Bo Ram Choi

The role of the lignan constituents in the effect of Schisandra chinensis fruit extract on penile erection.

The effect of the ethanol extract and active components of the fruit of Schisandra chinensis was evaluated on rabbit penile corpus cavernosum (PCC). PCC, pre‐contracted with 10−5 m phenylephrine (Phe), was treated with extracts of S. chinensis at five different compositions of ethanol and water (95%, 70%, 50%, 30% and ethanol/water [v/v]) and three fractions (0.1, 0.5, 1 and 2 mg/mL). The effect of the extracts and active lignans (schisandrol A and schisandrol B) from S. chinensis on sildenafil citrate pre‐incubated PCC was also evaluated. The PCC relaxation induced by the 95% ethanol extraction and the n‐hexane fraction was concentration‐dependent and the ethanol extract enhanced sildenafil citrate‐induced PCC relaxation. The active components of S. chinensis (schisandrol A and schisandrol B) significantly enhanced sildenafil citrate‐induced relaxation >2‐fold; schisandrol A had the highest relaxant effect on sildenafil citrate pre‐incubated PCC. The lignans, schisandrol A and schisandrol B, isolated from the fruits of S. chinensis enhanced sildenafil citrate‐induced relaxation and may have synergistic action in patients who do not completely respond to sildenafil. Copyright

The role of capillarisin from Artemisia capillaris on penile erection.

The objective of this study was to evaluate the effect and mechanism of capillarisin from Artemisia capillaris (A. capillaris) on rabbit penile corpus cavernosum (PCC). The pre‐contracted New Zealand White rabbit (2.5–3.0 kg) penis with phenylephrine (Phe; 10‐5 m) was treated with various concentrations of ethanol extract of A. capillaris (0.1, 0.5, 1, and 2 mg/mL) and capillarisin, the active component of A. capillaris (10‐7, 10‐6, 10‐5 and 10‐4 m). Capillarisin was also applied to PCC tissues contracted with Phe, which were pre‐incubated with phosphodiesterase type 5 inhibitors (PDE5 Is). Cyclic nucleotides in the perfusate were measured by radioimmunoassay. The tissues were pre‐incubated with Nω nitro‐l‐arginine‐methyl ester (L‐NAME, 10‐3 m) and 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ, 10‐5 m) to block nitric oxide (NO) synthase and guanylate cyclase, respectively. Capillarisin induced penile relaxation and enhanced PDE5 Is‐induced relaxation. Capillarisin increased cGMP and cAMP in the perfusate. The application of capillarisin on PCC pre‐treated with L‐NAME and ODQ significantly inhibited the relaxation. Capillarisin exerts the relaxing effect on PCC by activating the NO‐cGMP and adenylyl cAMP signaling pathways and may become an alternative medicine for patients who want to use natural products to improve erectile function or do not completely respond to PDE5 Is. Copyright

Is Transforming Growth Factor-β Signaling Activated in Human Hypertrophied Prostate Treated by 5-Alpha Reductase Inhibitor?

Background and Aim. It is well known that androgen deprivation relates to penile fibrosis, so we hypothesize that long-term treatment with 5-alphareductase inhibitors (5ARIs) may increase the risk of fibrosis of prostate. Patients and Methods. Thirty-two BPH patients who underwent transurethral resection of the prostate were enrolled. The patients were divided into two groups: group one, 16 patients underwent TURP who had been treated with tamsulosin for 2 years; group two, 16 patients underwent TURP who had been treated with combination of tamsulosin and dutasteride for at least 1 year. We evaluated the expressions of nNOS, iNOS, eNOS, TGF-β1, TGF-β2, phosphorylated-Smad2/3 (p-Smad2/3), E-cadherin, N-cadherin, and α-smooth muscle actin in the resected prostate tissues by western blotting, and the TGF-β concentration was determined by ELISA kit. Results. The expressions of 3 isoforms of NOS were significantly increased in group 2 except of eNOS in lateral prostate, and the expressions of TGF-β1, TGF-β2, and p-Smad2/3 increased about 2-fold compared with group 1. In group 2, the E-cadherin expression decreased while N-cadherin expression increased significantly. Conclusions. The overexpression of nNOS may contribute to prostate smooth muscle relaxation; however, long-time treatment with 5 ARI increases the risk of fibrosis of prostate.

Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress

Cisplatin (CIS) is used in the treatment of cancer, but its nonspecific systemic actions lead to toxic effects on other parts of the body. This study investigated the severity of CIS toxicity by increasing its dose over a constant time period. Sprague Dawley rats were divided into five treatment groups and control group with CIS (2, 4, 6, 8, and 10 mg/kg) administered intraperitoneally for 5 days. The body and organs were weighed, epididymal sperm was counted, and sperm motility and sperm apoptosis were evaluated. Blood samples were evaluated for complete blood count, reactive oxygen and nitrogen species, malondialdehyde levels, and total testosterone. The testicular tissue was examined for steroidogenic acute regulatory protein and endoplasmic reticulum stress protein. Epididymal sperm was collected for CatSper Western blot. The toxic effects of different doses of CIS on the testis and kidney were compared histologically. The weights of body, testis, epididymis, prostate, seminal vesicle, and kidney; sperm count; sperm motility; steroidogenic acute regulatory protein level; and epididymal sperm count were significantly lower in the CIS-treated groups than in the control group. In contrast, sperm apoptosis, plasma reactive oxygen and nitrogen species, and malondialdehyde, testosterone, red blood cell, hematocrit, hemoglobin, and endoplasmic reticulum stress protein levels all increased. Though CIS effectively treats cancer, at an increased dose it is toxic and life-threatening to the genitourinary system and other parts of the body.

Analysis of testicular-internal spermatic vein variation and the recreation of varicocoele in a Sprague-Dawley rat model.

Many laboratories tried to recreate the varicocoele model have met with varied success. To recreate a consistent varicocoele model by exploring the anatomic variability of the testicular‐spermatic venous system in Sprague‐Dawley (SD) rats. Seventy‐two sexually mature SD male rats were randomly divided into three groups containing 24 rats per group. Partial ligation of the left renal vein and internal spermatic vein (ISV) communicating branches to common iliac vein and ISV communicating branches ligation (RVISVCBCIV) or partial ligation of the left renal vein and ISV communicating branches ligation (RVISVCB). The results showed that the mean diameter of the left ISV was significantly increased in the RVISVCBCIV group compared with the control and RVISVCB groups (p < 0.001). Using ISV as the reference, the sensitivity of varicocoele was 71.43%, and the specificity was 80%. In addition, the positive predictive value was 83.33%, and the negative predictive value was 66.67%. Sperm count, motility, Johnsen score and the spermatogenic cell density were lower in the RVISVCBCIV group compared with the control (p < 0.01). The apoptotic index was higher in the RVISVCBCIV group compared with control groups (p < 0.01). The RVISVCBCIV provides a more effective method for establishing a varicocoele‐induced model.

Protective effect of DA-9401 in finasteride-induced apoptosis in rat testis: inositol requiring kinase 1 and c-Jun N-terminal kinase pathway

Finasteride is used to treat male pattern baldness and benign prostatic hyperplasia. This study investigated the toxicity of finasteride and recovery by DA-9401 using Sprague Dawley (SD) rats. Forty adult male SD rats were assigned to four groups: control (CTR), finasteride 1 mg/kg/day (F), finasteride 1 mg/kg + DA-9401 100 mg/kg/day (F + DA 100) and finasteride 1 mg/kg + DA-9401 200 mg/kg/day (F + DA 200). Treatments were by oral delivery once daily for 90 consecutive days. The gross anatomical parameters assessed included: genital organ weight; vas deferens sperm count and sperm motility; testosterone, dihydrotestosterone (DHT) and malondialdehyde levels; and histological and terminal deoxynucleotidyl transferase enzyme mediated dUTP nick-end labeling (TUNEL) staining of testis for spermatogenic cell density, Johnsen’s score and apoptosis. Testicular tissue was also used for evaluating endoplasmic reticulum (ER) stress and apoptotic proteins. Epididymis weight, seminal vesicle weight, prostate weight, penile weight and vas deferens sperm motility showed significant differences between the F group and the CTR, F + DA 100 and F + DA 200 groups. There was no significant change in the testosterone level. DHT level decreased significantly in the F group compared with the CTR group. Testis tissue revealed significant changes in spermatogenic cell density, Johnsen’s score and apoptotic index. Western blot showed significant changes in the ER stress and apoptotic markers. Finasteride resulted in reduced fertility and increased ER stress and apoptotic markers, which were recovered by administration of DA-9401 in the SD rats.

Effect of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid on the intraurethral pressure in a rat model of benign prostatic hyperplasia

To investigate the effect of 4‐chloro‐7‐trifluoromethyl‐10H‐benzo[4,5]furo[3,2‐b]indole‐1‐carboxylic acid, a new benzofuroindole derivative, on the intraurethral pressure in a rat model of benign prostatic hyperplasia.

Additive effects of Artemisia capillaris extract and scopoletin on the relaxation of penile corpus cavernosum smooth muscle.

