Safety and Efficacy Assessment of Red Ginseng Oil (RXGIN) in Men with Lower Urinary Tract Symptoms in a Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of red ginseng oil (RXGIN) in men with lower urinary tract symptoms. MATERIALS AND METHODS: Men aged between 40 and 75 years with a total International Prostate Symptom Score (IPSS) of 8 to 19 points were recruited from April 2020 to December 2020. Subjects were randomly assigned to either the RXGIN group or the control group in a 1:1 ratio and received either RXGIN or placebo daily for 12 weeks. For the primary outcome, changes in IPSS scores at 6 and 12 weeks from baseline were analyzed. The secondary outcomes were changes in International Index of Erectile Function (IIEF), maximum urinary flow rate, and post-void residual volume at weeks 6 and 12 compared to baseline. Urine analysis and blood tests were additionally performed for safety assessment. RESULTS: A total of 88 subjects (RXGIN group, 46; control group, 42) completed the study. The total IPSS and IPSS subscores (residual urine sensation, frequency, intermittency, urgency, weak stream, straining, nocturia, and quality of life) were significantly improved in the RXGIN group compared to the control group at weeks 6 and 12. Total IIEF and sexual desire were significantly improved in the RXGIN group at week 6 and week 12, respectively, but there were no significant changes in the level of serum testosterone or dihydrotestosterone. The serum prostate-specific antigen showed significant decrease at weeks 12. No serious adverse events leading to discontinuation of the study drug were observed in the RXGIN group. CONCLUSIONS: Red ginseng oil (RXGIN) appears to be safe and effective in improving lower urinary tract symptoms in men and may also improve some aspects of sexual function.

Cervi Parvum Cornu complex for men with lower urinary tract symptoms: a multicenter, randomized, double-blind, placebo-controlled trial.

Background: To evaluate the efficacy and safety of Cervi Parvum Cornu, Angelicae Gigantis Radix and Glycyrrhizae Radix complex (CAG) in men with moderate lower urinary tract symptoms (LUTS). Materials and methods: From November 2020 to January 2022, participants with International Prostate Symptom Score (IPSS) of 12-19 in two centers were recruited and randomize into three groups: a CAG 500 mg/day group (CAG 500), a CAG 1000 mg/day group (CAG 1000), and a placebo group (PG). They were treated for 12 weeks. The primary endpoint was change of IPSS at the end of study from baseline. Secondary end points included change of prostate specific antigen (PSA), testosterone, dihydrotestosterone (DHT), maximum urinary flow rate (Q max), post-void residual volume (PVR), International Index of Erectile Function (IIEF), and drug safety. Results: A total of 103 patients were able to finish the study according to the study protocol. Total IPSS and sub-scores (residual urine sensation, frequency, weak stream, hesistancy, nocturia, and quality of life) in CAG 500 and CAG 1000 were significantly improved at the 12th week compared to those of the PG. Changes of serum PSA, DHT, and testosterone levels at the 12th week from baseline did not show significant differences among the three groups. Q max and PVR changes did not show significant differences among the three groups either. Total IIEF and sub-scores (erectile function, orgasmic function, sexual desire, intercourse satisfaction) in CAG 1000 were significantly improved at 12th week compared to those in PG. No significant adverse events were found. Conclusions: CAG is well tolerated in patients with moderate LUTS. Treatment with CAG for 12 weeks has a therapeutic effect on moderate LUTS.

Anti-inflammatory and Antimicrobial Effects of Anthocyanin Extracted from Black Soybean on Chronic Bacterial Prostatitis Rat Model.

