Tomato lipidic extract plus selenium decrease prostatic hyperplasia, dihydrotestosterone and androgen receptor expression versus finasteride in rats.

PURPOSE: Evaluate the therapeutic effect of a tomato lipidic extract (STE) in combination with selenium (Se) on rats with prostatic hyperplasia (PH) and to observe its possible mechanisms of action and synergism versus finasteride. MATERIALS AND METHODS: 54 male Wistar rats of nine weeks old were divided in Control (C), PH, Finasteride (F), STE, Se, F + STE, F + Se, STE + Se and F + STE + Se with testosterone enanthate (except C). After 4 weeks of treatment administration, prostate weight, bladder weight, diuresis, prooxidant and antioxidant activity, dihydrotestosterone (DHT), androgen receptor (AR) expression and anatomopathological analysis were determined. RESULTS: STE + Se decreased prostate weight 53.8% versus 28% in F group, also STE + Se decreased significatively glandular hyperplasia, prooxidant activity, DHT and AR expression and increased diuresis and antioxidant activity versus finasteride which increased MDA in prostate. CONCLUSIONS: These results demonstrate a greater therapeutic and beneficial effect of tomato lipidic extract in combination with Se in young rats with PH with respect to finasteride without increase prooxidant activity.

Effects of Alginate Oligosaccharide on Testosterone-Induced Benign Prostatic Hyperplasia in Orchiectomized Rats.

Benign prostatic hyperplasia (BPH) is an age-related disease of the urinary system that affects elderly men. Current treatments for BPH are associated with several adverse effects, thus highlighting the need for alternative agents. Alginate oligosaccharide (AOS), a water-soluble functional oligomer derived from brown algae, inhibits prostate cancer cell proliferation. However, the effects of AOS on BPH and the underlying molecular mechanisms remain unclear. Therefore, here, we aimed to investigate the therapeutic potential of AOS in BPH by using human benign prostatic epithelial cells (BPH-1) and a rat model of testosterone-induced BPH. Treatment with AOS inhibited in vitro and in vivo proliferation of prostatic epithelial cells and the testosterone-induced expression of androgen receptor (AR) and androgen-associated genes, such as those encoding 5α-reductase type 2 and prostate-specific antigen. Oral administration of AOS remarkably reduced the serum levels of dihydrotestosterone (DHT) and testosterone as well as the expression of proliferating cell nuclear antigen, inflammatory cytokines, and enzymes, which showed increased levels in prostatic tissues of rats with testosterone-induced BPH. Taken together, these data demonstrate that AOS suppresses testosterone-induced BPH in rats by downregulating AR and the expression of androgen-associated genes, supporting the hypothesis that AOS might be of potential use for the treatment of BPH.

Panax ginseng C.A. meyer alleviates benign prostatic hyperplasia while preventing finasteride-induced side effects.

Panax ginseng C.A. Meyer, a widely used traditional medicine in East Asia, shows many beneficial effects on immune function, male erectile dysfunction, cancer, excessive oxidants, and aging issues. However, its effect on benign prostatic hyperplasia (BPH) and its potential in the treatment of side effects related to finasteride (Fi), an FDA-approved drug for BPH, are less known. This study aimed to verify the therapeutic effects of a water extract of P. ginseng (PGWE) on BPH in testosterone propionate (TP)-induced BPH rats and TP-treated RWPE-1 human epithelial cells, and the inhibitory potential on the Fi-induced side effects is also explored. In the TP-induced BPH rat model, PGWE alleviated the pathological markers of BPH such as weight and epithelial thickness of the prostate, and the serum level of dihydrotestosterone. PGWE downregulated androgen-related BPH factors such as 5α-reductase 2 and androgen receptor. PGWE also showed prostatic cell apoptosis accompanied by increased expression of Bax and decreased expression of Bcl-xL and cleaved-caspase 3, respectively, in addition to increasing mitochondrial dynamics in both in vivo and in vitro BPH models. Notably, reduced sperm count, one of the serious side effects of Fi, in the epididymis of BPH rats was recovered with PGWE treatment, suggesting less toxicity to sperm development by PGWE. PGWE also protected against Fi-induced sperm loss when PGWE was administered in combination with Fi without compromising the therapeutic effects of Fi on BPH. Based on these findings, we propose that PGWE could be an alternative therapeutic agent for BPH.

