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Honey varies depending on plant origin and environmental conditions. Chemical constituents can be used to determine the origins, characteristics, and storage period of a specific honey. Styrax japonica (snowbell) honey has excellent flavor, but very few studies have been carried out on its chemical constituents. Therefore, the present study was aimed to identify chemical constituents containing in snowbell honey and to screen candidate marker compounds for predicting the storage period of snowbell honey using the identified compounds. Twelve compounds including three new compounds were purified and isolated from the snowbell honey. Three new compounds were elucidated as 1α,3β,5β-bornetriol, 7-hydroxy-2,2,6-trimethyl-1-oxaspiro[2.5]oct-5-en-4-one, and 2-benzyl-2,3-dihydroxybutanoic acid, based on ESI-MS and NMR experiments. 6,7-Dihydroxylinalool and 6,7-dihydroxygeraniol isolated as known compounds in this study were identified for the first time in snowbell honey as well as in other honeys. The isolated compounds were qualified and quantified by LC-ESI-Q-TOF-MS/MS analysis. All compounds were detected in snowbell honeys of different production years. The levels of tyrosol, 7-hydroxy-2,2,6-trimethyl-1-oxaspiro[2.5]oct-5-en-4-one, and (–)-dihydroxyphaseic acid were lower in snowbell honey with long storage period than in short storage period, which is suggested to be used as candidate marker compounds for predicting the storage period of snowbell honey.

Background Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chinensis Lamark (Convolvulaceae) and spiraeoside from the outer scales of Allium cepa L. (Liliceae) in a ratio of 6.69:0.41:3.61. Monotropein, astragalin, and spiraeoside are well-known antioxidants, anti-inflammatory, and antinociceptive agents. The current investigation aims to study the molecular mechanism of varicocele-induced male infertility and the underlying pharmacological mechanisms of MAS. Methods Four groups were included: control (CTR), MAS 200 group (MAS 200 mg/kg), varicocele group (VC), and VC + MAS 200 group (MAS 200 mg/kg). Sprague-Dawley (SD) rats were treated with 200 mg/kg MAS or vehicle once daily for 28 days. The possible signaling mechanism and effects of MAS were measured via histological staining, immunohistochemistry, western blot, and biochemical assays. Results Parameters such as sperm motility and count, Johnsen’s scores, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and expression of the steroidogenic acute regulatory protein (StAR) improved significantly in the VC + MAS 200 group compared with the VC group. MAS treatment of varicocele-induced group significantly decreased the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as testicular interleukin-6 (IL6), tumor necrosis factor-α (TNF-α), ROS/RNS, and malondialdehyde (MDA). It also decreased the apoptotic index and reduced the expression of endoplasmic reticulum (ER) protein levels (Grp78, p-IRE1α, and p-JNK) and apoptotic markers such as cleaved caspase-3 and Bax/Bcl2 ratio. Conclusion This study suggests that the crosstalk between oxidative stress, ER stress, and mitochondrial pathway mediates varicocele-induced testicular germ cell apoptosis. MAS promotes spermatogenesis in varicocele-induced SD rat, probably by decreasing cytokines (IL-6, TNF-α) levels, regulating abnormal sex hormones, and decreasing oxidative stress, ER stress, and apoptosis.

Biocatalytic transformation of carbamate formed readily from CO2 and NH3 provides attractive green routes for mitigation of these important environmental pollutants. Accordingly, a coupled-enzyme system was developed for the one-pot production of citrulline through carbamoylation of ornithine in aqueous solutions of CO2 and NH3. Hyperthermophilic ornithine carbamoyltransferases are produced recombinantly in E. coli with carbamate kinases known to have a propensity for carbamoyl phosphate synthesis. Importantly, in vitro biocatalysis is carried out by E. coli cell lysate prepared through coexpression of the required recombinant enzymes in a single bacterial culture, greatly reducing limitations normally associated with protein production and purification. Acetate kinase that is endogenous in the lysate also recycles the required ATP cofactor, which would otherwise have been required in costly stoichiometric amounts. Recombinant lysates catalyze the production of carbamoyl phosphate with substoichiometric A...

Gui-A-Gra, a commercial insect powder from Gryllus bimaculatus, is registered as an edible insect by the Korean food and drug administration. The aim of this study was to investigate the effect of Gui-A-Gra on testicular damage induced by experimental left varicocele in male Sprague Dawley rats. A total of 72 rats were randomly divided into the following six groups (12 rats in each group): a normal control group (CTR), a group administrated with Gui-A-Gra 1.63 gm/kg (G1.63), a group administrated with Gui-A-Gra 6.5 gm/kg (G6.5), a varicocele (VC)-induced control group (VC), a VC-induced group administrated with Gui-A-Gra 1.63 gm/kg (VC + G1.63), and a VC-induced group administrated with Gui-A-Gra 6.5 gm/kg (VC + G6.5). Rats were administrated 1.63 or 6.5 gm/kg Gui-A-Gra once daily for 42 days. Indicators of sperm parameters, histopathology, reproductive hormones, oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and mitochondrial apoptosis were analyzed to evaluate effects of Gui-A-Gra on VC-induced testicular dysfunction. Gui-A-Gra administration to VC-induced rats significantly (p < 0.05) increased sperm count and sperm motility, Johnsen score, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, GPx4, and steroidogenic acute regulatory protein (StAR) level. Moreover, pretreatment with Gui-A-Gra significantly (p < 0.05) decreased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive cells/tubules, serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), testicular tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), reactive oxygen species (ROS)/reactive nitrogen species (RNS) level, glucose-regulated protein-78 (Grp-78), phosphorylated c-Jun-N-terminal kinase (p-JNK), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1α (p-IRE1α), cleaved caspase-3, and BCL2 associated X protein: B-cell lymphoma 2 (Bax: Bcl2) ratio in VC rats. These results suggest that protective effects of Gui-A-Gra on VC-induced testicular injury might be due to its antioxidant, anti-inflammatory, and androgenic activities that might be mediated via crosstalk of oxidative stress, ER stress, and mitochondrial apoptosis pathway.

Background and Objective This study has evaluated the pharmacokinetic parameters and bioavailabilities of monotropein, kae-mpferol-3-O-glucoside, and quercetin-4’-O-glucoside after administration of MOTILIPERM in rats. Material and Methods Following the administration of MOTILIPERM, the plasma concentrations of each compound in rats were simultaneously determined by using liquid chromatography tandem mass spectrometry (LC-MS/MS). Results The pharmacokinetic parameters of monotropein in rats were AUCinf 20,020.44±3944.67 and 11,915.53±1190.91 min·ng/mL and Cmax 286.99±38.37 and 56.23±9.02 ng/mL for intravenous and oral administration, respectively. The pharmacokinetic parameters of kaempferol-3-O-glucoside in rats were AUCinf 287.86±126.17 min·ng/mL and not estimated; Cmax 5.80±1.87 and 1.24±0.41 ng/mL for intravenous and oral administration, respectively. The pharmacokinetic parameters of querce-tin-4’-O-glucoside in rats were AUCinf 511.38±248.11 and 481.44±65.72 min·ng/mL; Cmax 10.72±2.70 and 2.83±0.34 ng/mL for intravenous and oral administration, respectively. Conclusion The absolute bioavailabilities of monotropein and quercetin-4’-O-glucoside for oral administration were evaluated and calculated as 3.0 and 4.7%, respectively. The absolute bioavailability of kaemp-ferol-3-O-glucoside was not calculated because the elimination rate constant could not be estimated. These results may be applied to the basic data in a further study in order to develop functional foods or herbal medicinal products.

