Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
28 巻 , 12 号
選択された号の論文の36件中1~36を表示しています
Biochemistry
Regular Articles
  • Jong Keun Son, Min Jung Son, Eunkyung Lee, Tae Chul Moon, Kun Ho Son, ...
    2005 年 28 巻 12 号 p. 2181-2184
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A2 inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase-2 (COX-2) in vitro effect. Ginkgetin inhibits COX-2 dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50 values of 0.75 μM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD2 product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 0.33 μM. These results demonstrate that ginkgetin has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound also inhibited degranulation reaction in a dose dependent manner, with an IC50 value of 6.52 μM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.
Notes
  • Futoshi Shibata, Ai Ito, Yoshiaki Ohkuma, Ken-ichiro Mitsui
    2005 年 28 巻 12 号 p. 2312-2314
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    S100A9 is a calcium binding protein found in high amounts in granulocytes and monocytes. We have shown that S100A9 stimulated the proliferation of fibroblasts, but its mechanism remains unknown. In this report, S100A9 is shown to be mitogenic and to stimulate fibroblast proliferation without other growth factors in the serum. Although an S100A8/S100A9 heteropolymer inhibited the growth of fibroblasts by chelating zinc ions, these ions had no effect on the growth-stimulating activity of S100A9. The effects of serum and S100A9 on fibroblast growth were additive, and S100A9 stimulated the growth without serum. Furthermore, S100A9 stimulated the incorporation of bromodeoxyuridine in fibroblasts. However, the effect of S100A9 on the activation of extracellular signal regulated protein kinases (ERK) was small. These results suggest that S100A9 is involved in the regulation of inflammatory processes by modulating fibroblast proliferation.
  • Masahiro Fujimuro, Tadashi Nishiya, Yasuyuki Nomura, Hideyoshi Yokosaw ...
    2005 年 28 巻 12 号 p. 2315-2318
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Polyubiquitination plays key roles in various proteasome-dependent and independent cellular events. To elucidate roles in stress response of polyubiquitin chains formed via specific chain linkages in mammalian cells, we established NIH3T3 stable cell lines that are capable of conditionally expressing K29R, K48R and K63R ubiquitin mutants, in which the Lys29, Lys48 and Lys63 residues of ubiquitin had been changed to Arg, and we examined the effects of various stresses on their cell viabilities. The expression of K63R ubiquitin mutant decreased viability of the cells post-exposed to ethanol, H2O2 and methyl methanesulfonate (MMS), while that of K48R mutant decreased viability of the cells post-exposed to heat shock as well as ethanol, H2O2 and MMS. Thus, these results suggest that polyubiquitin chains formed via specific chain linkages are involved in the respective stress responses in mammalian cells.
Molecular and Cell Biology
Regular Articles
Pharmacology
Regular Articles
  • Ponugoti Vasantha Rao, Atsushi Shimazaki, Masaki Ichikawa, Jorge A. Al ...
    2005 年 28 巻 12 号 p. 2189-2196
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    To determine efficacy and therapeutic index in the context of ocular hypotensive activity of the new ethacrynic acid (ECA) derivatives of the 8000 series (SA8248 and SA8389), 9000 series (SA9000, SA9622 and SA9995) and ticrynafen, we undertook a comparative evaluation of the dose-dependent effects of these compounds on human trabecular meshwork (HTM) cell shape, actin cytoskeletal organization, focal adhesions and transcellular fluid flow. Responses were either scored using an arbitrary scale of 1—5 or quantified. Compounds of the 9000 series (SA9995>SA9000>SA9622) were found to be 14- to 20-fold more potent than ECA, ticrynafen or analogs from the 8000 series (SA8389>SA8248) in terms of ability to induce cell shape alterations in HTM cells. Similarly, compounds of the 9000 series (SA9995>SA9622>SA9000) were found to be much stronger (2 to 20 fold) than ECA, ticrynafen or analogs of the 8000 series in terms of affecting decreases in actin stress fiber content in HTM cells. Analogs of the 9000 series (SA9622>SA9995>SA9000) were also observed to be 8 to 10 fold more potent than ECA (SA8389>ECA>SA8248>ticrynafen) at eliciting decreases in cellular focal adhesions. Interestingly, analogs of the 9000 series (SA9000>SA9622>SA9995) and SA8248 demonstrated a huge increase (by many folds) in transcellular fluid flow of HTM cell monolayers as compared to ECA and ticrynafen. Collectively, these analyses revealed that the structural modification of ECA improves its ocular hypotensive efficacy, indicating that the SA9000 series compounds might be promising novel ocular hypotensive drugs.
