Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
29 巻 , 6 号
選択された号の論文の46件中1~46を表示しています
Analytical Biochemistry
Notes
Biochemistry
Notes
  • Hyeon Gyeong Yoo, Jin Sook Kim, Se Rah Lee, Hyun Keol Pyo, Hyung In Mo ...
    2006 年 29 巻 6 号 p. 1246-1250
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Androgenetic alopecia (AGA) is a dihydrotestosterone (DHT)-mediated process, characterized by continuous miniaturization of androgen reactive hair follicles and accompanied by perifollicular fibrosis of follicular units in histological examination. Testosterone (T: 10−9—10−7 M) treatment increased the expression of type I procollagen at mRNA and protein level. Pretreatment of finasteride (10−8 M) inhibited the T-induced type I procollagen expression at mRNA (40.2%) and protein levels (24.9%). T treatment increased the expression of transforming growth factor-beta 1 (TGF-β1) at protein levels by 81.9% in the human scalp dermal fibroblasts (DFs). Pretreatment of finasteride decreased the expression of TGF-β1 protein induced by an average of T (30.4%). The type I procollagen expression after pretreatment of neutralizing TGF-β1 antibody (10 μg/ml) was inhibited by an average of 54.3%. Our findings suggest that T-induced TGF-β1 and type I procollagen expression may contribute to the development of perifollicular fibrosis in the AGA, and the inhibitory effects on T-induced procollagen and TGF-β1 expression may explain another possible mechanism how finasteride works in AGA.
  • Miki Hiasa, Yoshinori Moriyama
    2006 年 29 巻 6 号 p. 1251-1253
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    D-Aspartate is a putative modulator of neuroendocrine functions, and is present in various neuroendocrine cells as well as the central nervous system. Here we show that the islet of Langerhans is a D-aspartate-containing endocrine organ. Immunohistochemical analysis with specific antibodies against D-aspartate indicated that D-aspartate is present in all islet cells, and predominantly present in α cells and a subpopulation of F-cells. Since these cells are glutamatergic in nature, it is possible that D-aspartate is involved in the glutamate signaling pathways in the islets.
Molecular and Cell Biology
Regular Articles
  • Tsutomu Fujimura, Shigeru Moriwaki, Mitsuyuki Hotta, Takashi Kitahara, ...
    2006 年 29 巻 6 号 p. 1075-1081
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Contraction forces generated by non-muscle cells such as fibroblasts play important roles in determining cell morphology, vasoconstriction, and/or wound healing. However, few factors that induce cell contraction forces are known, such as lysophosphatidic acid and thrombin. Our study analyzed various plant extracts for ingredients that induce generation of cell contraction forces in fibroblasts populating collagen gels. We found that an extract of Horse chestnut (Aesculus hippocastanum) is able to induce such contraction forces in fibroblasts. The involvement of actin polymerization and stress fiber formation in the force generation was suggested by inhibition of this effect by cytochalasin D and by Rhodamine phalloidin. Rho kinase inhibitors (Y27632 and HA1077) and a Rho inhibitor (exoenzyme C3) significantly inhibited the force generation induced by the Horse chestnut extract. H7, which inhibits Rho kinase as well as other protein kinases, also significantly inhibited induction of force generation. However, inhibitors of other protein kinases such as myosin light chain kinase (ML-9), protein kinase C (Calphostin), protein kinase A (KT5720), and tyrosine kinase (Genistein, Herbimycin A) had no effect on force generation induced by Horse chestnut extract. These results suggest that the Horse chestnut extract induces generation of contraction forces in fibroblasts through stress fiber formation followed by activation of Rho protein and Rho kinase but not myosin light chain kinase or other protein kinases.
  • Kang Beom Kwon, Eun Kyung Kim, Mi Jeong Han, Byung Cheul Shin, Yong Kw ...
    2006 年 29 巻 6 号 p. 1082-1086
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Radix Paeoniae Alba has been used as a constituent of herbal medicine prescriptions for the treatment of inflammation, cancer, and other diseases. The aim of this study was to investigate the mechanism of Radix Paeoniae Alba extract (RPAE)-induced apoptosis in HL-60 leukemic cells. We observed that RPAE induced apoptotic changes in a dose-dependent manner, which was confirmed by DNA fragmentation and poly-(ADP-ribose) polymerase (PARP) cleavage. We also found release of cytochrome c from mitochondria to the cytosol in RPAE-treated HL-60 cells. The caspases, caspase-9 and -3, but not caspase-8, were found to be activated in response to RPAE treatment, and the caspase-3 inhibitor, Ac-DEVD-CHO, and the caspase-9 inhibitor, z-LEHD-FMK, but not the caspase-8 inhibitor, z-IETD-FMK, attenuated RPAE-induced DNA fragmentation and PARP cleavage. These results suggest that RPAE-induced apoptosis is stimulated by the release of cytochrome c to the cytosol, by procaspase-9 processing, and via a caspase-3 dependent mechanism.
  • Mika Hori, Taketoshi Asanuma, Osamu Inanami, Mikinori Kuwabara, Hideyo ...
    2006 年 29 巻 6 号 p. 1087-1091
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The Escherichia coli Orf17 (NtpA, NudB) protein, a MutT-type enzyme, hydrolyzes oxidized deoxyribonucleotides, including 8-hydroxy-2′-deoxyadenosine 5′-triphosphate and 8-hydroxy-2′-deoxyguanosine 5′-triphosphate, in vitro. To examine its in vivo role(s) in bacteria, plasmid DNAs containing the orf17 gene in the sense and antisense orientations were introduced. When the Orf17 protein was overexpressed in mutT cells, the rpoB mutant frequency was decreased. On the other hand, similar effects were not observed when Orf17 was overexpressed in wild type and orf135 cells. Expression of the antisense RNA of the orf17 gene did not produce an obvious phenotype, such as increased mutant frequency and resistance to ionizing radiation. These results suggest that the role of the Orf17 protein is to back up the MutT function, and to assist in the elimination of 8-hydroxy-2′-deoxyguanosine nucleotides.
Notes
  • Yuichiro Kanno, Yusuke Takane, Tomomi Izawa, Takayuki Nakahama, Yoshio ...
    2006 年 29 巻 6 号 p. 1254-1257
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The variant cell lines stably expressing aryl hydrocarbon receptor repressor (AhRR), MCFRR1 and MCFRR4, were established from human breast cancer MCF-7 cells by transfecting with AhRR-expression construct followed by selection, in order to analyze the effect of AhRR on the cell growth and expression of cell cycle-related genes. The variant cells showed higher levels of AhRR mRNA compared with the parental cells. MCFRR4 cells grew slowly compared with MCF-7 in both cell number and proliferation rate measured by the MTS method. Among cell cycle-related genes such as E2F, cyclin E1, cyclin D1, PCNA, p53, Rb, c-myc and p27Kip1, and estrogen responsive genes such as cathepsin D and hsp27, the expression levels of E2F, cyclin E1, PCNA and cathepsin D mRNA in MCFRR4 cells were lower than those in MCF-7 cells, while those of Rb, p27Kip1, c-myc and hsp27 mRNA were not significantly affected and that of cyclin D1 mRNA was enhanced in variant cells. Based on these results, AhRR might be suppressive on cell growth of MCF-7 by disturbing the transcriptional and/or posttranscriptional regulations of estrogen-responsive and cell cycle-related genes.
