Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
26 巻 , 11 号
選択された号の論文の28件中1~28を表示しています
Analytical Biochemistry
Notes
Biochemistry/Molecular Biology
Regular Articles
  • Li Ou, Ling-Yi Kong, Xian-Ming Zhang, Masatake Niwa
    原稿種別: Regular Article
    専門分野: Biochemistry/Molecular Biology
    2003 年 26 巻 11 号 p. 1511-1516
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Plant peroxidases were found to play an important role in plant physiology such as the metabolism and transformation of small complexes. In the present research, a novel Momordica charantia peroxidase (MCP) from fruits was purified to electrophoretic homogeneity by combining consecutive treatment of ammonium sulfate fractionation, ion exchange chromatography on DEAE-Sepharose FF, affinity chromatography on concanavalin A (Con A) Sepharose and gel filtration on Sephadex G-150. The physical and chemical characters of MCP were also investigated. MCP catalyzed the oxidation of ferulic acid (FA) to dehydrodimer (FA-2) in aqueous acetone system at pH 5.0. Its structure was identified by spectral analyses including IR, 1H-, 13C-NMR and electrospray ionization mass spectroscopy (ESI-MS). The anti-inflammatory activities of FA, FA-2 and other derivatives were examined. FA-2 significantly inhibited the release of proinflammatory factors such as TNF-α, NO and proliferation of spleen cells induced by phytohemagglutinin (PHA) and Con A and promoted a greater DNA fragmentation of spleen cells than that of other complexes. These results suggested that MCP as a tool enzyme transformed some complexes such as FA to more active derivatives, and that FA-2 was a potential inhibitor on inflammation through interference with immune response in the process of inflammation, which maybe was associated with apoptosis of immune related cells induced by FA-2.
  • Qin Li, Feng Yang, Jinghai Zhang, Yingjie Chen
    原稿種別: Regular Article
    専門分野: Biochemistry/Molecular Biology
    2003 年 26 巻 11 号 p. 1517-1522
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Editor's Note:

    The Editorial Committee of this Journal wishes to acknowledge with regret that "Proteomic Analysis of Proteins that Binds Specifically to the Homologous Repeat Regions of White Spot Syndrome Virus" by Qin Li, Feng Yang, Jinghai Zhang, and Yingjie Chen which was published in Vol. 26 (2003), p. 1517 of this Journal, has been found to contain no reproducible results, according to proposal by the authors.

    Thus it should be noted that the above-mentioned paper by Qin Li, Feng Yang, Jinghai Zhang, and Yingjie Chen should be deleted or totally revised.

    For this reason, as of March 19, 2004, this article (including its abstract and references) has been removed from this site.
  • Tadatoshi Yamaguchi, Hajime Nomura, Kazuhisa Matsunaga, Shigeru Ito, J ...
    原稿種別: Regular Article
    専門分野: Biochemistry/Molecular Biology
    2003 年 26 巻 11 号 p. 1523-1527
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The effects on the viability of cell lines treated with 2,3-dihydro-5,6-dimethylpyrazine and its derivatives, which revealed DNA strand-breakage activity by the generation of radicals in vitro, were recognized from certain morphological changes and the detection of apoptosis-related proteins: cleaved PARP and SAPK/JNK. These results would suggest that sugar-derived dihydropyrazines induce changes in the cells of certain organs and cause various internal injuries in vivo. The biodistribution of 14C-labelled 2,3-dihydro-5,6-dimethylpyrazine was studied in mouse and the autoradiograms showed highly contrasting results. Radioactivity was high in the brain, spinal cord, salivary gland, and thymus and low in the heart, stomach, and blood. The result was supported by the activity (% dose per organ).
  • Koji Abe, Nobuaki Watanabe, Toshiyuki Kosaka, Makiko Yamada, Taro Toku ...
