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Hu-Nan Sun, Mei-Hua Jin, Bing Han, Li Feng, Ying-Hao Han, Gui-Nan Shen ...
2014 Volume 37 Issue 7 Pages
1096-1102
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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Supplementary material
The free radical nitric oxide (NO), a main member of neuroinflammatory cytokine and a gaseous molecule produced by activated microglia, has many physiological functions, including neuroinflammation. In the present study, we evaluated the effects of serial 16-dehydropregnenolone-3-acetate derivatives on lipopolysaccharide (LPS)-induced NO production and inducible nitric oxide synthase (iNOS) expression in BV-2 microglial cells. Among the six derivatives tested, the increases in NO production and iNOS expression observed in BV-2 microglial cells after LPS stimulation were significantly inhibited by treatment with 16α, 17α-epoxypregnenolone-20-oxime. Moreover, the inhibitory effect of 16α,17α-epoxypregnenolone-20-oxime on NO production was similar to that of
S-methylisothiourea sulfate (SMT), an iNOS inhibitor. Further studies showed that 16α,17α-epoxypregnenolone-20-oxime inhibited c-Jun N-terminal kinase (JNK) phosphorylation but not inhibitor kappa B (IκB)-α degradation. Our data in LPS-stimulated microglia cells suggest that 16α,17α-epoxypregnenolone-20-oxime might be a candidate therapeutic for treatment of NO induced neuroinflammation and could be a novel iNOS inhibitor.
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Naoki Takahashi, Yukiyasu Asano, Koji Maeda, Nobuhide Watanabe
2014 Volume 37 Issue 7 Pages
1103-1108
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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We recently reported that the novel thyroid hormone receptor β (TRβ) selective agonists SKL-12846 and SKL-13784 reduce blood cholesterol levels without affecting thyroid-stimulating hormone (TSH) in cholesterol-fed rats. Our aim in this study was to elucidate what sets apart these SKL-compounds as TRβ agonists with no effect on TSH. To this end, we determined SKL-compounds pharmacokinetics and tissue distribution in normal rats and compared them to those of GC-1, a liver-selective TRβ agonist with concomitant effect on TSH. The present study explains why SKL-12846 and SKL-13784 have beneficial effects on lowering lipids without affecting heart rate and TSH production at the therapeutic dose in cholesterol-fed rats. In addition, we found that SKL-13784 shows no sign of escape phenomenon in fructose-fed rats. These results demonstrate the advantages of extremely high liver specificity to TRβ agonists. However, SKL-13784 has been found significantly to reduce endogenous T
4 levels at doses lower than its lipid-lowering dose, which may raise concerns over this compound’s ability to alter thyroid hormone metabolism in the liver. While the mechanism by which SKL-13784 reduces endogenous T
4 levels is still unclear, our results would help design better liver-selective TRβ modulators.
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Noriaki Nagai, Yoshimasa Ito
2014 Volume 37 Issue 7 Pages
1109-1118
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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We designed new oral formulations containing indomethacin (IMC) solid nanoparticles, and investigate their usefulness by evaluating bioavailability and gastrointestinal lesions. The IMC solid nanoparticles were prepared using methylcellulose (MC), 2-hydroxypropyl-β-cyclodextrin (HPβCD), and the bead mill method, and high quality dispersions containing 1.0% IMC nanoparticles were prepared (IMC
nano, particle size: 76±58 nm, means±S.D.). The fate of serum IMC and the induction of paw edema in adjuvant-induced arthritis (AA) rats receiving low-doses IMC
nano (0.4 mg/kg) were similar to those following the administration of a therapeutic dose of conventional IMC prepared with MC and HPβCD (conventional IMC, 2 mg/kg), and the bioavailability in 0.4 mg/kg IMC
nano was 5.3-fold higher in comparison with that in 2 mg/kg conventional IMC. IMC-induced gastrointestinal lesions in AA rats administered IMC
nano (8 mg/kg), in consideration of bioavailability, were significantly less than for conventional IMC (40 mg/kg). On the other hand, the toxicity caused by conventional IMC and IMC
nano was similar in Caco-2 cells. It is possible that the oral administration of IMC solid nanoparticles will show increased effectiveness in treating RA without causing IMC-induced gastrointestinal lesions, since the bioavailability is higher than that of conventional IMC. An oral drug delivery system using drug nanoparticles may expand the usage of NSAIDs for therapy in the inflammatory field.
