Hyun Cheol Jeong

Administration of Goji (Lycium chinense Mill.) Extracts Improves Erectile Function in Old Aged Rat Model

Purpose This study investigated the effect of goji (Lycium chinense Mill.) on erectile dysfunction in old-aged rats. Materials and Methods Twenty-four 18-month-old male Sprague-Dawley rats (defined as old-aged rats) were used. Treatment groups contained eight rats each: a control group, goji extract of 150 mg/kg/day group, and goji extract of 300 mg/kg/day group. Treatment was by orogastric tube once daily for 6 weeks. After 6 weeks of treatment, testes weight, serum testosterone, superoxide dismutase, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, intracavernous pressure/mean arterial pressure, and histological changes were examined. Results Treatments with goji extracts increased serum testosterone level, increased the expression of endothelial NO synthase, neuronal NO synthase, and cGMP, improved the oxidative stress marker, and decreased corporal fibrosis. Conclusions Our results indicate that goji extract may have a positive effect on erectile dysfunction via its antioxidant effects.

Antioxidant and Antifibrotic Effect of a Herbal Formulation In Vitro and in the Experimental Andropause via Nrf2/HO-1 Signaling Pathway

The Korean herbal formulation Ojayeonjonghwan is used for improving late-onset hypogonadism (LOH) symptoms such as erectile dysfunction (ED). A previous research suggested that a modified Ojayeonjonghwan (KH-204) could be used as an alternative to the treatment for ED. The pharmacological effects were examined in different conditions, including in vitro and in vivo. We measured the survival rate of TM3 Leydig cells under the oxidative stress condition. The s.c. injection of leuprorelin was used to induce androgen deprivation. We measured serum testosterone levels, oxidative stress, and apoptosis. The results of the treatment by KH-204 (1) preserved TM3 cells from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1); (2) lowered the expression of transforming growth factor-beta (TGF-β) 1/SMAD; (3) increased the average of serum testosterone in androgen-deprived male rats; (4) kept the activation of spermatogenesis; (5) upgraded the contents of 8-hydroxy-20-deoxyguanosine (8-OHdG) and degraded the contents of superoxide dismutase (SOD); and (6) reduced apoptosis. We studied that KH-204 improved testicular dysfunction in LOH. It is likely, at least in part, to degrade oxidative stress through the Nrf2/HO-1 pathway. These findings may offer credible evidences for the use of new alternative therapies to treat LOH.

Anti-Inflammatory and Antimicrobial Effects of a Novel Herbal Formulation (WSY-1075) in a Chronic Bacterial Prostatitis Rat Model

Purpose The aim of this study was to investigate the anti-inflammatory and anti-oxidative effects of a multi-herbal formula known as WSY-1075 in the treatment of chronic bacterial prostatitis in a rat model. Materials and Methods Experimental chronic bacterial prostatitis was induced in 32 Wistar rats by instillation of a bacterial suspension (Escherichia coli, 108 colony-forming units [CFU]/mL) into the prostatic urethra. After the induction of prostatitis, the rats were randomly divided into one of 4 treatment groups: control (n=8), ciprofloxacin (n=8), WSY-1075 (400 mg/kg) (n=8), and WSY-1075 (400 mg/kg)+ciprofloxacin (n=8). After 4 weeks of treatment, microbiological data from prostate tissue cultures, level of prostatic pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6, and IL-8), anti-oxidant effects (superoxide dismutase [SOD]), and histological findings were noted. Results The WSY-1075, ciprofloxacin, and WSY-1075+ciprofloxacin groups showed fewer CFUs in prostate tissue cultures than the control group. The WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups showed statistically significantly lower levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-8 than the control group. SOD levels in the WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups were significantly higher than in the control group. Conclusions This study found that WSY-1075 had anti-microbial effects, anti-inflammatory effects, and anti-oxidative effects in a chronic bacterial prostatitis rat model. We expect the WSY-1075 may be useful for the clinical treatment of chronic bacterial prostatitis.

Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

Purpose Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED. Materials and Methods Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated. Results In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p<0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p<0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Massons trichrome staining (p<0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p<0.05). Conclusions Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.