OBJECTIVE: To investigated the anti-inflammatory and antimicrobial effects of anthocyanins extracted from black soybean on the chronic bacterial prostatitis (CBP) rat model. METHODS: The Sprague-Dawley rats were divided into 4 groups, including control, ciprofloxacin, anthocyanins and anthocyanins with ciprofloxacin groups (n=8 in each group). Then, drip infusion of bacterial suspension (Escherichia coli Z17 O2:K1:H-) into Sprague-Dawley rats was conducted to induce CBP. In 4 weeks, results of prostate tissue, urine culture, and histological analysis on the prostate were analyzed for each group. RESULTS: The use of ciprofloxacin, anthocyanins, and anthocyanins with ciprofloxacin showed statistically significant decreases in bacterial growth and improvements in the reduction of prostatic inflammation compared with the control group (P<0.05). The anthocyanins with ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the ciprofloxacin group (P<0.05). CONCLUSIONS: These results suggest that anthocyanins may have anti-inflammatory and antimicrobial effects, as well as a synergistic effect with ciprofloxacin. Therefore, we suggest that the combination of anthocyanins and ciprofloxacin may be effective in treating CBP to obtain a higher rate of treatment success.

Suppression of Oxidative Stress of Modified Gongjin-Dan (WSY-1075) in Detrusor Underactivity Rat Model Bladder Outlet Induced by Obstruction.

OBJECTIVE: To investigate the anti-oxidative stress and preventive effect of modified Gongjin-dan (WSY-1075) in a detrusor underactivity rat model. METHODS: Rats were randomly allocated to three groups: shamoperated (control), bladder outlet obstruction-induced detrusor underactivity (BOO-DU), and BOO-DU with WSY-1075 (WSY) groups. WSY-1075 was orally administrated to rats 200 mg daily for 2 weeks prior to the operation and 4 weeks after the operation. Bladder outlet obstruction was surgically induced in rats by ligation around the urethra avoiding total obstruction. Cystometrography was conducted on rats in each group for examination of bladders. RESULTS: Compared with the control group, bladder outlet obstruction led to a significant increase in oxidative stress with consequent changes to molecular composition, and decrease in maximal detrusor pressure (P<0.05). WSY-1075 treatment significantly suppressed oxidative stress and prevented degenerative and dysfunctional changes in bladder, as compared with BOO-DU group (P<0.05). CONCLUSION: WSY-1075 had beneficial effect on prevention of BOO-DU.

An Asian traditional herbal complex containing Houttuynia cordata Thunb, Perilla frutescens Var. acuta and green tea stimulates hair growth in mice.

BACKGROUND: Houttuynia cordata Thunb (HC) is a traditional herbal medicine widely used in Asia for the treatment of patients with alopecia, usually in combination with other two herbal medicines (Perilla frutescens var. acuta (PFVA) and green tea (GT)). However, the effect of this herbal complex has not been clearly demonstrated. We sought to determine the hair growth-promoting effect of this herbal complex (HC, PFVA, and GT) in the animal model. METHODS: Six-week-old male C57BL/6 mice were randomly divided into four groups (negative control, finasteride (1 mg/kg) as a positive control, and two (200 and 400 mg/kg) concentrations of the herbal complex as experimental groups) and were fed its corresponding medications orally for 25 days. Hair growth was evaluated visually and microscopically. Western blot analysis for insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-ß1 was performed. RESULTS: The herbal complex exhibited hair growth-promoting activity in C57BL/6 mice. Grossly, the area of hair regrowth was 55.1 (±3.8) %, 70.2 (±6.3) % and 83.5 (±5.7) % in negative control, herbal complex 200 mg/kg and 400 mg/kg group, respectively. In histologic examination, the hair follicle count in deep subcutis was 2.6 (±0.7), 5.8 (±0.7) and 8.6 (±1.2) and the diameter of hair follicles was 11.9 (±5.0) µm, 17.4 (±3.9) µm and 22.8 (±5.2) µm in negative control, herbal complex 200 and 400 mg/kg group, respectively. The expression of IGF-1 was 0.14 (±0.01), 0.23 (±0.02) and 0.24 (±0.01) and the expression of TGF-ß1 was 0.26 (±0.01), 0.19 (±0.02) and 0.15 (±0.01) in negative control, the 200 and 400 mg/kg group, respectively. CONCLUSIONS: This data provides adequate preliminary experimental evidence to support the hair regeneration effect of this herbal complex.