  • Shuishi Jiang, Tae Tsumuro, Miho Takubo, Yoko Fujii, Chiaki Kamei
    2005 年 28 巻 12 号 p. 2197-2200
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    The effect of ethanol extract obtained from Bulgaria inquinans on the scratching behavior and vascular permeability changes induced by compound 48/80, histamine and serotonin in ICR mice was studied. The extract dose-dependently inhibited scratching behavior induced by compound 48/80 and serotonin. A significant inhibition was observed at doses of 300 and 600 mg/kg when Bulgaria inquinans extract was administered orally. However, no inhibitory effect was observed on the histamine-induced scratching behavior by the extract, even at a dose of 600 mg/kg. In addition, it also inhibited the increase in the vascular permeability induced by compound 48/80 and serotonin at doses of 300 and 600 mg/kg; however, it failed to inhibit the increased vascular permeability induced by histamine, even at a dose of 600 mg/kg. Bulgaria inquinans extract showed a potent inhibitory effect on histamine release induced by compound 48/80. These results suggest that Bulgaria inquinans extract is effective in cutaneous pruritus and erythema, which were probably mediated by inhibiting the release of histamine from mast cells and antagonizing the effect on serotonin.
  • Ying Yang, Jian Qiao, Zhenlong Wu, Yue Chen, Mingyu Gao, Deyuan Ou, Hu ...
    2005 年 28 巻 12 号 p. 2201-2205
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Evidence has indicated that endothelin-1 is related to the pathogenesis of hypertension. To characterize the role of endothelin-1 (ET-1) in the development of pulmonary hypertension syndrome in broilers, the blockade effect of ETA receptor (ETA) antagonist, BQ123, on blood pressure in experimental models of pulmonary hypertension was examined. Birds were locally anesthetized and instrumented with venous catheters for pulmonary arterial pressure (PAP) and right ventricular pressure (RVP), followed by packed cell volume (PCV) and Ascites heart index (AHI) measured, after exposed to low ambient temperature for 7 or 14 d. In treated groups, BQ123 (0.4 or 2.0 μg/kg each time, 2 times a day), administered in abdominal cavities for 7 or 14 d during birds kept in low ambient temperature, prevented both PAP and RVP increasing, especially the high dose BQ123 lowered PAP and RVP to normotensive levels as that in control under normal temperature, whereas significant increases (p<0.05) were found in the two parameters of broilers in both untreated and saline treated group under low ambient temperature compared with those of birds in control. Furthermore, there was also a reduction in low ambient temperature-induced right ventricular hypertrophy in the groups administered BQ123. The preventive effect of BQ123 suggests that ET-1 is associated with the development of broilers' pulmonary hypertension, which leads to the development of ascites, and BQ123 can prevent the occurrence of pulmonary hypertension.
  • Su-Hui Chao, An-Bang Wu, Chia-Jung Lee, Fu-An Chen, Ching-Chiung Wang
    2005 年 28 巻 12 号 p. 2206-2210
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Indomethacin is used as an anti-inflammatory drug and a nonselective cyclooxygenase inhibitor. When indomethacin in methanol was photo-irradiated with an Hg lamp, methyl ester, ethyl ester, and γ-lactone derivatives of indomethacin were produced. In the present study, we found that the methyl ester derivative of indomethacin (M-IN) could more potently inhibit prostaglandin E2 (PGE2) and nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX 2) protein expression from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells than indomethacin, similar to the effect of a non-steroidal anti-inflammatory drugs (NSAID). On the other hand, the results showed that M-IN with an IC50 value maintained at 36.9 μg/ml for 12 h exhibited stronger cytotoxicity than ethyl ester, γ-lactone derivatives of indomethacin, and indomethacin in promyelocytic leukemia HL-60 cells. Moreover, a series of biochemical analyses determined that M-IN caused apoptotic bodies, DNA fragmentation, and enhanced PARP and pro-caspase 3 degradation in HL-60 cells. These above results indicate that the photosynthesized product, M-IN, had stronger anti-inflammatory effects in LPS-stimulated RAW 264.7 cells and cytotoxicity effects in HL-60 cells than the parent drug, indomethacin.