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Hidetoshi Arakawa, Makiko Takasaki, Noriko Tajima, Haruka Fukamachi, T ...
2014 Volume 37 Issue 7 Pages
1119-1123
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
Advance online publication: May 03, 2014
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Persimmon, a deciduous tree of the family Ebenaceae, is found throughout East Asia and contains high levels of tannins. This class of natural compounds exhibit favorable toxicity profiles along with bactericidal activity without the emergence of resistant bacteria, suggesting potential medical applications. Consistent with these observations, persimmon leaves show antibacterial activity. However, the mechanism of persimmon antibacterial activity remains unknown. In the present work, we demonstrate that the antibacterial activity of persimmon reflects the generation of reactive oxygen from tannins. The identification and quantification of reactive oxygen generated from persimmon and the level of antibacterial activity were determined.
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Takuro Kobori, Shinichi Harada, Kazuo Nakamoto, Shogo Tokuyama
2014 Volume 37 Issue 7 Pages
1124-1131
Published: July 01, 2014
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Supplementary material
Previously, we reported that repeated oral administration of etoposide (ETP) increases P-glycoprotein (P-gp) expression in association with activation of ezrin/radixin/moesin (ERM)
via Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase (ROCK) signaling in the small intestine. However, the detailed mechanisms of this pathway have yet to be fully elucidated. Recently, phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], one of the most abundant phosphoinositides in the plasma membrane, has attracted attention regarding its involvement in the plasma membrane localization of various membrane proteins. PtdIns(4,5)P2 is an essential factor in the dissociation and subsequent membrane translocation (activation) of ERM, and its synthetic pathway is known to be highly regulated by RhoA/ROCK signaling. Here, we examined the involvement of PtdIns(4,5)P2 in the mechanism by which ETP treatment increases small intestinal P-gp levels, and we determined which protein within ERM contributes to this phenomenon. Repeated oral treatment with ETP (10 mg/kg/d) over 5 d significantly increased PtdIns(4,5)P2 expression in the ileal membrane as measured by dot blot. Furthermore, this increase was suppressed by co-administration of a RhoA inhibitor, rosuvastatin (5 mg/kg/d,
per os (
p.o.)), or a ROCK inhibitor, fasudil (5 mg/kg/d, p.o.). In immunoprecipitation assays, radixin (but not ezrin or moesin) binding to PtdIns(4,5)P2 was observed to increase in association with the up-regulation of P-gp in the same fraction, and immunofluorescence studies indicated that radixin co-localized with PtdIns(4,5)P2 in the ileal tissue. In conclusion, ETP treatment appears to up-regulate PtdIns(4,5)P2 expression
via RhoA/ROCK signaling, leading to the activation of ERM, presumably through the physical interaction of radixin with PtdIns(4,5)P2. This in turn increases the expression of ileal P-gp.
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Tomoko Hatano, Yuka Sameshima, Mami Kawabata, Shizuo Yamada, Kazumasa ...
2014 Volume 37 Issue 7 Pages
1132-1138
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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Supplementary material
St. John’s wort (SJW), or
Hypericum perforatum, is a perennial herb that has been used in the treatment of depression in several countries. Though its therapeutic effect on depression has been extensively studied, its influence on metabolic syndrome is yet to be fully characterized. Therefore, we investigated the effect of SJW extract on adipocyte differentiation and its anti-inflammatory effects by using 3T3-L1 preadipocytes. Oil Red O staining indicated that SJW promotes adipocyte differentiation, while immunoblots indicated that SJW increases the expression of peroxisome proliferator activated receptor γ (PPARγ), a nuclear receptor regulating adipocyte differentiation, and adiponectin, an anti-inflammatory adipokine. Furthermore, the anti-inflammatory activity of SJW was demonstrated by its inhibition of the activation of nuclear factor-κB (NF-κB), an inflammatory transcription factor. Stimulation of mature 3T3-L1 adipocytes by tumor necrosis factor-α (TNF-α) decreased the expression of the NF-κB inhibitor IκBα, and increased its phosphorylation. Treatment with SJW further decreased the TNF-α-induced perturbation in IκBα expression and phosphorylation, which indicated that SJW mediated the inhibition of NF-κB activation. In addition, SJW decreased the TNF-α-induced increase in the mRNA levels of pro-inflammatory adipokines, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Collectively, our results indicate that SJW treatment could promote adipocyte differentiation probably through its anti-inflammatory activity, which in turn suggests that SJW has the potential to minimize the risk factors of metabolic syndrome.