Assessment of the anti-hair loss potential of Camellia japonica fruit shell extract in vitro.

OBJECTIVE: Hair loss is caused by various factors. Impacts of these factors are often overlapped and intensified. Currently, mitigation of hair loss is being studied by proliferating dermal papilla cells (DPCs) and inhibiting deleterious factors such as dihydrotestosterone (DHT) and oxidative stress on hair growth. Camellia japonica (C. japonica) fruit shell is a discarded part. Its biological activity remains to be elucidated. In this study, we investigated the capacity of C. japonica fruit shell extract (CJFSE) for hair loss mitigation. METHODS: MTT assay, spheroid culture and quantitative RT-PCR were performed to observe the proliferative effect of CJFSE on hair follicle dermal papilla cells (HFDPCs). Effects of CJFSE on DHT-induced hair loss were confirmed by Dkk-1 ELISA, ß-galactosidase (ß-gal) and 5α-reductase activity assay. In addition, effects of CJFSE on oxidative stress were confirmed through DPPH and ROS production assays. RESULTS: CJFSE increased the proliferation and spheroid size of HFDPCs. Expression levels of VEGF-A, Wnt-1, c-Myc and Cyclin D1 were upregulated by CJFSE. CJFSE also suppressed 5α-reductase activity and DHT-induced decrease in cell proliferation, Dkk-1 secretion and ß-gal activity. Moreover, CJFSE showed DPPH scavenging activity and ameliorated hydrogen peroxide-induced ROS production and ß-gal activity. Finally, gallic acid and protocatechuic acid were observed in CJFSE through HPLC analysis. CONCLUSION: CJFSE has the potential to alleviate hair loss by promoting hair cell growth and suppressing effects of DHT and oxidative stress on hair.

OBJECTIF: Divers facteurs sont responsables de la perte de cheveux. Souvent, les conséquences de ces facteurs se superposent et s'intensifient. Actuellement, on étudie comment atténuer la perte de cheveux en faisant proliférer les cellules de la papille dermique (DPC) et en inhibant les facteurs délétères tels que la dihydrotestostérone (DHT) et le stress oxydatif sur la croissance des cheveux. La coque du fruit du Camélia du Japon (Camelia japonica) est habituellement rejetée. Son utilité biologique reste à élucider. Dans cette étude, nous avons étudié la capacité de l'extrait de la coque du fruit du Camélia du Japon (CJFSE) dans la mitigation de la perte de cheveux. MÉTHODES: Un test MTT, une culture de sphéroïdes et une RT-PCR Quantitative ont été effectués pour observer la prolifération de CJFSE sur les cellules de la papille dermique du follicule pileux (HFDPC). Les effets du CJFSE sur la perte de cheveux induite par la DHT ont été confirmés par Dkk-1 ELISA, ß-galactosidase (ß-gal) et 5α-réductase. De plus, les effets du CJFSE sur le stress oxydatif ont été confirmés par des tests de production de DPPH et de ROS. RÉSULTATS: Le CJFSE a augmenté la prolifération et la taille sphéroïde des HFDPC. Les niveaux d'expression de VEGF-A, Wnt-1, c-Myc et cycline D1 ont été régulés de manière efficace par le CJFSE. Le CJFSE a également supprimé l'activité de la 5α-réductase et a induit la réduction de la DHT et de la prolifération cellulaire, ainsi que de la sécrétion de Dkk-1 et de l'activité ß-gal. Le CJFSE a en outre montré une activité de capture du DPPH et amélioré la production de ROS induite par le peroxyde d'hydrogène et l'activité ß-gal. Pour finir, les acides gallique et protocatéchuique ont été observés dans le CJFSE après analyse des HPLC. CONCLUSION: Le CJFSE a le potentiel d'atténuer la perte de cheveux en favorisant la croissance des cellules ciliées et en supprimant les effets de la DHT et du stress oxydatif sur les cheveux.

Dehydroepiandrosterone Supplementation Results in Varying Tissue-specific Levels of Dihydrotestosterone in Male Mice.