    原稿種別: Regular Article
    専門分野: Biochemistry/Molecular Biology
    2003 年 26 巻 11 号 p. 1528-1533
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Pyroglutamyl aminopeptidase I (PAP-I) is a cytosolic cysteine peptidase, which hydrolytically removes the L-pyroglutamate residue from the amino terminus of endogenous proteins and peptides. L-Pyroglutamyl p-nitroanilide serves as the synthetic substrate of this enzyme, while there is a possibility of other hydrolases being involved in the hydrolysis of this xenobiotic substrate. We cloned a full-length cDNA encoding rat PAP-I from a rat liver cDNA library and expressed this cDNA in Escherichia coli to obtain a recombinant PAP-I as a single protein. The cDNA encoded a sequence of 209 amino acids with a calculated molecular weight of 22913 Da. The homology of the deduced amino acid sequence of rat PAP-I was 98.6 and 94.3% to mouse and human PAP-Is, respectively. The biochemical properties of the recombinant rat PAP-I were almost identical to those of the recombinant mouse and human PAP-Is and the purified rat liver cytosolic PAP-I in terms of the molecular weight, subunit structure, affinity to the substrate, inhibitor profile and pH optimum. Immunoblot analysis using an antibody raised against recombinant rat PAP-I showed that rat PAP-I is present almost exclusively in the cytosolic fraction of the rat liver. Moreover, the hydrolyzing activity for L-pyroglutamyl p-nitroanilide in rat liver cytosolic fraction was completely inhibited by the antibody, strongly suggesting that this xenobiotic substrate is hydrolyzed solely by PAP-I.
Pharmacology
Regular Articles
  • Shrishailappa Badami, Sudheer Moorkoth, Sujay Rammanoharsingh Rai, Ela ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2003 年 26 巻 11 号 p. 1534-1537
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Antioxidant activity of Caesalpinia sappan heartwood was studied both by in vitro and in vivo models. The ethyl acetate, methanol and water extracts exhibited strong antioxidant activity as evidenced by the low IC50 values in both 1,1-diphenyl-2-picryl hydrazyl (DPPH) and nitric oxide methods. The values were found to be less or comparable to those of ascorbic acid and rutin, the standards used. Administration of the successive methanol and water extracts at 50 and 100 mg/kg body weight given for four days prior to carbon tetrachloride (CCl4) treatment caused a significant increase in the level of superoxide dismutase (SOD) and catalase and a significant decrease in the level of thiobarbituric acid reactive substances (TBARS), when compared to CCl4 treated control in both liver and kidney. These changes observed at 100 mg/kg body weight treatment were comparable to those observed for standard vitamin E at 50 mg/kg treatment. The results support significant antioxidant nature of Caesalpinia sappan heartwood extracts.
  • Gustavo Massaro Onusic, Regina Lúcia Nogueira, Ana Maria Soares ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2003 年 26 巻 11 号 p. 1538-1542
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    We investigated the effects of chronic oral treatment with a water–alcohol extract from the inflorescence of Erythrina mulungu (Leguminosae-Papilionaceae) (EM, 50, 100, 200 mg/kg) in rats submitted to different anxiety models: the elevated T-maze (ETM, for inhibitory avoidance and escape measurements), the light/dark transition, and the cat odor test. These models were selected for their capacity to elicit specific subtypes of anxiety disorders as recognized in clinical practice. Treatment with EM impaired inhibitory avoidance latencies in a way similar to the reference drug, diazepam (DZP). Additionally, both EM and DZP increased the number of transitions and the time spent in the lighted compartment of the light/dark transition model. Furthermore, neither EM nor DZP altered behavioral responses of rats to a cloth impregnated with cat odor. In contrast to DZP, however, EM also altered ETM one-way escape. These results were not due to motor alterations since no significant effects were detected in the number of crossings or rearings in the arena. The present observations suggest that chronic EM exerts anxiolytic-like effects in defensive behaviors related to generalized anxiety and panic disorder. Although alkaloids appear to be one of the main constituents of EM, the possible mechanisms through which the extract exerts its anxiolytic action should be further investigated.
  • Ying Zhang, Li-Jun Wu, Shin-ichi Tashiro, Satoshi Onodera, Takashi Ike ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2003 年 26 巻 11 号 p. 1543-1547
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    We have reported that in A375-S2 cells, evodiamine isolated from Evodia rutaecarpa induces cell death of human melanoma, A375-S2, through two distinct pathways: apoptosis and necrosis. In the present study, we further demonstrate two different mechanisms by which evodiamine induces apoptosis and necrosis. Although caspase-1 and -10 inhibitors failed to block cell death, pan-caspase inhibitor and caspase-3, -8, and -9 inhibitors had marked inhibitory effects on apoptosis induced by 15 μM evodiamine. Furthermore, evodiamine-induced activation of caspase-3 resulted in the down-regulation of anti-apoptotic Bcl-2 expression and up-regulation of proapoptotic Bax expression. After 24 h incubation with evodiamine, no caspase inhibitor had any influence on cell death, but p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) attenuated cell death; in contrast, extracellular signal-regulated protein kinase (ERK) MAPK inhibitor (PD98059) augmented cell death, as was further confirmed by cotreatment with SB203580 or PD98059 and pan-caspase inhibitor. Moreover, evodiamine increased the phosphorylation of p38 and decreased the expression and phosphorylation of ERK in caspase-independent necrosis. Consequently, evodiamine induced the caspase- and Bax-mediated apoptosis at an early stage, but, initiated MAPKs-dependent necrosis at a later stage.