  • Jun-Dong Zhang, Yong-Bing Cao, Zheng Xu, Hui-Hua Sun, Mao-Mao An, Lan ...
    2005 年 28 巻 12 号 p. 2211-2215
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We have isolated eight steroid saponins from Tribulus terrestris L., namely TTS-8, TTS-9, TTS-10, TTS-11, TTS-12, TTS-13, TTS-14 and TTS-15. TTS-12 and TTS-15 were identified as tigogenin-3-O-β-D-xylopyranosyl(1→2)-[β-D-xylopyranosyl(1→3)]-β-D-glucopyranosyl(1→4)-[α-L-rhamnopyranosyl(1→2)]-β-D-galactopyranoside and tigogenin-3-O-β-D-glucopyranosyl(1→2)-[β-D-xylopyranosyl(1→3)]-β-D-glucopyranosyl(1→4)-β-D-galactopyranoside, respectively. The in vitro antifungal activities of the eight saponins against six fluconazole-resistant yeasts, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, and Cryptococcus neoformans were studied using microbroth dilution assay. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and C. neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against fluconazole-resistant C. albicans (MIC80=4.4, 9.4 μg/ml), C. neoformans (MIC80=10.7, 18.7 μg/ml) and inherently resistant C. krusei (MIC80=8.8, 18.4 μg/ml). So in vivo activity of TTS-12 in a vaginal infection model with fluconazole-resistant C. albicans was studied in particular. Our studies revealed TTS-12 also showed in vivo activities against fluconazole-resistant yeasts. In conclusion, steroid saponins TTS-12 and TTS-15 from Tribulus terrestris L. have significant in vitro antifungal activity against fluconazole-resistant fungi, especially TTS-12 also showed in vivo activity against fluconazole-resistant C. albicans.
  • Dong-Seok Kim, So-Young Kim, Seo-Hyoung Park, Yeong-Gon Choi, Sun-Bang ...
    2005 年 28 巻 12 号 p. 2216-2219
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    In this study, we investigated the effects of 4-n-butylresorcinol on melanogenesis in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Our results show that 4-n-butylresorcinol significantly inhibits melanin synthesis in a concentration-dependent manner. In addition, it was also found to inhibit the activity of tyrosinase, the rate-limiting melanogenic enzyme. Several reports have indicated that the activation of extracellular signal-regulated kinase (ERK) or of Akt reduces melanin synthesis via microphthalmia-associated transcription factor (MITF) down-regulation. Accordingly, we examined the effects of 4-n-butylresorcinol on the ERK and Akt signaling pathways. 4-n-Butylresorcinol did not induce ERK, Akt activation, or MITF degradation, and had no effect on cAMP response element binding protein (CREB) phosphorylation, which stimulates MITF expression. In contrast, 4-n-butylresorcinol strongly reduced tyrosinase activity in a cell-free system. Moreover, 4-n-butylresorcinol showed an additive effect in combination with hinokitiol, which reduces MITF expression. These results show that the hypopigmentary effect of 4-n-butylresorcinol results from its direct inhibition of tyrosinase.
  • Dong-Chan Kim, Sun-Hee Kim, Bo-Hwa Choi, Nam-In Baek, Daeho Kim, Mahn- ...
    2005 年 28 巻 12 号 p. 2220-2224
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Curcuma longa has been commonly used as a traditional remedy for a variety of symptoms such as inflammation, gastritis and gastric ulcer. When C. longa extract was administered per os to pylori-ligated rat stomachs, it reduced gastric acid secretion and protected against the formation of gastric mucosal lesions. We therefore tested whether C. longa extract inhibits gastric ulcers by blocking the H2 histamine receptor. Dimaprit, a H2 histamine receptor agonist, induced intracellular cAMP production in U937 and HL-60 promyelocytes. Pretreatment with C. longa extract significantly blocked dimaprit-induced cAMP production in a concentration dependent manner, but had no effect on the elevation of cAMP levels triggered by isoproterenol-induced β2-adrenoceptor activation in U937 cells. To identify the active component(s) of C. longa extract, we sequentially fractionated it by extraction with ethyl acetate, n-butanol and water. We found that the ethyl acetate extract showed the most potent H2R antagonistic effect against dimaprit-induced cAMP production. However, curcumin, a major component of C. longa extract, showed no H2R blocking effect. C. longa ethanol extract and ethylacetate extract also blocked the binding of [3H]-tiotidine to membrane receptors on HL-60 cells. These findings suggest that the extract from C. longa specifically inhibits gastric acid secretion by blocking H2 histamine receptors in a competitive manner.