It is well established that physiological stress has an adverse effect on the male reproductive system. Experimental studies have demonstrated the promising effects of MOTILIPERM in male infertility. MOTILIPERM extract is composed of three crude medicinal herbs: Morinda officinalis How (Rubiaceae) roots, Allium cepa L. (Liliaceae) outer scales, and Cuscuta chinensis Lamark (convolvulaceae) seeds. The present study aimed to investigate the possible mechanisms responsible for the effects of MOTILIPERM on testicular dysfunction induced by immobilization stress. Fifty male Sprague Dawley rats were divided into five groups (10 rats each): a normal control group (CTR), a control group administered MOTILIPERM 200 mg/kg (M 200), an immobilization-induced stress control group (S), an immobilization-induced stress group administered MOTILIPERM 100 mg/kg (S + M 100), and MOTILIPERM 200 mg/kg (S + M 200). Stressed rats (n = 30) were subjected to stress by immobilization for 6 h by placing them in a Perspex restraint cage, while controls (n = 20) were maintained without disturbance. Rats were administrated 100 or 200 mg/kg MOTILIPERM once daily for 30 days 1 h prior to immobilization. At the end of the treatment period, we measured body and reproductive organ weight; sperm parameters; histopathological damage; reproductive hormone levels; steroidogenic acute regulatory protein (StAR); biomarkers of oxidative stress; and apoptosis markers. MOTILIPERM treatment improved testicular dysfunction by up-regulating (p < 0.05) sperm count, sperm motility, serum testosterone level, StAR protein level, Johnsen score, and spermatogenic cell density in stressed rats. MOTILIPERM decreased oxidative stress by increasing (p < 0.05) testicular superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione peroxidase-4 (GPx 4), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) levels and decreasing (p < 0.05) malondialdehyde (MDA) and reactive oxygen species/reactive nitrogen species (ROS/RNS) levels. Furthermore, MOTILIPERM down-regulated (p < 0.05) cleaved caspase 3 and BCL2 associated X protein (Bax) levels; increased pro caspase-3 and B-cell lymphoma 2 (Bcl-2) levels; and upregulated testicular germ cell proliferation in stressed rats. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels also significantly (p < 0.05) decreased after pretreatment with MOTILIPERM in stressed rats. Collectively, our results suggest that, in immobilization-mediated stress-induced testicular dysfunction, MOTILIPERM sustains normal spermatogenesis via antioxidant and anti-apoptotic activities by activating the NRF/HO-1 signaling pathway.

작은벌집딱정벌레(Small hive beetle(SHB), Aethina tumida(Coleoptera: Nitidulidae)는 아프리카 대륙 사하라 사막 이남 지역이 원산지이다. 벌통내 양봉산물과 꿀벌에 직·간접적인 피해를 준다. 국내에서는 밀양지역에서 2016년 9월 첫 피해 보고되었다. 현재 발생 지역은 밀양과 그 주변지역인 창녕, 양산, 기장에서 발생하고 있다. 이에 국내 작은벌집딱정벌레 확산 방지 및 방제를 위해 본 연구를 실시하였다. 본 연구는 유인제 선호성, 방제 약제 선발, 꿀벌안전성 평가, 선발 약제를 이용한 현장 적용 평가로 나눌 수 있다. 유인제 선호성은 유충과 성충을 대상으로 이루어졌으며, 유충은 대용화분을 가장 선호하였으며, 성충은 분쇄화분+설탕물을 가장 선호하였다. 이에 유충과 성충은 기본적으로 화분성분을 선호하여, 방제 약제 개발시 약제와 화분을 혼합하여 사용할 수 있게 개발하였다. 방제 약제 선발은 국외 문헌 조사를 통해 일차적으로 coumaphos, fluvalinate, cymiazole hydrochlorid을 후보 목록으로 선정하였다. 이에 대해 실내 독성 평가를 통해 적합 약제를 선발하였다. 선발된 약제는 coumaphos이며, 방제 효율이 높으며, 꿀벌에 안전한 것으로 나타났다. coumaphos를 이용하여 대용화분과 혼합하여 섭식을 통해 방제하였으며, 유충에 대한 방제 농도는 1,000ppm, 성충은 10,000ppm으로 설정되었으며, 꿀벌 안전성 평가를 위해 실내·외 평가에서도 coumaphos 10,000ppm 혼합 대용화분은 안전한 것으로 나타났다. 이를 이용하여 CD형 케이스에 coumaphos 10,000ppm 혼합 대용화분과 Apitor, 오일 트랩을 이용하여 작은벌집딱정벌레 발생 현장에서 실험한 결과 높은 방제 효율이 나타났다. 이에 coumaphos 1,000ppm(유충), 10,000ppm(성충)을 대용화분과 혼합하여CD형 케이스에 넣어 사용한다면 발생현장에서 작은벌집딱정벌레 방제에 적합한 것으로 나타났다.

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.

// Jung Nyeo Chun 1, 2, * , Soonbum Park 1, * , Sanghoon Lee 3 , Jae-Kyung Kim 1 , Eun-Jung Park 1 , MinJi Kang 1 , Hye Kyung Kim 4, 5 , Jong Kwan Park 5 , Insuk So 1, 2 and Ju-Hong Jeon 1, 2 1 Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea 2 Institute of Human-Environment Interface Biology, Seoul National University, Seoul 03080, Korea 3 Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA 4 College of Pharmacy, Kyungsung University, Busan 48434, Korea 5 Department of Urology, Medical School, and Institute for Medical Sciences, Chonbuk National University, Jeonju 54896, Korea * These authors contributed equally to this work Correspondence to: Ju-Hong Jeon, email: jhjeon2@snu.ac.kr Keywords: schisandra chinensis; schisandrol B; schisandrin B; TGFβ1; NF-κB Received: June 30, 2017 Accepted: November 15, 2017 Published: December 14, 2017 ABSTRACT Aberrant transforming growth factor β1 (TGFβ1) signaling plays a pathogenic role in the development of vascular fibrosis. We have reported that Schisandra chinensis fruit extract (SCE), which has been used as a traditional oriental medicine, suppresses TGFβ1-mediated phenotypes in vascular smooth muscle cells (VSMCs). However, it is still largely unknown about the pharmacologic effects of SCE on various TGFβ1 signaling components. In this study, we found that SCE attenuated TGFβ1-induced NF-κB activation and nuclear translocation in VSMCs. Among the five active ingredients of SCE that were examined, schisandrol B (SolB) and schisandrin B (SchB) most potently suppressed TGFβ1-mediated NF-κB activation. In addition, SolB and SchB effectively inhibited IKKα/β activation and IκBα phosphorylation in TGFβ1-treated VSMCs. The pharmacologic effects of SolB and SchB on NF-κB activation were independent of the Smad-mediated canonical pathway. Therefore, our study demonstrates that SCE and its active constituents SolB and SchB suppress TGFβ1-mediated NF-κB signaling pathway in a Smad-independent mechanism. Our results may help further investigations to develop novel multi-targeted therapeutic strategies that treat or prevent vascular fibrotic diseases.