Dehydroepiandrosterone (DHEA), an adrenal androgen precursor, can be metabolized in target tissues into active sex steroids. It has been proposed that DHEA supplementation might result in restoration of physiological local sex steroid levels, but knowledge on the effect of DHEA treatment on local sex steroid levels in multiple tissues is lacking. To determine the effects of DHEA on tissue-specific levels of sex steroids, we treated orchiectomized (ORX) male mice with DHEA for 3 weeks and compared them with vehicle-treated ORX mice and gonadal intact mice. Intra-tissue levels of sex steroids were analyzed in reproductive organs (seminal vesicles, prostate, m. levator ani), major body compartments (white adipose tissue, skeletal muscle, and brain), adrenals, liver, and serum using a sensitive and validated gas chromatography-mass spectrometry method. DHEA treatment restored levels of both testosterone (T) and dihydrotestosterone (DHT) to approximately physiological levels in male reproductive organs. In contrast, this treatment did not increase DHT levels in skeletal muscle or brain. In the liver, DHEA treatment substantially increased levels of T (at least 4-fold) and DHT (+536%, P < 0.01) compared with vehicle-treated ORX mice. In conclusion, we provide a comprehensive map of the effect of DHEA treatment on intra-tissue sex steroid levels in ORX mice with a restoration of physiological levels of androgens in male reproductive organs while DHT levels were not restored in the skeletal muscle or brain. This, and the unexpected supraphysiological androgen levels in the liver, may be a cause for concern considering the uncontrolled use of DHEA.

Camellia Seed Cake Extract Supports Hair Growth by Abrogating the Effect of Dihydrotestosterone in Cultured Human Dermal Papilla Cells.

Autocrine and paracrine factors play key roles in the process of Androgenetic alopecia (AGA), which are secreted by balding dermal papilla cells (DPCs) after dihydrotestosterone (DHT) induction. Camellia seed cake is an oriental oil extraction byproduct, and its extract has been traditionally used to wash hair in China. This study elucidated the hair growth-promoting effects of Camellia seed cake extract (CSCE) in DHT-treated cultured DPCs and its underlying mechanisms. The effect of CSCE on cell viability and release of inflammatory factors IL-6 and IL-1α was performed on human dermal papilla cells (DPCs) incubated with DHT. Relative expression of bax, bcl-2, p53, androgen receptor (AR) and 5α- reductase type II (SRD5A2) was determined by PCR. Senescence-associated was examined by ß-galactosidase (SA-ß-Gal) assays. CSCE restored DHT-induced cell damage in a dose-dependent manner, and effectively reduced the production of IL-6 and IL-1α in DHT-treated DPCs. CSCE exhibited an anti-apoptotic effect, which increased the expression of bcl-2, and decreased the expressions of bax and p53 in DHT-incubated DPCs. CSCE also showed an anti-androgenic effect reversing the increase in AR and SRD5A2 expressions in DPCs driven by DHT incubation. In addition, CSCE inhibited the ß-galactosidase enzyme activity and slowed down the cell senescence of DPCs which is crucial for AGA progression. In this study, we found that CSCE may have the potential to prevent and alleviate AGA by abrogating the effect of DHT in cultured DPCs.

Therapeutic role of Glycyrrhiza Uralensis fisher on benign prostatic hyperplasia through 5 alpha reductase regulation and apoptosis.

BACKGROUND: Benign prostatic hyperplasia (BPH) is an age-related disease in adult men. There are two pharmacological treatments for BPH. However, these synthetic materials have various risks, many studies are being conducted to develop new drugs from natural sources. PURPOSE: In this study, we proposed a beneficial effect of Glycyrrhiza uralensis Fischer on the development and progression of BPH, focusing on the androgen receptor (AR) and 5α-reductase 2 (5AR2) signaling axis. METHODS: To explain the therapeutic efficacy of a water extract of G. uralensis (GUWE) for BPH, we used testosterone propionate (TP)-induced BPH rat models and TP-treated RWPE-1 human prostate epithelial cells. RESULTS: In the TP-induced BPH rat models, GUWE reduced the enlarged prostate weight, prostate index, prostate epithelial thickness, and serum DHT levels. In addition, the protein levels of AR and 5AR2 in prostate tissues were significantly decreased by GUWE treatment. Furthermore, GUWE induced apoptosis signaling through an increase of Bcl-2 associated X protein (Bax), caspase 3, and Poly (ADP-ribose) polymerase (PARP) and a decrease of B-cell lymphoma-extra-large (Bcl-xL) in prostate tissues of TP-induced BPH rats. These findings were also confirmed in TP-treated RWPE-1 cells. Fi treatment markedly decreased the sperm count in the epididymis of BPH rats, but GUWE treatment did not affect the sperm count, suggesting less toxicity. CONCLUSION: These findings suggested that GUWE reduces the development of BPH by inhibiting AR-5AR2 and activating the apoptosis signaling pathway. Furthermore, unlike finasteride, GUWE did not affect sperm count. Therefore, we suggest that GUWE has a potential as a safer alternative option for BPH treatment.