Microbiology
Regular Articles
  • Adriana Meri Mestrimer Felipe, Vinicius Pires Rincão, Fabr&iacu ...
    2006 年 29 巻 6 号 p. 1092-1095
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Crude extract (CE) and aqueous (AqF) and ethyl acetate (EtOAcF) fractions of Guazuma ulmifolia LAM., Sterculiaceae and the corresponding AqF, EtOAcF of Stryphnodendron adstringens (MART.) COVILLE, Leguminosae were tested for their antiviral activity against poliovirus 1 (P-1) and bovine herpesvirus 1 (BHV-1) in HEp-2 cultured cells. The antiviral activity was monitored by plaque assay and immunofluorescence assay (IFA) under virucidal and therapeutic protocols. The therapeutic protocol demonstrated statistically significant positive results with both plants and for both virus strains. The highest percentages of viral inhibition were found for G. ulmifolia EtOAcF which inhibited BHV-1 and P-1 replication by 100% and 99%, respectively (p<0.05, Student's t-test). For S. adstringens, AqF was the most efficient, inhibiting BHV-1 and P-1 by 97% and 93%, respectively (p<0.05). In the virucidal protocol, G. ulmifolia CE inhibited the replication of BHV-1 and P-1 by 60% and 26%, respectively (p<0.05), while, for S. adstringens, inhibition of 62% (p<0.05) was demonstrated only with EtOAcF for P-1. IFA demonstrated that the greatest reduction in fluorescent cell number occurred with G. ulmifolia, under the therapeutic protocol for both virus strains. However, AqF and EtOAcF of S. adstringens were most efficient with the virucidal protocol for P-1. In conclusion, we demonstrated that G. ulmifolia and S. adstringens inhibited BHV-1 and P-1 replication, as well as, blocked the synthesis of viral antigens in infected cell cultures.
Pharmacology
Regular Articles
  • Lin-Hao Li, Li-Jun Wu, Shin-ichi Tashiro, Satoshi Onodera, Fumiaki Uch ...
    2006 年 29 巻 6 号 p. 1096-1101
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Silymarin is a polyphenolic flavonoid from milk thistle (Silybum marianum), which has anti-inflammatory, cytoprotective, and anticarcinogenic effects.1) In this study, we assessed the effect of silibinin (Fig. 1), the major active compound in silymarin, on ultraviolet light (UV)-induced cell apoptosis in HaCaT cells, a human keratinocyte cell line. Pretreatment with silibinin 500 μM significantly inhibited UV-induced apoptosis in HaCaT cells after 9 h incubation. The expression of Fas-associating protein with death domain (FADD), a downstream molecule of the death receptor pathway, was completely eliminated by silibinin treatment in UV-irradiated HaCaT cells, followed by inhibition of cleavage of procaspase-8, whose activation induced cell apoptosis2) and decreased the release of cytochrome c from mitochondria. The caspase-8 inhibitor z-IETD-fmk at 10 μM increased the ratio of UV-irradiated HaCaT cell viability, suggesting that UV-induced HaCaT cell apoptosis was partially due to activation of the caspase-8 pathway. Moreover, UV-induced cleavage of procaspase-3 and digestion of its substrates, the inhibitor of caspase-activated DNase (ICAD) and poly-(ADP-ribose) polymerase (PARP), were also reduced by silibinin pretreatment. While unexpectedly, it was found in our study that pretreatment with silibinin increased HaCaT cell death by CD95 agonistic antibody CH11. Consequently, the protective effect of silibinin against UV irradiation in HaCaT cells is exerted by inactivation of caspase-8 after direct down-regulation of FADD expression, resulting in blockage of UV-induced apoptosis.
  • Akiko Rokudai, Yasuhito Terui, Ryoko Kuniyoshi, Yuji Mishima, Yuko Mis ...
    2006 年 29 巻 6 号 p. 1102-1109
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Allergic asthma and allergic dermatitis are chronic inflammatory diseases and are characterized by an accumulation of eosinophils at sites of inflammation. Eotaxin-1/CCL11 and eotaxin-3/CCL26 are members of the CC chemokine family, which are known to be potent chemoattractants for eosinophils. We observed that a human lung fibroblast, HFL-1 produces eotaxin-1 and -3 in response to TNF-α plus IL-4 stimulation, accompanied with NF-κB and STAT6 activation. We explored which signaling pathways are operative in the production of eotaxin-1 and -3 using several inhibitors. Eotaxin-1/CCL11 production was inhibited by a p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, but not by the MEK (MAPK/ERK kinase) inhibitors, PD98059 and U0126. In contrast, eotaxin-3/CCL26 production was inhibited similarly by PD98059 as well as U0126 and SB203580. In addition, two proteasome inhibitors, N-acetyl-leucyl-leucyl-norleucinal (ALLN) and bortezomib with significant inhibitory activity on NF-κB activation, inhibited eotaxin-1/CCL11 production with IC50 8 μM for ALLN and IC50 16 nM for bortezomib. In contrast, eotaxin-3/CCL26 production was not inhibited significantly up to 10 μM of ALLN (IC50 16 μM) and up to 10 nM of bortezomib (IC50 11 nM), giving inhibition of eotaxin-3/CCL26 less sensitive than eotaxin-1/CCL11 production by the proteasome inhibitors. Synergistic inhibition was observed among lower doses of SB203580 and proteasome inhibitors, particularly in the eotaxin-1/CCL11 production. No such prominent synergism was found on the eotaxin-3/CCL26 production. The suppression of eotaxin family production by these inhibitors may be efficacious against allergic diseases.
