Retraction Note: Effects of DA-5513 on alcohol metabolism and alcoholic fatty liver in rats.

[This retracts the article DOI: 10.5625/lar.2018.34.2.49.].

Effects of DA-5513 on alcohol metabolism and alcoholic fatty liver in rats.

Hangover is characterized by a number of unpleasant physical and mental symptoms that occur after heavy alcohol drinking. In addition, consistently excessive alcohol intake is considered as a major reason causes liver disease. The present study investigated the in vivo effects of DA-5513 (Morning care® Kang Hwang) on biological parameters relevant to hangover relief and alcoholic fatty liver. Blood alcohol and acetaldehyde concentrations were determined in rats administered a single dose of alcohol and treated with DA-5513 or commercially available hangover relief beverages (Yeomyung® and Ukon®). The effects of DA-5513 on alcoholic fatty liver were also determined in rats fed alcohol-containing Lieber-DeCarli diets for 4 weeks. Serum liver function markers (aspartate and alanine aminotransferase activities) and serum/liver lipid levels were assessed. Blood alcohol and acetaldehyde concentrations were lower in the groups treated with DA-5513 or Yeomyung®, as compared with control rats. However, Ukon® did not produce any significant effects on these parameters. Treatment with DA-5513 significantly reduced serum aspartate and alanine aminotransferase activities and markedly reduced serum cholesterol and triglyceride levels, as compared with control rats. Histological observations using Oil Red O staining found that DA-5513 delayed the development of alcoholic fatty liver by reversing hepatic fat accumulation. These findings suggest that DA-5513 could have a beneficial effect on alcohol-induced hangovers and has the potential to ameliorate alcoholic fatty liver.

Preclinical and Clinical Studies Demonstrate That the Proprietary Herbal Extract DA-5512 Effectively Stimulates Hair Growth and Promotes Hair Health.

The proprietary DA-5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA-5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA-5512. DA-5512 significantly enhanced the viability of hDPCs in a dose-dependent manner (p < 0.05), and 100 ppm of DA-5512 and 1 µM minoxidil (MXD) significantly increased the number of Ki-67-positive cells, compared with the control group (p < 0.05). MXD (3%) and DA-5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p < 0.05). The groups treated with DA-5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA-5512 after 16 weeks compared with the groups treated with placebo or 3% MXD (p < 0.05). In conclusion, DA-5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.

The Pharmacological Effects of Benachio-F(®) on Rat Gastrointestinal Functions.

Functional dyspepsia (FD) is a prevalent idiopathic upper gastrointestinal (GI) disorder characterized by diverse symptomatology including epigastric pain or discomfort, postprandial fullness, and early satiety. Although its pathophysiological mechanisms have not yet been fully established, the available studies suggest that the etiology of FD is invariably multifactorial. Benachio-F(®) (BF) is a proprietary liquid formulation of 7 herbal extracts that has been proposed to address this multifactorial etiology using multi-drug phytotherapy. The pharmacological effects of BF, in comparison with those of two other herbal products (Whalmyungsu(®); WM and Iberogast(®); IB) were evaluated in rats. In a laparotomy-induced rat model of delayed GI transit, BF significantly accelerated the delayed gastric emptying caused by morphine, apomorphine, and cisplatin, and also significantly increased mean gastric transit, as compared to the control animals. BF markedly increased gastric accommodation in rats and produced higher gastric volume values than did the control treatment. The effects of BF were generally comparable or superior to those of WM and IB in these models. Furthermore, BF significantly stimulated biliary flow, as compared to the control treatment. These results indicated that BF might have great potential as an effective phytotherapeutic agent capable of reducing GI symptoms and increasing quality of life in FD patients.

Evaluation of muscle damage using ultrasound imaging.

[Purpose] This study aimed to quantitatively analyze characteristics of and changes in internal muscle structure according to the time of delayed onset muscle soreness (DOMS) using ultrasound imaging, thereby presenting clinical evidential data for evaluation of muscle damage. [Subjects] We recruited 38 male subjects. [Methods] Ultrasound images of the medial gastrocnemius muscle prior to induction of DOMS and immediately after, 24 hours after, 48 hours after, and 72 hours after induction of DOMS were obtained, and the thickness and pennation angle of the muscle were measured. [Results] The muscle thickness gradually increased until 48 hours after induction of DOMS and decreased after 72 hours. The pennation angle also gradually increased until 48 hours after induction of DOMS and decreased after 72 hours. [Conclusion] Ultrasound imaging is considered useful for assessment of structural characteristics of muscles when muscle damage like DOMS takes place.