Purple Corn Extract Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis.

Purple corn (Zea mays L.), utilized as a natural pigment in food production and processing, has been used to treat obesity, cystitis, and urinary tract infections. However, no reports of its use for benign prostatic hyperplasia (BPH) exist. Purple corn extract (PCE) contains anthocyanins, particularly cyanidin-3-O-glucoside, which have various pharmacological characteristics. Therefore, this study sought to elucidate the ameliorative effect of PCE on BPH in dihydrotestosterone (DHT)-stimulated WPMY-1 cells and testosterone propionate (TP)-induced rats. Expression levels of the upregulated androgen receptor (AR) and its related genes in DHT-stimulated WPMY-1 cells were reduced by PCE, and proapoptotic gene expression increased by modulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling cascade. PCE reduced the weight of the enlarged prostate by inhibiting the androgen/AR signaling-related markers. Histological variations in the prostate epithelium caused by TP injection were restored by PCE. Thus, PCE alleviates BPH by modulating prostate cell proliferation and apoptosis.

Regulation of Cytokines and Dihydrotestosterone Production in Human Hair Follicle Papilla Cells by Supercritical Extraction-Residues Extract of Ulmus davidiana.

This study was conducted to examine the anti-hair loss mechanism of the supercritical fluid extraction-residues extract of Ulmus davidiana by the regulation of cytokine production and hormone function in human dermal follicle papilla cells (HDFPCs). To investigate the modulatory effects on H2O2-induced cytokines, we measured transforming growth factor-beta and insulin-like growth factor 1 secreted from HDFPCs. To investigate the regulatory effects of supercritical extraction-residues extract of Ulmus davidiana on dihydrotestosterone hormone production, cells were co-incubated with high concentrations of testosterone. The supercritical extraction-residues extract of Ulmus davidiana significantly inhibited the secretion of transforming growth factor-beta but rescued insulin-like growth factor 1 in a dose-dependent manner. The supercritical extraction-residues extract of Ulmus davidiana markedly reduced dihydrotestosterone production. These results suggest that the supercritical fluid extract residues of Ulmus davidiana and their functional molecules are candidates for preventing human hair loss.

Bioactivity of 11 keto and hydroxy androgens in yeast and mammalian host cells.

Recent studies have highlighted the potential role of 11oxygenated (keto or hydroxy) androgens in human reproductive function with 11keto androgens circulating at concentrations comparable with testosterone in women and children. However, the intrinsic androgenic bioactivities of 11 keto and hydroxy androgens are not fully characterized. We therefore investigated the full androgen dose-response curves using complementary in vitro yeast and mammalian (HEK293) host cell bioassays of 11 keto and hydroxy derivatives of the potent androgens, testosterone (T) and dihydrotestosterone (DHT), compared with their parent non-11 oxygenated steroids together with the pro-androgen precursor (androstenedione (A4)) and metabolites (androstanedione, androsterone). For potent androgens, the mammalian HEK293 host cell bioassay was 22-138 times more sensitive than the yeast host cell bioassay. In both androgen bioassays, 11keto derivatives displayed androgenic bioactivity but significantly lower molar potency than their parent non-keto steroids. By contrast, the 11hydroxy derivatives had minimal or no androgenic bioactivity. In both bioassays 5α-reduction increased androgenic potency. These findings confirm that that 11keto androgens may contribute directly to androgen status in women, children, and other conditions apart from healthy eugonadal men whereas 11hydroxy androgens have negligible androgenic potency although it cannot be excluded that they may be converted to more potent androgens in vivo.