  • Koji Hayashi, Rhyoji Kojima, Mikio Ito
    2006 年 29 巻 6 号 p. 1110-1119
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    We have already reported that slowly progressive non-insulin-dependent diabetes mellitus (NIDDM) is produced by a single i.p. injection of a subdiabetogenic dose (100 mg/kg) of streptozotocin (STZ) to 8-week-old male ICR mice. The aim of the present study was to clarify whether or not the progressive NIDDM is induced in ddY, BALB/c, C57BL/6 and ICR mice by the administration of STZ. Eight-week-old male mice of the 4 different strains were administered a single i.p. injection of STZ at various doses (ICR, ddY and BALB/c: 100—200 mg/kg; C57BL/6: 75—150 mg/kg). Among the ddY, BALB/c and C57BL/6 mice, a time course-related rise in non-fasting serum glucose levels throughout the observation period of 1—12 weeks after STZ administration was only induced in the 125 mg/kg STZ ddY and 100 mg/kg STZ ICR mice. In contrast with serum glucose levels, the area of islets and the percentage of the relative number of insulin-immunoreactive cells (β-cells) to glucagon-immunoreactive cells (α-cells) in the 100 mg/kg STZ ICR and 125 mg/kg STZ ddY mice continued to decrease gradually over time. In addition, in low dose STZ mice of both strains, the insulin response to glucose stimulation was extremely impaired over time, although non-fasting serum insulin levels were maintained near normal levels. The rate of the progression of diabetes was faster in the 125 mg STZ ddY mice than in the 100 mg/kg STZ ICR mice.
  • In-Bae Kim, Dong-Young Kim, Su-Jin Lee, Min-Jung Sun, Myung-Sook Lee, ...
    2006 年 29 巻 6 号 p. 1120-1125
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The attraction of leukocytes to tissues is essential in order for inflammation and the host response to infection to occur. Airway inflammation is a very common cause illness with a substantial impact on health care. Neutrophils play an essential role in the host defense and in inflammation, but the latter may trigger and sustain the pathogenesis of a range of acute and chronic diseases. Infiltration of neutrophils occurs as a response to chemoattractant molecules by resident tissue cells. The recruitment of neutrophils in airway inflammation may account for the generation of IL-8. To evaluate the effectiveness of green tea polyphenols in the modulation of airway inflammation through the blocking of neutrophil chemokine production, nasal mucosal fibroblasts and A549 bronchial epithelial cells were analyzed for the production of IL-8. Both nasal mucosal fibroblasts and bronchial epithelial cells produced significant amounts of IL-8 through stimulation of IL-1β. Tea polyphenols were very effective in the inhibition of IL-8 production. Among the polyphenols tested, EGCG and ECG showed strong inhibitory activity in dose-dependent manners. EGC and EC showed moderate inhibition at 48 h culture, whereas (−)catechin was not effective. Production of IL-8 after stimulation by proinflammatory cytokines in both nasal fibroblasts and bronchial epithelial cells was significantly blocked by pretreatment with green tea polyphenols.
  • Sirintorn Yibchok-anun, Sirichai Adisakwattana, Cheng Yu Yao, Polkit S ...
    2006 年 29 巻 6 号 p. 1126-1131
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The protein from Thai bitter gourd (Momordica charantia) fruit pulp was extracted and studied for its hypoglycemic effect. Subcutaneous administration of the protein extract (5, 10 mg/kg) significantly and markedly decreased plasma glucose concentrations in both normal and streptozotocin-induced diabetic rats in a dose-dependent manner. The onset of the protein extract-induced antihyperglycemia/hypoglycemia was observed at 4 and 6 h in diabetic and normal rats, respectively. This protein extract also raised plasma insulin concentrations by 2 fold 4 h following subcutaneous administration. In perfused rat pancreas, the protein extract (10 μg/ml) increased insulin secretion, but not glucagon secretion. The increase in insulin secretion was apparent within 5 min of administration and was persistent during 30 min of administration. Furthermore, the protein extract enhanced glucose uptake into C2C12 myocytes and 3T3-L1 adipocytes. Time course experiments performed in rat adipocytes revealed that M. charantia protein extract significantly increased glucose uptake after 4 and 6 h of incubation. Thus, the M. charantia protein extract, a slow acting chemical, exerted both insulin secretagogue and insulinomimetic activities to lower blood glucose concentrations in vivo.
  • Wei Wang, Qing-Long Guo, Qi-Dong You, Kun Zhang, Yong Yang, Jun Yu, We ...
    2006 年 29 巻 6 号 p. 1132-1137
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The anticancer effects of wogonin on murine sarcoma S180 both in vitro and in vivo were investigated, and its pro-apoptotic molecular mechanism was further studied. Wogonin treatment resulted in significant inhibition of S180 cells in a concentration-dependent manner detected by MTT assay. The IC50 value for 48 h was (7.37±1.53)×10−5 M. Typical morphological changes and apoptosis bleb phenomenon in S180 cells exposed to wogonin were distinctly observed by the inverted light microscope and the fluorescence microscope, respectively. According to protocols of transplanted tumor research,1) mice were transplanted with tumor cells S180. The weight of tumor and the peripheral leucocyte count were observed after the treatment of wogonin. The significant suppression of tumor growth was observed, and the peripheral leucocyte count of S180-bearing mice remained no significant changes compared with control group. After the treatment of 40 mg/kg wogonin, the inhibitory rate of tumor weight was 53.01%. Additional DNA fragmentation assay showed that wogonin induced apoptosis on murine sarcoma S180 tissue. RT-PCR results indicated that the increasing mRNA levels of bax and p53 and the decreasing mRNA level of bcl-2 were induced by wogonin. Western-blot assay showed that the increasing protein level of bax and the decreasing protein level of bcl-2 were induced by wogonin. Collectively, wogonin could induce apoptosis in murine sarcoma S180 thereby inhibiting the tumor growth both in vitro and in vivo. The pro-apoptotic effects might be related to the improvement of mRNA level of p53, the improvement of mRNA and protein levels of bax, and the reduction of mRNA and protein levels of bcl-2.
  • WeiGang Duan, LiXin Sun, Jun Liu, XuDong Wu, LuYong Zhang, Ming Yan
    2006 年 29 巻 6 号 p. 1138-1142
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Rho kinase (ROCK) inhibitors are effective candidates for neural or cardiovascular disorders. High throughput model for screening ROCK inhibitors is a basic foundation to pick up ROCK inhibitors from thousands of compounds for drug developing. The high throughput model was established based on purified recombinant rat ROCK catalytic domain (rROCK-CD) from Escherichia coli (E. coli). There are two steps of reaction in the model: incubation of 5.0 μl recombinant rROCK-CD (2.0 μg/ml), 5.0 μl different compounds, 5.0 μl fluorescent S6-peptide (200 nM), and 5.0 μl ATP (10 μM) at 37 °C for 60 min was made the first reaction, and the second reaction was made by incubating them with additional 60 μl binding reagent at ambient temperature for 30 min. The phosphorylated S6 peptide can bind to a binding reagent, and the fluorescence varies from low polarization to high according to the amount of the phosphorylated peptide. IC50 was calculated based on polarization variation. Compound, which IC50 was less than 10 μM, was recognized as a lead compound which taken bioactivity evaluation in PC12 by observing neurite outgrowth. The Z′-factor of the model is 0.81 (above 0.5). The model screened five lead compounds from 3294, which promoted neurite outgrowth to different extent. The results suggested that the model is suitable for high throughput screening (HTS), and the five lead compounds are worth of further investigation.
