• The Journal of Internal Korean Medicine
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• v.31 no.1
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• pp.166-176
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• 2010

Objective : Benign prostatic hyperplasia(BPH) is one of the most common diseases among elderly men. In BPH, dihydrotestosterone (DHT) acts as a potent cellular androgen and promotes prostate growth. Many reports conclude the component melittin in bee venom has the potential to treat various diseases including prostate cancer. In this study, we investigated the therapeutic effects and action mechanism of Bee venom herbal acupuncture with BPH induced by castration and testosterone treatment. Methods : Sprague-Dawley rats were treated with testosterone after castration for induction of experimental BPH. A total of 24 rats were equally divided into four groups: Group 1 was the model group; Group 2 served as control (sham-operated group); Group 3 animals were treated with Bee venom herbal acupuncture as an experimental specimen; Group 4 served as a positive control group and was treated with finasteride at a dose of 1 mg/kg. The drugs were administered orally. The prostates were evaluated by prostatic weight, volume, histopathological changes and testosterone levels. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Bee venom herbal acupuncture showed a diminished range of tissue damage and showed significant decrease in their prostatic weights, volume and histopathological examination. Conclusions : These results suggest that Bee venom herbal acupuncture may protect the glandular epithelial cells and also inhibit stromal proliferation. From theses results, we suggest that Bee venom herbal acupuncture could be a useful remedy agent for treating the benign prostatic hyperplasia.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.639-652
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• 2006

Objective : The etiology of chronic prostatitis is likely multifactorial, resulting from either a cascade of events after an initiating factor or from a variety of etiologic mechanisms. There is substantiating evidence to support the role of the inflammatory responses in its pathogenesis, and the clinical value in the evaluation of therapeutic efficacy. Forsythiae Frucus has been traditionally used in treatment of inflammatory diseases, including of prostatitis and urinary tract inflammation. In this study, we investigated the effects of Forsythiae Frucus on inflammatory cytokines and cyto-pathological alternation in the rat model of chronic non-bacterial prostatitis induced by castration and $17{\beta}$-estradiol treatment. Methods : Two-month-old rats were treated with $17{\beta}$-estradiol after castration for induction of experimental non-bacterial prostatitis. which is similar to human chronic prostatitis in histopathological profiles. Forsythiae Frucus as an experimental specimen, and testosterone as a positive control, were administered orally. The prostates were evaluated by histopathologlcal parameters including the epithelial score and epithelio-stromal ratio for glandular damage. and the expression of inflammatory cytokine genes including interleukin (IL)-$1{\beta}$, IL-5, IL-12, tumor necrosis factor (TNF)-$\alpha$. eotaxin, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(cox-2). Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation. the rats treated with Forsythiae Frucus showed a diminished range of tissue damage. Epithelial score was improved in the Forsythiae Frucus group over that of the control (P<0.05). The epithelia-stromal ratio was lower in the Forsythiae Frucus group when compared to that of the control (P<0.05). In the reverse transcription-polymerase chain reaction (RT-PCR) of inflammatory cytosine genes. Forsythiae Frucus inhibited the expression of IL-$1{\beta}$, TNF-$\alpha$, iNOS, cox-2 genes, while it modulated the expression of IL-5, which is an anti-inflammatory cytokine. Conclusions : These findings suggest that Forsythiae Frucus may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the immune modulation including the suppression of inflammatory cytokines and increase of anti-inflammatory cytokines. From theses results. we suggest that Forsythiae Frucus could be a useful remedy agents for treating chronic non-bacterial prostatitis.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.51-62
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• 2006

Objective: Although chronic non-bacterial prostatitis is a common disease, it is very difficult to treat effectively. Lygodium japonicum has traditionally been used in treatment of urinary tract inflammation and voiding disturbance. In this study, we investigated the therapeutic effects and action mechanism of Lygodium japonicum in the rat model of non-bacterial prostatitis induced by castration and testosterone treatment. Methods: Five-month-old rats were treated with $17\beta-estradiol$ after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histopathological profiles. Lygodium japonicum and testosterone were administered as an experimental specimen and a positive control, respectively. The prostates were evaluated by histopathological parameters including the epithelial score and epithelio-stromal ratio for glandular damage, proliferating cell nuclear antigen (PCNA) labeling index for cyto-proliferation and a TUNEL (deoxyuridine triphosphate biotin nick end-labeling) assay for cell apoptosis. Results: While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Lygodium japonicum showed a lesser range of tissue damage. Epithelial score was improved in Lygodium japonicum than that of the control (P<0.05). The epithelio-stromal ratio was lower in Lygodium japonicum when compared to that of the control (P<0.05). Although there was no difference in PCNA and TUNEL positive cells of the glandular epithelia, we found an decreased number of PCNA positive cell and concurrent increase of TUNEL positive cells in the stroma of Lygodium japonicum treated rats (P<0.01). Conclusions: These findings suggest that Lygodium japonicum may protect the glandular epithelial cells and also inhibit stromal proliferation in association with suppression of cyto-proliferation and stimulation of apoptosis. We concluded that Lygodium japonicum may be a useful remedy agent for treating the chronic non-bacterial prostatitis.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.664-676
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• 2006