Kiran Kumar Soni,1,* Yu Seob Shin,1,* Bo Ram Choi,1 Keshab Kumar Karna,1 Hye Kyung Kim,2 Sung Won Lee,3 Chul Young Kim,4 Jong Kwan Park1 1Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, Jeonju, 2College of Pharmacy, Kyungsung University, Busan, 3Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University Medical School, Seoul, 4College of Pharmacy, Hangyang University, Ansan, Republic of Korea *These authors contributed equally to this work Abstract: 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 Fgroup 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. Keywords: finasteride, DA-9401, infertility, sperm, dihydrotestosterone, endoplasmic reticulum stress, apoptosis&nbsp

N-Heterocyclic carbenes (NHCs) bind strongly to gold and other metals. This work experimentally probes the effect of NHCs on the work function (WF) of gold for the first time, theoretically analyzes the origin of this effect, and examines the effectiveness of NHC-modified gold as an electron-injecting electrode. UV photoelectron spectroscopy shows the WF of planar gold is reduced by nearly 2 eV to values of 3.3–3.5 eV. This effect is seen for NHCs with various heterocyclic cores, and with either small or large N,N′-substituents. DFT calculations indicate the WF reduction results from both the interface dipole formed between the NHC and the gold and from the NHC molecular dipole. For N,N′-diisopropyl-NHCs, an important contributor to the former is charge transfer associated with coordination of the carbene carbon atom to gold. In contrast, the carbene carbon of N,N′-2,6-diisopropylphenyl-NHCs is not covalently bound to gold, resulting in a lower interface dipole; however, a larger molecular dipole partiall...

Ginger was steamed at 121 ℃ and 1.5 lb/in2 for 30 min, dried at 60℃ for 12 h, and each step was repeated nine times. During processing, the lightness (L* value) and yellowness (b* value) decreased from 85.65±0.33 and 26.99±0.20 in the non-treated ginger to 56.91±0.25 and 16.69±0.06 in ginger treated for the ninth treatment. On the other hand, redness (a* value) increased from -1.51±0.03 to 7.34±0.08 on the eight treatment and then decreased to 7.21±0.04 on the ninth theatment. The contents of 6-gingerol decreased from 3.257±0.067 mg/g in the non-treated ginger to 0.567±0.036 mg/g on the theatment, whereas the contents of 6-shogaol increased from 1.299±0.050 mg/g to 2.999±0.089 mg/g on the sixth treatment and decreased to 2.099±0.039 on the ninth treatment. The contents of 10-gingerol decreased slightly from 1.106±0.125 mg/g to 0.806±0.026 mg/g. Unlike the 6- and 10-gingerol, the contents of 8-gingerol did not change greatly, with values between 0.916±0.005 mg/g and 1.106±0.005 mg/g being observed during processing. The tyrosinase inhibitory activities were increased from 43.42±11.45% in the non-treated ginger to 100% on the sixth treatment and then decreased to 51.98±7.36% on the theatment. The antioxidative active-ity was retained during processing.

Introduction The development of novel therapeutic options is imperative in patients with erectile dysfunction, especially those non-responsive to phosphodiesterase type 5 inhibitors. LDD175, a potent BKCa channel opener, has a relaxation effect on the in vitro cavernosal smooth muscle strip. Aim To investigate the effect of LDD175 on erectile function using in vivo animal disease model. Methods Male Sprague-Dawley rats were assigned to a normal control group and seven diabetic groups: diabetic control, sildenafil (1 and 5 mg/kg), LDD175 (5 and 10 mg/kg), LDD175 5 mg/kg plus sildenafil 1 mg/kg, and LDD175 10 mg/kg plus tetraethylammonium. Main Outcome Measures Intracavernosal pressure (ICP), ratio of ICP to mean arterial pressure (MAP), and the area under curve of ICP/MAP of eight groups were compared using in vivo pelvic nerve stimulation. Results The ICP, ICP/MAP ratio, and area under curve of the ICP/MAP ratio of the normal control rats increased with an increase in electrical field stimulation voltage. All parameters in the diabetic control group were significantly lower than those in the normal control rats, with an electrical field stimulation ranging from 1 to 5 V (P < .05). LDD175 improved the erectile response in diabetic rats in a dose-dependent manner. The combination of sildenafil (1 mg/kg) and LDD175 (5 mg/kg) showed a significant additive effect (P < .05) on the improvement of erectile function compared with sildenafil (1 mg/kg) alone. The enhancement of erectile function by LDD175 was completely blocked by tetraethylammonium. Conclusion The results showed that the BKCa channel opener LDD175 improved erectile function in an in vivo diabetic rat model. Furthermore, combination therapy of LDD175 and sildenafil had an additive effect on the improvement of erectile function in diabetic rats. LDD175 could be a new candidate for the treatment of erectile dysfunction.

Kiran Kumar Soni,1 Hye Kyung Kim,2 Bo Ram Choi,1 Keshab Kumar Karna,1 Jae Hyung You,1 Jai Seong Cha,1 Yu Seob Shin,1 Sung Won Lee,3 Chul Young Kim,4 Jong Kwan Park1 1Department of Urology, Institute for Medical Sciences, Chonbuk National University Medical School– Biomedical Research and Institute and Clinical Trial Center for Medical Devices, Chonbuk National University Hospital, Jeonju, 2College of Pharmacy, Kyungsung University, Busan, 3Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University Medical School, Seoul, 4College of Pharmacy, Hanyang University, Ansan, Republic of Korea Abstract: 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. Keywords: cisplatin, testicular toxicity, oxidative stress, StAR protein, CatSper, endoplasmic reticulum stress

Schisandra chinensis Baillon (SC) has been utilized for its antioxidants and anti-inflammatory activities in a broad variety of medical applications. However, SC uses for improving fertility in males and related disorders with proper scientific validation remain obscure. The present study aimed to investigate the effects of SC on varicocele (VC)-induced testicular dysfunction and the potential molecular mechanism associated with VC-induced germ cell apoptosis. The male Sprague&ndash, Dawley rats were equally divided into four groups consisting of 10 rats in a normal control group (CTR), a control group administered SC 200 mg/kg (SC 200), a varicocele-induced control group (VC), and a varicocele-induced group administered SC 200 mg/kg (VC + SC 200). Rats were administrated 200 mg/kg SC once daily for 28 days after induction of varicocele rats and sham controls. At the end of the treatment period, body and reproductive organ weight, sperm parameters, histopathological damages, proinflammatory cytokines, apoptosis markers, biomarkers of oxidative stress, endoplasmic reticulum (ER) stress, and steroidogenic acute regulatory protein (StAR) were evaluated. The effects of SC extract on human sperm motility were also analyzed. SC treatment reduces VC-induced testicular dysfunction by significantly increasing testicular weight, sperm count and sperm motility, serum testosterone level, Johnsen score, spermatogenic cell density, testicular superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase level, and steroidogenic acute regulatory protein (StAR) level. Furthermore, the effects of SC on malondialdehyde (MDA) level, reactive oxygen species (ROS)/reactive nitrogen species (RNS) level, apoptotic index, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, Glucose-regulated protein-78 (Grp 78), phosphorylated c-Jun-N-terminal kinase (p-JNK), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1&alpha, (p-IRE1&alpha, ), cleaved caspase 3, and Bax:Bcl2 in VC-induced rats were significantly decreased. Treatment with SC extracts also increased sperm motility in human sperm. Our findings suggest that the SC ameliorate testicular dysfunction in VC-induced rats via crosstalk between oxidative stress, ER stress, and mitochondrial-mediated testicular germ cell apoptosis signaling pathways. SC promotes spermatogenesis by upregulating abnormal sex hormones and decreasing proinflammatory cytokines (interleukin-6, TNF-&alpha, ).