Estimation of mercury speciation in soil standard reference materials with different extraction methods by ion chromatography coupled with ICP-MS.

Analytical methods for the speciation of mercury, based on microwave extraction and sonication extraction, have been tested to determine the inorganic mercury and methyl mercury contents in two standard soil reference materials: SRM 2710 Montana Soil and BCR 580 estuarine sediment. Prior to applying the speciation extraction methods, the mineral compositions were analyzed via XRD analysis, with SRM 2710 shown to be composed mostly of aluminum silicate minerals, while carbonate minerals were the major constituent in BCR 580. Two extraction methods, microwave and sonication, were tested for the analysis and recovery efficiency of total mercury. The accuracy and efficiency of each extraction method was also compared. In the analysis of total mercury, the microwave extraction method, with using methanol and HCl as extractants, was better for SRM2710, while the application of the sonication extraction method was more efficient for the calcite-based BCR 580. The results showed good separation and recovery efficiencies, with values reaching 100% of those estimated. The sonication method was selected for the speciation of mercury, especially in BCR 580. An extraction solution comprising of a 1:1 mixture of methanol and HCl was used for the sonication extraction of BCR 580, with the resulting extractants analyzed by IC-HG-ICP-MS for methyl mercury and inorganic mercury. As a simple, rapid, sensitive, and accurate method, sonication extraction was found to be satisfactory.

Microarray analysis of gene expression profile in the corpus cavernosum of hypercholesterolemic rats after chronic treatment with PDE5 inhibitor.

Gene expression changes in the corpus cavernosum of hypercholesterolemic rats were not fully assessed, which were not previously known to be associated with hypercholesterolemia-related erectile dysfunction (ED). To provide molecular insight into pathophysiology of hypercholesterolemia-related ED and to investigate the effects of Udenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on gene expression, we performed microarray gene expression analysis via gene discovery methods using GenoCheck platinum cDNA chip (Ansan, S. Korea). Sixteen male Sprague-Dawley rats were fed 2% cholesterol diet for 5 months. Half of them were orally treated with Udenafil (20 mg/kg/day) simultaneously. Eight age-matched rats fed normal diet were served as normal control. RNA was extracted from corpus cavernosum and microarray analysis was performed. Decreased erectile responses and hypercholesterolemia were observed in hypercholesterolemic control group. In microarray analysis, 122 candidate genes were noted to be altered based on the magnitude of expression changes, which includes 44 down-regulated and 78 up-regulated genes compared with the age-matched normal controls. These changes were, however, significantly attenuated by treatment with Udenafil. Out of the 78 up-regulated genes, 8 genes were significantly decreased by the chronic treatment with Udenafil. The altered genes were cytochrome oxidase biogenesis protein OXA1, skeletal muscle myosin heavy chain, lipophilin, fast skeletal muscle isoforms beta/alpha, myosin light chain 3, cytochrome c oxidase, adipocyte fatty acid binding protein and one EST gene. In contrast, among the 44 down-regulated genes, Kruppel-like factor 5 and cyclin D1 genes were increased after the Udenafil treatment. These results provide the molecular basis for understanding the pathogenesis of hypercholesterolemia-related ED and offer clues on determining the underlying action mechanism of a PDE5 inhibitor.

Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet-induced obese rats.

AIM: To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 (PDE5) inhibitor, on penile erection in obese rats. METHODS: The rats were fed a high-energy diet for 12 weeks and divided into three groups: an obesity-resistant (OR) control group, an obesity-prone (OP) control group, and an OP-DA-8159 treatment (DA-8159) group. The electrostimulation-induced erectile responses were measured in all groups. The body weight, plasma cholesterol, triglyceride and glucose levels were also measured. RESULTS: In the OP control group, the maximum intracavernous pressure (ICP) and ICP/blood pressure (ICP/BP) ratio after electric stimulation were significantly lower than those in OR control group. The corresponding area under the curve (AUC) of the ICP/BP ratio, the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group, but this difference was not significant. The body weight gain, plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159, a significant increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding AUCs in the DA-8159 group were also higher than those in the two control groups. Furthermore, the detumescence time was significantly prolonged after treatment with DA-8159. CONCLUSION: These results demonstrate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction (ED) can be improved by the treatment with DA-8159, indicating DA-8159 might be a treatment option for ED associated with obesity.