  • Abdelnaser Abdelghany Elzaawely, Tran Dang Xuan, Shinkichi Tawata
    2005 年 28 巻 12 号 p. 2225-2230
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    We evaluated total phenolic content, antioxidant activity, reducing power and antibacterial activity of ethanol, hexane, chloroform, ethyl acetate and aqueous extracts of aerial parts of Rumex japonicus HOUTT. The ethyl acetate extract had the highest amount of phenolic compounds. It also exhibited the highest reducing power and antioxidant activity when assayed by the 1,1-diphenyl-2-picrylhydrazyl (DPPH), β-carotene bleaching and superoxide radical methods. The ethyl acetate extract possessed the strongest antibacterial activity against Bacillus subtilis, B. cereus and E. coli. GC-MS analysis indicated that ethyl acetate extract contained a variety of phenolic compounds. HPLC analysis showed that pyrogallol was the predominant phenolic compound in this extract. Thus, our study verified that the ethyl acetate extract has strong antioxidant and antibacterial activities which are correlated with its high level of phenolic compounds, particularly pyrogallol and pyrocatechin. This extract of R. japonicus aerial parts can be utilized as an effective and safe source of antioxidants.
  • Mai Thanh Thi Nguyen, Suresh Awale, Yasuhiro Tezuka, Liying Shi, Syed ...
    2005 年 28 巻 12 号 p. 2231-2234
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    The effects of acacetin (1) and 4,5-O-dicaffeoylquinic acid methyl ester (2), compounds contained in the flowers of Chrysanthemum sinense SABINE, on the serum uric acid level were investigated using the rats pretreated with the uricase inhibitor potassium oxonate as an animal model for hyperuricemia. When administered per orally at doses of 20 and 50 mg/kg, 1 reduced the serum uric acid level by 49.9 and 63.9%, respectively and 2 reduced the level by 31.2 and 44.4%, respectively. On the other hand, when the same doses were given intraperitoneally, both of compounds also exhibited a dose-dependent and more marked reduction of the serum uric acid level (% reduction at 20 and 50 mg/kg were 63.0 and 95.1% in 1, respectively and 66.9 and 86.5% in 2, respectively). Furthermore, the compounds 1 and 2 inhibited the rat liver xanthine oxidase activity with IC50 values of 2.22 μM and 5.27 μM, respectively. These results demonstrated the hypouricemic action of 1 and 2, which may be attributable to their xanthine oxidase inhibitory activity.
  • Yoshikazu Goto, Shirou Itagaki, Shinichiro Umeda, Masaki Kobayashi, Ta ...
    2005 年 28 巻 12 号 p. 2235-2239
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Telmisartan is the most recently marketed angiotensin II type 1 receptor antagonist. Drug–drug interactions involving transporters can directly affect the therapeutic safety and efficacy of many important drugs. In clinical practice, telmisartan is coadministered with many kinds of drugs. However, little is known about the contribution of transporters to the intestinal transport of telmisartan. The aim of this study was to determine the transport mechanism of telmisartan across intestinal epithelial cells. In the presence of an inwardly directed proton gradient, the apical-to-basal transport of telmisartan was greater than basal-to-apical transport. Thus, we focused on the uptake mechanism of telmisartan across brush-border membranes. The uptake of telmisartan by Caco-2 cells was shown to be energy- and proton-dependent. Although some monocarboxylates inhibited the uptake of telmisartan, L-lactic acid, which is a typical substrate of the monocarboxylate transporter (MCT) 1—MCT4, did not affect the uptake of telmisartan. Preloading of acetic acid enhanced the uptake of telmisartan, showing a trans-stimulation effect. These results suggest that the carrier-mediated transport system is involved in the uptake of telmisartan by Caco-2 cells and that the apical-localized transport system is similar to MCTs, but not MCT1—MCT4. It is possible that telmisartan reduce the absorption of coadministered drugs by sharing the MCTs. Since MCTs have an important role in the intestinal absorption of pharmacologically active compounds, it is important to be aware of the potential of telmisartan–drug interactions involving MCTs and to act in order to prevent undesirable and harmful consequences.