Polygonum cuspidatum (PC) has been used as traditional Korean medicine to treat various diseases including asthma, hypertension, cancer, and arteriosclerosis. In this study, we assessed the antibacterial and anti-inflammatory effects of PC ethanol extract. Persistent antibacterial activity against Streptococcus mutans for up to 23 days was observed when the extract was used at a concentration of 10 mg/mL. The minimum inhibitory concentration of PC against S. mutans was 0.2 mg/mL and the minimum bactericidal concentration was 10 mg/mL. We compared the antimicrobial activities of S. mutagens cultured with or without PC. Bacterial activity was observed only in the group where RE was not added. The anti-inflammatory effect of PC on RAW264.7 cells was assessed using the MTT assay; changes in nitric oxide (NO) production and inflammatory cytokine levels (tumor necrosis factor [TNF]-α and interleukin [IL]-6) were measured in the presence of PC. In lipopolysaccharide-induced RAW264.7 cells, PC inhibited NO production by 68.6% when used at a concentration of 50 µg/mL. The expression of TNF-α and IL-6 was reduced by PC in a concentration-dependent manner. These results suggest that the ethanol extract of PC could be used as a mouthwash component with antibacterial and anti-inflammatory effects.

This study was conducted to compare nutritional composition and taste-related compounds of breast and thigh meats from four lines of Korean native chickens (KNC) Yeonsan Ogye, Hyunin Black, Hwangbong, and Hoengseong Yakdak. White Leghorn (WL) was used as a control. Fifteen male chickens (three chickens in each line) were grown under same condition and slaughtered at 53 weeks old. The contents of Fe and K in KNC, especially Hwangbong breast meat and thigh meat of Hyunin Black and Hoengseong Yakdak, were higher than WL. The contents of Na were lower in KNC compared with WL regardless of parts (p contents were lower in Hoengseong Yakdak than other lines. Vitamin were higher in breast meat of four lines of KNC and thigh meat of Hoengseong Yakdak than WL. Total amino acid contents were higher in breast meat of KNC than WL. The level of good-tasting amino acids were significantly higher in breast meat of Hoengseong Yakdak and WL, and thigh meat of Hyunin Black and WL than other lines of chickens (p

Objective To investigate the gastroprotective effects of Acanthopanax senticosus leaves (ASLs) extrusion on acute gastric mucosal lesion in rats induced by compound 48 / 80 (C48 / 80). Methods Rats were divided into six groups: normal; C48/80-induced gastric lesion control; gastric lesion positive control (famotidine 4 mg/kg); gastric lesion administered with two levels of extruded ASLs (ASLE, 40 and 200 mg/kg); and gastric lesion treated with ASLs (ASL 200 mg/kg). Mucus secretion / damage was determined by immunohistological staining. Immunofluorescence and western blotting were performed to determine gastric mucosal Bax and Bcl-2 expression. Gastric mucosal oxidative-stress-related enzymes and malondialdehyde were determined. Results C48/80-induced mucus depletion and inflammation in the gastric mucosa were significantly attenuated by ASLs. The increased serum serotonin and histamine concentrations in C48/80-treated rats were also attenuated by ASLs. Gastric mucosal Bax protein expression was increased and Bcl-2 expression was decreased after C48/80 treatment, and ASLs ameliorated Bax and Bcl-2 expression. The extrusion process significantly augmented the effects of ASLs in a dose-dependent manner. ASLEs at 200 mg/kg normalized mucus damage / secretion, C48 / 80-induced increases of mucosal myeloperoxidase activity (index of inflammation), xanthine oxidase, and malondialdehyde content (index of lipid peroxidation). The effects of ASLs on Bax and Bcl-2 expression were also enhanced by extrusion. Furthermore, these effects of ASLEs at 200 mg/kg were similar to those of famotidine, a histamine H2-receptor antagonist commonly used to treat gastric ulcers. Conclusion ASLEs prevented acute gastric mucosal lesion progression induced by C48/80, possibly by inducing mucus production, and reduced inflammation and oxidative stress in gastric mucosa through an anti-apoptotic mechanism.

The main objective of this study was to develop and validate a simpler and less time consuming analytical method for determination of propofol glucuronide from hair sample, by using mixed mode anion exchange cartridge and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The study uses propofol glucuronide, a major metabolite of propofol, as a marker for propofol abuse. The hair sample was digested in sodium hydroxide solution and loaded in mixed-mode anion cartridge for solid phase extraction. Water and ethyl acetate were used as washing solvents to remove interfering substances from the hair sample. Consequently, 2% formic acid in ethyl acetate was employed to elute propofol glucuronide from the sorbent of mixed-mode anion cartridge, and analyzed by LC-MS/MS. The method validation parameters such as selectivity, specificity, LOD, LLOQ, accuracy, precision, recovery, and matrix effect were also tested. The linearity of calibration curves showed good correlation, with correlation coefficient 0.998. The LOD and LLOQ of the propofol glucuronide were 0.2 pg/mg and 0.5 pg/mg, respectively. The intra and inter-day precision and accuracy were acceptable within 15%. The mean values of recovery and matrix effect were in the range of 91.7-98.7% and 87.5-90.3%, respectively, signifying that the sample preparation, washing and extraction procedure were efficient, and there was low significant hair matrix effect for the extraction of propofol glucuronide from hair sample on the mixed mode anion cartridge. To evaluate the suitability of method, the hair of propofol administered rat was successfully analyzed with this method.

Cyanobacteria play a major role as direct producers of biofuels, such as ethanol and butanol, with the aid of genetic engineering. However, development of a new harvesting-technology is essential to achieve economic viability of biofuel production from cyanobacteria. In this study, we demonstrated the feasibility of harvesting the unicellular cyanobacterium Synechocystis sp. PCC 6803 using pre-made filamentous fungal pellets and investigated key factors affecting efficiency of harvest, including fungal strain, pellet quantity (number of pellets), initial pH, and organic carbon source. Synechocystis sp. PCC 6803 cells attached to Aspergillus oryzae pellets, indicating that this fungal pellet had a desirable harvesting effect, while Rhizopus oryzae pellets had no effect on harvesting. Increasing pellet quantity and adding organic carbon sources, such as glucose and xylose, improved the harvesting efficiency of Aspergillus oryzae pellet; efficiency was not affected by the initial pH.

Bo Ram Choi,1–3 Hye Kyung Kim,4,* Kiran Kumar Soni,1–3 Keshab Kumar Karna,1–3 Sung Won Lee,5 Insuk So,6 Jong Kwan Park1–3,* 1Department of Urology, Chonbuk National University, Jeonju, Republic of Korea; 2Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea; 3Clinical Trial Center of Medical Device of Chonbuk National University, Jeonju, Republic of Korea; 4College of Pharmacy, Kyungsung University, Busan, Republic of Korea; 5Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 6Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea *These authors contributed equally to this work Objective: We investigated the benefits of the BKCa agonist 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (LDD175) combined with tamsulosin and finasteride, in a benign prostatic hyperplasia (BPH) rat model.Materials and methods: Castration was performed by bilateral orchiectomy under ketamine anesthesia. A rat model of BPH was established by daily intramuscular administration of testosterone propionate plus 17β-estradiol for 8 weeks. Model rats were administered combinations of 20 mg/kg LDD175, 0.01 mg/kg tamsulosin and 1 mg/kg finasteride once daily by oral gavage for 4 weeks from week 6 to 9 post-surgery. Intraurethral pressure induced by electrostimulation of the hypogastric nerve was measured at the end of administration. Body and genitourinary organ weights were recorded, serums were assayed for hormone concentrations, and tissues were subjected to histopathology, and analyses of α1-adrenoceptor mRNA and protein expression levels after treatment.Results: Combined LDD175, tamsulosin, and finasteride significantly decreased prostatic index, serum hormone levels, epithelial thickness, and prostate expression of α1-adrenoceptors in BPH model rats. The 3-drug combination was more effective than any other combination or LDD175 alone.Conclusion: These results suggest that LDD175 addition to tamsulosin and finasteride may be beneficial for the treatment of BPH patients who do not respond to tamsulosin plus finasteride. Keywords: α1-adrenoceptors, α1-adrenergic receptor antagonists, benzofuroindole, intraurethral pressure, 5α-reductase inhibitors&nbsp

