosterone propionate (TP). CF was administered daily by oral gavage, along with the TP injections, and finasteride, a selective inhibitor of $5{\alpha}$-reductase type 2, was used as a positive control. The results show that CF significantly reduces prostate weight and histopathologic changes while also decreasing levels of serum dihydrotestosterone, similar to the finasteride-treated group. CF also suppresses TP-induced $5{\alpha}$-reductase expression and concentration in prostate tissue and serum, respectively. Furthermore, CF markedly inhibited TP-induced expression of the androgen receptor (AR) and the steroid receptor coactivator 1, an AR coactivator, which was associated with a decrease in prostate-specific antigen levels in both serum and prostate tissue. In conclusion, the results of this study indicate that CF weakens BPH status by inactivation of $5{\alpha}$-reductase and AR.

• Natural Product Sciences
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• v.5 no.2
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.4
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• pp.507-515
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• 2014

Benign prostatic hyperplasia (BPH), which is commonly found in aging men, is characterized by hyperplasia of prostatic stromal and epithelial cells beginning in the periurethral zone of the prostate. The prevalence of BPH increases in an age-dependent manner. Here, we investigated the protective effects of unripe Rubus occidentalis extracts (UROE) on BPH development using a prostate cancer cell line and testosterone-induced BPH rat model. Experiments using an established hormone-dependent prostate cancer cell line (LNCaP) showed that UROE treatment significantly decreased expression of androgen-related genes, including androgen receptor (AR), prostate specific antigen (PSA), and 5-alpha reductase 2, but not 5-alpha reductase 1, which was also observed in flutamide-treated cells. Further, AR and PSA gene expression was reduced by UROE treatment under androgen-stimulated conditions using dihydrotestosterone (DHT). BPH animals displayed elevated prostate weights. However, UROE as well as finasteride treatment significantly reduced prostate weights and DHT levels compared to testosterone-induced BPH animals. Histopathological analysis also showed that UROE treatment suppressed testosterone-induced prostatic hyperplasia. Taken together, the results suggest that UROE may effectively inhibit the development of BPH and thus may be a useful agent in BPH treatment.

• Nutrition Research and Practice
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• v.11 no.5
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• pp.373-380
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• 2017

BACKGROUND/OBJECTIVES: This study was conducted to investigate the effect of a corn silk extract on improving benign prostatic hyperplasia (BPH). MATERIALS/METHODS: The experimental animals, 6-week-old male Wistar rats, were divided into sham-operated control (Sham) and experimental groups. The experimental group, which underwent orchiectomy and received subcutaneous injection of 10 mg/kg of testosterone propionate to induce BPH, was divided into a Testo Only group that received only testosterone, a Testo+Fina group that received testosterone and 5 mg/kg finasteride, a Testo+CSE10 group that received testosterone and 10 mg/kg of corn silk extract, and a Testo+CSE100 group that received testosterone and 100 mg/kg of corn silk extract. Prostate weight and concentrations of dihydrotestosterone (DHT), $5{\alpha}$- reductase $2(5{\alpha}-R2)$, and prostate specific antigen (PSA) in serum or prostate tissue were determined. The mRNA expressions of $(5{\alpha}-R2)$ and proliferating cell nuclear antigen (PCNA) in prostate tissue were also measured. RESULTS: Compared to the Sham group, prostate weight was significantly higher in the Testo Only group and decreased significantly in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups (P < 0.05), results that were consistent with those for serum DHT concentrations. The concentrations of $(5{\alpha}-R2)$ in serum and prostate as well as the mRNA expression of $(5{\alpha}-R2)$ in prostate were significantly lower in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups than that in the Testo Only group (P < 0.05). Similarly, the concentrations of PSA in serum and prostate were significantly lower in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups (P < 0.05) than in the Testo Only group. The mRNA expression of PCNA in prostate dose-independently decreased in the Testo+CSE-treated groups (P < 0.05). CONCLUSIONS: BPH was induced through injection of testosterone, and corn silk extract treatment improved BPH symptoms by inhibiting the mRNA expression of $(5{\alpha}-R2)$ and decreasing the amount of $(5{\alpha}-R2)$, DHT, and PSA in serum and prostate tissue.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.38 no.4
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• pp.311-319
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• 2012