Lycium chinense Mill improves hypogonadism via anti-oxidative stress and anti-apoptotic effect in old aged rat model

Abstract Purpose: To evaluate the pharmacological effects of goji berry (Lycium chinense P. Mill) in an animal model of late-onset hypogonadism (LOH). Materials and methods: Thirty 18-month-old male Sprague–Dawley (SD) rats were used as the LOH aged rat model. Rats were divided into five groups: a control group (nu2009=u20096), low concentration goji berry extract group (150u2009mg/kg/day) (nu2009=u20096), high concentration goji berry extract group (300u2009mg/kg/day) (nu2009=u20096), low concentration goji berry complex extract group (150u2009mg/kg/day) (nu2009=u20096), and high goji berry complex concentration extract group (300u2009mg/kg/day) (nu2009=u20096). After six weeks of treatment, sperm counts and motility, serum testosterone level, androgen receptor (AR) expression, oxidative stress marker, and apoptotic factors were examined. Results: Goji berry extracts increased testosterone level to 2.07u2009±u20090.06u2009pmol/L in the goji berry 150u2009mg/kg group, 2.39u2009±u20090.08u2009pmol/L in the goji berry 300u2009mg/kg group, 2.97u2009±u20090.03u2009pmol/L in the goji berry complex 150u2009mg/kg group, and 3.34u2009±u20090.04u2009pmol/L in the goji berry complex 300u2009mg/kg group compared to 1.86u2009±u20090.03u2009pmol/L in the control group, respectively (pu2009<u2009.05). AR expressions were increased in testis tissue significantly but were not significant in prostate tissue. Conclusions: Goji berry might improve LOH by reversing testicular dysfunction via an anti-oxidative stress mechanism without inducing prostate disease.

A randomized, controlled study of treatment with ojayeonjonghwan for patients with late onset hypogonadism

Abstract Objectives: We investigate the effects of Ojayeonjonghwan (KH-204) in men with late-onset hypogonadism (LOH) symptoms. Material and methods: Initial PSA, testosterone, lipid profile and questionnaires about LOH-related symptoms were checked. After 8u2009weeks of the treatment (control or KH-204), questionnaires and serological tests were repeated to evaluate the efficacy of the agent. The changes of variables in each group and the difference between two groups were compared. Results: A total of 78 men were enrolled, and randomly assigned to the control group (nu2009=u200939) or KH-204 group (nu2009=u200939). Baseline characteristics of both group are comparable. AMS total score of control and KH-204 group were both improved at 8u2009weeks (pu2009=u2009.010,u2009<.001), and there was a statistically significant difference between the two groups (favorable in KH-204 group, pu2009=u2009.006). At 8u2009weeks, total IIEF score of control and KH-204 group were both improved, and there was no statistically significant difference in the degree of improvement between the two groups (pu2009=u2009.303). There was no statistically significant difference of laboratory findings, in intra-group changes and inter-group comparisons. Conclusions: KH-204 was found to be effective in all LOH symptoms without changing of laboratory results. KH-204 may be safely used for treatment of male with LOH-related symptoms.

Efficient Promotion of Autophagy and Angiogenesis Using Mesenchymal Stem Cell Therapy Enhanced by the Low-Energy Shock Waves in the Treatment of Erectile Dysfunction

Background Mesenchymal stem cell therapy (MSCT) and defocused low-energy shock wave therapy (ESWT) has been shown to ameliorate erectile dysfunction (ED). However, the interactions and effects of action between MSCT and ESWT remain poorly understood. In this study, we investigated the mechanisms of combination therapy with MSCT and ESWT in a rat model of diabetic ED. Materials and Methods Eight-week-old male Sprague-Dawley rats were randomly divided into 2 parts. Diabetic rats induced by streptozotocin (65u2009mg/kg) were randomly divided into 4 groups: (1) DM control group, (2) DMu2009+u2009ESWT group, (3) DMu2009+u2009MSCT group, and (4) DMu2009+u2009ESWTu2009+u2009MSCT group. The sham group was a normal control group (without streptozotocin). MSCT and (or) ESWT were, respectively, administered to each group according to the proposal for 8 weeks. Immediately after recording of intracavernous pressure (ICP), the penis was then harvested for histologic analysis, ELISA, and Western blotting. Results The ratio of ICP/MAP was significantly higher in the DMu2009+u2009ESWTu2009+u2009MSCT group than in ESWT or MSCT treated group (P < 0.05). Also, the treatment stimulated angiogenesis and vasodilatation in the corpus cavernosum (P < 0.05). ESWT increased the quantity of MSCs in the corpus cavernosum and also induced MSCs to express more VEGF in vitro and vivo (P < 0.05) which activated the PI3K/AKT/mTOR and NO/cGMP signaling pathways in the corpus cavernosum. The combination approach stimulated autophagy and decreased apoptosis in the corpus cavernosum. NGF and BDNF expressions were higher in the DMu2009+u2009ESWTu2009+u2009MSCT group than in the DM control group (P < 0.01). Furthermore, the treatment promoted the MSC recruitment by inducing penile tissues to express more PECAM and SDF-1. Conclusions Combination of LI-ESWT and MSCT can get a better result than a single treatment by expressing more VEGF which can take part in autophagy by triggering the PI3K/AKT/mTOR signaling pathway. This cooperative therapy would provide a new research direction in ED treatment for the future.

