著者

Uchida Eriko Mizuguchi Hiroyuki Ishii-Watabe Akiko HAYAKAWA Takao

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.25, no.7, pp.891-897, 2002-07-01

被引用文献数

3 96

---

Non-viral gene transfer into a wide range of human cells was examined in order to clarify the factors that affect the efficiency and safety of non-viral vectors and to optimize the conditions so that high efficiency and low toxicity could be achieved. Six non-viral vectors (Lipofectin, LipofectAMINE PLUS, SuperFect, Effectene, DMRIE-C and DOTAP) were used to transfect a mammalian expression plasmid pCMVβ into 16 types of human primary cells and cultured cell lines. Transfection efficiency was quantified using a galactosidase assay. Cytotoxic effects were measured by lactate dehydrogenase (LDH) assay and WST-8 assay. In serum-free conditions, LipofectAMINE PLUS, Effectene and SuperFect, on average, transfected DNA more successfully than Lipofectin, DMRIE-C, and DOTAP, although the levels of gene expression with these vectors varied remarkably in different cells. The most effective vector also differed depending on the cell type. Serum was found to inhibit gene transfer and reduce the cytotoxicity of all of these vectors except Effectene. The efficiency and toxicity of the non-viral vectors used depended on the type of vector, the DNA/vector ratio, the type of cell, and the presence of serum. These results provided useful information for the optimization of transfer conditions of these non-viral vectors.

著者

YANG Ling AKAO Teruaki KOBASHI Kyoichi HATTORI Masao

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.19, no.5, pp.701-704, 1996-05-15

参考文献数

15

被引用文献数

1 8

---

Bifidobacterium sp. strain SEN was isolated and characterized by hydrolytic conversion of sennosides to sennidins (Akao et al., Appl. Environ. Microbiol., 60, 1041 (1994)). The sennoside-hydrolyzing capacity of the strain SEN was disappeared following the addition of glucose to the media in spite of good bacterial growth and potent activity hydrolyzing p-nitrophenyl β-D-glucopyranoside (pNPG). In a fructose-containing medium, no such suppressing effect was shown. Following a 10 h incubation in 50 mM potassium phosphate buffer (pH 7.4), the sennoside-hydrolyzing activity of the bacterium increased, dose-dependently, with the addition of sennoside B. Inhibition of the substrate-induced increase in sennoside-hydrolyzing activity was observed following the addition of some antibiotics (chloramphenicol, streptomycin, and rifampicin). In particular, chloramphenicol completely inhibited the increase of sennoside-hydrolyzing activity while 38% pNPG-hydrolyzing activity remained. It is suggested that the strain SEN produces two different β-glucosidases of which the sennoside-hydrolyzing enzyme is inducible. In addition, the glucosides pNPG, esculin, salicin, or amygdalin stimulated the induction of the sennoside β-glucosidase, but less markedly than sennoside. Sennidin A or sugars (glucose, fructose, cellobiose, or maltose) did not induce the enzyme.

著者

Unno Keiko Kishido Takahiro Hosaka Maho OKADA Shoji

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.20, no.12, pp.1240-1244, 1997-12-15

被引用文献数

1 8

---

To investigate the role of constitutive hsp70 in protein folding and to probe the supplementation by other hsps in this folding, yeast cells expressing reduced constitutive hsp70 proteins, ssa1ssa2,were transformed with a plasmid expressing a bacterial luciferase protein. With several independent clone cells of transformants, the levels of luciferase activity and some hsps, such as hsp104,hsp90,hsp70 and hsp26,were examined. The luciferase activity was significantly lower in ssa1ssa2 transformants than in the wild type (wt) cell transformed with the same plasmid. Among several clone cells of ssa1ssa2,the cells with higher luciferase activities exhibited higher amounts of Ssa4 which is known to be expressed instead of lacking Ssa1 and Ssa2. The luciferase activity closely correlated with the amount of Ssa proteins, more than with the amount of other hsps. It is suggested that consitutional Ssa "chaperones" are needed for the folding of proteins and, in cells lacking Ssa1 and Ssa2,the increased Ssa4 is thought to partly compensate for their role in the folding of luciferase in vivo.