  • Kazuki Kushida, Kota Ishida, Jun Kikuta, Masatoshi Kato, Toshimitsu Uc ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2003 年 26 巻 11 号 p. 1548-1551
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The present study examined the role of the noradrenergic system in the modulation of acetylcholine (ACh) release in the rostral ventrolateral medulla (RVLM) using in vivo microdialysis of morphine. The basal level of ACh was 325.0±21.1 fmol/20 μl/15 min in the presence of neostigmine (10 μM). Intraperitoneal (i.p.) administration of 5 and 10 mg/kg morphine significantly increased ACh release by the RVLM. This enhancement was reversed by naloxone (1 mg/kg, i.p.). In addition, pretreatment with yohimbine (0.5 mg/kg, i.p.) or prazosin (0.2 mg/kg, i.p.) attenuated the systemic morphine-induced release of ACh in the RVLM. However, propranolol (0.2 mg/kg, i.p.) did not affect the morphine-induced ACh release. The addition of morphine (10−4 M) to the perfusion medium increased the ACh release by 72.4% of the predrug values. The increased ACh release induced by local application of morphine was attenuated by pretreatment with yohimbine, but not prazosin. These findings suggest that morphine exerts an indirect stimulatory effect on the release of ACh by the RVLM and that the morphine-induced increase in ACh release is modulated by α2-adrenoceptors in freely moving rats.
  • Saburo Yoshioka, Atsuhide Hamada, Tailin Cui, Junko Yokota, Sayaka Yam ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2003 年 26 巻 11 号 p. 1552-1559
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    When normal rabbits were administered various samples of deep-sea water, their biochemical values changed within normal limits, and no differences from distilled water administration (control) group levels were observed. Furthermore, no histopathological changes were observed in internal organs on the 28th day after administration. The serum total cholesterol (T-Cho) and low density lipoprotein cholesterol (LDL-Cho) levels of normal rabbits fed with a 1% cholesterol-containing diet simultaneously administered deep-sea water (desalinated water, hardness 28, 300, and 1200) increased with time up to about 1500 mg/dl. However, the degrees of increase were smaller than those of the control group, which received distilled water. Furthermore, when prepared hyperlipemia rabbits were administered deep-sea water (desalinated water, hardness 28, 300, and 1200), there were no significant changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), high density lipoprotein cholesterol (HDL-Cho), or triglyceride (TG) levels. On the other hand, T-Cho and LDL-Cho levels were reduced when the rabbits were changed to normal food, and the degree of reduction was more than that of the control group. In the liver and main artery bow, as the hardness of the deep-sea water increased, the accumulation of lipid and permeation of macrophages was reduced. This result was well in agreement with the results of the T-Cho and LDL-Cho levels. From these results, it is clear that deep-sea water controls the increase of serum lipid values (T-Cho and LDL-Cho) of cholesterol-fed rabbits, and promotes the reduction of serum lipid hyperlipemia rabbits. The minerals in deep-sea water greatly influence this effect.
  • Kazuho Abe, Yoshiaki Niikura, Miwa Misawa
    原稿種別: Regular Article
    専門分野: Pharmacology
    2003 年 26 巻 11 号 p. 1560-1562
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Electrical stimulation of the basolateral amygdala (BLA) evoked synaptic potentials in the dentate gyrus (DG) of the hippocampus in anesthetized rats. To determine if this pathway possesses synaptic plasticity, we investigated the impact of several conditions of high-frequency stimulation on BLA-DG synaptic potentials in these rats. Application of two trains of 100-pulse, 100-Hz stimulation or theta-burst stimulation to the BLA reproducibly induced long-term potentiation (LTP) of BLA-DG synaptic potentials. Paired-pulse facilitation was unchanged during LTP, suggesting that postsynaptic mechanisms are involved in the expression of LTP. In addition, the induction of LTP was not affected by the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate, suggesting that activation of NMDA receptors is not required. This novel form of LTP should be a valuable model for elucidating neural mechanisms underlying the formation of emotional memory.