The objective was to investigate the cellular effect and action mechanism of Artemisia capillaris extract (ACE) and its component, scopoletin, on penile corpus cavernosum smooth muscle (PCCSM). In vitro study with PCCSM, the precontracted PCCSM with phenylephrine was treated with ACE or scopoletin. Cyclic nucleotides in the perfusate were measured by radioimmunoassay and expression of protein and mRNA of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase in the perfused PCCSM were measured by western blot and real-time PCR, respectively. The interaction of ACE or scopoletin with udenafil was also evaluated. ACE and scopoletin exerted a significant and concentration-dependent relaxation in PCCSM. The perfusion with ACE or scopoletin significantly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) and the perfusion with ACE or scopoletin increased the expression of eNOS mRNA and protein. Furthermore, ACE or scopoletin enhanced udenafil-inducing relaxation in PCCSM. ACE and scopoletin relaxed the PCCSM mainly by activating nitric oxide–cGMP system and cAMP pathway and they may be additive therapeutic candidates for ED patients who do not completely respond to udenafil.

Protective effect of MOTILIPERM in varicocele-induced oxidative injury in rat testis by activating phosphorylated inositol requiring kinase 1α (p-IRE1α) and phosphorylated c-Jun N-terminal kinase (p-JNK) pathways

Abstract Context: MOTILIPERM was prepared as a mixture of extracts of three medicinal herbs [roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliaceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae)]. Objective: To investigate the role of reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress in a rat model of varicocele and the therapeutic efficacy of MOTILIPERM in this model. Materials and methods: Sixty male rats were divided into five experimental groups: a normal control group (CTR + vehicle), a control group administered MOTILIPERM 200 mg/kg (CTR + M 200), a varicocele-induced control group (VC + vehicle) and two varicocele-induced groups administered MOTILIPERM 100 (VC + M 100) or 200 (VC + M 200) mg/kg for 4 weeks. Testis weights were recorded and serums were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathology, analyses of ER response protein expression levels and oxidative stress were assessed by measuring ROS, reactive nitrogen species (RNS), malondialdehyde (MDA) level and ratios of total glutathione (GSH)/oxidized GSH (GSSG). Results: MOTILIPERM treatment of varicocele-induced groups significantly increased left testis weight, testosterone level, sperm motility, count and spermatogenic cell density. ER-response protein expression levels were dose-dependently decreased in VC + M 200 group compared with VC + vehicle group. MOTILIPERM treatment also decreased MDA and ROS/RNS level but increased GSH/GSSG ratio. Discussion and conclusions: This study suggests that ROS-related ER stress may play a major role in varicocele-induced infertility and MOTILIPERM, a novel compound targeting ROS-based ER stress, may be therapeutically useful in treatment of varicocele, or as a supplement for the treatment of infertility.

Penile Erection Induced by Scoparone from Artemisia capillaris through the Nitric Oxide-Cyclic Guanosine Monophosphate Signaling Pathway

Purpose The objective of this study was to evaluate the relaxant effect of scoparone from Artemisia capillaris on rabbit penile corpus cavernosum smooth muscle (PCCSM) and to elucidate the mechanism of action of scoparone for the treatment of erectile dysfunction (ED). Materials and Methods PCCSM that had been precontracted with phenylephrine was treated with 3 Artemisia herbs (A. princeps, A. capillaris, and A. iwayomogi) and 3 fractions (n-hexane, ethyl acetate, and n-butanol) with different concentrations (0.1, 0.5, 1.0, and 2.0 mg/mL). Four components (esculetin, scopoletin, capillarisin, and scoparone) isolated from A. capillaris were also evaluated. The PCCSM was preincubated with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ). Cyclic nucleotides in the perfusate were measured by a radioimmunoassay. The interactions of scoparone with udenafil and rolipram were also evaluated. Results A. capillaris extract relaxed PCCSM in a concentration-dependent manner. Scoparone had the highest relaxant effect on PCCSM among the 4 components (esculetin, scopoletin, capillarisin, and scoparone) isolated from the ethyl acetate fraction. The application of scoparone on PCCSM pretreated with L-NAME and ODQ led to significantly less relaxation. Scoparone also increased the cyclic guanosine monophosphate (cGMP) levels in the perfusate in a concentration-dependent manner. Furthermore, scoparone enhanced udenafil- and rolipram-induced relaxation of the PCCSM. Conclusions Scoparone relaxed the PCCSM mainly by activating the nitric oxide-cGMP signaling pathway, and it may be a new promising treatment for ED patients who do not completely respond to udenafil.