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Ponwanit Charoenputtakun, Boonnada Pamornpathomkul, Praneet Opanasopit ...
2014 Volume 37 Issue 7 Pages
1139-1148
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
Advance online publication: May 03, 2014
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In the present study, terpene composited lipid nanoparticles and lipid nanoparticles were developed and evaluated for dermal delivery of all-
trans-retinoic acids (ATRA). Terpene composited lipid nanoparticles and lipid nanoparticles were investigated for size, size distribution, zeta potential, entrapment efficiency, photostability, and cytotoxicity.
In vitro skin permeation of ATRA lipid formulations were also evaluated. To explore the ability of lipid nanocarriers to target the skin, the distribution of rhodamine B base in the skin was investigated using confocal laser scanning microscopy (CLSM). The results indicated that the physicochemical characteristics of terpene composited lipid nanoparticles influenced skin permeability. All lipid nanocarriers significantly protected ATRA from photodegradation and were non-toxic to normal human foreskin fibroblast cells
in vitro. Solid lipid nanoparticles containing 10% limonene (10% L-SLN) had the highest ATRA skin permeability. Terpene composited SLN and nanostructured lipid carriers (NLC) showed higher epidermal permeation of rhodamine B across the skin based on CLSM image analysis. Our study suggests that terpene composited SLN and NLC can be potentially used as dermal drug delivery carriers for ATRA.
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Jinmei Xu, Qi Xiang, Junhui Su, Penghui Yang, Qihao Zhang, Zhijian Su, ...
2014 Volume 37 Issue 7 Pages
1149-1157
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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Disabilities triggered by neurodegeneration mainly result in mortality in the elderly, and patients with neurodegenerative disease also display deficits in olfactory function. Therefore drug distribution to the brain through intranasal administration has become one of the most difficult challenges in the treatment of central nervous system (CNS) diseases. TAT-human acidic fibroblast growth factor (HaFGF) is a new fused protein retaining the neuroprotective activities of HaFGF, and is a promising prospect in the treatment of neurodegenerative diseases. TAT (a cell-penetrating peptide) contains a high relative abundance of positively charged amino acids such as lysine and arginine, which have a powerful attraction to the negatively charge on the nasal epithelial membrane. The present study focused on the evaluation of the safety and absorption characteristics of TAT-HaFGF following intranasal administration. After TAT-HaFGF intranasal administration (100, 300, 600 µg/kg) for 5 weeks, hematoxylin–eosin (HE) staining showed no pathology in any of the investigated tissues and organs. The expression of olfactory marker protein (OMP) was observed with immunohistochemical staining, which showed no altered expression in the sensory neurons of the nasal epithelium. Nasal ciliotoxicity studies carried out using an
in situ palate model and optical microscope showed that TAT-HaFGF had no nasal ciliotoxicity. The distribution of the TAT-HaFGF following intranasal administration was assessed using a radioisotopic tracing method. Radioactivity was observed in the brain after 15 min. This became stronger at 30 min and weaker at 1 h. All of the results confirmed the
in vivo safety of TAT-HaFGF
via intranasal administration.
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Yugo Chisaki, Satoshi Noda, Daiki Hira, Shin-ya Morita, Yoshitaka Yano ...