Stauntonia hexaphylla Extract Ameliorates Androgenic Alopecia by Inhibiting Androgen Signaling in Testosterone-induced Alopecia Mice.

Background: Stauntonia hexaphylla has been a traditional folk remedy for alleviating fever and providing anti-inflammatory properties. Androgenetic alopecia (AGA) is the most common form mediated by the presence of the dihydrotestosterone (DHT). Objectives: In this study, we evaluated the effects of an extract of S. hexaphylla on AGA models and its mechanisms of action. Methods: We studied S. hexaphylla extract to evaluate 5α-reductase and androgen receptor (AR) levels, apoptosis, and cell proliferation in vitro and in vivo. In addition, paracrine factors for androgenic alopecia, such as transforming growth factor beta-1 (TGF-ß1) and dickkopf-a (DKK-1), were examined. Apoptosis was investigated, and the evaluation of proliferation was examined with cytokeratin 14 (CK-14) and proliferating cell nuclear antigen (PCNA). Results: In human follicular dermal papilla cells, the 5α-reductase and AR were decreased following S. hexaphylla treatment, which reduced the Bax/Bcl-2 ratio. Histologically, the dermal thickness and follicle number were higher in the S. hexaphylla groups compared with the AGA group. In addition, the DHT concentration, 5α-reductase, and AR were decreased, thereby downregulating TGF-ß1 and DKK-1 expression and upregulating cyclin D in S. hexaphylla groups. The numbers of keratinocyte-positive and PCNA-positive cells were increased compared to those in the AGA group. Conclusions: The present study demonstrated that the S. hexaphylla extract ameliorated AGA by inhibiting 5α-reductase and androgen signaling, reducing AGA paracrine factors that induce keratinocyte (KC) proliferation, and inhibition apoptosis and catagen prematuration.

Ficus benghalensis as Potential Inhibitor of 5α-Reductase for Hair Growth Promotion: In Vitro, In Silico, and In Vivo Evaluation.

The screening of hair follicles, dermal papilla cells, and keratinocytes through in vitro, in vivo, and histology has previously been reported to combat alopecia. Ficus benghalensis has been used conventionally to cure skin and hair disorders, although its effect on 5α-reductase II is still unknown. Currently, we aim to analyze the phytotherapeutic impact of F. benghalensis leaf extracts (FBLEs) for promoting hair growth in rabbits along with in vitro inhibition of the steroid isozyme 5α-reductase II. The inhibition of 5α-reductase II by FBLEs was assessed by RP-HPLC, using the NADPH cofactor as the reaction initiator and Minoxin (5%) as a positive control. In silico studies were performed using AutoDock Vina to visualize the interaction between 5α-reductase II and the reported phytoconstituents present in FBLEs. Hair growth in female albino rabbits was investigated by applying an oral dose of the FBLE formulation and control drug to the skin once a day. The skin tissues were examined by histology to see hair follicles. Further, FAAS, FTIR, and antioxidants were performed to check the trace elements and secondary metabolites in the FBLEs. The results of RP-HPLC and the binding energies showed that FBLEs reduced the catalytic activity of 5α-reductase II and improved cell proliferation in rabbits. The statistical analysis (p < 0.05 or 0.01) and percentage inhibition (>70%) suggested that hydroalcoholic FBLE has more potential in increasing hair growth by elongating hair follicle's anagen phase. FAAS, FTIR, and antioxidant experiments revealed sufficient concentrations of Zn, Cu, K, and Fe, together with the presence of polyphenols and scavenging activity in FBLE. Overall, we found that FBLEs are potent in stimulating hair follicle maturation by reducing the 5α-reductase II action, so they may serve as a principal choice in de novo drug designing to treat hair loss.