著者

Unno Keiko Kishido Takahiro Okada Shoji

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.21, no.6, pp.631-633, 1998-06-15

被引用文献数

1 4

---

Mammalian small heat shock protein (s-hsp) has been suggested to participate not only in stress tolerance but also in the growth regulation and differentiation of cells. To confirm the role of s-hsp in cell growth, we investigated the relationship between the expression of hsp26 and yeast cell growth. Cells lacking constitutive hsp70,ssa1ssa2,have been known to have a poor growth rate and to over-express hsp26 and some other hsps. We obtained several cell clones of ssa1ssa2 whose doubling times were different from one another. The amount of hsp26 was closely linked to the doubling time of ssa1ssa2 cells. This result suggests that the expression of hsp26 modulates the growth rate of yeast cells lacking constitutive hsp70,similarly to mammalian cells.

著者

Jeon Jeong-Ryae Kim Jong-Yeon

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.29, no.10, pp.2111-2115, 2006-10-01

参考文献数

19

被引用文献数

1 28

---

The present study examined the anti-obesity effects of pine needle extract (PNE) in 3T3-L1 preadipocytes and <i>in vivo</i> studies. PNE treatment suppressed both glycerol-3-phosphate dehydrogenase activity and expression of peroxisome proliferator-activated receptor (PPAR) &gamma; in cultured 3T3-L1 adipocytes. To investigate the effect of PNE on obesity in rats fed high-fat diet, four types of diet, which included a normal diet (ND), high-fat diet (HFD), ND+PNE, and HFD+PNE diets, were fed to the rats <i>ad libitum</i> for 6 weeks. The PNE supplement significantly decreased body weight gain and visceral fat mass compared to the HFD group. The total cholesterol, TG, and leptin levels in the plasma were significantly reduced by PNE supplementation compared with those of the HFD group. Histological findings in liver tissue showed that PNE supplementation alleviated steatosis induced by HFD. In conclusion, PNE treatment suppressed differentiation of 3T-L1 adipocytes, in part by down-regulating expression of PPAP&gamma; mRNA, and reduced adipose tissue mass, hyperlipidemia, and hepatic steatosis in obese rats fed HFD. Therefore, pine needle water extract may be considered for use in therapy to control obesity.

著者

Harada Shigeyoshi Haneda Eiji Maekawa Toshiro MORIKAWA Yuko FUNAYAMA Shinji NAGATA Nobuyuki OHTSUKI Kenzo

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.22, no.10, pp.1122-1126, 1999-10-15

参考文献数

18

被引用文献数

7 33

---

The physiological significance of the casein kinase II (CK-II)-mediated phosphorylation of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on its three enzymatic activities [RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP) and ribonuclease H (RNase H)] was investigated in vitro. It was found that (i) the purified recombinant RT (rRT) functioned as an effective phosphate acceptor for CK-II; (ii) the RDDP, DDDP and RNase H activity of rRT was stimulated about 2.8-, 4.1- and 3.9-fold, respectively, after full phosphorylation by CK-II; and (iii) this stimulation was selectively inhibited by potent CK-II inhibitors, such as neocarzinostatin-chromophore (NCS-chrom) and three polyphenol-containing anti-oxidant compounds [quercetin, epigallocatechin gallate (EGCG) and 8-chloro-3', 4', 5,7-tetrahydroxyisoflavone (8C-3', 4', 5,7-THI)]. These results suggest that (i) CK-II may be responsible for activation of RT in HIV-1-infected cells; and (ii) the selective inhibition of CK-II-mediated activation of HIV-1 RT by potent CK-II inhibitors may be involved in the mechanism of their anti-HIV-1 effects at the cellular level.