Carbamate kinases catalyze the conversion of carbamate to carbamoyl phosphate, which is readily transformed into other compounds. Carbamate forms spontaneously from ammonia and carbon dioxide in aqueous solutions, so the kinases have potential for sequestrative utilization of the latter compounds. Here, we compare seven carbamate kinases from mesophilic, thermophilic, and hyperthermophilic sources. In addition to the known enzymes from Enterococcus faecalis and Pyrococcus furiosus , the previously unreported enzymes from the hyperthermophiles Thermococcus sibiricus and Thermococcus barophilus , the thermophiles Fervidobacterium nodosum and Thermosipho melanesiensis , and the mesophile Clostridium tetani were all expressed recombinantly, each in high yield. Only the clostridial enzyme did not show catalysis. In direct assays of carbamate kinase activity, the three hyperthermophilic enzymes display higher specific activities at elevated temperatures, greater stability, and remarkable substrate turnover at alkaline pH (9.9 to 11.4). Thermococcus barophilus and Thermococcus sibiricus carbamate kinases were found to be the most active when the enzymes were tested at 80°C, and maintained activity over broad temperature and pH ranges. These robust thermococcal enzymes therefore represent ideal candidates for biotechnological applications involving aqueous ammonia solutions, since nonbuffered 0.0001 to 1.0 M solutions have pH values of approximately 9.8 to 11.8. As proof of concept, here we also show that carbamoyl phosphate produced by the Thermococcus barophilus kinase is efficiently converted in situ to carbamoyl aspartate by aspartate transcarbamoylase from the same source organism. Using acetyl phosphate to simultaneously recycle the kinase cofactor ATP, at pH 9.9 carbamoyl aspartate is produced in high yield and directly from solutions of ammonia, carbon dioxide, and aspartate. IMPORTANCE Much of the nitrogen in animal wastes and used in fertilizers is commonly lost as ammonia in water runoff, from which it must be removed to prevent downstream pollution and evolution of nitrogenous greenhouse gases. Since carbamate kinases transform ammonia and carbon dioxide to carbamoyl phosphate via carbamate, and carbamoyl phosphate may be converted into other valuable compounds, the kinases provide a route for useful sequestration of ammonia, as well as of carbon dioxide, another greenhouse gas. At the same time, recycling the ammonia in chemical synthesis reduces the need for its energy-intensive production. However, robust catalysts are required for such biotransformations. Here we show that carbamate kinases from hyperthermophilic archaea display remarkable stability and high catalytic activity across broad ranges of pH and temperature, making them promising candidates for biotechnological applications. We also show that carbamoyl phosphate produced by the kinases may be efficiently used to produce carbamoyl aspartate.

Background and ObjectiveThis study has evaluated the pharmacokinetic parameters and bioavailabilities of monotropein, kae-mpferol-3-O-glucoside, and quercetin-4’-O-glucoside after administration of MOTILIPERM in rats.Material and MethodsFollowing the administration of MOTILIPERM, the plasma concentrations of each compound in rats were simultaneously determined by using liquid chromatography tandem mass spectrometry (LC-MS/MS).ResultsThe pharmacokinetic parameters of monotropein in rats were AUCinf 20,020.44±3944.67 and 11,915.53±1190.91 min·ng/mL and Cmax 286.99±38.37 and 56.23±9.02 ng/mL for intravenous and oral administration, respectively. The pharmacokinetic parameters of kaempferol-3-O-glucoside in rats were AUCinf 287.86±126.17 min·ng/mL and not estimated; Cmax 5.80±1.87 and 1.24±0.41 ng/mL for intravenous and oral administration, respectively. The pharmacokinetic parameters of querce-tin-4’-O-glucoside in rats were AUCinf 511.38±248.11 and 481.44±65.72 min·ng/mL; Cmax 10.72±2.70 and 2.83±0.34 ng/mL for intravenous and oral administration, respectively. ConclusionThe absolute bioavailabilities of monotropein and quercetin-4’-O-glucoside for oral administration were evaluated and calculated as 3.0 and 4.7%, respectively. The absolute bioavailability of kaemp-ferol-3-O-glucoside was not calculated because the elimination rate constant could not be estimated. These results may be applied to the basic data in a further study in order to develop functional foods or herbal medicinal products.

Recently, illegal sildenafil analogues have emerged, causing serious social issues. In spite of the importance of sildenafil analogues, their metabolic profiles or clinical effects have not been reported yet. In this study, new metabolites of illegal sildenafil analogues such as hongdenafil, homosildenafil, and hydroxyhomosildenafil were determined using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS) and tandem mass spectrometry (LC-Q-TOF-MS/MS). To prepare metabolic samples, in vitro and in vivo studies were performed. For in vivo metabolites analysis, urine and feces samples of rats treated with sildenafil analogues were analyzed. For in vitro metabolites analysis, human liver microsomes incubated with sildenafil analogues were extracted and analyzed. All metabolites were characterized by LC-Q-TOF-MS and LC-Q-TOF-MS/MS. As a result, five, six, and seven metabolites were determined in hongdenafil, homosildenafil, and hydroxyhomosildenafil treated samples, respectively. These results could be applied to forensic science and other analytical fields. Moreover, these newly identified metabolites could be used as fundamental data to determine the side effect and toxicity of illegal sildenafil analogues.

The biological conversion of CO2 and H2 into formate offers a sustainable route to a valuable commodity chemical through CO2 fixation, and a chemical form of hydrogen fuel storage. Here we report the first example of CO2 hydrogenation utilising engineered whole-cell biocatalysts. Escherichia coli JM109(DE3) cells transformed for overexpression of either native formate dehydrogenase (FDH), the FDH from Clostridium carboxidivorans, or genes from Pyrococcus furiosus and Methanobacterium thermoformicicum predicted to express FDH based on their similarity to known FDH genes were all able to produce levels of formate well above the background, when presented with H2 and CO2, the latter in the form of bicarbonate. In the case of the FDH from P. furiosus the yield was highest, reaching more than 1 g L−1 h−1 when a hydrogen-sparging reactor design was used.

The anti-inflammatory effects of Acanthopanax senticosus leaves (ASL) and the effects of extrusion were evaluated. ASL exhibited in vitro and in vivo antiinflammatory activities in experimental systems. Extrusion increased the effect of ASL. ASL reduced C48/80-induced histamine release from HMC-1 cells as well as in vivo model, suggesting that ASL induces mast cell stabilization and has an anti-histamine activity. The effects of ASL and extruded ASL (ASLE) on pro-inflammatory cytokine production were evaluated. ASL treatment reduced MCP- 1, TNF-α, and IL-1β mRNA expressions and decreased their protein levels in HMC-1 cells. Decreases in serum NO, MDA, and TNF-α levels were observed in acute inflammatory rats, and extrusion increased the effects of ASL in a dose-dependent manner. These data support pharmacological basis of ASL and the effect of extrusion for future treatment of inflammation.