  • Keigo Hanada, Kazuyuki Furuya, Noriko Yamamoto, Hiroaki Nejishima, Kiy ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2003 年 26 巻 11 号 p. 1563-1569
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    A novel nonsteroidal androgen receptor (AR) binder, S-40503, was successfully generated in order to develop selective androgen receptor modulators (SARMs). We evaluated the binding specificity for nuclear receptors (NRs) and osteoanabolic activities of S-40503 in comparison with a natural nonaromatizable steroid, 5α-dihydrotestosterone (DHT). The compound preferentially bound to AR with nanomolar affinity among NRs. When S-40503 was administrated into orchiectomized (ORX) rats for 4 weeks, bone mineral density (BMD) of femur and muscle weight of levator ani were increased as markedly as DHT, but prostate weight was not elevated over the normal at any doses tested. In contrast, DHT administration caused about 1.5-fold increase in prostate weight. The reduced virilizing activity was clearly evident from the result that 4-week treatment of normal rats with S-40503 showed no enlargement of prostate. To confirm the bone anabolic effect, S-40503 was given to ovariectomized (OVX) rats for 2 months. The compound significantly increased the BMD and biomechanical strength of femoral cortical bone, whereas estrogen, anti-bone resorptive hormone, did not. The increase in periosteal mineral apposition rate (MAR) of the femur revealed direct bone formation activity of S-40503. It was unlikely that the osteoanabolic effect of the compound was attribute to the enhancement of muscle mass, because immobilized ORX rats treated with S-40503 showed a marked increase in BMD of tibial cortical bone without any actions on the surrounding muscle tissue. Collectively, our novel compound served as a prototype for SARMs, which had unique tissue selectivity with high potency for bone formation and lower impact upon sex accessory tissues.
Notes
  • Takafumi Naito, Hiroki Itoh, Masaharu Takeyama
    原稿種別: Note
    専門分野: Pharmacology
    2003 年 26 巻 11 号 p. 1609-1613
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Hange-koboku-to (Banxia-houpo-tang), a Chinese herbal (Kampo) medicine, has been used for improvement of hoarse voice, something foreign body sensation in the throat and/or esophagus, and swallowing reflex, among other conditions. One of the mechanisms of the empirical effects is assumed to be due to local changes in neuropeptide levels locally. We investigated the effects of Hange-koboku-to on neuropeptides, calcitonin gene-related peptide (CGRP), substance P, somatostatin, and vasoactive intestinal peptide (VIP) in plasma and saliva, as well as on salivary secretion in healthy subjects. A single oral administration of Hange-koboku-to caused significant increases in substance P-immunoreactive substance (IS) (40 min) in plasma, and slightly increased in CGRP-IS and somatostatin-IS in plasma compared with placebo. In saliva neuropeptides, Hange-koboku-to caused significant increases in substance P-IS (20 min) and somatostatin-IS (40, 60 min), and a slight increase in VIP-IS. However, a single Hange-koboku-to stimulation did not have a significant effect of sialosis volume. These results seem to suggest that Hange-koboku-to improves hoarse voice, something foreign body sensation in the throat and esophagus, and swallowing reflex disorder, by stimulation of neuropeptidergic nerves locally.
  • Kenji Yamada, Miwa Sano, Hisato Fujihara, Akihiro Ohta
    原稿種別: Note
    専門分野: Pharmacology
    2003 年 26 巻 11 号 p. 1614-1617
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Effect of 2,5-dimethylpyrazine (2,5-DMP) on oxytocic agent-induced late pregnant uterine contraction in female rats was studied. Oxytocic agents induced-hypercontraction in the late phase of pregnant uterine movements were inhibited by administration of 2,5-DMP. The inhibition of uterine contraction was obtained more strengthening by presence of a low dose of ritodrine hydrochloride than 2,5-DMP alone. These results suggests that 2,5-DMP has an inhibitory action on uterine hypercontraction induced by oxytocic agent through the β2-adrenoceptor in the pregnant uterus and supports the appllicability of relaxing drugs for oxytocic agent-induced accidents.