Role of age and sex in determining antibiotic resistance in febrile urinary tract infections.

OBJECTIVES: To identify the age- and sex-specific antimicrobial susceptibility patterns of Gram-negative bacteria (GNB) in outpatient febrile urinary tract infections (UTIs) in Korea. METHODS: A total 2262 consecutive samples collected from patients aged 1-101 years with febrile UTIs, during the period January 2012 to December 2014, were analyzed in this multicentre, retrospective cohort study. RESULTS: The sensitivities to cefotaxime and cefoxitin were over 85% for females but under 75% for males. Sex played an important role in the susceptibility of GNB to cefotaxime (p<0.001) and cefoxitin (p<0.001). The sensitivity to ciprofloxacin (age >20 years) was under 75% in both sexes, and was not influenced by sex (p=0.204). Age distributions of the incidences of resistance to cefotaxime, cefoxitin, and ciprofloxacin (age >20 years) were similar to the age distribution of the incidence of GNB, which indicates that the resistance patterns to these drugs were not affected by age (Kolmogorov-Smirnov test, female/male: p=0.927/p=0.509, p=0.193/p=0.911, and p=0.077/p=0.999, respectively). CONCLUSIONS: Age is not a considerable factor in determining the antibiotic resistance in febrile UTIs. Ciprofloxacin should be withheld from both sexes until culture results indicate its use. Second- or third-generation cephalosporins such as cefoxitin and cefotaxime can be used empirically only in females.

The effects of new herbal formula (KBMSI-2) on penile erection and expression of nitric oxide synthase isoforms in streptozotocin-induced diabetic rat model.

OBJECTIVE: To investigate the effects of new herbal formula (KBMSI-2) on erectile dysfunction in streptozotocin (STZ)-induced diabetic rat model. METHODS: Twenty four Sprague-Dawley male rats were randomly divided into three groups; control (n=8), diabetes model (n=8), diabetes + KBMSI-2 200 mg/kg treatment (n=8) groups. The diabetes induced groups received a single intraperitoneal injection of STZ. Distilled water was administered in the control and model groups. To investigate the penile erection, intracavernosal pressure (ICP) and intracavernosal pressure/mean arterial pressure (ICP/MAP) were recorded in all groups. Serial sections of the penis were used to perform Masson's trichrome stain. The expression of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and cyclic guanosine monophosphate (cGMP) concentration in the isolated corpus cavernosum were analyzed by Western blotting. RESULTS: Peak ICP/MAP ratio was increased in the KBMSI-2 treatment group compared with the model group (P<0.05). Masson's trichrome staining confirmed that the smooth muscle component was increased in the KBMSI-2 treatment group compared with the model group (P<0.05). The nNOS, eNOS and cGMP expression of KBMSI-2 200 mg/kg treatment group was increased compared with the model group (P<0.05). CONCLUSION: This study showed that herbal formula of KBMSI-2 improved the erectile function by preserving the smooth muscle content and inhibiting the fibrosis of the corpus cavernosum in STZ-induced diabetic rat model.

The Anti-Inflammatory Effects of a New Herbal Formula (WSY-1075) in a Nonbacterial Prostatitis Rat Model.