Nonalcoholic fatty liver disease (NAFLD) is caused by the hepatic accumulation of saturated fatty acids involving the ER stress mechanism. Secretion of apo lipid carrier proteins and their binding to hepatic TG and cholesterol are affected by ER stress. This study was designed to identify ER stress regulators with potential effects against hepatic lipid accumulation. Ixeris dentata (IXD) is a traditional herbal remedy for indigestion, hepatitis, and diabetes used in Korea, Japan, and China. To examine the regulatory effects of IXD against hepatic lipid accumulation and elucidate its suggested mechanism of ER stress, HepG2 hepatocytes were treated with IXD extract in the presence of palmitate. While palmitate induced an ER stress response in hepatocytes, as indicated by the upregulation of PERK, increased eukaryotic initiation factor 2α (eIF2α) phosphorylation, enhanced expression of GADD153/C/EBP homologous protein (CHOP), and reduced secretion of apoB resulting in hepatic cellular accumulation of triglycerides (TG) and cholesterol, IXD extract significantly inhibited the lipid accumulation and PERK/eIF2α/CHOP-axis of the ER stress response. The inhibition of the PERK/eIF2α/CHOP signaling pathway by IXD in palmitate-treated cells suggests that IXD regulates hepatic dyslipidemia through the regulation of ER stress.

Department of Animal Products and Food Science, Kangwon National University, Chuncheon 200-701, KoreaABSTRACT The objective of this literature review is to prove that egg cholesterol is not related with heart disease based upon research results of the past 50 years. As a result, it was reported that the dietary intake cholesterol did not affected cholesterol levels in blood. Moreover, it was reported that adding two eggs a day to a healthful diet did not significantly increase blood cholesterol levels in young or middle-aged men and women with normal or even moderately elevated blood cholesterol levels. Cholesterol feeding studies demonstrate that dietary cholesterol increases both LDL and HDL cholesterol with little change in the LDL:HDL ratio as an important risk indicator of heart disease. Especially a good indicator in the elderly from increased HDL-cholesterol, so cholesterol intake appeared to be good for the prevention of heart disease. Thus the consumption of eggs is bad for your health is not known as a fact, but rather was found to be effective in preventing heart disease. Also, all consumers may consume without worrying because there are no official standards regarding egg intake. Therefore, these evidences would clear up some misunderstanding and mistrust on egg cholesterol regarding the consumption of egg as well as give some desirable advice on how to maintain healthy life.(Key words : egg, heart disease, HDL-cholesterol, LDL-cholesterol)

Described herein is the development of practical routes to 8-aminoquinolines by using readily installable and easily deprotectable amidating reagents. Two scalable procedures were optimized under Rh(III) -catalyzed conditions: i) the use of pre-generated chlorocarbamates and ii) a two-step one-pot process that directly employs carbamates. Both approaches are highly convenient for the gram-scale synthesis of 8-aminoquinolines under mild conditions. Facile deprotection of the synthetically versatile amidating groups was achieved under the Pd-catalyzed transfer hydrogenation conditions with simultaneous deoxygenation of quinoline N-oxides, thus yielding 8-aminoquinolines in excellent overall efficiency.

UV exposure is associated with oxidative stress and is the primary factor in skin photoaging. UV-induced reactive oxygen species (ROS) cause the up-regulation of metalloproteinase (MMPs) and the degradation of dermal collagen and elastic fibers. Garlic and its components have been reported to exert antioxidative effects. The present study investigated the protective effect of garlic on UV-induced photoaging and MMPs regulation in hairless mice. Garlic was supplemented in the diet, and Skh-1 hairless mice were exposed to UV irradiation five days/week for eight weeks. Mice were divided into four groups; Non-UV, UV-irradiated control, UV+1% garlic powder diet group, and UV+2% garlic powder diet group. Chronic UV irradiation induced rough wrinkling of the skin with hyperkeratosis, and administration of garlic diminished the coarse wrinkle formation. UV-induced dorsal skin and epidermal thickness were also ameliorated by garlic supplementation. ROS generation, skin and serum malondialdehyde levels were significantly increased by UV exposure and were ameliorated by garlic administration although the effects were not dose-dependent. Antioxidant enzymes such as superoxide dismutase and catalase activities in skin tissues were markedly reduced by UV irradiation and garlic treatment increased these enzyme activities. UV-induced MMP-1 and MMP-2 protein levels were suppressed by garlic administration. Furthermore, garlic supplementation prevented the UV-induced increase of MMP-1 mRNA expression and the UV-induced decrease of procollagen mRNA expression. These results suggest that garlic may be effective for preventing skin photoaging accelerated by UV irradiation through the antioxidative system and MMP regulation.

This study was carried out to investigate the isolation and characterization of lactic acid bacteria (LAB) from naturally fermented sauce-type kimchi. Sauce-type kimchi was prepared with fresh, chopped ingredients (Korean cabbage, radish, garlic, ginger, green onion, and red pepper). The two isolated bacteria from sauce-type kimchi were identified as Pediococcus pentosaceus and Lactobacillus brevis by 16S rDNA sequencing and tentatively named Pediococcus sp. IJ-K1 and Lactobacillus sp. IJ-K2, respectively. Pediococcus sp. IJ-K1 was isolated from the early and middle fermentation stages of sauce-type kimchi whereas Lactobacillus sp. IJ-K2 was isolated from the late fermentation stage. The resistance of Pediococcus sp. IJ-K1 and Lactobacillus sp. IJ-K2 to artificial gastric and bile acids led to bacterial survival rates that were 100% and 84.21%, respectively.

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 © 2011 John Wiley & Sons, Ltd.

Previously, we identified methoxsalen (8-methoxy-2',3',6,7-furocoumarin) as the bioactive compound probably responsible for acetylcholinesterase (AchE) inhibition achieved by feeding crude extract of Poncirus trifoliate. To confirm the activity of methoxsalen, Institute of Cancer Research (ICR) mice were fed a control or a methoxsalen-supplemented diet for 4 weeks, and then learning and memory enhancing effects with respect to trimethyltin (TMT)-induced neurotoxicity were evaluated. The brain tissues of ICR mice were dissected after completion of the behavioral tests for biochemical analysis. Methoxsalen effectively reversed TMT-induced memory impairment on both Y-maze and passive avoidance tests. Brain AchE activity was inhibited by the oral consumption of all concentrations of methoxsalen. Moreover, the level of oxidative stress was significantly ameliorated in the groups on methodsalen containing diets. This is the first in vivo study conducted with methoxsalen in the field of AD research, and it indicates that further investigation of methoxsalen is warranted.

What's known on the subject? and What does the study add? Schisandra chinensis extract (SCE) has been known to have relaxative effects on penile smooth muscle. A recent study showed that SCE could enhance slidenafil citrate-induced relaxation of penile corpus cavernosum. The current study investigated the mechanism of action of SCE and its constituents on corporal smooth muscle cells. And this study shows that SCE induced relaxation of CSM primarily through an endothelium independent pathway and the relaxation effects of SCE on corporal smooth muscle are, in part, due to the activation of K+ channels and inhibition of TRPC6 channels, resulting in decreased [Ca2+]. OBJECTIVE • To evaluate the relaxant effects of Schisandra chinensis extract (SCE) on corporal tissue in the penis and to investigate the mechanism of action of SCE and its constituents on corporal smooth muscle (CSM) cells. MATERIALS AND METHODS • The fruit of SC was collected and extracted with ethanol. Six SC lignans (schisandrol A, schisandrol B, schisandrin A, schisandrin B, gomisin N, and schisandrin C) were isolated and purified, and the chemical structures were confirmed by 1H-nuclear magnetic resonance (NMR) and 13C-NMR data. • Isolated rabbit CSM strips were mounted in an organ-bath system, and the effects of SCE were evaluated. • To estimate the intracellular Ca2+ level ([Ca2+]i), we used a Fura-2 fluorescent technique, and a conventional whole-cell patch-clamp technique was used to measure the calcium-sensitive K+ channels (KCa), inward rectifier K+ channels (KIR), and canonical transient receptor potential cation channel 6 (TRPC6) currents. RESULTS • SCE induced concentration-dependent relaxation in contracted CSM tissue, and the removal of the endothelium did not significantly affect their relaxation potencies. • In CSM cells, extracellular application of SCE significantly increased whole-cell KCa currents (117.4%) and KIR currents (110.0%). These effects were completely abolished by charybdotoxin or BaCl2. • In contrast, carbachol-induced TRPC6 channel activity was significantly inhibited (87.3%) by SCE in green fluorescent protein-TRPC6 pcDNA transfected HEK 293 cells. [Ca2+]i measurements showed that SCE effectively reduced basal [Ca2+]i in both cell lines (CSM cells and A7r5 cells) and the [Arg8]-vasopressin (AVP)-induced [Ca2+]i increase in A7r5 cells. • Among the six SC lignans, schisandrin A and schisandrin B most effectively attenuated the AVP-induced [Ca2+]i increase. CONCLUSIONS • SCE induced relaxation of CSM that occurred primarily via an endothelium-independent pathway. • The relaxation effects of SCE on CSM were, in part, due to the activation of K+ channels and inhibition of TRPC6 channels, resulting in decreased [Ca2+]i.