  • Susumu Imaoka, Noriko Obata, Toyoko Hiroi, Mayuko Osada-Oka, Rie Hara, ...
    2005 年 28 巻 12 号 p. 2240-2243
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Liver–kidney microsomal antibodies type 1 (LKM-1) are a diagnostic marker for autoimmune hepatitis type II (AIH-II). However, LKM autoantibodies are also detected in a small percentage of patients with chronic hepatitis C. The autoantigen to anti-LKM-1 has been identified to be CYP2D6. To identify the specific antigenic site of CYP2D6 for LKM-1 serum, we established an ELISA with peptides spanning the entire sequence of CYP2D6. Human CYP2D6 containing histidine tag was expressed in Escherichia coli. Purified CYP2D6 was digested by lysyl endopeptidase. The linker including the histidine tag has a lysine residue in its C-terminal and can be removed by digestion. Digested peptides were separated by reversed-phase HPLC and coated on ELISA plates chemically with glutaraldehyde. The immunoreactivity of two LKM-1-positive sera (HCV-negative) and five HCV-positive sera from Japanese patients was investigated with the plates. These sera recognized peptides 1—146, 181—214, 246—281, 284—391, and 412—429. The peptide 1—146 was recognized by LKM-1-positive sera but not HCV-positive sera and is a new epitope found in this study. Seven short peptides spanning peptide 1—146 were synthesized and ELISAs were conducted with these peptides. However, two sera recognized none of these peptides, suggesting that two LKM-1-positive sera recognize the conformational immunogenic site of peptide 1—146.
  • Tomoka Nakamura, Motoko Honda, Satoko Kimura, Mitsuo Tanabe, Sen-ichi ...
    2005 年 28 巻 12 号 p. 2244-2247
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    To examine the relationship between motor ataxia and monoamine levels in the central nervous system, the contents and concentrations of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the cerebellum, brain stem and spinal cord were measured in rolling mouse Nagoya (RMN), a murine model of spinocerebellar atrophy. The tissue weight of the cerebellum and spinal cord, but not that of the brain stem was significantly lower in RMN than in the control group. In RMN, the NA content of the brain stem and spinal cord, but not the cerebellum were decreased relative to the control, and the concentration of NA in the spinal cord was also lower, but not significant. The DA and 5-HT contents in each tissue did not differ from those of the control, but the concentrations of monoamines, except for DA, were elevated in the brain stem and spinal cord in RMN. In particular, the concentrations of NA, DA and 5-HT in the cerebellum were significantly increased in RMN. Repeated administration of tartilerin hydrate, an analog of thyrotropin-releasing hormone, improved the ataxia of RMN, and elicited no obvious changes in either monoamine content or concentration of cerebellum, brain stem and spinal cord. These results indicate that the concentration of DA, as well as NA and 5-HT, increased in the RMN cerebellum, and that tartilerin improves the motor function of these mice via mechanisms other than changes in the levels of NA, DA and 5-HT in the central nervous system.
Notes
  • Pragada Rajeswara Rao, Veeravalli Krishna Kumar, Routhu Kasi Viswanath ...
    2005 年 28 巻 12 号 p. 2319-2322
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    It has been suggested that the beneficial effects of reperfusing the myocardium might be in part reversed by the occurrence of reperfusion injury. Oxidative stress was suggested to be implicating in the pathogenesis of ischemia-reperfusion (I/R) injury. Many antioxidative plants were shown to be cardioprotective in experimental models of myocardial ischemia-reperfusion (I/R) injury. The present study was designed to investigate the effects of pretreatment with alcoholic extract of Tinospora cordifolia in an in vivo rat model. The model adopted was that of surgically-induced myocardial ischemia, performed by means of left anterior descending coronary artery occlusion (LAD) for 30 min followed by reperfusion for another 4 h. Infarct size was measured by using the staining agent TTC (2,3,5-triphenyl tetrazolium chloride). Lipid peroxide levels in serum and in heart tissue were estimated spectrophotometrically by the methods developed by Yagi and Ohkawa et al. respectively. A lead II electrocardiogram was monitored at various intervals throughout the experiment. A dose dependent reduction in infarct size and in lipid peroxide levels of serum and heart tissue were observed with the prior treatment of T. cordifolia with various doses for 7 d compared to control animals. Hence, the present study suggests the cardioprotective activity of T. cordifolia in limiting ischemia-reperfusion induced myocardial infarction.