  • Katsutoshi Yayama, Hiromi Hiyoshi, Kaori Sugiyama, Hiroshi Okamoto
    2006 年 29 巻 6 号 p. 1143-1147
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Our present study aimed to characterize the effects of lipopolysaccharide (LPS) on the expression of the bradykinin B2-receptor in the mouse heart, which may have a role in cardiac depression during sepsis. We found that LPS induced the up-regulation of B2-receptor mRNA in the heart in vivo and in cultured cardiac myocytes in vitro. Like LPS, tumor necrosis factor-α (TNF-α) but not interleukin (IL)-1-β, IL-6 or endothelin-1 stimulated B2-receptor expression in cultured myocytes. The effect of LPS on the expression of B2-receptor mRNA was also mimicked in cardiac myocytes by Ang II via Ang II type 1 (AT1-) receptor. Losartan, an AT1-receptor antagonist, inhibited about 50% of the LPS-induced up-regulation of B2-receptor mRNA in the heart in vivo and in cultured cardiac myocytes in vitro. Furthermore, the up-regulation of B2-receptor mRNA by either LPS or Ang II in cultured myocytes was abolished by anti-TNF-α antibody. These results suggest that the up-regulation of cardiac B2-receptor expression by LPS is mediated through TNF-α, which is produced in the myocardium by two different mechanisms in an AT1-receptor-dependent and independent manners, implying the role of the cardiac kallikrein-kinin system in the development of cardiac dysfunction during sepsis.
  • Seung-Ho Lee, Yong Sung Sohn, Kyung Koo Kang, Jong Won Kwon, Moohi Yoo
    2006 年 29 巻 6 号 p. 1148-1153
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Asthma is one of the major public health problems worldwide and the morbidity and mortality of asthma has increased in the past two decades. Accumulating data suggest that unnecessary immune responses and inflammation should be suppressed to treat asthma. The purpose of this study is to investigate the anti-asthmatic effects of DA-9201, an ethanolic extract of black rice (Oryza sativa L. var japonica), on an ovalbumin (OVA)-induced mouse model of asthma. Balb/c mice immunized with OVA were administered with DA-9201 (30, 100 or 300 mg/kg, p.o.) or dexamethasone (3 mg/kg, p.o.) and challenged with 1% aerosolized OVA for 30 min. The effects on airway inflammation, airway hyperresponsiveness (AHR), antibody profiles and cytokines were evaluated. DA-9201 treatment significantly reduced the number of eosinophils in bronchoalveolar lavage fluid (BALF) and ameliorated the AHR. Lung histological features also showed that DA-9201 reduced airway inflammation. Furthermore, DA-9201 treatment decreased IFN-γ as well as IL-4, IL-5 and IL-13 levels in the supernatant of cultured splenocytes, and suppressed the level of OVA-specific IgG, IgG2a, IgG1 and total IgE in plasma. DA-9201 showed anti-asthmatic effects by suppressing unnecessary immune responses, airway inflammation, eosinophilia, AHR and IgE level. These results suggest DA-9201 might be beneficial for the treatment of asthma.
  • Mani Vasudevan, Milind Parle
    2006 年 29 巻 6 号 p. 1154-1161
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.
  • Daichi Matsumura, Takeshi Nabe, Nobuaki Mizutani, Masanori Fujii, Shig ...
    2006 年 29 巻 6 号 p. 1162-1166
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    In Japan, an increasing number of people suffer from pollenosis, a typical atopic disease. Japanese cedar (Cryptomeria japonica) pollen is the most common allergen that causes pollenosis. Although Cry j 1 and Cry j 2 are the common allergenic proteins contained in the pollen, there is a small population of patients who exhibit positive skin reactions to the pollen extract but are negative for both Cry j 1 and Cry j 2. This suggests that the pollen may contain other antigenic proteins besides these two molecules. In this study, we used sodium dodecyl sulfate-polyacrylamide gel electrophoresis to examine partially purified pollen extract (PPPE) and determine if there were other proteins that reacted to anti-PPPE sera collected from sensitized guinea pigs, mice and rabbits. Subsequently, we detected four bands of proteins with molecular weights around 7, 15, 20 and 31 kDa, which were different from those normally seen for Cry j 1 and Cry j 2. Among these, the 7, 15 and 20 kDa proteins could not be detected when anti-Cry j 1 monoclonal anti-body (mAb) and anti-Cry j 2 mAb were used as antibodies for Western blotting. Therefore, these three proteins may differ from Cry j 1 and Cry j 2 not only in molecular weight but also in antigenicity. In conclusion, three new antigenic proteins that are not identical to Cry j 1 and Cry j 2 have been shown to exist in Japanese cedar pollen. Structural analyses of these proteins may be useful in the development of new therapeutic methods, including specific immunotherapy for pollenosis.
  • Tomonori Nakamura, Tomoko Terajima, Taeko Ogata, Koichi Ueno, Naotake ...
    2006 年 29 巻 6 号 p. 1167-1174
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    This study was performed in order to establish a mouse model that represents the non-obese type 2 diabetes reflecting a majority of diabetic patients among Asian races and to show its pathophysiological profiles. Streptozotocin (STZ) was administered to C57BL/6J mice with or without nicotinamide (120 or 240 mg/kg, STZ/NA120 or STZ/NA240), twice with an interval of 2 d, and plasma glucose concentration, body weight, water intake, insulin contents and insulin signal-related proteins were monitored. STZ-induced hyperglycemia (fasting and non-fasting), body weight loss and polyposia were significantly depressed by NA dose-dependently. In STZ/NA120 and STZ/NA240 mice, pancreatic insulin content was retained by 28 and 43% of normal control (10.5±0.93 μU/ml), respectively, and histological damage of pancreatic beta cells was also less severe than that observed in STZ mice. When given the calorie-controlled high fat diet, the STZ/NA mice caused hyperlipidemia, and significantly increased insulin resistance. These observations suggest that the combined administration of STZ and NA causes partial depletion of pancreatic insulin and that the high fat constituents lead to insulin resistance in this model. The present mouse model, therefore, well exhibits the recent diabetic pathophysiological characteristics of a majority of Asian patients.
  • Yuka Kuwabara, Tatsuya Watanabe, Shingo Yasuoka, Kohsuke Fukui, Jiro T ...