Inhibition of intestinal glucose uptake is beneficial in reducing the blood glucose level for diabetes. To search for an effective intestinal glucose uptake inhibitor from natural sources, 70 native edible plants, fruits and vegetables were screened using Caco-2 cells and fluorescent D-glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG). A compound that was able to inhibit glucose uptake was isolated from methanol extract of Punica granatum L. and called PG-1a. PG-1a appears to be a phthalic acid-diisononyl ester-like compound (PDE) with molecular weight of 418. The inhibitory effect of PG-1a on intestinal glucose uptake was dose-dependent with 89% inhibition at 100 ㎍/㎖. Furthermore, the intestinal glucose uptake inhibitory effect of PG-1a was 1.2-fold higher than phlorizin, a well known glucose uptake inhibitor. This study suggests that PG-1a could play a role in controlling the dietary glucose absorption, and that PG-1a can effectively improve the diabetic condition, and may be used as an optional therapeutic and preventive agent.

This study was conducted to evaluate the effect of whole egg supplementation on the blood lipid profiles and cholesterol levels of C57BL/6 mice. Sixty-six mice were divided into two groups: normal-diet supplemented and high-cholesterol diet supplemented. Lyophilized whole egg powder was mixed with the two diets at 2 and 10%: normal diet only, normal diet with 2 and 10% whole egg powder, high cholesterol diet only, high cholesterol diet with 2 and 10% whole egg powder. The mixed diets were fed for 5 wk and feeding condition (body weight change, feed intake, and feed efficiency ratio (FER)), blood lipid profiles (total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein cholesterol, hepatic and fecal lipids (TG, TC)), and fecal bile acids were determined. No significant differences were found in body weight gain or FER after whole egg supplementation in both the normal and high-cholesterol diet fed groups. In the normal-diet fed mice, HDL-C increased significantly in the 2 and 10% whole-egg powder groups. In the highcholesterol diet fed mice, administering 10% egg powder increased the atherogenic index compared to the control. Furthermore, administration of whole egg powder increased fecal bile acids dose dependently (p

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.

In this study, traditionally fermented Korean soybean paste, eoyukjang, was characterized and its microorganisms were isolated. The contents of amino-type and ammonia-type nitrogens in the pastes we examined were 89.60 to 98.93 mg/% and 0.32 to 0.30 mM, respectively. Antioxidant activity increased during ripening, with antioxidant activities in 1- and 4-year-old pastes measured at 9.80 and 13.84 μmol of Trolox equivalents/g, respectively. Twenty-two and 19 microorganisms were isolated from soybean pastes under aerobic and anaerobic conditions, respectively. After identification, Bacillus amyloliquefaciens, Bacillus subtilis, and Bacillus vallismortis were dominant. In the enzyme activities, protease and lipoxygenase activities were observed from 0.065 to 0.733 unit/mg protein and 0.016 to 0.19 unit/mg protein, respectively. Amylase activity was, however, broad between 43.1 to 571.8 unit/mg protein.

Hyperactivation of phosphoinositol 3-kinase (PI3K) has been suggested to be a potential mechanism for endoplasmic reticulum (ER) stress-enhanced airway hyperresponsiveness, and PI3K inhibitors have been examined as asthma therapeutics. However, the regulatory mechanism linking PI3K to ER stress and related pathological signals in asthma have not been defined. To elucidate these pathogenic pathways, we investigated the influence of a selective PI3Kδ inhibitor, IC87114, on airway inflammation in an ovalbumin/lipopolysaccharide (OVA/LPS)-induced asthma model. In OVA/LPS-induced asthmatic mice, the activity of PI3K, downstream phosphorylation of AKT and activation of nuclear factor-κB (NF-κB) were all significantly elevated; these effects were reversed by IC87114. IC87114 treatment also reduced the OVA/LPS-induced ER stress response by enhancing the intra-ER oxidative folding status through suppression of protein disulfide isomerase activity, ER-associated reactive oxygen species (ROS) accumulation and NOX4 activity. Furthermore, inositol-requiring enzyme-1α (IRE1α)-dependent degradation (RIDD) of IRE1α was reduced by IC87114, resulting in a decreased release of proinflammatory cytokines from bronchial epithelial cells. These results suggest that PI3Kδ may induce severe airway inflammation and hyperresponsiveness by activating NF-κB signaling through ER-associated ROS and RIDD-RIG-I activation. The PI3Kδ inhibitor IC87114 is a potential therapeutic agent against neutrophil-dominant asthma.

To determine the effects of kaempferol, rat pheochromocytoma cells (PC12) and Institute of Cancer Research (ICR) mice were utilized as neuronal models. Using in vitro assays, kaempferol was shown to have protective effects against oxidative stress-induced cytotoxicity in PC12 cells. Administration of kaempferol also significantly reversed amyloid beta peptide (Abeta)-induced impaired performance in a Y-maze test. Taken altogether, the results reported here suggest that further investigation is warranted of the influence of kaempferol on pathways related to Alzheimer's disease.

Chronic ultraviolet (UV) exposure induces photoaging and oxidative stress in the skin. We investigated whether Machilus thunbergii Sieb et Zucc (M. thunbergii) could reduce UV-induced photoaging and oxidative stress in hairless mice. The dorsal skin of hairless mice was treated topically with M. thunbergii for 2 h prior to UV irradiation. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were then measured in skin and/or serum samples. Histological changes in the skin were assessed by hematoxylin-eosin (HE) staining. In addition, proteomes from the skin of hairless mice in each group were analyzed. The thickness of the dorsal skin and epidermis was significantly decreased by M. thunbergii treatment. We also found that MDA levels decreased after M. thunbergii treatment and the SOD levels were increased by M. thunbergii compared with those in the UV-only treated group. Proteomic analysis revealed 17 proteins associated with photoaging. These data indicate that M. thunbergii might have antiphotoaging effects. Copyright © 2010 John Wiley & Sons, Ltd.