  • Rong Jie Zhao, Byung Soo Koo, Geun Woo Kim, Eun Young Jang, Jong Rok L ...
    2005 年 28 巻 12 号 p. 2323-2326
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Behavioral sensitization, as evidenced by the progressive enhanced locomotor response to a subsequent injection of the drug, is the major behavioral outcome produced by repeated injections of nicotine, and a model for studying drug addiction. It is putatively regarded that the alteration of extracellular dopamine release in the nucleus accumbens is closely associated with nicotine-induced behavioral sensitization. The present study was performed to evaluate the effects of the essential oil from Angelica gigas NAKAI (on fragrance inhalation) on repeated nicotine-induced locomotor activity and extracellular dopamine levels in the nucleus accumbens of rats using in vivo microdialysis. Rats were given repeated injections of saline or nicotine (0.4 mg/kg s.c., twice a day for 7 d), followed by one challenge injection on the 4th day after the last daily injection. Systemic challenge with nicotine (0.4 mg/kg s.c.) produced a larger increase in locomotor activity in nicotine-pretreated rats than in saline-pretreated rats. A direct local challenge of 3 mM nicotine via a microdialysis probe also induced a larger increase in dopamine release in nicotine-pretreated rats than in saline-pretreated rats. Most importantly, our results showed that inhalation of the essential oils from Angelica gigas NAKAI significantly decreased both dopamine release in the nucleus accumbens and locomotor activity induced by a nicotine challenge. These results suggest that the essential oils from Angelica gigas NAKAI inhibit nicotine-induced behavioral and neurochemical sensitization, and imply that the essential oil from Angelica gigas NAKAI may be effective in treating nicotine addiction, possibly by modulating dopamine release in the nucleus accumbens.
  • Sundaramahalingam Manikandan, Ramasundaram Srikumar, Narayanaperumal J ...
    2005 年 28 巻 12 号 p. 2327-2330
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Exposure to continuous loud noise is a serious health problem due to excess production of oxygen free radicals. In medical research, more attention is paid to the antioxidant properties of medicinal plants to minimize the harmful effects of radicals. The aim of this study was to evaluate the protective effect of both ethyl acetate and methanolic extract of Acorus calamus LINN against noise stress (30 d, 100 dBA/4h/d) induced changes in the rat brain. We measured the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and the levels of reduced glutathione (GSH), vitamin C, vitamin E, protein thiols and lipid peroxidation (LPO) for the evaluation of oxidative stress status in discrete regions of the rat brain like cerebral cortex, cerebellum, pons-medulla, midbrain, hippocampus and hypothalamus. The results indicated that during exposure of noisy environment ROS generation led to increase in corticosterone, LPO and SOD, but decrease in CAT, GPx, GSH, protein thiols, vitamins C and E levels. Both the ethyl acetate and methanolic extract of Acorus calamus protected most of the changes in the rat brain induced by noise-stress.
  • Keiichiro Kizaki, Muneyoshi Okada, Ryoichi Ito, Kazuki Yoshioka, Kazuy ...
    2005 年 28 巻 12 号 p. 2331-2334
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Gene expression of heparanase, matrix metalloproteinases (MMP)-2 and MMP-9 were examined in ventricles after chronic treatment with isoproterenol (ISO) induced cardiac hypertrophy in rats. Rats were treated with ISO (4 mg/kg, intraperitoneal) twice daily for 4 d. Ventricle weight of the heart and the ventricle weight/body weight ratio were increased respectively by 22% and 25% compared with control rats. Histology showed considerable cardiomyocyte hypertrophy in the ISO-treated rats in comparison to control rats. Northern blot hybridization revealed that heparanase and MMP-2 gene transcripts increased significantly in the ventricles of ISO-treated rats, whereas MMP-9 gene expression was not induced. Thus, heparanase and MMP-2 gene expressions are induced in the ventricle after chronic treatment with ISO, indicating that they might play an important role in development of ISO-induced cardiac hypertrophy.