PURPOSE: The aim of this study was to investigate the anti-inflammatory effects of a new herbal formula (WSY-1075) in a nonbacterial prostatitis rat model. MATERIALS AND METHODS: Prostatitis was induced in male Wistar rats (n=32) by treatment with 17 beta-estradiol and dihydrotestosterone for 4 weeks. After the induction of prostatitis, the rats were randomly divided into one of four treatment groups: control (n=8), ciprofloxacin (n=8), WSY-1075 (100 mg/kg) (n=8), and WSY-1075 (400 mg/kg) (n=8). After 4 weeks of treatment, the prostatic proinflammatory cytokine (tumor necrosis factor-α, interleukin [IL]-6, and IL-8) levels and histological findings were noted. RESULTS: The ciprofloxacin and WSY-1075 treatment groups showed significantly decreased proinflammatory cytokine levels compared with the control group. Histologically, treatment with ciprofloxacin and WSY-1075 significantly suppressed the severity of prostatitis lesions compared with those in the control group. No differences in the proinflammatory cytokine levels or histologic findings were observed with the dose dependent treatment of WSY-1075. CONCLUSIONS: The new herbal formula, WSY-1075, showed effective anti-inflammatory activities in the prostate and may be useful for the clinical treatment of nonbacterial prostatitis. Our findings suggest that WSY-1075 has a beneficial effect on the prevention and treatment of nonbacterial prostatitis.

Antimicrobial susceptibility pattern and epidemiology of female urinary tract infections in South Korea, 2010-2011.

This study aimed to (i) investigate the antimicrobial susceptibilities of bacteria that cause urinary tract infections (UTIs) in outpatient and inpatient settings and (ii) evaluate the risk factors for emerging antimicrobial drug resistance in UTIs in South Korea. In total, 3,023 samples without duplication were collected from females between 25 and 65 years of age who had been diagnosed with a urinary tract infection. Multicenter patient data were collected using a Web-based electronic system and then evaluated. The isolation rates of Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium in the outpatient setting were 78.1, 4.7, and 1.3%, respectively; in the inpatient setting, the isolation rates of these microorganisms were 37.8, 9.9, and 14.8%, respectively. The susceptibilities of E. coli to amikacin, amoxicillin-clavulanic acid, cefotaxime, cefoxitin, ciprofloxacin, piperacillin-tazobactam, and imipenem in the outpatient setting were 99.4, 79.8, 89.4, 92.8, 69.8, 96.9, and 100.0%, respectively; in the inpatient setting, the susceptibilities to these antibiotics were 97.8, 73.9, 73.7, 82.1, 53.6, 93.2, and 100.0%, respectively. The most unique and common risk factor for emerging antimicrobial-resistant E. coli, K. pneumoniae, and E. faecium was previous exposure to antimicrobials. On the basis of these data, the use of fluoroquinolones should be reserved until culture data are available for the treatment of UTIs in South Korea. The present study will serve as a useful reference for Far Eastern Asia.

Protective effect of cyanidin-3-O-ß-D-glucopyranoside fraction from mulberry fruit pigment against oxidative damage in streptozotocin-induced diabetic rat bladder.

AIMS: To determine whether cyanidin-3-O-ß-D-glucopyranoside (C3G) fraction from mulberry fruit pigment has protective effects against bladder dysfunction on streptozotocin-induced diabetic rats METHODS: Sprague-Dawley rats were divided into three groups (n = 12 in each): normal, diabetes (DM), and DM treated with C3G fraction (DM + C3G). The DM and DM + C3G groups received a single injection of streptozotocin (50 mg/kg) intraperitoneally. Four weeks after the induction of diabetes, the DM + C3G group was treated with daily oral C3G (10 mg/kg) dissolved in water, for 8 weeks. After 12 weeks of streptozotocin injections, rats in each group underwent cystometrography and bladders were used for evaluation of apoptosis and oxidative stress. RESULTS: The DM group showed a markedly lower maximal intravesical pressure than that observed in the control group, whereas rats in the DM + C3G group showed improved maximum intravesical pressure associated with minimization of apoptosis, and increased levels of Akt and Bad phosphorylation, implying inhibition of pro-apoptotic stimuli. The level of 8-hydroxy-2-deoxyguanosine, a marker of oxidative stress, was significantly greater in the DM group compared to the control group and it was significantly reduced in the C3G treated group. Immunoblotting revealed a significant decrease in the levels of the superoxide dismutase protein and nerve growth factor in the DM group compared with the control group; however, these proteins were upregulated in the DM + C3G group compared with the DM group. CONCLUSIONS: The study is the first to suggest that C3G fraction have a potency to protect the bladder under conditions of diabetes-induced oxidative stress.