Chronic administration of phosphodiesterase 5 inhibitor improves erectile and endothelial function in a rat model of diabetes.

This study was conducted to determine if the long-term administration of the phosphodiesterase type 5 (PDE 5) inhibitor, DA-8159, to diabetic rats can ameliorate the development of erectile dysfunction (ED) and endothelial dysfunction. After inducing diabetes with streptozotocin, DA-8159 was orally administered at a dose of 3 mg/kg or 10 mg/kg for 8 weeks. To examine the effect on erectile response, electrostimulation of the cavernous nerve with the parameters of 3 V, 5 ms, 5 Hz or 10 Hz, was performed to measure the intracavernous pressure (ICP) and mean arterial pressure (MAP). Thoracic aorta relaxation in vitro was evaluated by adding acetylcholine (Ach) cumulatively to the bathing medium. In addition, the plasma endothelin-1 (ET-1) levels were measured in order to investigate the effect of DA-8159 on endothelial dysfunction. The area under the curve (AUC) from the ICP/MAP ratio in the 10 Hz stimulation showed a significantly increased AUC after the 10 mg/kg treatment compared with the diabetic group (8891 +/- 619 vs. 6316 +/- 1016, respectively, p < 0.05). At the 5 Hz frequency, DA-8159 10 mg/kg also induced a significant increase in the AUC compared with the diabetic control. The maximum ICP/MAP ratio (%) of the 10 mg/kg treatment group was significantly higher in both the 10 Hz and 5 Hz frequency groups (p < 0.05). A treatment of 3 mg/kg tended to increase the AUC and peak ICP/MAP but was not statistically significant. The Ach EC50 value of the diabetic group was significantly higher than in the normal control (120.50 +/- 22.90 nm vs. 86.80 +/- 9.30 nm, respectively), and 10 mg/kg treatment group showed a significantly lower EC(50) value (88.38 +/- 19.7 nm). The ET-1 level was lower in groups treated with DA-8159, 3 mg/kg and 10 mg/kg treatment induced a statistical difference compared with the diabetic control (1.15 +/- 0.34 fmol/mL vs. 2.51 +/- 0.55 fmol/mL, respectively, p < 0.05). These results demonstrate that chronic administration of DA-8159 could attenuate the development of the ED in diabetes and its effect is associated with an improvement in the endothelial function.

Penile erectile responses to electric stimulation are enhanced by a new phosphodiesterase type-5 inhibitor.

AIM: This study was conducted to investigate the effect of DA-8159, a new phosphodiesterase type-5 (PDE5) inhibitor, on electrostimulation-induced penile erection in rats. METHODS: Intracavernous pressure (ICP) and arterial blood pressure (BP) were simultaneously recorded through electric pelvic-ganglion stimulation (2-10 Hz) after the oral administration of DA-8159 (3 or 10 mg/kg) in normal and streptozotocin-induced diabetic rats. Statistical analysis was performed on the maximal intracavernous pressure (ICP), detumescence time, maximal intracavernous pressure/blood pressure (ICP/BP) ratio, and the area under the curve (AUC) of the ICP/BP ratio. RESULTS: In normal and diabetic rats, electrical stimulation of the pelvic ganglion induced a frequency- and dose-dependent increase in the intracavernous pressure. The ICP/BP ratio and the corresponding AUC values were also significantly and dose-dependently increased after DA-8159 administration. In addition, the detumescence time significantly increased after DA-8159 administration compared to that of the controls. CONCLUSIONS: These results show that the DA-8159 significantly increased the intracavernous pressure response and prolonged the decay period induced by electrical stimulation of the pelvic ganglion, and suggest that DA-8159 might be a potential therapeutic agent for the treatment of erectile dysfunction.