2014 Volume 37 Issue 7 Pages
1158-1161
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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The purpose of this study was to retrospectively examine the effect of concomitant administration of gastric secretion inhibitors or gastrectomy on the frequency of gastrointestinal toxicity caused by 5-fluorouracil (5-FU) in gastric cancer patients receiving chemotherapy with S-1. In 62 gastric cancer patients treated with S-1 alone, data relating to the occurrence of gastrointestinal toxicity (diarrhea, vomiting, and nausea) and possible contributing factors were retrospectively collected, and logistic regression analysis was performed. Time-to-event data relating to the occurrence of gastrointestinal toxicity were also collected, and the effect of gastric secretion inhibitors on the time-to-event profiles was examined using a log-rank test. Logistic regression analysis suggested that the frequency of gastrointestinal toxicity was significantly reduced by the administration of gastric secretion inhibitors (
p=0.01; odds ratio, 0.197; 95% confidence interval (CI), 0.056–0.694) and that gastrointestinal toxicity correlated with the estimated glomerular filtration rate (
p=0.04; odds ratio, 0.956; 95% CI, 0.916–0.997). The median time-to-event of gastrointestinal toxicity was 85 d for patients that received gastric secretion inhibitors, which was significantly different from the 42 d for patients that did not receive the inhibitors (
p=0.02, log-rank test). No clear effect of gastrectomy was found in the present study. The prophylactic use of gastric secretion inhibitors in gastric cancer patients treated with S-1 may decrease and delay the occurrence of gastrointestinal toxicity.
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Ji-young Lee, Jun-Gu Oh, Jin Sook Kim, Kwang-Won Lee
2014 Volume 37 Issue 7 Pages
1162-1167
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
Advance online publication: April 24, 2014
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Advanced glycation end-products (AGEs) have been implicated in the development of diabetic complications. We report the antiglycating activity of chebulic acid (CA), isolated from
Terminalia chebula on breaking the cross-links of proteins induced by AGEs and inhibiting the formation of AGEs. Aminoguanidine (AG) reduced 50% of glycated bovine serum albumin (BSA) with glycolaldehyde (glycol-BSA)-induced cross-links of collagen at a concentration of 67.8±2.5 mM, the level of CA required for exerting a similar antiglycating activity was 38.8±0.5 µM. Also, the breaking activity on collagen cross-links induced by glycol-BSA was potent with CA (IC
50=1.46±0.05 mM), exhibiting 50-fold stronger breaking activity than with ALT-711, a well-known cross-link breaker (IC
50=72.2±2.4 mM). IC
50 values of DPPH· scavenging activity for CA and ascorbic acid (AA) were 39.2±4.9 and 19.0±1.2 µg dry matter (DM) mL
−1, respectively, and ferric reducing and antioxidant power (FRAP) activities for CA and AA were 4.70±0.06 and 11.4±0.1 mmol/FeSO
4·7H
2O/g DM, respectively. The chelating activities of CA, AG and ALT711 on copper-catalyzed oxidation of AA were compared, and in increasing order, ALT-711 (IC
50 of 1.92±0.20 mM)<CA (IC
50 of 0.96±0.07 mM)<AG (0.47±0.05 mM). Thus, CA could be a breaker as well as an inhibitor of AGE cross-linking, the activity of which may be explained in large part by its chelating and antioxidant activities, suggesting that CA may constitute a promising antiglycating candidate in intervening AGE-mediated diabetic complications.
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Masamichi Hirose, Toshihide Shibazaki, Tsutomu Nakada, Toshihide Kashi ...
2014 Volume 37 Issue 7 Pages
1168-1176
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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Phlorizin is a type of flavonoids and has a peroxynitrite scavenging effect. This study aimed to elucidate the effects of phlorizin on ischemia-induced ventricular tachyarrhythmia (VT). Optical signals from the epicardial surface of the ventricle or left ventricular end diastolic pressure (LVEDP) were recorded during acute global ischemia in 42 Langendorff-perfused guinea pig hearts. Experiments were performed in the control condition and in the presence of phlorizin or
N-2-mercaptopropionylglycine (2-MPG), a peroxynitrite scavenger, respectively. Mean action potential duration at 20 min of ischemia did not differ among the three interventions. Impulse conduction time-dependently slowed during 20 min of ischemia in the control. Phlorizin but not 2-MPG improved the ischemic conduction slowing at 15 and 20 min of ischemia. Programmed stimulation induced VT at 20 min of ischemia in the control and in the presence of 2-MPG but not in the presence of phlorizin (
p<0.05). LVEDP was increased during 30 min of ischemia in the control and in the presence of 2-MPG but not in the presence of phlorizin. These results indicate that phlorizin prevents VT through the improvement of impulse conduction slowing during ischemia. Phlorizin may be more useful for ischemia-induced VT than 2-MPG.