Toxicology
Notes
Medicinal Chemistry
Regular Articles
Notes
Pharmacognosy
Regular Articles
  • Wook-Joon Yu, Beom-Jun Lee, Sang-Yoon Nam, Deok-Chun Yang, Young-Won Y ...
    原稿種別: Regular Article
    専門分野: Pharmacognosy
    2003 年 26 巻 11 号 p. 1574-1580
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The modulating effects of Korean ginseng saponins on ovarian functions were investigated in immature rats superovulated with pregnant mare serum gonadotropin (PMSG). A single dose of 1 mg (0.1 ml/head) of Korean ginseng total saponin (GTS), Korean ginseng protopanaxatriol saponin (GPT), Korean ginseng protopanaxadiol saponin (GPD), or ginsenoside-Rb1 (Gin-Rb1) was intravenously injected via jugular vein catheter three times at 1 h (early follicular phase), 25 h (middle follicular phase), and 50 h (late follicular phase) after 30 IU PMSG administration. GPD and Gin-Rb1 significantly suppressed excessive ovulatory response caused by PMSG (p<0.05). All Korean ginseng saponins significantly improved oocyte quality by decreasing the proportion of abnormal oocytes (p<0.05). Gin-Rb1 significantly decreased preovulatory serum levels of androgens and 17β-estradiol, while GPD increased preovulatory serum progesterone level (p<0.05). GPD significantly the increased postovulatory serum progesterone level (p<0.05). These results provide strong evidence that Korean ginseng saponins have a curative effect on ovarian dysfunction caused by excessive stimulation with PMSG.
  • Eun-Kyung Park, Min-Kyung Choo, Eun-Jin Kim, Myung Joo Han, Dong-Hyun ...
    原稿種別: Regular Article
    専門分野: Pharmacognosy
    2003 年 26 巻 11 号 p. 1581-1584
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The antiallergic activities of ginsenosides, which were isolated from acid-treated ginseng (Panax ginseng, Araliaceae), and their metabolites by human intestinal bacteria were measured. Ginsenoside Rh2, which is a main metabolite, had the most potent inhibitory activity on β-hexosaminidase release from RBL-2H3 cells and in the passive cutaneous anaphylaxis reaction. The inhibitory activity of ginsenoside Rh2 was more potent than that of disodium cromoglycate, a commercial antiallergic drug. This compound showed membrane stabilizing action upon differential scanning calorimetry and inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide-stimulated RAW cells. However, this ginsenoside Rh2 did not inhibit the activation of hyaluronidase and did not scavenge active oxygen. These results suggest that ginsenoside Rh2 can exhibit antiallergic activity originating from cell membrane-stabilizing activity and antiinflammatory activity by the inhibition of NO and PGE2 production.
  • Ju-Xiu He, Teruaki Akao, Tadato Tani
    原稿種別: Regular Article
    専門分野: Pharmacognosy
    2003 年 26 巻 11 号 p. 1585-1590
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Paeoniflorin (PF) is an active glucoside in Shaoyao (peony root), and is transformed into an antispasmodic metabolite, paeonimetabolin-I (PM-I), by intestinal bacteria in the gut after oral administration of Shaoyao or Shaoyao-Gancao-tang (SGT, Shakuyaku-Kanzo-To in Japanese). SGT is a pain-relieving traditional Chinese formulation (Kampo-medicine in Japanese) and is often used together with antibacterial synthetic drugs, such as amoxicillin and metronidazole (AMPC-MET), in peptic ulcer therapy. Since the bioavailability of PF in SGT has been reported to be significantly reduced by co-administered antibacterial drugs, we investigated how to minimize this reducing effect of antibacterial treatment in the present study. We found that repetitive administration of SGT starting 24 h after AMPC-MET treatment rapidly restored the plasma PM-I concentration from SGT reduced by AMPC-MET, due to its restorative effect on the decreased PF-metabolizing activity of intestinal bacteria in rat feces. The present findings suggest that it may be clinically useful to administer SGT repetitively, starting 1 or 2 d after treatment with a mixture of AMPC-MET during their combination therapy, to accelerate the recovery of the reduced bioavailability of PF in SGT. Similar administration regimens may also be useful in other combination therapies involving traditional Chinese formulations and antibacterial synthetic drugs to ensure the efficacy of the bioactive glycosides in the formulations.