Objective : Although chronic non-bacterial prostatitis is a common disease, it is very difficult to treat effectively. Lygodium japonicum has been traditionally used in treatment of urinary tract inflammation and voiding disturbance. In this study, we investigated the therapeutic effects and action mechanism of Lygodium japonicum in the rat model of non-bacterial prostatitis induced by castration and testosterone treatment. Methods : Five-month-old rats were treated with 17$\beta$-estradiol after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histopathological profiles. Lygodium japonicum and testosterone were administered as an experimental specimen and a positive control. respectively. The prostates were evaluated by histopathological parameters including the epithelial score and epithelio-stromal ratio for glandular damage. PCNA labeling index for cyto-proliferation and a TUNEL(deoxyuridine triphosphate biotin nick end-labeling) assay for cell apoptosis. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Lygodium japonicum showed a diminished range of tissue damage. Epithelial score was improved in the Lygodium japonicum group over that of the control (P<0.05). The epithelio-stromal ratio was lower in the Lygodiutn japonicum group when compared to that of the control (P<0.05). Although there was no difference in PCNA and TUNEL positive cells of the glandular epithelia. we found an decreased number of PCNA positive cell and concurrent increase of TUNEL positive cells in the stroma of Lygodium japonicum treated rats (P<0.01). Conclusions : These findings suggest that Lygodium japonicum may protect the glandular epithelial cells and also inhibit stromal proliferation in association with suppression of cyto-proliferation and stimulation of apoptosis. We concluded that Lygodium japonicum could be a useful remedy agents for treating chronic non-bacterial prostatitis.

• Korean Journal of Pharmacognosy
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• v.39 no.2
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• pp.80-85
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• 2008

Benign prostatic hyperplasia (BPH) is one of the common diseases in elderly men. Recently, the old-aged population has increased, with the interest in the clinical importance of BPH ever growing. This study is designed to investigate the effects of KH-305 on BPH induced rat. The herb formulation KH-305 is consisted of Rubus coreanus, Cornus officinalis and Cuscuta chinensis. An experimental prostatic hyperplasia was induced in male rats by the administration of testosterone propionate, 3 mg/kg SC, for 2 months. The rats were divided into 3 experimental groups: the control, BPH-induced, oral KH-305 ingestion group. After 2 months, the prostates were removed, and analyzed for their prostatic weight and histological examination. The prostate weights were measured in each group, and found to be 820${\pm}$38mg, 3140${\pm}$26mg, 1880${\pm}$21mg in the control, BPH-induced, and oral KH-305 ingestion group, respectively. The BPH induced group showed statistically significant increases in their prostatic weights compared with control group(p<0.05) but oral KH-305 ingestion group showed more significant decreases than BPH-induced group statically(p<0.05). Histologically injected testosterone lead to prostatic hyperplasia in rats, but oral KH-305 ingestion decreased this change. These results suggest that KH-305 may be effective in treatment of BPH, and complementary medicine of BPH.

• 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.