著者

尾崎 幸紘

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.18, no.4, pp.559-562, 1995-04-15

参考文献数

23

被引用文献数

5 40

---

This study was carried out to examine the antiinflammatory effect of aqueous extracts of Kakkon-to (K), Kakkon-oren-ogon-to (KO), Kikyo-to (KK), Haino-to (H), Haino-san (HS), Mao-to (M) and Senkinkeimei-san (SK), which have been used for the treatment of stomatitis, tonsillitis, cold and chronic inflammatory diseases, and to elucidate the mode of their effects. Oral administration of K, KO, KK, H, HS, M and SK inhibited dose-dependently the increase of dye leakage induced by acetic acid in mice. Further antiinflammatory study was carried out on KK, H and HS which showed potent inhibition. All three extracts significantly inhibited the carrageenin-induced edema and the cotton pellet-induced granuloma formation. From these results, it is suggested that KK, H and HS may inhibit both the early exudative stage and the late proliferative stage in inflammatory processes. These extracts are comprised of Platycodon root as do other crude drugs, and the root may be partly responsible for the antiinflammatory effects induced.

著者

Gul Halise Inci Gul Mustafa Vespalainen Jouko ERCIYAS Ercin HANNINEN Osmo

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.5, pp.631-637, 2003-05-01

参考文献数

38

被引用文献数

2 23

---

Acetophenone derived mono-Mannich bases (Ig1&mdash;Ig4), 1-aryl-3-amino-1-propanone hydrochlorides, which are known to have cytotoxicity in Jurkat cells, were synthesized. Then, they were converted to corresponding azine derivatives (D1&mdash;D4), <i>N</i>, <i>N</i>&prime;-bis(3-amino-1-aryl-propylidene)hydrazine dihydrochlorides, which are bifunctional agents. The aryl part was replaced by phenyl in Ig1, Ig2, Ig3, D1, D2, and D3, and by <i>p</i>-hydroxyphenyl in Ig4 and D4. The amine part was replaced by dimethylamine in Ig1, D1, Ig4 and D4, by piperidine in Ig2 and D2, and by morpholine in Ig3 and D3. The aim of this study was to investigate whether the modification in chemical structure, converting the mono-Mannich base to a corresponding azine derivative, improves the cytotoxicity. In addition, the effect of the representative compound, D3, <i>N</i>, <i>N</i>&prime;-bis(3-morpholine-4-yl-1-phenylpropylidene)hydrazine dihydrochloride, on cellular glutathione level after 1 h exposure in phosphate buffer at 37 &deg;C was also determined to provide information on a possible mechanism of cytotoxic action. Compounds D2&mdash;D4 are reported for the first time in this study. Except for Ig2 and D2, the cytotoxicity of mono-Mannich bases, Ig1, Ig3 and Ig4 and corresponding azine derivatives, D1, D3 and D4 were higher than the reference compound 5-FU. Azine derivatives D1 and D4 had almost equal cytotoxic potency with corresponding mono-Mannich bases Ig1 and Ig4, respectively. On the other hand, azine derivatives D2 and D3, had 1.28 and 1.90-times less cytotoxicity in Jurkat cells compared with the mono-Mannich bases, Ig2 and Ig3, respectively, from which they are derived. Azine derivative D3 dose-dependently decreased the total cellular glutathione level, suggesting that azine derivatives may exert cytotoxicity by thiol alkylation. Azine derivatives with equal or less cytotoxic potency compared to the mono-Mannich bases they are derived from seemed to be less suitable derivatives for the development of new cytotoxic compounds.