Effects of Saussurea costus on apoptosis imbalance and inflammation in benign prostatic hyperplasia.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea costus (synonym: Aucklandia lappa Decne) is a medicinal plant distributed in Yunnan, Guangxi, and Sichuan in China. In traditional Korean medicine, the plant parts (especially the root-"radix aucklandiae") is widely used to treat vomiting, diarrhea, and inflammation. However, little has been reported on its effect on benign prostatic hyperplasia (BPH), which is common in middle-aged men. AIM OF THE STUDY: BPH is caused by apoptosis imbalance and inflammation due to aging of the prostate. Therefore, the aim of this was to prove the efficacy of S. costus by analyzing its effect on the biological mechanisms leading to BPH progression. MATERIALS AND METHODS: Wistar rats were injected subcutaneously with a single dose of testosterone (125 mg/kg) to induce BPH, and were later administered with S. costus (20, 40 mg/kg). After 12 weeks, histological changes in the prostate and hormone regulation factors were assessed in all animals. Furthermore, apoptotic protein and apoptotic body values were analyzed to confirm the improvement of apoptosis imbalance, and inflammatory cytokines were analyzed to confirm the anti-inflammatory efficacy of S. costus. RESULTS: In the serum and tissue of S. costus-treated BPH rats, a significant reduction in prostate weight, prostate index, and hormone regulation factors was observed. S. costus also increased the levels of apoptosis marker proteins and reduced the levels of inflammatory cytokines. It also decreased the expression of B-cell lymphoma 2 (BCL-2) and increased the expression of BCL-2 associated X protein (BAX) in the prostate. Histological changes such as epithelial thickness significantly increased in BPH induced group but significantly decreased in the S. costus-treated groups (p < 0.001). CONCLUSIONS: S. costus may prevent and treat BPH occurrence by modulating inflammation and apoptosis imbalance.

Extracts of Phyllostachys pubescens Leaves Represses Human Steroid 5-Alpha Reductase Type 2 Promoter Activity in BHP-1 Cells and Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rat Model.

Benign prostatic hyperplasia (BPH) is the most common symptomatic abnormality of the human prostate characterized by uncontrolled proliferation of the prostate gland. In this study, we investigated the effect of bamboo, Phyllostachys pubescens, leaves extract (PPE) on human 5α-reductase type 2 (SRD5A2) gene promoter activity in human prostate cell lines and the protective effect of PPE on a testosterone-induced BPH rat model. PPE repressed human SRD5A2 promoter activity and its mRNA expression. The rats treated with PPE for 4 weeks showed a significantly attenuated prostate weight compared to vehicle control. PPE-treated rats also showed reduced serum dihydrotestosterone, testosterone, prostate-specific antigen, and SRD5A2 levels by testosterone injection. Quantitative real-time polymerase chain reaction showed that PPE treatment significantly decreased mRNA expression of SRD5A2, androgen receptor (AR), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor 2 compared with the vehicle-treated, testosterone-injected rats in the prostate. Furthermore, PPE treatment showed reduced AR, PCNA, and tumor necrosis factor alpha expression in the prostate via immunohistofluorescence staining. In conclusion, oral administration of PPE prevented and inhibited the development and progression of enlarged prostate lesions in testosterone-induced animal models through various anti-proliferative and anti-inflammatory pharmacological effects and induced suppression of SRD5A2 gene expression.

Activation of Hair Cell Growth Factors by Linoleic Acid in Malva verticillata Seed.

Hair loss by excessive stress from work and lifestyle changes has become a growing concern, particularly among young individuals. However, most drugs for alopecia impose a plethora of side effects. We have found the powerful impact of Malva verticillata seed extracts on alleviating hair loss. This study further isolated effective chemicals in M. verticillata seed extracts by liquid silica gel column chromatography. Under the screening for the growth rate (%) of human follicles dermal papilla cells (HFDPCs), we identified linoleic acid (LA) and oleic acid in n-hexane of M. verticillate (MH)2 fraction. LA treatment activated Wnt/ß-catenin signaling and induced HFDPCs growth by increasing the expression of cell cycle proteins such as cyclin D1 and cyclin-dependent kinase 2. LA treatment also increased several growth factors, such as vascular endothelial growth factor, insulin-like growth factor-1, hepatocyte growth factor, and keratinocyte growth factor, in a dose-dependent manner. Besides, LA significantly inhibited Dickkopf-related protein expression (DKK-1), a primary alopecia signaling by dihydrotestosterone. Our findings suggest that LA treatment may alleviate a testosterone-induced signaling molecule and induces HFDPCs growth by activating Wnt/ß-catenin signaling.