Objectives We have investigated whether endoplasmic reticulum stress and Bcl-2 proteins were linked to the protective effect exerted by flavonoids on ischaemia/reperfusion-induced cardiac damage. Methods Cell viability and immunoblotting were performed. Key findings H9c2 cardiac muscle cells were exposed to flavonoids such as biochanin A, daidzein, genistein, luteolin, quercetin and rutin, followed by ischaemia 12 h/reperfusion 4 h. The flavonoids protected against cell death induced by ischaemia/reperfusion. Flavonoid treatment significantly increased the expression level of the anti-apoptotic protein, Bcl-2, but decreased that of the proapoptotic protein, Bax. The flavonoids down-regulated the expression levels of endoplasmic reticulum stress proteins, glucose-regulated protein-78, activating transcription factor 6α, X-box binding protein 1, inositol-requiring protein-1, phosphor-eukaryotic initiation factor 2α, and C/EBP-homologous protein. Conclusions This study suggested that the protective mechanisms of flavonoids included regulation of Bcl-2/Bax proteins as well as the endoplasmic reticulum stress proteins.

BACKGROUND/OBJECTIVES This study evaluated the effects and molecular mechanisms of the Schisandra chinensis fruit extract (SC) and its major compound gomisin A (GA), on the contractility of rabbit penile corpus cavernosum smooth muscle (PCCSM). MATERIALS/METHODS PCCSM was exposed to SC or GA after appropriate pretreatment with nitric oxide synthase (NOS) blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker. Subsequently, we evaluated the cyclic nucleotide in the perfusate by radioimmunoassay, protein expression level of neuronal NOS (nNOS) and endothelial NOS (eNOS) by western blot, and the interaction of SC or GA with udenafil and rolipram. RESULTS Both SC and GA induce PCCSM relaxations in a concentration-dependent manner. Pretreatment with NOS blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker result in significantly decreased relaxation. SC and GA also induce the levels of cyclic nucleotide in the perfusate in a concentration-dependent manner. Perfusion with GA also showed significantly higher levels of eNOS protein. Furthermore, the udenafil and rolipram induced relaxations of PCCSM were enhanced after exposure to SC and GA. Our results indicate that SC and GA induce the relaxation of PCCSM via the nitric oxide (NO)-cGMP and cAMP signaling pathways. CONCLUSIONS The SC and GA are potential alternative treatments for men who want to consume natural products to ameliorate erectile function, or who do not respond to the commercially available medicines.

The objective of this study was to evaluate the antiobesity effect of perilla leaf extract (PLE) in animal models of high fat diet-induced obesity. C57BL/6J mice were fed a standard diet (STD) or high fat diet (HFD) for 5 weeks to induce obesity. The experimental groups were four groups with 10 mice per group and fed for 4 weeks: a STD group, a HFD group, a HFD containing 1% PLE (HFD+PLE 1%) group and a HFD containing 3% PLE (HFD+PLE 3%) group. The PLE supplementation significantly decreased body weight gain, food efficiency ratio, and relative liver and epididymal fat mass compared with those of the HFD group. Also, triglyceride, total cholesterol and LDL levels in the plasma were significantly reduced by PLE supplementation compared with the HFD group. Histological changes in the liver of the PLE supplemented group showed an inhibition of steatosis induced by HFD. Furthermore, PLE reversed the HFD induced changes in the expression patterns of epididymal adipose tissue genes: acetyl CoA carboxylase (ACC), glycerol-3-phosphate dehydrogenase (GPDH) and peroxisome proliferator-activated receptor gamma (PPARgamma). These results suggest that the PLE supplement suppressed body weight gain and improved the blood lipid profiling, in part by down-regulating adipogenic transcription factor and other specific target genes.

Amyloid beta peptide (Abeta)-induced oxidative stress may be linked to neurodegenerative disease. Ethanol extracts of Rosa laevigata protected PC12 cells from hydrogen peroxide-induced oxidative stress. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reduction assays revealed a significant increase in cell viability when oxidatively stressed PC12 cells were treated with R. laevigata extract. The effect of R. laevigata on oxidative stress-induced cell death was further investigated by lactate dehydrogenase release assays and trypan blue exclusion assays. Administration of 1,2-benzenedicarboxylic acid dinonyl ester from R. laevigata extract to mice infused with Abeta significantly reversed learning and memory impairment in behavioural tests. After behavioural testing, the mice were sacrificed and brains were collected for the examination of lipid peroxidation, catalase activity and acetylcholinesterase (AchE) activity. These results suggest that 1,2-benzenedicarboxylic acid dinonyl ester from R. laevigata extract may be able to reduce Abeta-induced neurotoxicity, possibly by reducing oxidative stress. Therefore, R. laevigata extract may be useful for the prevention of oxidative stress-induced neurodegenerative disorders.

The improvement of diabetic complications such as lipid lowering and anti-oxidative potential of Hydrangea Dulcis Folium (HDF) was studied in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into 3 groups after induction of streptozotocin (STZ)-diabetes: normal control; diabetic control; diabetic-HDF supplement (hot water extract 40 g/kg diet); and fed experimental diets for 3 weeks. Serum glucose and insulin concentrations, serum lipid profile, intraperitoneal glucose tolerance test, and liver cytosolic antioxidant enzyme levels were measured. The HDF supplement significantly decreased serum glucose concentration, increased insulin level, and improved glucose homeostasis in diabetic control rats. The total cholesterol and triglyceride concentrations in the serum and liver were markedly reduced by HDF treatment in STZ-diabetic rats. Moreover, low density lipoprotein (LDL)-, VLDL-, and high density lipoprotein (HDL)-cholesterol levels were ameliorated in HDF supplemented diabetic rats. Decreased fecal excretions of cholesterol, triglyceride, and bile acid in diabetic rats were significantly increased by HDF consumption. HDF supplement reversed the effects of the oxidative stress system of liver in diabetic rats. Lipid peroxidation of diabetic rats, assessed by thiobarbituric acid reactive substance (TBARS), as well as superoxide dismutase (SOD) activities were significantly increased, and glutathione contents were decreased in diabetic rats. HDF supplement reverted these parameters to near normal value. Our data suggest that HDF supplement could be used to improve the glucose and lipid metabolism as well as to reduce the imbalance between the generation of reactive oxygen species (ROS) and the scavenging enzyme activity in preventing diabetic complications.

A single particle analytical technique, named low-Z particle electron probe X-ray microanalysis, was applied to characterize four samples collected at an underground shopping area connected to Dongdeamun subway station, in January and May 2006. Based on the analysis of their chemical compositions of the samples, many distinctive particle types are identified and the major chemical species are observed to be soil-derived particles, iron-containing particles. sulfates. nitrates, and carbonaceous particles. which are encountered both in coarse and fine fractions. Carbonaceous particles exist in carbon-rich and organic. Soil derived particles such as aluminosilicates, AlSi/C, are more frequently encountered in spring samples than winter samples. Nitrate- and sulfate-con taming particles are more frequently encountered in winter samples, and those nitrate- and sulfate-containing particles mostly exist in the chemical forms of . Fe-containing particles which came from nearby subway platform are in the range of about 10% relative abundances for all the samples. It is observed that nitrate- and sulfate-containing particles and carbonaceous particles are much more frequently encountered in indoor aerosol samples than in outdoor aerosols, implying that , and VOCs at the underground shopping area were more partitioned into aerosol phase.

Immature peels of Citrus reticulata extract (CR) are widely used as traditional herbal medicine in Korea. We studied its effects on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 macrophage cells. NO production was assessed by nitrite assay and iNOS expression was identified by reverse transcription-polymerase chain reaction (RT-PCR), Real-time PCR and Western blot. The promoter activity of iNOS gene was also determined by luciferase reporter gene assay using 5'-flanking region of murine iNOS gene. Activation of nuclear factor kappa B (NF-kappaB) was determined by electrophoretic mobility shift assay (EMSA). CR (20, 50, and 100 microg/ml) significantly inhibited the lipopolysaccharide (LPS)-induced NO production (P