著者

Jiang Saho Jun Zhou Xiao Jun

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.1, pp.66-68, 2003-01-01

参考文献数

16

被引用文献数

1 39

---

The epidermal permeability barrier appears to be regulated primarily by the lamellar arrangement of lipid bilayers between coneocytes of the stratum corneum and presents a significant barrier to the transdermal delivery of drugs. The aim of the present study was to investigate the effects of oleic acid on the ultrastructure of stratum corneum lipids in rat skin. Wistar rats were treated topically with 10% oleic acid/propylene glycol for 2 h, the structure of stratum corneum was examined by electron microscopy using osmium tetroxide or ruthenium tetroxide postfixation, and the epidermal barrier function was evaluated in a lanthanum tracer study. Ultrastructural examination revealed that there was a marked alteration in the stratum corneum and the tracer penetrated into the intercellular spaces of the stratum corneum after application of oleic acid. These results suggest that ruthenium tetroxide postfixation is a powerful tool for the study of the stratum corneum lipid structure. Oleic acid might increase the epidermal permeability through a mechanism involving the perturbation of stratum corneum lipid bilayers and lacunae formation to enhance transdermal drug delivery.

著者

Ha Jeoung-Hee Lee Maan-Gee Chang Soo-Min LEE Jae-Tae

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.29, no.7, pp.1414-1417, 2006-07-01

被引用文献数

11

---

Fossilia Mastodi Ossis, which is a skeletal fossil of a Mastodon, an ancient mammal, has been found to have anxiolytic, sedative and anticonvulsant activities in Oriental medicine. In this study, in vivo characterization of the sedative activities of Fossilia Mastodi OSSIS was performed in order to obtain basic information for the development of a putative natural sedative. The 80% methanol extract of Fossilia Mastodi OSSIS given per os at a dose of 3g/kg in mice showed anxiolysis, potentiation of pentobarbital sleeping time, reduced locomotor activity, and anticonvulsive activity. Fossilia elicited GABA_A receptor-mediated anxiolysis. The data obtained suggest that the 80% methanol extract of Fossilia Mastodi OSSIS contains some biologically active principles with sedative activity.

著者

Sandoval Moises Burgos Johanna Sepulveda Francisco V. Cid L. Pablo

出版者

公益社団法人 日本薬学会

雑誌

Biological & Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.34, no.6, pp.803-809, 2011

被引用文献数

10

---

The importance of intracellular pH (pH_i) in the regulation of diverse cellular activities ranging from cell proliferation and differentiation to cell cycle, migration and apoptosis has long been recognised. More recently, extracellular pH (pH_o), in particular that of relatively inaccessible compartments or domains that occur between cells in tissues, has begun to be acknowledged as a relevant signal in cell regulation. This should not be surprising given the abundant reports highlighting the pH_o-dependence of the activity of membrane proteins facing the extracellular space such as receptors, transporters, ion channels and enzymes. Changes in pH affect the ionisation state of proteins through the effect on their titratable groups. There are proteins, however, which respond to pH shifts with conformational changes that are crucial for catalysis or transport activity. In such cases protons act as signalling molecules capable of eliciting fast and localised responses. We provide examples of ion channels that appear fastidiously designed to respond to extracellular pH in a manner that suggests specific functions in transporting epithelia. We shall also present ideas as to how these channels participate in complex transepithelial transport processes and provide preliminary experiments illustrating a new way to gauge pH_o in confined spaces of native epithelial tissue.

著者

Koga Kenjiro Murakami Masahiro Kawashima Susumu

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.22, no.4, pp.402-406, 1999-04-15