Preventive effect of selenium on chronic bacterial prostatitis.

The antibiotic treatment rate of chronic bacterial prostatitis (CBP) is low, and long-term administration can result in adverse events and bacterial resistance. For these reasons, a new preventive modality, which can replace traditional antibiotic therapy, is required. To evaluate the preventive effect of selenium on CBP, the pre-treatments were divided into four groups, administered for 4 weeks, as follows: (1) control, (2) ciprofloxacin, (3) selenium, and (4) ciprofloxacin and selenium. Then, drip infusion of a bacterial suspension (Escherichia coli Z17, O2:K1; H-) into the prostatic urethra of Wistar rats was conducted to induce CBP. In 4 weeks, the results of microbiological culture of prostate and urine samples as well as histological findings of the prostate in each group were analyzed. Selenium decreased bacterial infection significantly; the decrease in infiltration rate of inflammatory cells into prostate tissues in the selenium group was similar to that in the control group. The effect of hindering bacterial infection on prostate tissue was greater in the group administered both selenium and an antibiotic than in other groups given only one of the agents. Although the findings of this study suggest that selenium can have a preventive effect against the occurrence of CBP, methods to prevent CBP are still controversial.

Anti-inflammatory and antimicrobial effects of nanocatechin in a chronic bacterial prostatitis rat model.

Chronic bacterial prostatitis (CBP) is one of the most common relapsing urinary tract infection (UTI) in males. Catechin, an extract of green tea, is known to have anti-inflammatory and antimicrobial effects against various bacteria. However, catechin can be easily degenerated during digestion, and this may result in decreased absorption into the body. Nanocatechin is catechin coated with hydroxypropyl methyl cellulose by nanotechnology. It reduces degeneration during digestion and enhances absorption of catechin into the body. We evaluated the anti-inflammatory and antimicrobial effect of nanocatechin on CBP and also analyzed plasma concentration of catechins to evaluate absorptivity in an animal model. Forty rats demonstrating CBP were randomly divided into four groups: control, ciprofloxacin, catechin, and nanocatechin. After treatment, the results of microbiological culture of prostate and urine samples as well as histological findings of the prostate in each group were analyzed. Plasma concentration of catechins in catechin and nanocatechin groups was compared. The use of ciprofloxacin, catechin, and nanocatechin showed statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the control group. The nanocatechin group showed statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the catechin group. Plasma concentrations of epicatechin, gallocatechin gallate, and epigallocatechin gallate were significantly higher in the nanocatechin group than those in the catechin group. These results suggest that nanocatechin has better antimicrobial and anti-inflammatory effects on rat CBP than catechin due to higher absorption into the body.

Anthocyanin extracted from black soybean reduces prostate weight and promotes apoptosis in the prostatic hyperplasia-induced rat model.

Anthocyanin is a natural plant pigment and potent antioxidant. This study was designed to investigate the effects of anthocyanin extracted from black soybeans on a rat model of benign prostatic hyperplasia (BPH), a disease associated with the geriatric population. Thirty male rats were divided into five experimental groups: a control group, a BPH-induced group, and three BPH-induced groups that received oral doses of anthocyanin (40, 80, and 160 mg/kg). Prostate hyperplasia was induced by the administration of testosterone propionate for 4 weeks. Following BPH induction, the anthocyanin-treated groups received the compound for 4 weeks. After anthocyanin treatment, the prostates from the rats in all groups were removed, weighed, and subjected to histological examination. Apoptosis in the prostates was measured by the TUNEL assay. The mean prostate weight for the control animals was 674.17 ± 28.24 mg, whereas the BPH-induced rats had a mean prostate weight of 1098.33 ± 131.31 mg. The mean prostate weights for the rats receiving 40, 80, and 160 mg/kg anthocyanin were 323.00 ± 22.41, 324.00 ± 26.80, and 617.50 ± 31.08 mg, respectively. The average prostate weight in the BPH-induced group was significantly higher than in the control group (p < 0.05), whereas the prostate weights in the anthocyanin-administered groups were significantly lower than in the BPH-induced group (p < 0.05). Injected testosterone led to prostatic hyperplasia as observed histologically, but anthocyanin administration helped to prevent this change. Apoptotic body counts were significantly higher in groups receiving anthocyanin than in the BPH-induced group (p < 0.05). These results suggest that anthocyanin may be effective in decreasing the volume and suppressing the proliferation of the prostate. Further studies are needed to better understand the mechanisms and actions of anthocyanin, and these studies may lead to the clinical application of anthocyanin in treating BPH.

