Udenafil Induces the Hair Growth Effect of Adipose-Derived Stem Cells

Udenafil, which is a PDE5 inhibitor, is used to treat erectile dysfunction. However, it is unclear whether udenafil induces hair growth via the stimulation of adipose-derived stem cells (ASCs). In this study, we investigated whether udenafil stimulates ASCs and whether increased growth factor secretion from ASCs to facilitate hair growth. We found that subcutaneous injection of udenafil-treated ASCs accelerated telogen-to-anagen transition in vivo. We also observed that udenafil induced proliferation, migration and tube formation of ASCs. It also increased the secretion of growth factors from ASCs, such as interleukin-4 (IL-4) and IL12B, and the phosphorylation of ERK1/2 and NFκB. Furthermore, concomitant upregulation of IL-4 and IL12B mRNA levels was attenuated by ERK inhibitor or NFκB knockdown. Application of IL-4 or IL12B enhanced anagen induction in mice and increased hair follicle length in organ culture. The results indicated that udenafil stimulates ASC motility and increases paracrine growth factor, including cytokine signaling. Udenafil-stimulated secretion of cytokine from ASCs may promote hair growth via the ERK and NFκB pathways. Therefore, udenafil can be used as an ASC-preconditioning agent for hair growth.

Udenafil, a Phosphodiesterase 5 Inhibitor, Reduces Body Weight in High-Fat-Fed Mice

PURPOSE: High-fat (HF) feeding induces hypothalamic leptin resistance via the activation of toll-like receptor 4 (TLR4). TLR4 deficiency confers resistance to diet-induced obesity. Udenafil, an anti-impotence drug, inhibits TLR4 in airway epithelial cells in vitro. In this study, we evaluated whether udenafil suppressed the hypothalamic expression of TLR4 and reduced body weight. MATERIALS AND METHODS: The hypothalamic expression of TLR4, phosphodiesterase 5 (PDE5), nuclear factor-κB (NF-κB), and myeloid differentiation primary response gene 88 (Myd88) was analyzed by real-time polymerase chain reaction after treating mice for 2 days with udenafil (0, 12, 120, or 600 µg/d). Furthermore, the hypothalamic expression of TLR4, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY) was analyzed after 9 days' treatment with udenafil and/or leptin. We also measured body weight and food intake following 9 days of udenafil and/or leptin treatment in control- and HF-fed mice. RESULTS: Udenafil suppressed hypothalamic TLR4 mRNA expression dose-dependently. The changes were associated with decreased PDE5, NF-κB, and Myd88 expression. Udenafil treatment for 9 days reduced body weight and caloric intake in HF-fed mice. This may have been associated with the suppression of NPY expression that was elevated by HF feeding. POMC expression was not affected by udenafil. However, udenafil did not augment the effects of leptin on the reduction of body weight and caloric intake in HF-fed mice. CONCLUSIONS: These results suggested that udenafil reduced body weight by suppressing hypothalamic TLR4 mRNA expression in HF-fed mice and the combination effect of udenafil and leptin was additive rather than synergistic.

Oral udenafil and aceclofenac for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: a randomized multicenter study

BACKGROUND/AIMS: Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Combination therapy w ith ora l udenafil and aceclofenac may reduce the occurrence of post-ERCP pancreatitis by targeting different pathophysiological mechanisms. We investigated whether combining udenafil and aceclofenac reduced the rates of post-ERCP pancreatitis. METHODS: A prospective, randomized, double-blind, placebo-controlled, multicenter study was conducted in four academic medical centers. Between January 2012 and June 2013, a total of 216 patients who underwent ERCP were analyzed for the occurrence of post-ERCP pancreatitis. Patients were determined to be at high risk for pancreatitis based on validated patient and procedure-related risk factors. RESULTS: Demographic features, indications for ERCP, and therapeutic procedures were similar in each group. There were no significant differences in the rate (15.8% [17/107] vs. 16.5% [18/109], p = 0.901) and severity of post-ERCP pancreatitis between the udenafil/aceclofenac and placebo groups. One patient in each group developed severe pancreatitis. Multivariate analyses indicated that suspected dysfunction of the sphincter of Oddi and endoscopic papillary balloon dilation without sphincterotomy were associated with post-ERCP pancreatitis. CONCLUSIONS: Combination therapy with udenafil and aceclofenac is not effective for the prevention of post-ERCP pancreatitis.