参考文献数

22

被引用文献数

1

---

The effects of fatty acid glycerol esters and Tweens on the intestinal transport of ceftibuten were studied using a diffusion chamber system. The apparent permeation coefficient (P<SUB>app</SUB>) was used as an index of the mucosal permeability to ceftibuten. The P<SUB>app</SUB> markedly increased by the addition of hexaglycerol monostearate (HGMS) or hexaglycerol sesquistearate (HGSS) under an H<SUP>+</SUP>-gradient condition, while hexaglycerol tristearate (HGTS) and Tweens showed no effect on the absorptive ceftibuten permeability. These result are in agreement with those obtained in the previous study in the brush-border membrane vesicles. On the other hand, in the absence of an H<SUP>+</SUP>-gradient, the S-to-M transport of ceftibuten was proven to be significantly higher than the M-to-S one. In addition, either ATP-depletion of the mucosa or the addition of probenecid proved to enhance significantly the permeability of ceftibuten. These findings suggest the existence of an active secretory transport system for ceftibuten in the jejunal mucosa. To estimate potential effects of glycerol esters on efflux pumps as well as peptide transporters, the mucosal-to-serosal (M-to-S) and serosal-to-mucosal (S-to-M) permeability in the presence of the esters was further examined. HGMS, HGSS and HGTS markedly enhanced the M-to-S but not the S-to-M transport in the ATP-depleted jejunum without an H<SUP>+</SUP>-gradient, in which conditions contributions of both peptide transporter and efflux pump should be substantially small. HGMS and HGSS significantly enhanced the M-to-S ceftibuten transport in the ATP-depleted jejunum with an H<SUP>+</SUP>-gradient (p<0.01 vs. M-to-S transport without surfactant under the same conditions). Whereas, these glycerol esters were fround hardly to affect the P<app> of the S-to-M transport. These results indicate that the enhanced intestinal transport of ceftibuten due to the glycerol esters may be based on their effects on peptide transporters but neither on efflux pumps nor on the passive permeation routes.

著者

KITAGAWA Shuji SUGAYA Yoshio

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.19, no.2, pp.268-273, 1996-02-15

参考文献数

34

被引用文献数

4 1

---

Characteristics of transport of an oral aminocephalosporin, cefroxadine, in rabbit small intestinal brush border membrane vesicles were examined. Uptake rate of cefroxadine was saturable in the presence of an inward H<SUP>+</SUP> gradient, and kinetic parameters were similar to those of cephradine. However, the uptake rate was almost linear with the concentration in the absence of an inward H<SUP>+</SUP> gradient up to 5mM. Overshoot phenomenon was observed in the presence of an inward H<SUP>+</SUP> gradient at 37°C, but it disappeared with decrease of temperature. The Arrhenius plot of uptake rate constant showed a break point at approximately 30°C. Cefroxadine uptake was optimum in the vicinity of pH 5.5 at 37°C, but the dependence on extravesicular pH disappeared at 15°C. The uptake of cefroxadine in the presence of an inward H<SUP>+</SUP> gradient was markedly inhibited by other aminocephalosporins such as cephalexin, but the inhibition was only slight in the absence of an inward H<SUP>+</SUP> gradient. Alkyl alcohols such as n-hexyl alcohol also inhibited H<SUP>+</SUP>-coupled uptake of cefroxadine at the concentration range at which the alcohols increased the membrane fluidity, and overshoot phenomenon diminished, suggesting that H<SUP>+</SUP>-coupled transport of cefroxadine is sensitive to the alcohol-induced increase in membrane fluidity. On the other hand, the alcohols rather stimulated its uptake in the absence of an H<SUP>+</SUP> gradient.

著者

松村 靖夫 喜多 紗斗美 森本 史郎 秋元 健吾 古谷 真優美 岡 直美 田中 隆治

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.18, no.7, pp.1016-1019, 1995-07-15

被引用文献数

18 93

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We investigated the antihypertensive effect of sesamin, a lignan from sesame oil, using deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The animals were unilaterally nephrectomized, and then separated into a sham-operated group (sham group) and a DOCA-salt-treated group. The latter was further separated into a normal diet group (control group) and a sesamin-containing diet group (sesamin group). The systolic blood pressure of control group progressively increased in comparison with that of sham group. This DOCA-salt-induced hypertension was markedly suppressed by feeding a sesamin-containing diet. Systolic blood pressure after 5 weeks was 130.6±1.9mmHg in the sham group, 198.1±7.3mmHg in the control group and 152.5±8.4mmHg in the sesamin group, respectively. The treatment with DOCA and salt for 5 weeks significantly increased the weight of the left ventricle plus the septum. However, this increase was signiflcantly suppressed in the sesamin group. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, there were significant increases in wall thickness, wall area and the wall-to-lumen ratio in the control group, compared with the sham. Sesamin feeding ameliorated the development of DOCA-salt-induced vascular hypertrophy in both the aorta and mesenteric artery. These findings strongly suggest that sesamin is useful as a prophylactic treatment in the development of hypertension and cardiovascular hypertrophy.