Notes
Biopharmacy
Regular Articles
  • Toshiaki Igarashi, Ikuko Yano, Hideyuki Saito, Ken-ichi Inui
    原稿種別: Regular Article
    専門分野: Biopharmacy
    2003 年 26 巻 11 号 p. 1591-1595
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Cyclosporin A pharmacokinetics was studied in rats with cisplatin-induced acute renal failure (ARF) using microemulsion preconcentrate (MEPC) and completely dissolved formulations. Although the pharmacokinetics of cyclosporin A was unchanged after intravenous administration, maximum concentration of cyclosporin A in ARF rats was significantly reduced to 608±62 and 999±189 ng/ml compared with 1720±142 and 1832±250 ng/ml in controls after oral administration of MEPC and completely dissolved formulations, respectively. In an in situ intestinal loop sac study, the amount absorbed plus metabolized and the blood concentration of cyclosporin A were similar between control and ARF rats, and taurocholic acid, one of the bile acids, significantly increased absorption of cyclosporin A using the MEPC formulation in both control and ARF rats; the amount absorbed plus metabolized with taurocholic acid was increased to 137 and 186%, and simultaneously the blood concentration was increased to 155 and 158% of that without taurocholic acid in control and ARF rats, respectively. The bile flow in ARF rats was decreased compared with that in controls. These results suggested that renal dysfunction decreased the absorption of cyclosporin A in spite of the MEPC formulation, and the alternation of bile secretion partly affected the absorption rate of cyclosporin A in the gastrointestinal tract.
Notes
  • Takashi Mizuma, Takuo Narasaka, Shoji Awazu
    原稿種別: Note
    専門分野: Biopharmacy
    2003 年 26 巻 11 号 p. 1625-1628
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Intestinal absorption of peptides in linear form has been studied extensively, but there is little knowledge of peptides in a cyclic form. In this report, intestinal absorption of cyclic phenylalanylserine (cyclo(Phe-Ser)), a precursor of gliotoxin, was studied in isolated rat small intestine as a model cyclic dipeptide. Absorption clearance (CLabs) decreased in the presence of glycylsarcosine, cephalexin or cephradine, substrates for H+/oligopeptide cotransporter (PEPT1). CLabs of cyclo(Phe-Ser) also decreased at 4 °C, thus indicating that cyclo(Phe-Ser) is in part transported by PEPT1. However, the Eadie-Hofstee plot of absorption revealed an atypical profile at lower concentrations of cyclo(Phe-Ser) (around 0.1 mM). Moreover, comparative experiments of absorptive and excretive transport showed that excretive transport from the serosal to mucosal side of isolated intestinal tissue at a 0.1 mM cyclo(Phe-Ser) was superior to absorptive transport from the mucosal side to the serosal side, and vice versa at a 1 mM cyclo(Phe-Ser). A kinetic model was constructed, in which cyclo(Phe-Ser) concentration for excretive transport was assumed to be at the binding site of excretive transporter, but not the unbound cytoplasmic concentration. These results as well as the results of kinetic analysis indicate that intestinal absorption consists of passive transport, carrier-mediated absorptive transport by PEPT1 and carrier-mediated excretive transport, resulting in atypical absorption. Although cyclic dipeptides have potentials as drugs, their intestinal absorption may be complex. The results of this study lead us to conclude that absorptive and excretive transport by the small intestine acts as an interface between the body and ingested compounds.
  • Kwang Sik Suh, Yeon Ho Nam, Young Min Ahn, Nam Jae Kim, Cheol Young Pa ...
    原稿種別: Note
    専門分野: Biopharmacy
    2003 年 26 巻 11 号 p. 1629-1632
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Endothelial cell apoptosis has been postulated as the initial trigger of the progression of microvascular disease in patients with diabetes mellitus. To investigate the role of Scutellariae radix extract, we examined its effect on the endothelial cell proliferation using the [3H]-thymidine incorporation method. Scutellariae radix extract significantly stimulated endothelial cell proliferation in a dose-dependent manner. We focused on the protective action of Scutellariae radix extract on the endothelial cell apoptosis induced by high glucose concentrations. Determination of endothelial cell apoptosis was performed using DNA gel electrophoresis, terminal deoxynuclotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and an ELISA kit. Exposure of vascular endothelial cell to high glucose (16.7 mM) for 72 h resulted in a significant increase in apoptosis, compared with the normal glucose concentrations (5.5 mM). Scutellariae radix extract inhibited high glucose-induced endothelial cell apoptosis. This result suggests that Scutellariae radix extract may contribute to antiapoptotic action against vascular endothelial cells, resulting in a beneficial effect in preventing diabetes-associated microvascular complications.