    2006 年 29 巻 6 号 p. 1175-1179
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    We previously reported that a novel hydrophilic γ-tocopherol (γ-Toc) derivative, γ-tocopheryl-N,N-dimethylglycinate hydrochloride (γ-TDMG) gets converted to the antioxidant γ-Toc in skin. We also found that this derivative displayed greater bioavailability than γ-Toc itself. In the present study, we determined whether γ-TDMG could reduce UV-induced skin pigmentation in brownish guinea pigs. γ-TDMG (0.1 or 0.5%) was topically applied to the skin before and after it was exposed to UVB plus UVA (3 times/week for 1 week), and then 10 times/week for 4 weeks thereafter. Treatment with 0.5% γ-TDMG resulted in significant skin lightening (70% of the pigmentation of irradiated controls). We also found that melanin synthesis was dose-dependently inhibited by γ-TDMG in murine B16 melanoma cells. When γ-TDMG or kojic acid (250 μM) were added to homogenates of B16 melanoma cells, their tyrosinase activity was significantly inhibited by approximately 40% and 75%, respectively. Mushroom tyrosinase activity was significantly inhibited by 200 μM γ-Toc and kojic acid, but not γ-TDMG. When B16 cells were incubated with 250 μM γ-TDMG for 24 or 48 h, their intracellular γ-Toc concentrations rose over 100 fold to 10.5 and 11.2 nmol/106 cells, respectively, suggesting that γ-TDMG was rapidly converted to γ-Toc in these cells and that their reduced melanin synthesis may have been due to the activity of γ-Toc. Our data further suggest that the topical application of γ-TDMG may be efficacious in preventing photo-induced skin pigmentation in humans.
Notes
  • Kyung Hee Jung, Mi-Ja Kim, Eunyoung Ha, Yoon Kyung Uhm, Hye Kyung Kim, ...
    2006 年 29 巻 6 号 p. 1258-1261
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    While the anti-oxidant properties of Punica granatum methanol extract (PGMF) are well documented, little is known concerning the anti-inflammatory effect of Punica granatum. PGMF was pretreated in BV2 microglial cells and cells were stimulated to induce inflammation by lipopolysaccharide (LPS). The effect of PGME on the production and expression of tumor necrosis factor α (Tnf, previously known as Tnf α) was determined by enzyme-linked immunosorbent assay (ELISA), western blotting, and reverse transcription-polymerase chain reaction (RT-PCR). In addition, the expression of nuclear factor kappa b (Nfκb) was measured using an electrophoretic mobility shift assay (EMSA). By ELISA, PGME at the concentrations of 1, 5, 10, and 50 μg/ml inhibited Tnf production in LPS-stimulated cells by 30.2, 42.3, 57.6, and 88.4%, respectively, compared to LPS-stimulated cells. The LPS-stimulated Tnf production was reduced with a dose-dependent manner. Immuno blot and RT-PCR analyses revealed that PGME of 5 and 50 μg/ml inhibited the expression of both protein and mRNA levels of Tnf compared to LPS-stimulated cells. EMSA revealed that PGME of 5 and 50 μg/ml blocked the LPS-stimulated activation of Nfκb. These data suggest that PGME may suppress LPS-stimulated Tnf production through inhibition of Nfκb in BV2 microglia cells.
Medicinal Chemistry
Regular Articles
Notes
Pharmacognosy
Regular Articles
  • Alma Rosa Cortés, Alba Jady Delgadillo, Marcela Hurtado, Adrian ...
    2006 年 29 巻 6 号 p. 1186-1190
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The antispasmodic activity of extracts from the aerial parts of Buddleja scordioides and Buddleja perfoliata (family: Scrophulariaceae) was studied on isolated tissue preparations from rabbit and guinea pig intestine. The chloroformic extract from the plants exhibited a significant relaxation on the spontaneous contraction of isolated rabbit jejunum at concentrations ranging from 1 to 400 μg/ml, and also caused an inhibitory effect on both K+ and Ca2+ induced contractions in the same tissue. The extracts at moderate doses (50 μg/ml) reduced 5-hydroxytryptamine (5-HT), acetylcholine and histamine induced contractions on isolated guinea pig ileum. Therefore, B. scordioides and B. perfoliata possess similar relaxant mechanism of action, in view of the fact that both inhibit K+ induce contraction and act through serotoninic, muscarinic and histaminic receptors. So, these data support the idea that the extracts may interfere either with calcium mobilization from intracellular stores, or with calcium interaction with regulatory proteins (e.g., calmodulin), or in other steps in the calcium signaling pathway. This leads us to suggest that the spasmolytic effect of both Buddleja species on smooth muscular contractility are due to the same or similar compounds occurring in these two species, which might be present in similar quantities.
  • Toshiyuki Kubo, Susumu Terabayashi, Shuichi Takeda, Hiroshi Sasaki, Ma ...
    2006 年 29 巻 6 号 p. 1191-1196
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    We newly developed an indoor cultivation technique for Wolfiporia cocos (WOLF) RYVARDEN et GILBERTSON (Syn. Poria cocos WOLF), not with soil, but using mushroom culture bottles with pine logs, and clarified some cultural characteristics of sclerotia in the laboratory. To determine the optimum conditions for sclerotia growth, the weight of sclerotia and concentration of CO2 in three different air filters; cloth, paper and urethane resin, and closed bottles were tested. When the cloth air filter was used, the growth rate was the fastest and the yield was maximal. These results suggested that the aeration was an important environmental factor for cultivation. To clarify the characteristics of culture in the cloth air filtered and closed bottles, the weight of sclerotia, the compositions of pine logs and the contents of pachymic acid and dehydropachymic acid were examined during 24 weeks. The growth of scleroia and the wood decaying efficiency in the cloth air filtered bottles were better than those in the closed bottles. Also, it was found that W. cocos was a brown rot fungus due to the alkaline solubility of pine logs in the wood decay process. In addition, the contents of pachymic acid and dehydropachymic acid and the TLC pattern between the cultivated and commercial sclerotia did not differ remarkably.
  • Jun Mori, Toshimitsu Hayashi, Makoto Iwashima, Takayuki Matsunaga, Har ...
    2006 年 29 巻 6 号 p. 1197-1201
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Previously, we reported the anti oxidative and anti viral effects of plastoquinones (compounds 1, 2) extracted from the seaweed Sargassum micracanthum (KUETZING) ENDLICHER and a new chromene compound (compound 3), which was converted from the plastoquinones. Recently, we have also demonstrated the antiulcer effects of these compounds and assessed the effects using a rat model of acute gastric lesion and fundus strips isolated from rats. In hydrochloric acid/ethanol rat ulcer tests: 1) oral administrations of compounds 1, 2, and 3 1—10, 3—30 and 10—30 mg/kg, respectively, and omeprazole 3—30 mg/kg showed dose-dependent antiulcer effects: 2) the antiulcer effects after intraduodenal administration of the respective compounds at the dose of 30 mg/kg were found to be significant: and 3) a decrease in the hexosamine level of the gastric mucosa was slightly improved by oral administration of compounds 1, 2, and 3 30 mg/kg. In indomethacin-induced gastric ulcer tests, the antiulcer effects of compounds 1, 2, and 3 10 mg/kg (p.o.) were not significant. Compounds 1, 2, and 3 showed slight contracting effects on the fundus isolated from rats and these effects were inhibited by pretreatment with AH6809, an inhibitor of prostaglandin DP, EP1, and EP2 receptors. These results suggest that the protection of the mucosa via endogenous prostaglandins might be related to the antiulcer effects of compounds 1, 2, and 3.