• Development and Reproduction
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• v.17 no.4
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• pp.435-440
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• 2013

Previous studies, including our own, have demonstrated that the intratesticular injection of hypertonic saline (20%) decreased serum testosterone level which was similar to the surgical castration in the rat, showing the state of chemical castration. In the present study, we further verify the efficacy of this less invasive method as an alternative of surgical orchidectomy in the andrological field. Sterilized 20% saline was directly injected into the adult male rats (750 ${\mu}l$ per testis). The tested rats were divided into 3 groups including intact group (intact), orchidectomy group (ORX) and saline injection group (SAL) after bilateral orchidectomy was performed at the same day of injection. All rats were sacrificed at 4 weeks after injection. The reproductive organs (testes, epididymis, seminal vesicles and prostates) were collected and used for DNA and protein pattern analyses. Also, patho-histological studies on the testes were performed. In contrast to the intact group, similar DNA damages of testis and seminal vesicle were appeared in ORX group and SAL group. The DNA degradations seemed to be the results of necrosis rather than apoptosis. In the protein pattern analysis, all the testing tissues exerted similar patterns in the ORX group and the SAL group compared to the those of intact group. Patho-histological studies revealed that severe degenerative changes in testicular seminiferous tubules and massive infiltration of immune cells in SAL group. The present study confirmed that direct injection of hypertonic saline into the testis caused the equivalent biochemical changes in the accessory sex organs as shown in the orchidectomized animals. These results suggest that hypertonic saline injection model could be a useful castration model which can substitute for surgical castration when its safety is secured through further study in the future.

• Journal of Food Hygiene and Safety
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• v.31 no.2
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• pp.113-118
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• 2016

Proprotein convertase subtilisin/kexin type 9 (PCSK9), is a protein mainly secreted by a liver. The PCSK9 plays an important role in low density lipoprotein (LDL) metabolism acting as a repressor of LDL receptor through transportation of the LDLR to the lysosome for degradation. Thus, the PCSK9 inhibitor suppresses PCSK9-regulated degradation of the LDL receptor as a LDL-lowering medicine. However, little is known about the role of PCSK9 in the reproductive system. Therefore, in the present study, we investigated Pcsk9 expression in male reproductive tracts including penises, prostates and testes using rats in response to their diets between a normal diet and a high-fat diet with cholesterol. Based on our previous study, the high-fat diet elevates concentration of total cholesterol and LDL in serum whereas it reduces the concentration of plasma high density lipoprotein (HDL). In addition, it dramatically affects to morphological changes of the male reproductive organs. Consistent with these results, the expression of Pcsk9 was substantially decreased in the penile tissues (P < 0.001) from rats fed a high fat diet as compared to a normal diet. Moreover, it slightly reduced in the prostate and testes (P < 0.05) of rats in response to a high fat diet. Localization of Pcsk9 was predominantly detected in urethral epithelium of penises, cylinder-shaped cells of prostate glands, and spermatogonia, spermatocytes and spermatid of testes of rats. Collectively, results of current study provide invaluable insights into the Pcsk9 gene with respect to its tissue- and cell-specific expression by a high fat diet with cholesterol.

• Development and Reproduction
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• v.12 no.3
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• pp.251-259
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• 2008

The plasticizer di(2-ethylhexyl)phthalate(DEHP) is one of the most well known endocrine disrupting chemicals (EDCs) because of its strong anti-androgenic effects on the reproductive and developmental process in male rodents and human. The present study was performed to examine whether prepubertal exposure to DEHP can make any alteration during the maturation of accessory sex organs in male rats. As a result, there was no significant change in body weights, serum T levels and tissue weights except of seminal vesicle and ventral prostate in DEHP-treated animals compared to vehicle-treated ones. The seminal vesicle weights in high-dose group (200 mg/kg) were significantly lower than those from the control group (p<0.05), and ventral prostate weights were significantly lower than those from the control group (p<0.05) in both low-dose (20 mg/kg) and high-dose group. Histological studies revealed that the seminal vesicles from DEHP-treated groups showed reduced areas of mucosal folds. Pseudostratified columnar epithelia were observed in the ventral prostates of DEHP-treated samples while cuboidal epithelia were found in the control group. The transcriptional activities of ER-$\alpha$ in seminal vesicle from high-dose group (p<0.05) were significantly higher than those from the control group, and ER-$\beta$ expression was significantly decreased in low-dose group (p<0.05) compared to the control. In ventral prostate, ER-$\beta$ mRNA levels from low-dose group (p<0.05) were significantly lower than those from the control group, and significantly increased in high-dose group (p<0.01). AR expressions, however, were not significantly different in all experimental groups of both seminal vesicle and ventral prostate. In conclusion, the present study demonstrated that (i) adverse effect (s) of DEHP on sexual maturation during prepubertal period could be limited, (ii) seminal vesicle and prostate gland were sensitive targets to DEHP in prepubertal rats and (iii) the deleterious effects of DEHP might be mediated through ER-associated mechanism.