Development of a Liquid Chromatography/Mass Spectrometry-Based Inhibition Assay for the Screening of Steroid 5-α Reductase in Human and Fish Cell Lines.

Steroid 5-α reductase (5AR) is responsible for the reduction of steroids to 5-α reduced metabolites, such as the reduction of testosterone to 5-α dihydrotestosterone (DHT). A new adverse outcome pathway (AOP) for 5AR inhibition to reduce female reproduction in fish (AOP 289) is under development to clarify the antiestrogenic effects of 5AR inhibitors in female fish. A sensitive method for the DHT analysis using chemical derivatization and liquid chromatography-tandem mass spectrometry was developed. A cell-based 5AR inhibition assay that utilizes human cell lines, a transient overexpression system, and fish cell lines was developed. The measured IC50 values of two well-known 5AR inhibitors, finasteride and dutasteride, were comparable in the different systems. However, the IC50 of dutasteride in the fish cell lines was lower than that in the human cell lines. Finasteride showed a higher IC50 against the RTG-2 cell line. These results demonstrated that 5ARs inhibition could differ in terms of structural characteristics among species. The assay has high sensitivity and reproducibility and is suitable for the application in 5AR inhibition screening for various endocrine disruption chemicals (EDCs). Future studies will continue to evaluate the quantitative inhibition of 5AR by EDCs to compare the endocrine-disrupting pathway in different species.

Psoralea corylifolia L. extract ameliorates benign prostatic hyperplasia by regulating prostate cell proliferation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. seed (PCL), commonly known as "Poguzhi" or "BuguZhi", has been widely used to treat kidney yang deficiency in traditional Chinese medicine (TCM) where tonifying the yang deficiency is a representative understanding for treatment of hormonal deficiency disorders such as enuresis, oliguria, and prostatic diseases. Although PCL has been commonly used to treat problems of the urinary system, its efficacy against benign prostatic hyperplasia (BPH) has not yet been reported. AIM OF THE STUDY: In the present study, we aimed to assess the in vitro and in vivo efficacy of PCL against BPH, a condition which negatively impacts quality of life in men. MATERIALS AND METHODS: Normal human prostate cell lines, RWPE-1 and WPMY-1 cells, were stimulated with 10 nM dihydrotestosterone (DHT) to establish an in vitro BPH model. Subsequently, cells were treated with 100 or 200 µg/ml PCL, which inhibited cell proliferation without cytotoxicity, to evaluate the anti-BPH effect of PCL. Eight-week-old male Wistar rats were castrated, except for those in the control group (Con), and BPH was induced by subcutaneous injection of 10 mg/kg testosterone propionate (TP). Concurrent with daily TP injections, 5 mg/kg of finasteride (Fina) and 50 or 100 mg/kg PCL were orally administrated daily for four weeks, excluding the weekends. RESULTS: In DHT-stimulated RWPE-1 and WPMY-1 cells, expression of androgen receptor (AR) androgen signaling-related markers such as 5α-reductase 2 (5AR2), AR, and prostate-specific antigen (PSA) was upregulated, whereas 100 or 200 µg/ml of PCL treatment downregulated these markers. Furthermore, PCL significantly reduced the mRNA expression of anti-apoptotic genes and increased the mRNA expression of pro-apoptotic gene. In vivo, administration of PCL reduced prostate size and weight in TP-induced BPH rats. Moreover, histological alterations in epithelium thickness were significantly restored by the administration of PCL. Immunohistochemical analysis revealed increased expression of AR and proliferating cell nuclear antigen (PCNA) in TP-induced BPH prostates; these changes were suppressed by administration of 50 or 100 mg/kg PCL. CONCLUSIONS: We demonstrated the effect of PCL against BPH, mediated by the regulation of prostate cell proliferation and apoptosis, in DHT-stimulated normal human prostate cell lines and TP-induced BPH rats. These findings suggest that PCL could be a potential therapeutic agent against BPH.

Cranberry Powder Attenuates Benign Prostatic Hyperplasia in Rats.