Effect of Udenafil on MUC5B Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucus hypersecretion in the airway may lead to increased frequency and duration of infection, declined lung function, and increased morbidity and mortality in inflammatory respiratory diseases. Udenafil, a phosphodiesterase (PDE) 5 inhibitor, is an oral medication for erectile dysfunction. Recent studies show that PDE5 inhibitor has various anti-inflammatory properties. However, the effect of udenafil on mucus secretion in human airway epithelial cells is unclear. Therefore, the effect and brief signaling pathway of udenafil on MUC5B expression were investigated in human airway epithelial cells. MATERIALS AND METHOD: We analyzed the effects and brief signaling pathway of udenafil on the lipopolysaccharide (LPS) induced MUC5B expression in mucin-producing NCI-H292 epithelial cells using reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblot analysis. RESULTS: Udenafil attenuated the LPS-induced MUC5B mRNA expressions and glycoprotein production in NCI-H292 epithelial cells. It also attenuated LPS-induced toll like receptor 4 (TLR4) mRNA expression and phosphorylation of extracellular regulated kinase1/2 (ERK1/2) and p38 in NCI-H292 epithelial cells. CONCLUSION: These results suggest that udenafil attenuates the LPS induced MUC5B expression via TLR4, ERK1/2 and p38 mitogen activated protein kinase (MAPK) pathway in human airway epithelial cells, and that it could be a novel therapeutic agent for controlling chronic airway disease.

Anterior Ischemic Optic Neuropathy Associated with Udenafil

We report a case of anterior ischemic optic neuropathy associated with udenafil. A 54-year-old male presented with an acute onset visual field defect of the right eye after udenafil use. Examination revealed a relative afferent pupillary defect and a swollen disc. Automated visual fields revealed an enlarged blind spot and a narrowed visual field. Fluorescein angiography revealed both an inferior choroidal filling delay and an inferior sector filling delay of the optic disc in the arteriovenous phase as well as diffuse leakage of the optic disc in the late phase. Optical coherent tomography revealed increased thickness of the retinal nerve fiber layer, especially in the area of the inferior disc. The patient was counseled to discontinue the use of udenafil and to monitor his blood pressure regularly. The disc swelling was resolved with residual optic atrophy one month after discontinuing the use of udenafil.

Effect of Udenafil on Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia in Rat Carotid Artery Injury Model

BACKGROUND AND OBJECTIVES: Neointimal hyperplasia, which was caused by smooth muscle cell proliferation, was noted to occur after performing percutaneous coronary intervention. Phosphodiesterase type 5 (PDE5) inhibitor has been shown to inhibit smooth muscle cell proliferation. Udenafil is one of the PDE5 inhibitors, and it is also expected to inhibit smooth muscle cell proliferation and reduce neointimal hyperplasia. We investigated the effect of udenafil on the smooth muscle cell proliferation and neointimal hyperplasia that occurs after balloon injury in the carotid arteries of rats. MATERIALS AND METHODS: Smooth muscle cells were treated with 1 mM, 100 micrometer, 10 micrometer, 1 micrometer and 100 nM concentrations of udenafil. The viability of the smooth muscle cells was evaluated by MTT assay. The carotid arteries of rats were injured with a balloon catheter. Udenafil (100 micrometer, 10 micrometer and 1 micrometer) was applied on the carotid artery adventitia after balloon injury. At 21 days after treatment, the carotid arteries were harvested and stained with H & E. The neointima and media area were measured with a computerized image analysis program. RESULTS: In the in vitro experiment, treatment with 1 mM udenafil reduced smooth muscle cell viability by 68.8+/-4.42% compared to the control group. In the balloon injured rat carotid artery, treatment with 100 micrometer udenafil reduced the neointima area by 71.8% compared to the control group. CONCLUSION: Udenafil administration effectively inhibited smooth muscle cell proliferation and it reduced neointimal hyperplasia in the balloon-injured rat carotid artery.