  • Hiroaki Yuasa, Kaori Hamamoto, Shin-ya Dogu, Takeshi Marutani, Aki Nak ...
    原稿種別: Note
    専門分野: Biopharmacy
    2003 年 26 巻 11 号 p. 1633-1636
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The permeability of glycerol, a small hydrophilic solute, across the intestinal membrane would be low, if passive diffusion restricted to the paracellular route is the principal transport mechanism as generally assumed for this class of solutes. However, in the present study using a closed loop of rat small intestine in situ, we found that the absorption of glycerol was faster than that of urea, a probe solute widely assumed to permeate exclusively via the paracellular route. This finding is inconsistent with the paracellular permeation hypothesis, which predicts that the absorption of glycerol, which is larger than urea in terms of molecular size, could not be faster than that of urea. We also found that glycerol absorption was saturable. These findings suggest the involvement of carrier-mediated transport in intestinal glycerol absorption. Glycerol absorption in the colon was also saturable, suggesting the involvement of carrier-mediated transport, although it was much slower than that in the small intestine. Carrier-mediated glycerol transport might play an important role in absorbing glycerol liberated from dietary triglyceride. It would be interesting to further examine the possibility that a carrier-mediated glycerol transport system (or systems) might be involved in drug absorption and also that it might be utilized for oral drug delivery.
Miscellaneous
Regular Articles
  • Yoshiharu Kobayashi, Noriko Tagawa, Kimie Muraoka, Yoshihiro Okamoto, ...
    原稿種別: Regular Article
    専門分野: Miscellaneous
    2003 年 26 巻 11 号 p. 1596-1599
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    We have investigated the serum levels of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) in type II collagen (CII)-induced arthritis (CIA) DBA/1J mice, an experimental model of human rheumatoid arthritis (RA). Serum levels of DHEA and DHEAS were measured by EIA and GC/MS, respectively. Sera were obtained from the mice on day 6, 13, 28 and 48 after the CII treatment. The disease onset of CIA was observed from day 28 (7%) to day 48 (80%) after CII immunization. The serum concentration of DHEA on day 13 did not differ from that on day 6 in CIA mice and untreated controls. Serum levels of DHEA on day 28 and 48 were significantly low compared with those on day 6 in controls. However, in CIA mice, DHEA levels on day 28 and 48 were not decreased from those on day 6. No difference in the serum DHEAS level on day 13 compared with day 6 was observed in either control or CIA mice. A significant decrease of DHEAS levels on day 28 and 48 compared with day 6 was found in both groups. The time point for the retention of DHEA in CIA mice, day 28 and day 48, coincided with the disease onset of CIA. In conclusion, endogenous DHEA may be produced as a result of physiological response for the protection against CIA.
  • Lien-Chai Chiang, Hua-Yew Cheng, Mei-Chi Liu, Wen Chiang, Chun-Ching L ...
    原稿種別: Regular Article
    専門分野: Miscellaneous
    2003 年 26 巻 11 号 p. 1600-1604
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    As an effort to search for new antiviral agents from traditional medicine, the hot water (HW) extract of twelve traditionally used medicinal plants in Taiwan was evaluated for their in vitro anti-herpes simplex viruses (HSV; including HSV-1 and HSV-2) and anti-adenoviruses (ADV; including ADV-3, ADV-8 and ADV-11) activities with a XTT-based colorimetric assay. Results showed that the tested HW extracts exhibited anti-HSV and anti-ADV activities at different magnitudes of potency. Among the twelve medicinal plants, Boussingaultia gracilis var. pseudobaselloides (Basellaceae) and Serissa japonica (Rubiaceae) possessed broad spectrum of antiviral activity. Ardisia squamulosa (Myrsinaceae) and Artemisai princeps var. orientalis (Compositae) were more effective in inhibiting ADV-8 replication than the other four viruses. Cell cytotoxic assay demonstrated that all tested HW extracts had CC50 values higher than their EC50 values. It was concluded that the twelve traditionally used medicinal plants in Taiwan possessed antiviral activity, and some of them merit further investigation.
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