Pharmacognosy
Regular Articles
  • Do-Young Choi, Jeong-Eun Huh, Jae-Dong Lee, Eun-Mi Cho, Yong-Hyeon Bae ...
    2005 年 28 巻 12 号 p. 2248-2252
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine the angiogenic properties of Uncaria rhynchophylla. Uncaria rhynchophylla significantly enhanced human umbilical vein endothelial cells (HUVECs) proliferation in a dose-dependent manner. Neutralization of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) by monoclonal antibody suppressed the Uncaria rhynchophylla stimulatory effect on proliferation. In addition, Uncaria rhynchophylla significantly increased chemotactic-migration on gelatin and tubular structures on Matrigel of HUVECs in a dose-dependent manner. Interestingly, Uncaria rhynchophylla dose-dependently increased VEGF, and bFGF gene expression and protein secretion of HUVEC. The angiogenic activity of Uncaria rhynchophylla was confirmed using an in vivo Matrigel angiogenesis model, showing promotion of blood vessel formation. These results suggest that Uncaria rhynchophylla could potentially used to accelerate vascular wound healing or to promote the growth of collateral blood vessel in ischemic tissues.
  • Ming Hong Lee, Jae Yeon Kim, Jae-Ha Ryu
    2005 年 28 巻 12 号 p. 2253-2257
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) switches the function of NO from a physiological neuromodulator to a neurotoxic effector in central nervous system (CNS) after brain injury. From the methanol extracts of Psoralea corylifolia, we purified two inhibitors of NO production in lipopolysaccharide (LPS)-activated microglia by activity guided purification along with two inactive compounds. The active compounds were identified as a chromenoflavanone [7,8-dihydro-8-(4-hydroxyphenyl)-2,2-dimethyl-2H,6H-benzo-(1,2-b:5,4-b′)dipyran-6-one] (1) and 4-hydroxylonchocarpin (2). And the inactive two compounds were identified as bavachinin (3) and bavachalcone (4) by spectral analysis. The compound 2 was isolated first time from this plant. Compounds 1 and 2 inhibited the production of NO in LPS-activated microglia in a dose dependent manner (IC50's were 11.4, 10.2 μM, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at 10 μM as observed in Western blot analysis and RT-PCR experiment. Furthermore they inhibited the degradation of I-κB-α in activated microglia. These results imply that compounds 1 and 2 can be lead compounds for the development of neuroprotective drug with the inhibitory activity of NO overproduction by activated microglial cells.
  • Hye-Jin Park, Masahiko Kurokawa, Kimiyasu Shiraki, Norio Nakamura, Jae ...
    2005 年 28 巻 12 号 p. 2258-2262
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    The antiviral activities of extracts from 5 species of marine algae collected at Haeundae (Pusan, Korea), were examined using plaque reduction assays. Although the activity of a methanol (MeOH) extract of Sargassum ringoldianum (Sargassaceae) was the most potent against several types of viruses, it was also cytotoxic. A MeOH extract of Symphyocladia latiuscula (Rhodomelaceae) and its fractions exhibited antiviral activities against acyclovir (ACV) and phosphonoacetic acid (PAA)-resistant (APr) herpes simplex type 1 (HSV-1), thymidine kinase (TK) deficient HSV-1 and wild type HSV-1 in vitro without cytotoxicity. The major component, 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (TDB) of a CH2Cl2-soluble fraction was active against wild type HSV-1, as well as APr HSV-1 and TK HSV-1 (IC50 values of 5.48, 4.81 and 23.3 μg/ml, respectively). The therapeutic effectiveness of the MeOH extract and TDB from S. latiuscula was further examined in BALB/c mice that were cutaneously infected with HSV-1 strain 7401H. Three daily oral administrations of the MeOH extract and TDB significantly delayed the appearance of score 2 skin lesions (local vesicles) and limited the development of further score 6 (mild zosteriform) lesions in infected mice without toxicity compared with controls. In addition, TDB suppressed virus yields in the brain and skin. Therefore TDB should be a promising anti HSV agent.
Notes
  • Quan-Bin Han, Susan Cheung, Joseph Tai, Chun-Feng Qiao, Jing-Zheng Son ...