著者

Sasaki Yohei Komatsu Katsuko Takido Michio TAKESHITA Kazuo KASHIWAGI Harutsugu NAGUMO Seiji

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.8, pp.1511-1515, 2007-08-01

参考文献数

13

被引用文献数

1 4

---

Kuma-zasa is Japanese folk medicine derived from plants of genus Sasa, family Bambusaceae. Although the plants of origin of Kuma-zasa were reported to be Sasa palmata, S. senanensis, S. yahikoensis, and S. kurilensis, authentication of those plants was difficult because of similarity in morphology. Several methods for the classification of genus Sasa are available, but none involve a genetic approach. Here, we performed the genetic profiling of genus Sasa, including the four species used medicinally. Thirteen sequences were observed in chloroplast DNA intron between rbcL and ORF106 and partial ORF106 regions of 34 specimens of 16 Sasa species and one specimen of Phyllostachys pubescens. We observed differences in alignment in this region among the specimens. The analyzed lengths varied from 759 to 821 bp depending on the specimen. There were nine base substitutions, eight successive thymines or adenines, and one to three repeat units of 31 bp. Moreover, we could not find species-specific alignment: different alignments were observed in specimens of the same species, while the same alignment was observed in specimens of different species. In the phylogenetic tree reconstructed by maximum parsimony analysis, medicinally used species did not form a cluster, although most of them were positioned close to each other. The genetic profiling of Sasa species would be of use in determining the botanical origin of the herbal medicine derived from the leaves of Sasa plants.

著者

Sasaki Hideki Akiyama Hiroshi Yoshida Yoshifumi KONDO Kazunari AMAKURA Yoshiaki KASAHARA Yoshimasa MAITANI Tamio

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.29, no.12, pp.2514-2518, 2006-12-01

被引用文献数

4 20

---

In autumn 2004, many Japanese patients with renal failure developed cryptogenic encephalopathy by consuming sugihiratake mushroom, a Japanese delicacy. To elucidate the relationship between the cryptogenic cases and this mushroom, we conducted a multivariate analysis of metabolites in 'Probably Toxic' sugihiratake collected from the area of encephalopathy outbreaks, and 'Probably Safe' sugihiratake collected from unaffected areas using UPLC/ToF MS. The results indicate that the presence of milligram quantities of vitamin D-like compounds per 10g of dried sugihiratake from the areas of encephalopathy outbreaks. Two hypotheses to induce the encephalopathy are proposed: the found metabolites are (1) vitamin D agonists, which induce acute and severe hypercalcemia and/or hyperammonemia and/or vitamin D toxicity, or (2) vitamin D antagonists, which induce acute and severe hypocalcemia.

著者

Morito Keiko Hirose Toshiharu Kinjo Junei HIRAKAWA Tomoki OKAWA Masafumi NOHARA Toshihiro OGAWA Sumito INOUE Satoshi MURAMATSU Masami MASAMUNE Yukito

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.24, no.4, pp.351-356, 2001-04-01

被引用文献数

26 473

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The human estrogen receptor(hER) exists as two subtypes, hER α and hER β, that differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activities of soy isoflavones after digestion with enteric bacteria in competition binding assays with hER α or hER β protein, and in a gene expression assay using a yeast system. The estrogenic activities of these isoflavones were also investigated by the growth of MCF-7 breast cancer cells. Isoflavone glycoside binds weakly to both receptors and estrogen receptor-dependent transcriptional expression is poor. The aglycones bind more strongly to hER hER β than to hER α. The binding affinities of genistein, dihydrogenistein and equol are comparable to the binding affinity of 17 β-estradiol. Equol induces transcription most strongly with hER α and β. The concentration required for maximal gene expression is much higher than expected from the binding affinities of the compounds, and the maximal activity induced by these compounds is about half activity of 17 β-estradiol. Although genistin binds more weakly to the receptors and induces transcription less than does genistein, it stimulates the growth of MCF-7 cells more strongly than does genistein.