  • Ji-eun Shin, Eun-Ah Bae, Young Chul Lee, Jin-Youl Ma, Dong-Hyun Kim
    2006 年 29 巻 6 号 p. 1202-1206
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    To understand the relationship between the metabolism and estrogenic activity of kakkalide and tectoridin, main isoflavones in the flower of Pueraria thunbergiana (family Leguminosae), these isoflavones and their metabolites by human intestinal microflora as well as their estrogenic effects were investigated. All human fecal specimens metabolized kakkalide and tectoridin. All isolated kakkalide-hydrolyzing intestinal bacteria also hydrolyzed kakkalide and tectoridin to irisolidone and tectorigenin, respectively. When the estrogenic effects of kakkalide and tectoridin were compared with those of their metabolites irisolidone and tectorigenin, the metabolites more potently increased proliferation of MCF-7 cells than kakkalide and tectoridin. These metabolites also potently induced estrogen-response c-fos and pS2 mRNA expression. These results suggest that kakkalide and tectoridin may be metabolized mainly to irisolidone and tectorigenin, respectively, by intestinal microflora in the intestines, and which may be subsequently absorbed into the blood where they can express their estrogenic effect.
  • Yahong Guo, Ayako Tsuruga, Shigeharu Yamaguchi, Koji Oba, Kasumi Iwai, ...
    2006 年 29 巻 6 号 p. 1207-1211
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Chloroplast chlB gene encoding subunit B of light-independent protochlorophyllide reductase was amplified from herbarium and crude drug specimens of Ephedra sinica, E. intermedia, E. equisetina, and E. przewalskii. Sequence comparison of the chlB gene indicated that all the E. sinica specimens have the same sequence type (Type S) distinctive from other species, while there are two sequence types (Type E1 and Type E2) in E. equisetina. E. intermedia and E. prezewalskii revealed an identical sequence type (Type IP). E. sinica was also identified by digesting the chlB fragment with Bcl I. A novel method for DNA authentication of Ephedra Herb based on the sequences of the chloroplast chlB gene and internal transcribed spacer of nuclear rRNA genes was developed and successfully applied for identification of the crude drugs obtained in the Chinese market.
Notes
  • Junping Kou, Youqing Tian, Yunkit Tang, Jin Yan, Boyang Yu
    2006 年 29 巻 6 号 p. 1267-1270
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    To provide further pharmacological evidence for its clinical use in thrombotic diseases, the antithrombotic activities of the aqueous extract of Radix Ophiopogon japonicus (ROJ-ext) were studied in mouse and rat models. The results showed that ROJ-ext remarkably decreased length of tail thrombus in mice at 48 h and 72 h after carrageenan injection at doses of 12.5 and 25.0 mg/kg. Meanwhile, ROJ-ext markedly inhibited thrombosis induced by arterial-venous (AV) shunt (silk thread) in rats at doses of 6.25 and 12.5 mg/kg. Furthermore, ROJ-ext and one of its components, ruscogenin, significantly inhibited platelet aggregation induced by adenosine diphosphate (ADP) in rats by oral administration of 12.5 mg/kg or 0.7 mg/kg for three times, however, ophiopogonin D 1.4 mg/kg only showed slight inhibition. On the other hand, ophiopogonin D (0.5—2.0 mg/kg, p.o.) and ruscogenin (0.25—1.00 mg/kg, p.o.) produced dose-related inhibition of venous thrombosis induced by tight ligation of the inferior vena cava for 6 h in mice by once oral administration. The findings of this study indicate that an aqueous extract of Radix Ophiopogon japonicus (ROJ-ext) exerted significant antithrombotic activity and ruscogenin and ophiopogonin D are two of its active components, which supported its therapeutic use for thrombotic diseases.
  • Naomi Shimamura, Toshio Miyase, Kaoru Umehara, Tsutomu Warashina, Sato ...
    2006 年 29 巻 6 号 p. 1271-1274
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    From the leaves of Aspalathus linearis, 24 known compounds and a new one, aspalalinin (25), were isolated. The structures of the compounds were determined mainly based on spectral evidence. The absolute configuration of aspalalinin was presented on the basis of X-ray analysis. Each isolate was assessed for its estrogenic activity by an estrogen ELISA assay. Compounds 12, 15, and 24 showed the estrogenic activity.
  • Kyoko Kobayashi, Tamaki Ishihara, Eriko Khono, Toshio Miyase, Fumihiko ...
    2006 年 29 巻 6 号 p. 1275-1277
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    From stem bark of Callistemon rigidus (Myrtaceae), piceatannol and scirpusin B were isolated as components that exhibit inhibitory effects on α-amylase activity in isolated mouse plasma. In particular, scirpusin B also inhibited α-amylase in mouse gastrointestinal tract. Thus, we expect the depressive effect on the elevation of postprandial blood glucose may be a new medicinal use of this compound as well as the plant itself.
  • Yoo-Jeong Kim, Young-Oh Shin, Young-Wan Ha, Sanghyun Lee, Jae-Keun Oh, ...
    2006 年 29 巻 6 号 p. 1278-1281
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Pinellia ternata is known as the herb effective in removing dampness-phlegm, one of the causes of obesity in traditional Korean medicine. Pinellia ternata water extract (PE) was fed to rats after mixing with diet once a day (400 mg·kg−1) for 6 weeks. We investigated its effect on the thermogenesis and fatty acids oxidation with obese Zucker rats. We also determined the gene expression of uncoupling protein 1 (UCP1), peroxisome proliferators-activated receptor α (PPARα), and PPARγ coactivator 1α (PGC1α). The PE treatment lowered the levels of triglyceride and free fatty acids (p<0.05) in blood of the obese rats and the body weight was also reduced slightly. It was also observed that PE significantly increased the expression of both UCP1 mRNA in brown adipose tissue (BAT) (p<0.001) and PPARα and PGC1α mRNA in white visceral adipose tissue (WAT) (p<0.05 and p<0.001, respectively), which may cause a reduction of obesity. These results suggested that PE would be able to affect anti-obesity through thermogenesis and fatty acid oxidation.
Biopharmacy
Regular Articles
  • Chol Seung Lim, Da-Qing Jin, Jin-Young Sung, Ji Hee Lee, Han Gil Choi, ...
    2006 年 29 巻 6 号 p. 1212-1216
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The antioxidant and anti-inflammatory properties of the marine red alga Neorhodomela aculeate (N. aculeata) MASUDA were investigated with neuronal and microglial cells. Extracts of N. aculeata had potent neuroprotective effects on glutamate-induced neurotoxicity and inhibited reactive oxygen species (ROS) generation in the murine hippocampal HT22 cell line. Also, extracts of N. aculeata inhibited H2O2-induced lipid peroxidation in rat brain homogenates. The properties of the extract as an anti-inflammatory agent were investigated in microglial activation by interferon-gamma (IFN-γ): it reduced the inducible nitric oxide synthase that consequently resulted in the reduction of nitric oxide. These results suggest that the marine red alga N. aculeata could be considered as a potential source for reducing reactive oxygen species and inflammation related to neurological diseases.