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Hyo-Hyun Park, Sun-Gun Kim, Mi Jin Kim, Jiean Lee, Bong-Keun Choi, Mei ...
2014 Volume 37 Issue 7 Pages
1177-1183
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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In this study, tomentosin, a sesquiterpene lactone was isolated from Inulae flos and its biological activities were investigated. The effects of tomentosin on the production of inflammatory mediators as well as on nuclear factor (NF)-κB and mitogen-activated protein (MAP) kinase activation were evaluated in RAW264.7 cells. Tomentosin decreased the production of nitric oxide (NO) and prostaglandin E
2 (PGE
2) by suppressing the protein expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, respectively. Additionally, tomentosin reduced the release of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Tomentosin not only attenuated lipopolysaccharide (LPS)-induced NF-κB activation
via the abrogation of inhibitory (I)κBα degradation and caused a subsequent decrease in nuclear p65 level, but it also suppressed the phosphorylation of MAP kinases (p38 and c-Jun N terminal kinase (JNK)). These results indicate that tomentosin exerts anti-inflammatory activities through the inhibition of inflammatory mediators (NO, iNOS, PGE
2, COX-2, TNF-α, and IL-6) by regulating NF-κB activation and phosphorylation of p38/JNK kinases in macrophages, thus suggesting that tomentosin could be a potential agent for the treatment of inflammatory diseases.
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Pachaiyappan Sampath Venkatesan, Munuswamy Deecaraman, Melanathuru Vij ...
2014 Volume 37 Issue 7 Pages
1184-1190
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
Advance online publication: April 05, 2014
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The aim of the present study was to evaluate the sub-acute oral toxicity of acetaminophen in Sprague Dawley (SD) rats at 250 to 1000 mg/kg body weight (b.wt.). The following observations were noticed during the study. No mortality in male and female rats, at and up to the dose of 1000 mg/kg b.wt. There were abnormal clinical signs observed on female animals at 1000 mg/kg b.wt. dose level. There were no difference in body weight gain and no effect on the daily feed consumption. No toxicologically significant effect on the haematological parameters but liver and kidney related biochemical parameter showed significant difference at 1000 mg/kg b.wt. in females. No toxicologically significant effect on the urinalysis parameters, absolute and relative organ weights and gross pathological alterations; whereas histopathological alterations were observed in female liver at dose level of 1000 mg/kg b.wt. were observed. Based on the findings of this study, the No Observed Adverse Effect Level (NOAEL) of acetaminophen in SD rats, following oral administration at the doses of 250, 500 and 1000 mg/kg on daily basis was found to be 500 mg/kg b.wt.
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Chien-Ming Wu, Kai-Wei Lin, Chi-Hung Teng, A-Mei Huang, Yu-Chian Chen, ...
2014 Volume 37 Issue 7 Pages
1191-1198
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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In an effort to develop potent cyclooxygenase-1 (COX-1) inhibitors used as anticancer agent, a series of 2′,5′-dimethoxychalcones was screened to evaluate their antiplatelet effect on human washed platelets suspension. Compound
2 exhibited potent inhibition of human washed platelet aggregation induced by collagen, significantly inhibited collagen- and arachidonic acid-induced thromboxane B
2 release, and revealed inhibitory effect on COX-1 activity. Molecular docking studies showed that
1,
2, and
4 were bound in the active site of COX-1. These indicated that the antiplatelet effect of these compounds were mainly mediated through the suppression of COX-1 activity and reduced the thromboxane formation. To investigate the mechanistic action of COX-1 inhibitor enhanced the cytotoxic effect against human bladder cancer cells, NTUB1, we assessed the cytotoxic effect of
2 against NTUB1. Treatment of NTUB1 cells with various concentrations of
2 led to a concentration-dependent increase of cell death and decrease of reactive oxygen species levels. The flow-cytometric analysis showed that
2 induced a G1 phase cell cycle arrest but did not accompany an appreciable sub-G1 phase in NTUB1 cells. In addition, compound
2 increased p21 and p27 expressions and did not inhibit the expression of COX-1 in NTUB1 cells. Our results suggested that
2 enhanced cell growth inhibition or antiproliferative activity in NTUB1 cells through G1 arrest by COX-1 independent mechanism.