Cranberry powder (CR) is reported to be effective against lower urinary tract symptoms (LUTS) and recurrent urinary tract infections. Benign prostatic hyperplasia (BPH) in men older than 50 years is a common cause of LUTS. Here, we attempted to evaluate if CR is also effective for treating BPH using a BPH-induced rat model, which was orally administered CR. Male Sprague-Dawley rats weighing 200-250 g were randomly divided into the following six groups (n = 9): noncastration group; castration group; BPH group; BPH and cranberry for 8-week (CR8W) group; BPH and cranberry for 4-week (CR4W) group; and BPH and saw palmetto group (saw palmetto). Compared with the BPH group, the CR8W group showed a significant decrease in prostate weight (by 33%), dihydrotestosterone (DHT) levels (by 18% in serum and 28% in prostate), 5-alpha reductase levels (18% reduction of type 1 and 35% of type 2), and histological changes. These results indicate that CR could attenuate BPH by inhibiting 5-alpha reductase and by reducing other biomarkers such as prostate weight and DHT levels. Thus, CR may be an effective candidate for the development of a functional food for BPH treatment. IACUC (USW-IACUC-R-2015-004).

Polygonum multiflorum extract support hair growth by elongating anagen phase and abrogating the effect of androgen in cultured human dermal papilla cells.

BACKGROUND: Dermal papilla cells (DPCs) play a key role in hair growth among the various cell types in hair follicles. Especially, DPCs determine the fate of hair follicle such as anagen to telogen transition and play a pivotal role in androgenic alopecia (AGA). This study was performed to elucidate the hair growth promoting effects of Polygonum multiflorum extract (PM extract) in cultured human DPCs and its underlying mechanisms. METHODS: The effects of PM extract on cultured DPCs were investigated. Cell viability and mitochondrial activity were measured by CCK-8 and JC-1 analysis, respectively. Western blotting, dot blotting, ELISA analysis, immunocytochemistry and real-time PCR analysis were also performed to elucidate the changes in protein and mRNA levels induced by PM extract. 3D cultured DPC spheroids were constructed for mimicking the in vivo DPs. The hair growth stimulatory effect of PM extract was evaluated using human hair follicle organ culture model. RESULTS: PM extract increased the viability and mitochondrial activity in cultured human DPCs in a dose dependent manner. The expression of Bcl2, an anti-apoptotic protein expressed dominantly in anagen was significantly increased and that of BAD, a pro-apoptotic protein expressed in early catagen was decreased by PM extract in cultured DPCs and/or 3D DPC spheroid culture. PM extract also decreased the expression of catagen inducing protein, Dkk-1. Growth factors including IGFBP2, PDGF and VEGF were increased by PM extract, revealed by dot blot protein analysis. We also have found that PM extract could reverse the androgenic effects of dihydrotestosterone (DHT), the most potent androgen. Finally, PM extract prolonged the anagen of human hair follicles by inhibiting catagen entry in human hair follicle organ culture model. CONCLUSION: Our data strongly suggest that PM extract could promote hair growth by elongating the anagen and/or delaying the catagen induction of hair follicles through activation of DPCs.

[Study on effect of extract from Tibetan medicine Urtica hyperborean on anti-prostatic hyperplasia].

In this study,mouse models of benign prostatic hyperplasia induced by subcutaneous injection of testosterone propionate was used to investigate the therapeutic effect and mechanism of Urtica hyperborean( UW) extracts on prostate hyperplasia in mice. The effects of UW extracts on prostate index,serum epidermal growth factor( EGF) and dihydrotestosterone( DHT) in model mice were observed,and the EGF and anti-apoptotic factor( Bcl-2) mRNA expression levels were detected as well as pathological changes in prostate tissue. The results showed that the ethyl acetate extraction and alcohol soluble fraction of the UW could significantly reduce the prostate index,reduce the serum DHT and EGF levels( P<0. 01),and significantly decrease the EGF and Bcl-2 mRNA expression( P<0. 01),significantly improved the morphological structure of prostate tissue. The above results confirmed that ethyl acetate extract and alcohol-soluble parts of UW have a good preventive effect on mice prostatic hyperplasia model,and its mechanism may be to reduce androgen levels by regulating polypeptide growth factors and/or inhibiting cell hyperproliferation and promoting apoptosis. This study laid the foundation for the further research on UW.