  • Li-Chao Zhang, Jin-Hong Hu, Ling Li, Li-Hong Gao, Quan-Gang Zhu, Zhen ...
    2006 年 29 巻 6 号 p. 1217-1222
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The present study was designed to evaluate skin permeation enhancement effect of essential oils from Ligusticum chuanxiong HORT (chuanxiong oil) in rabbits and to compare the in vivo absorption and in vitro permeation using flurbiprofen as a model drug. In vivo results demonstrated that chuanxiong oil showed a rapid and marked permeation enhancement effect. The group with 10% oil exhibited the highest value of area under the curve (AUC) of 418±124 μg/ml·h, which was 2.43 times the high of control. The AUC value of 3% oil group (245±81.6 μg/ml·h) was similar to that of 5% oleic acid group (235±74.5 μg/ml·h). Whereas in vitro results indicated the enhancement of chuanxiong oil was relatively weak. The group with 3% oil appeared to the highest flurbiprofen flux (84.9±19.3 μg/cm2/h), to some extent lower than 5% oleic acid group (107±5.85 μg/cm2/h). At 10% and 15% concentrations, chuanxiong oil even decreased the flux of flurbiprofen compared with the control. Both in vitro results with pretreated skin and flurbiprofen content accumulated in skin indicated the potential mechanism for the in vitro enhancement of chuanxiong oil was the weakened barrier function by improving in the partitioning of flurbiprofen to the stratum corneum. The discrepancy was noted between the in vivo and in vitro results, indicating only about the weakened barrier function was not enough to explain the sharply increment of in vivo absorption of flurbiprofen by chuanxiong oil. The GS-MS results indicated phthalides identified from chuanxiong oil might mainly contribute to enhance in vivo absorption of flurbiprofen because of its large quantities (91.15%).
  • Shinsuke Ogue, Yuri Takahashi, Hiraku Onishi, Yoshiharu Machida
    2006 年 29 巻 6 号 p. 1223-1228
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The usefulness of double liposomes (DL), liposomes containing liposomes inside, as an oral vaccine carrier was examined. Ovalbumin (OVA) encapsulating liposomes sized to 230 nm (small liposomes, SL) were prepared by the glass-beads (GB) method and sequential sonication and extrusion. For the purpose of stabilizing the model antigen, DL containing SL were prepared by the GB method and the reverse-phase evaporation (REV) method. They were named GB-DL and REV-DL, respectively. The morphological structure of DL was confirmed using confocal laser scanning microscopy and scanning electron microscopy by the freeze-fracture method. DL showed suppressed release of OVA and stabilized OVA in pepsin solution as compared with SL. BALB/c mice were immunized with OVA solution, SL and DL suspension by oral administration. Significantly higher levels of IgA in feces were observed in mice immunized with SL and REV-DL as compared with OVA solution, and REV-DL tended to show the higher level of IgA than SL. REV-DL elicited significantly higher anti-OVA IgG responses as compared with OVA solution. Furthermore, GB-DL tended to raise the IgG level as compared with SL. The results suggest that DL have the potential to be an effective carrier for oral immunization.
  • Koichi Yokogawa, Katsuhiro Toshima, Kayo Yamoto, Tatsuo Nishioka, Naok ...
    2006 年 29 巻 6 号 p. 1229-1233
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    We examined the usefulness of intranasal (i.n.) administration of a novel osteotropic prodrug of estradiol, estradiol-17β-succinate-(L-aspartate)6 (E2·17D6), for selective drug delivery to bone. E2·17D6 alone or with 5% 2,6-di-O-methyl-β-cyclodextrin (DMβCD), 5% β-cyclodextrin (βCD), or 10% hydroxypropyl cellulose (HPC) as an absorption enhancer was administered to ovariectomized (OVX) mice via the i.n. route. The oral and nasal bioavailability after p.o. or i.n. administration of E2·17D6 (3.7 μmol/kg) in mice amounted to 9.9 and 23.0% of the dose, respectively. The values of nasal bioavailability of E2·17D6 administered with DMβCD, βCD, and HPC were 74.9, 55.8, and 49.1%, respectively. The plasma concentration of E2·17D6 after i.n. administration of E2·17D6-DMβCD decreased rapidly to the endogenous level by 6 h, but the concentration in the bone was about 200 times higher than that in plasma, and decreased slowly over a period of about a week. When E2 (total dose 4.4 μmol/kg, i.n., every 3rd day) was administered to OVX mice for 35 d, bone mineral density (BMD), liver weight, and uterus weight increased, whereas E2·17D6-DMβCD (total dose 0.44 to 8.8 μmol/kg, i.n., every 7th day) increased only BMD in a dose-dependent manner. In conclusion, intranasally administered E2·17D6-DMβCD has a potent antiosteoporotic effect without side effects, and has potential to provide an improved quality of life for patients with osteoporosis.
  • Noriaki Nagai, Yoshimasa Ito, Mitsushi Inomata, Seigo Shumiya, Hideyuk ...
    2006 年 29 巻 6 号 p. 1234-1238
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    We discovered that the cataract development in the Shumiya cataract rat (SCR) can be prevented by the administration of deep-sea drinking water (DDW). A standard diet based on the American Institute of Nutrition guidelines (AIN-76) and DDW containing a high mineral concentration such as low, medium and high Mg2+ content (50, 200 and 1000 mg of Mg2+/l, respectively) were used in this study. SCRs were freely fed with combinations of the standard diet and purified water or DDW during 5—15 weeks of age. The opacities of SCR lenses were documented by anterior eye segment analysis system EAS-1000. The onset of opacification of cataractous SCR lenses administered a combination of standard diet and purified water started at 11 weeks of age, and mature cataracts had formed at 13 weeks of age. However, the supplementation of Mg2+ by administration with medium DDW showed the greatest effect of delay of cataract onset in SCR. In addition, even cataractous SCR lenses at 14 weeks of age showed differences in opacity level. The opacification and Ca2+ of the lenses in cataractous SCR administered medium DDW were lower than those administered purified water. In conclusion, the present study demonstrates that administration of DDW potently delays cataract development in SCR, and this may be caused by inhibiting the increase in Ca2+ levels in the lens.
Notes
  • Srinivasan Shanmugam, Eung Seok Lee, Sang Kyu Lee, Tae Won Jeon, Chul ...