著者

Nawawi As'ari Ma Chao-mei Nakamura Norio HATTORI Masao KUROKAWA Masahiko SHIRAKI Kimiyasu KASHIWABA Noriaki ONO Minoru

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.22, no.3, pp.268-274, 1999-03-15

被引用文献数

3 34

---

By screening water and MeOH extracts of 30 Chinese medicinal plants for their anti-herpes simplex virus (HSV)-1 activity, a MeOH extract of the root tubers of Stephania cepharantha HAYATA showed the most potent activity on the plaque reduction assay with an IC_<50> value of 18.0 μg/ml. Of 49 alkaloids isolated from the MeOH extract, 17 alkaloids were found to be active against HSV-1,including 13 bisbenzylisoquinoline, 1 protoberberine, 2 morphinane and 1 proaporphine alkaloids, while benzylisoquinoline and hasubanane alkaloids were inactive. Although N-methylcrotsparine was active against HSV-1,as well as HSV-1 thymidine kinase deficient (acyclovir resistant type, HSV-1 TK^-)and HSV-2 (IC_<50> values of 8.3,7.7 and 6.7 μg/ml, respectively), it was cytotoxic. FK-3000 was found to be the most active against HSV-1,HSV-1 TK^- and HSV-2 (IC_<50> values of 7.8,9.9 and 8.7 μg/ml) with in vitro therapeutic indices of 90,71 and 81,respectively. FK-3000 was found to be a promising candidate as an anti-HSV agent against HSV-1,acyclovir (ACV) resistant-type HSV-1 and HSV-2.

著者

Tsukiyama Muneo Akaishi Tatsuhiro Ueki Takuro OKUMURA Hidenobu ABE Kazuho

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.11, pp.2063-2068, 2007-11-01

参考文献数

20

被引用文献数

1 9

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Although the fruit of Nandina domestica THUNBERG (ND) has been used to treat respiratory disorders such as coughing and breathing difficulty in Japan for many years, very little is known about mechanisms underlying its action. In the present study, we investigated effects of the crude extract from ND (NDE) and one of its constituents, nantenine, on contractile responses in isolated guinea pig tracheal ring preparations. In normal experimental condition, guinea pig trachea remained tonically contracted during the resting state, and addition of NDE (1 mg/ml) caused a relaxation of tracheal smooth muscles, but had little effect on the responsiveness of trachea to acetylcholine. The basal, tonic contraction was abolished by the presence of atropine and indomethacin. In this condition, NDE at 0.1—1 mg/ml inhibited histamine-induced contraction in both competitive and non-competitive manners. NDE at 0.01—1 mg/ml inhibited serotonin-induced contraction in a competitive manner. Nantenine (2—20 μM) did not affect histamine-induced contraction, and slightly inhibited serotonin-induced contraction. These results suggest that NDE has inhibitory effects on tracheal smooth muscle contraction, and nantenine cannot account solely for this effect of NDE.

著者

松本 陽子 今村 主税 伊藤 貴俊 谷口 智穂 上岡 龍一

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.18, no.10, pp.1456-1458, 1995-10-15

被引用文献数

15 31

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The hybrid liposomes (90mol% DMPC/10mol% C_<12> (EO)_8 and 90mol% DMPC/10mol% C_<12> (EO)_<12>) have a highly inhibitory action against the growth of tumor cells. The uniform and stable structure of the hybrid liposomes was revealed on the basis of electron microscopy and dynamic light scattering measurements.