Gender- and cholesterol-specific predictive value of body mass index in renal cell carcinoma: A multicenter study

Recently, there have been some reports on preoperative body mass index (BMI) and total cholesterol (TC) as a prognostic predictor for patients with renal cell carcinoma (RCC) but the topic is controversial and still poorly understood. So we analyzed the effects of BMI and TC on the prognosis of RCC.

AB099. Improvement of persistent detrusor overactivity after relief of bladder outlet obstruction treated by phytotherapeutic agent

Background Many patients with benign prostatic hyperplasia need treatment for remaining storage symptoms after surgery. Therefore, we evaluated the effect of plant combination on persistent detrusor overactivity (DO) after relief of bladder outlet obstruction (BOO). Methods Rats were assigned as three groups: control (n=6), persistent DO (n=6), and persistent DO treated with the plant combination (n=6) groups. Persistent DO after relief of partial BOO was made and 6 of them were orally administered with the plant combination. Results After 4-week treatment with the plant combination, significantly reduced DO by cystometry was observed compared with persistent DO group. Moreover, oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptor were significantly increased. Additionally, significantly decreased oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptor in the bladder were observed after treatment with the plant combination. Conclusions Treatment with the plant combination improves persistent DO after relief of BOO mediated by antioxidative and anti-inflammatory effect. Further study is necessary to identify exact mechanism of treatment effect of the plant combination.

AB098. Defocused low-energy shock wave can stimulate penile tissues to produce more energy for growth and proliferation in a DMED rat model

Background Defocused low-energy shock wave therapy (DL-ESWT) is a novel and potential way in regeneration medicine, and now it has been used in many areas which have demonstrated its unique superiority. At present, some researchers have applied ESWT to clinical therapy for erectile dysfunction (ED), which achieves satisfactory therapeutic effects. However, the metabolic change of corpus cavernosum with ESWT is still unclear. To investigate the metabolic change of corpus cavernosum with ESWT in a rat model of DMED induced by streptozotocin (STZ). Methods We divided human umbilical vein endothelial cells (HUVECs) in three groups. Group 1 is control group, without ESWT. Group 2 is half treated group, with ESWT for former three passages. Group 3 is full treated group, and we applied ESWT to HUVECs for every passage. After five passages, we collected the cells, supernatants and proteins for ELISA and Western blot. The DMED rats were randomly divided into 2 groups (N=10 per group): 1 DMED group, 2 DMED + ESWT group. The normal group (N=10, without STZ) is the control group. Erectile function and other expression experiments were carried out after STZ injection of 8 weeks. ESWT was repeated 3 times per week with one day’s break, for a total duration of 4 weeks. Immediately after recording of intracavernous pressure (ICP), the penis was then harvested for histologic analysis, ELISA and western blotting. Results The ratio of ICP/MAP was significantly higher in the ESWT group than in the DMED groups (P<0.05). Expression of growth factors increases after ESWT in vitro (P<0.05). ESWT can promote proliferation of endothelial cells in corpus cavernosum. The result was significantly higher in the ESWT group than in the DMED group (P<0.05). ESWT can improve cell metabolism in vivo. The expression of mitochondrial membrane proteins is higher in the ESWT group than in the DMED group (P<0.05). And the lactate concentration is higher in the ESWT group than in the DMED group (P<0.05). Conclusions There was a metabolic coupling between oxidative phosphorylation and anaerobic glycolysis of cells in the corpus cavernosum. And after ESWT there were a lot of lactic acid produced by anaerobic glycolysis of endothelial cells taking part in the tricarboxylic acid cycle of cells in corpus cavernosum, which could generate a great deal of energy to support growth and proliferation.