Differential gene expression and lipid metabolism in fatty liver induced by acute ethanol treatment in mice.

Ethanol induces cumulative liver damage including steatosis, steatohepatitis and cirrhosis. The aim of this study is to investigate the global intrahepatic gene expression profile in the mouse liver treated with ethanol. A single oral dose of 0.5 or 5 g/kg ethanol was administered to male ICR mice, and liver samples were obtained after 6, 24 and 72 h. Histopathological evaluation showed typical fatty livers in the high-dose group at 24 h. Microarray analysis identified 28 genes as being ethanol responsive (two-way ANOVA; p<0.05), after adjustment by the Benjamini-Hochberg multiple testing correction; these genes displayed >or=2-fold induction or repression. The expression of genes that are known to be involved in fatty acid synthesis was examined. The transcript for lipogenic transcription factor, sterol regulatory element (SRE)-binding factor 1 (Srebf1), was upregulated by acute ethanol exposure. Of the genes known to contain SRE or SRE-like sequences and to be regulated by SRE-binding protein 1 (SREBP1), those encoding malic enzyme (Mod1), ATP-citrate lyase (Acly), fatty acid synthase (Fasn) and stearyl-CoA desaturase (Scd1) were induced by ethanol. Quantitative real-time PCR confirmed the changes in the expression levels of the selected genes. The change in the Srebf1 mRNA level correlates well with that of the SREBP1 protein expression as well as its binding to the promoters of the target genes. The present study identifies differentially expressed genes that can be applied to the biomarkers for alcohol-binge-induced fatty liver. These results support the hypothesis by which ethanol-induced steatosis in mice is mediated by the fatty acid synthetic pathway regulated by SREBP1.

Gene expression profiles of murine fatty liver induced by the administration of valproic acid.

Valproic acid (VPA) has been used as anticonvulsants, however, it induces hepatotoxicity such as microvesicular steatosis and necrosis in the liver. To explore the mechanisms of VPA-induced steatosis, we profiled the gene expression patterns of the mouse liver that were altered by treatment with VPA using microarray analysis. VPA was orally administered as a single dose of 100 mg/kg (low-dose) or 1000 mg/kg (high-dose) to ICR mice and the animals were killed at 6, 24, or 72 h after treatment. Serum alanine aminotransferase and aspartate aminotransferase levels were not significantly altered in the experimental animals. However, symptoms of steatosis were observed at 72 h with low-dose and at 24 h and 72 h with high-dose. After microarray data analysis, 1910 genes were selected by two-way ANOVA (P<0.05) as VPA-responsive genes. Hierarchical clustering revealed that gene expression changes depended on the time rather than the dose of VPA treatment. Gene profiling data showed striking changes in the expression of genes associated with lipid, fatty acid, and steroid metabolism, oncogenesis, signal transduction, and development. Functional categorization of 1156 characteristically up- and down-regulated genes (cutoff >1.5-fold) revealed that 60 genes were involved in lipid metabolism that was interconnected with biological pathways for biosynthesis of triglyceride and cholesterol, catabolism of fatty acid, and lipid transport. This gene expression profile may be associated with the known steatogenic hepatotoxicity of VPA and it may provide useful information for prediction of hepatotoxicity of unknown chemicals or new drug candidates through pattern recognition.