Seborrheic dermatitis (SD) is the skin disease occurred because of Malassezia yeast which grows on the skin and scalp, and this yeast lives on sebum lipid, and their metabolite, free lipid acids are thought to be the main irritant on skin. To find out effective cosmeceutical ingredients to treat SD symptoms, we established novel cell-based in vitro model mimicking SD symptoms. This in vitro model adopted the co-culture system with primary sebocyte & HaCaT keratinocyte. We used M. globosa yeast extract, arachidonic acid, linoleic acid and dihydrotestosterone as SD inducers. In the co-culture system with optimized concentrations for SD-inducing cocktail, the production of IL-8 and sebum lipids increased up to 2-fold, and then we screened with commercial essential oils by monitoring IL-8 as a key inflammatory biomarker. Then we found that Cinnamomum zeylanicum oil, Mentha arvensis oil effectively down-regulated IL-$1{\alpha}$, IL-6, IL-8 cytokines which over-produced by SD-inducing cocktail. Additionally, two essential oils also showed inhibitory effect on sebum lipid synthesis from primary sebocyte and growth inhibitory effect to M. globosa yeast (MICs were lower than 0.0625 %). Our recent results suggest that Cinnamomum zeylanicum oil and Mentha arvensis oil could be effective natural herbal remedies to relieve or protect scalp seborrheic dermatitis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.6
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• pp.374-379
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• 2017

Hair loss affects interpersonal relationships and causes psychological stress. In this study, we investigated the antioxidant activity of Cynanchi Wilfordii Radix (CWR) and its effects on dermal papilla (DP) cells. Antioxidant efficacy was examined by ABTS assay. To confirm the effect on cell activity, MTS assay was performed and cell count was directly measured by hemocytometer. The mRNA expression of genes involved in hair formation and hair loss formation was confirmed by quantitative RT-PCR. CWR has a strong antioxidant activity. Cell viability of DP cells was increased to 118.5% by treatment of 0.5 mg/ml CWR for 24 hours, but the effect on the cell number was insignificant. These results suggest that CWR increases mitochondrial activity without promoting cell proliferation. Treatment of DP cells with 0.5 mg/ml CWR resulted in 48.5% reduction of mRNA expression of type 2 $5{\alpha}$-reductase, a major cause of male hair loss. In addition, mRNA expression of bone morphogenetic pretein (BMP), fibroblast growth factor (FGF)7, and FGF10, which are closely related to hair growth, was also decreased. Reactive oxygen species (ROS) acts as a cause of hair loss. The excellent antioxidant efficacy of CWR is thought to be able to effectively remove ROS. The dihydrotestosterone produced by type 2 $5{\alpha}$-reductase in DP cells is a potent inducer of male pattern hair loss. The inhibitory effect of type 2 $5{\alpha}$-reductase mRNA on DP cells induced by CWR may induce a positive therapeutic effect of male pattern hair loss.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.354-360
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• 2020

The hair cycle (anagen, catagen, and telogen) is regulated by the interaction between mesenchymal cells and epithelial cells in the hair follicles. The proliferation of dermal papilla cells (DPCs), mesenchymal-derived fibroblasts, has emerged as a target for the regulation of the hair cycle. Here, we show that vanillic acid, a phenolic acid from wheat bran, promotes the proliferation of DPCs via a PI3K/Akt/Wnt/β-catenin dependent mechanism. Vanillic acid promoted the proliferation of DPCs, accompanied by increased levels of cell-cycle proteins cyclin D1, CDK6, and Cdc2 p34. Vanillic acid also increased the levels of phospho(ser473)-Akt, phospho(ser780)-pRB, and phospho(thr37/46)-4EBP1 in a time-dependent manner. Wortmannin, an inhibitor of the PI3K/Akt pathway, attenuated the vanillic acid-mediated proliferation of DPCs. Vanillic acid-induced progression of the cell-cycle was also suppressed by wortmannin. Moreover, vanillic acid increased the levels of Wnt/β-catenin proteins, such as phospho(ser9)-glycogen synthase kinase-3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin. We found that vanillic acid increased the levels of cyclin D1 and Cox-2, which are target genes of β-catenin, and these changes were inhibited by wortmannin. To investigate whether vanillic acid affects the downregulation of β-catenin by dihydrotestosterone (DHT), implicated in the development of androgenetic alopecia, DPCs were stimulated with DHT in the presence and absence of vanillic acid for 24 h. Western blotting and confocal microscopy analyses showed that the decreased level of β-catenin after the incubation with DHT was reversed by vanillic acid. These results suggest that vanillic acid could stimulate anagen and alleviate hair loss by activating the PI3K/Akt and Wnt/β-catenin pathways in DPCs.