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Xiaoyong Zhong, Ruhui Lin, Zuanfang Li, Jingjie Mao, Lidian Chen
2014 Volume 37 Issue 7 Pages
1199-1206
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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Salidroside (SA), a phenylpropanoid glycoside isolated from
Rhodiola rosea L., has been documented to exert a broad spectrum of pharmacological properties, including protective effects against neuronal death induced by various stresses. To provide further insights into the neuroprotective functions of SA, this study examined whether SA can attenuate cobalt chloride (CoCl
2)-induced hypoxia damage and mammalian target of rapamycin (mTOR) signaling repression in PC12 differentiated cells. Differentiated PC12 cells were exposed to CoCl
2 for 12 h to mimic hypoxic/ischemic conditions and treated with SA at the same time, followed by electron microscopy and analysis of cell viability, intracellular reactive oxygen species (ROS) level, hypoxia-inducible factor-1α (HIF-1α) level, and the regulated in development and DNA damage responses (REDD1)/mTOR/ p70 ribosomal S6 kinase (p70S6K) signaling pathway. Our data indicated that SA can dramatically attenuate the ultrastructural damage of mitochondria induced by CoCl
2 and significantly decrease CoCl
2-induced ROS production. Moreover, phosphorylated mammalian target of rapamycin (p-mTOR) was significantly reduced by CoCl
2, and this inhibition was relieved by the treatment of SA in PC12 cells, as evidenced by immunoblot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The SA effects were blocked by pretreatment of RAD001. The results indicate that SA can rescue CoCl
2-induced repression of REDD1/mTOR/ p70S6K signal transduction in PC12 cells. Our data demonstrate that SA is able to attenuate CoCl
2-induced hypoxia damage and mTOR signaling repression, suggesting that SA may protect brain neurons from ischemic injury through mTOR signaling, and provide new insights into the prevention and treatment of cerebral ischemic.
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Se Jin Park, Young Je Ahn, Sa Rang Oh, Younghwan Lee, Guyoung Kwon, Hy ...
2014 Volume 37 Issue 7 Pages
1207-1213
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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Supplementary material
Alzheimer’s disease, a neurodegenerative disorder, is characterized by progressive cognitive impairment associated with the disruption of cholinergic neurotransmission. The aim of the present study was to evaluate the effect of α- or β-amyrin, a type of pentacyclic triterpene, on the cognitive impairment induced by scopolamine, a muscarinic acetylcholine receptor antagonist. To measure the abilities of various types of learning and memory, we conducted step-through passive avoidance task. Scopolamine induced deficits in learning and memory processes in mice, which were antagonized by a single administration of α-amyrin (2 or 4 mg/kg) or β-amyrin (4 mg/kg), respectively. Additionally,
in vitro analysis revealed that acetylcholinesterase activity was inhibited by β-amyrin, but not by α-amyrin. Furthermore, Western blot analysis revealed that the expression levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK) and phosphorylated glycogen synthase kinase-3β (pGSK-3β) were significantly enhanced by a single administration of α- and β-amyrin in the hippocampus. Finally, the memory ameliorating effects of α- or β-amyrin on the scopolamine-induced cognitive impairments were significantly blocked by ERK inhibitor U0126. The present study suggests that α- and β-amyrin may ameliorate the cognitive impairment induced by hypocholinergic neurotransmission
via the activation of ERK as well as GSK-3β signaling.
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Hong-Li Zhang, Ling-Hao Dai, Yi-Hang Wu, Xiao-Ping Yu, Yong-Yong Zhang ...