    2006 年 29 巻 6 号 p. 1282-1285
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The pharmacokinetic parameters of theophylline in rats did not change significantly when the drug was intravenously administered after three consecutive days of pretreatment with 17 mg/kg, orally, of 1-furan-2-yl-3-pyridine-2-yl-propenone (FPP-3), an investigatory drug having dual inhibitory action on cyclooxygenase (COX) and 5-lipoxygenase (5-LOX). However, significant changes were found in the pharmacokinetic parameters of the drug at doses of 34 mg/kg and more of FPP-3. Results of cytochrome P450 activity test indicated that the alteration in pharmacokinetic parameters of the drug appears to be due to the inhibitory effect of FPP-3 on cytochrome P450 1A which is responsible for the metabolism of theophylline. Methoxyresorufin-O-demethylase (MROD) and ethoxyresorufin-O-deethylase (EROD) activity assays revealed that the relative activities of cytochrome P450 1A1 and 1A2 were dose-dependently reduced in the presence of 1, 5, and 10 μM FPP-3 concentrations. Taking into consideration that FPP-3 is intended to be primarily used by geriatric patients with chronic diseases and therefore may be used in long-term basis, the investigatory drug needs to be assessed thoroughly in terms of drug interaction with other commonly prescribed medications.
  • Yoshihiro Uesawa, Kiminori Mohri
    2006 年 29 巻 6 号 p. 1286-1289
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    In the present study, UV-irradiated grapefruit juice was used to investigate the effects of UV light on nifedipine pharmacokinetics. Grapefruit juice in quartz vessels was UV irradiated (302 nm) with a transilluminator for 0 to 6 h at 4 °C, and furanocoumarins, potent contributors to the pharmacokinetic interaction, in each juice sample were measured using HPLC. The concentrations of all three types of furanocoumarins, bergamottin, 6′,7′-dihydroxybergamottin, and bergaptol, decreased in a time-dependent manner. Concentrations of bergamottin, 6′,7′-dihydroxybergamottin, and bergaptol were decreased to 1.66, 1.98, and 5.58%, respectively, after UV irradiation for 6 h. Two milliliters of untreated and UV-irradiated grapefruit juice were preadministered into the duodenum in rats to assess the effects of UV irradiation on nifedipine pharmacokinetics in vivo. After 30 min, nifedipine was intraduodenally administered at a dose of 3 mg/kg body weight. The nifedipine concentrations in the plasma samples were determined using HPLC. A significant increase in the area under the concentration–time curve of nifedipine was observed in untreated grapefruit juice to 1.6-fold that in the control group, but not in the UV-irradiated grapefruit juice. These findings suggest that UV irradiation is useful to eliminate pharmacokinetic interactions with grapefruit juice.
  • Takashi Nakamura, Rumiko Moriguchi, Kentaro Kogure, Arisa Minoura, Tom ...
    2006 年 29 巻 6 号 p. 1290-1293
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    In this study, we developed novel double-membranous non-viral gene delivery system modified with SV-40 T antigen-derived nuclear localization signal (NLS-DMEND) for delivery of luciferase plasmid DNA to nucleus of non-dividing mouse bone marrow-derived dendritic cells (BMDC). Intracellular trafficking and gene expression of NLS-DMEND in the BMDC were evaluated. Condensed DNA was observed in the nucleus by confocal laser scanning microscopy, and the NLS-DMEND induced significant luciferase activity in the BMDC. It was suggested that the condensed DNA particle transferred into nucleus via energy dependent manner, since the nuclear transfer was inhibited by metabolic inhibitors. In conclusion, condensed plasmid DNA was delivered into the nucleus of non-dividing BMDC by NLS-DMEND.
  • Hiroshi Ochiai, Hideyoshi Harashima, Hiroyuki Kamiya
    2006 年 29 巻 6 号 p. 1294-1296
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    The intranuclear disposition of exogenous DNA is highly important for the therapeutic effects of the administrated DNA. Naked luciferase-plasmid DNA was transfected into cultured cells including HeLa by electroporation, and the amounts of intranuclear plasmid DNA and luciferase were quantitated at various time points. Decrease in expression efficiency from one copy of the exogenous DNA over time occurred as the case of mouse liver, and its degrees varied between cell lines. These results suggest that exogenous DNA is ‘silenced’ in the cultured cells as well as in mouse hepatocytes.
  • Naoya Koizumi, Hiroyuki Mizuguchi, Masuo Kondoh, Makiko Fujii, Tsuyosh ...
    2006 年 29 巻 6 号 p. 1297-1299
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Previously we reported fiber-modified adenovirus (Ad) vectors containing the Arg-Gly-Asp (RGD) motif on the HI loop of the fiber knob (Ad-RGD vectors) have high gene transfer efficacy into some human trophoblast cell lines. In the current study, we investigate transgene activity of Ad-RGD during differentiation of human cytotrophoblast BeWo cells into syncytiotrophoblast-like cells. Although cellular differentiation into syncytiotrophoblast cells was followed by a decrease in the coxsackievirus and adenovirus receptor levels on the cell membrane, the αVβ3 and αVβ5 integrin levels did not change. Conventional adenovirus vector had lower transduction activity in the differentiated cells than non-differentiated cells. In contrast, Ad-RGD vector had no influence on differentiation and had a ca. 2—5 fold higher transduction activity than that of the conventional Ad vector. Thus, Ad-RGD vector can be a powerful tool for gene transfer experiments in syncytiotrophoblast cells.
Miscellaneous
Notes
  • Shunsuke Hida, Noriko Nagi-Miura, Yoshiyuki Adachi, Naohito Ohno
    2006 年 29 巻 6 号 p. 1300-1303
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Collagen-induced arthritis (CIA) is an experimental model of rheumatoid arthritis (RA) used for studying the clinical, immunological and genetic factors of the disease. Many studies of genetic susceptibility to CIA have been performed, usually with two strains of mice, DBA/1 and B10.RIII, since they are highly susceptible to CIA. Furthermore, F1 hybrid mice of susceptible and resistant strains reportedly develop arthritis. Recently, we reported that particles of β-glucan, OX-CA, prepared from Candida albicans by NaClO-oxidation, acted as an adjuvant for CIA. Although, there have been many studies about the relationship between antigen and the major histocompatibility complex (MHC) in F1 hybrid mice, little is known argument about susceptibility to adjuvants. Therefore, we checked the susceptibility of F1 hybrids to CIA using OX-CA as an adjuvant. BALB/c and DBA/1 were mated to generate F1 hybrids which were then immunized with type II collagen (CII) plus Freund's complete adjuvant (FCA) or OX-CA. The results showed that F1 hybrids injected with CII plus FCA developed severe arthritis at an incidence ratio 80%, versus only 20% in mice injected with CII plus OX-CA. Furthermore, levels of anti-CII antibody, especially of the IgG2a subclass, in sera from mice treated with CII plus OX-CA were significantly low. Susceptibility to CIA might depend on not only MHC but also the adjuvant used for immunoactivation.
Errata
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