2014 Volume 37 Issue 7 Pages
1214-1220
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
Advance online publication: April 24, 2014
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Supplementary material
Hepatitis B is the most common serious liver infection in the world. To date, there is still no complete cure for chronic hepatitis B. Natural caffeic acid analogues possess prominent antiviral activity, especially anti-hepatitis B virus (HBV) and anti-human immunodeficiency virus effects. Cichoric acid is a caffeic acid derivative from
Cichorium intybus. In the study, the anti-hepatitis B property of cichoric acid was evaluated by the D-galactosamine (D-GalN)-induced normal human HL-7702 hepatocyte injury model, the duck hepatitis B virus (DHBV)-infected duck fetal hepatocytes and the HBV-transfected cell line HepG2.2.15 cells, respectively. The results showed that cichoric acid attenuated significantly D-GalN-induced HL-7702 hepatocyte injury at 10–100 µg/mL and produced a maximum protection rate of 56.26%. Moreover, cichoric acid at 1–100 µg/mL inhibited markedly DHBV DNA replication in infected duck fetal hepatocytes. Also, cichoric acid at 10–100 µg/mL reduced significantly the hepatitis B surface and envelope antigen levels in HepG2.2.15 cells and produced the maximum inhibition rates of 79.94% and 76.41%, respectively. Meanwhile, test compound at 50–100 µg/mL inhibited markedly HBV DNA replication. In conclusion, this study verifies the anti-hepatitis B effect of cichoric acid from
Cichorium intybus leaves. In addition, cichoric acid could be used to design the antiviral agents.
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Yeon Bok Kim, YouJin Shin, Pham Anh Tuan, Xiaohua Li, Yunji Park, Nam- ...
2014 Volume 37 Issue 7 Pages
1221-1227
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
Advance online publication: April 15, 2014
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Supplementary material
Prunella vulgaris L., commonly known as “self-heal” or “heal-all,” is a perennial herb with a long history of medicinal use. Phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumarate:coenzyme-A (CoA) ligase (4CL) are important enzymes in the phenylpropanoid pathway and in the accumulation of rosmarinic acid (RA), which is a major secondary metabolite in
P. vulgaris. In this study, we isolated cDNAs encoding PvPAL, PvC4H, and Pv4CL from
P. vulgaris using rapid amplification of cDNA ends polymerase chain reaction (PCR). The amino acid sequence alignments of PvPAL, PvC4H, and Pv4CL showed high sequence identity to those of other plants. Quantitative real-time PCR analysis was used to determine the transcript levels of genes involved in RA biosynthesis in the flowers, leaves, stems, and roots of
P. vulgaris. The transcript levels of
PvPAL,
PvC4H, and
Pv4CL1 were the highest in flowers, whereas
Pv4CL2 was the highest in roots. High-performance liquid chromatography analysis also showed the highest RA content in the flowers (3.71 mg/g dry weight). We suggest that the expression of the
PvPAL,
PvC4H, and
Pv4CL1 genes is correlated with the accumulation of RA. Our results revealed that
P. vulgaris flowers are appropriate for medicinal usage, and our findings provide support for increasing RA production in this plant.
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Masako Hashimoto, Yu Matsuzaki, Kumiko Kawahara, Hiroshi Matsuda, Geni ...
2014 Volume 37 Issue 7 Pages
1228-1233
Published: July 01, 2014
Released on J-STAGE: July 01, 2014
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To assess the reasons for barriers to home discharge by determining whether they were predicted by medication, clinical variables, and patient characteristics, the retrospective cohort study of 282 patients discharged from Kanazawa Red Cross Hospital in Kanazawa, Japan from January 2011 to December 2012 was performed. The percentage of patients discharged was 67.4%. By multivariate logistic analysis, significant differences in home discharge destination were determined by six factors: the duration of hospitalization before discharge (odds ratio (OR) 0.993; 95% 95% confidence interval (CI) 0.988–0.999), the presence of excretion assistance (OR 0.115; 95% CI 0.043–0.308), individual payment of medical expense (OR 0.344; 95% CI 0.146–0.811), the degree of independent living for the demented elderly (OR4.570; 95% CI 1.969–10.604), presence of the primary caregiver (OR 8.638; 95% CI 3.121–23.906), and admission to a hospital from home (OR 5.483; 95% CI 2.589–11.613). This study suggests that necessity of excretion assistance, long duration of hospitalization, and high individual payment of medical expense were barriers to home discharge. In contrast, three factors
i.e., admission to a hospital form home, low degree of independent living for the demented elderly, and presence of the primary caregiver, favored home discharge. The relation between a patient’s status (cognitive status and incontinence) and a caregiver has an important effect on the home discharge. However, medication characteristics appeared to have little effect on recuperation destination.
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