    2005 年 28 巻 12 号 p. 2335-2337
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    In this study, the stability of gambogic acid (GA), a polyprenylated xanthone with potent cytotoxicities against various cancer cell lines, was evaluated under several experimental conditions including addition of acids, alkalis and organic solvents. GA was stable when dissolved in acetone, acetonitrile, and chloroform, even when acids were added. However, a new derivative was produced after GA was stored in the methanol solution for a week at room temperature. The addition of alkalis could increase the rate of this chemical transformation. This derivative was determined to be gambogoic acid (GOA) by the HPLC-MS comparison with the known compound. GOA was proposed to be the product of neuclophilic addition of methanol to the olefinic bond at C-10 of GA. Furthermore, when these two compounds were tested for their cytotoxicity, GOA showed significantly weaker inhibitory effects than GA. It was therefore deduced that the α,β-unsaturated carbonyl moiety at C-10 contributed to the cytotoxicity of gambogic acid.
Biopharmacy
Regular Articles
  • Yujie Zhang, Qiang Zhang, Yikun Sun, Jianning Sun, Xiaoliang Wang, Min ...
    2005 年 28 巻 12 号 p. 2263-2267
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    The objective of this study was to investigate the feasibility of systemic absorption of recombinant hirudin-2 (rHV2) by nasal delivery, and its possible absorption mechanism. The degradation of rHV2 in the nasal tissue homogenate and extracts of mucosae of rabbit, as well as the degradation inhibition of enzyme inhibitor (bacitracin) was evaluated. The bioavailability of rHV2 and the improvement with enhancers, after nasal administration in rats was investigated. For further understanding of the transport and uptake characteristics of rHV2, in vitro transport experiment under various conditions using diffusion chamber technique in excised rabbit nasal epithelium was performed. It was found that rHV2 underwent rapid degradation in rabbit nasal homogenate, but it was more stable in the extracts of nasal mucosae surface. Bacitracin was able to inhibit the degradation of rHV2 to certain extent. rHV2 was detected in the rat plasma by chromogenic substrate assay after nasal administration and some enhancers also significantly increased the nasal absorption of rHV2. The transport and uptake of rHV2 across nasal epithelium was concentration-dependent and unsaturated, and was significantly inhibited by low temperature, NaN3, DNP and colchicines, while was less affected by alteration of transport direction. These results demonstrate that the possible absorption mechanism of rHV2 by nasal mucosa appears to be associated with the endocytosis as well as passive diffusion process.
  • Shigeharu Oie, Akira Kamiya
    2005 年 28 巻 12 号 p. 2268-2270
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    We evaluated particulate and microbial contamination in a total of 192 samples of in-use admixed and unadmixed parenteral nutrition solutions remaining in infusion bags in 10 hospitals. The mean numbers (range) of drug glass ampoules, plastic ampoules, and vials used in a total of 192 admixed solutions were 3.38 (1—13), 0.79 (0—7), and 1.2 (0—8), respectively. The mean number of particles (range) contained in the 192 samples according to the particle size (diameter) was 960.9 (30—9539)/ml for particles ≥1.3 μm, 42.8 (0—587)/ml for those ≥5 μm, 6.4 (0—146)/ml for those ≥10 μm, and 0.09 (0—1)/ml for those ≥50 μm. The number of particles ≥1.3 μm in diameter was significantly higher in the 192 samples than in 7 samples (controls) of solutions not mixed with any ampoule or vial (p<0.0001). In addition, the number of particles ≥1.3 μm in diameter was significantly higher in samples of solutions mixed with 4—13 glass ampoules than in those of solutions mixed with 1—3 glass ampoules (p<0.01). On the other hand, none of the 199 samples showed bacteria or fungi/5 ml residual solution. Measures against particulate contamination of admixed parenteral nutrition solutions are necessary.
  • Takeshi Kawata, Masato Homma, Yoshihiro Kakiuchi, Shinichi Inomata, Ma ...
    2005 年 28 巻 12 号 p. 2271-2273
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    We developed assay method for determination of plasma ropivacaine by using reversed-phase high performance liquid chromatography (HPLC) equipped with ordinary octadecylsilyl silica-gel (ODS) column. Plasma samples spiked with internal standard (bupivacaine) were treated by ethylacetate to extract ropivacaine and internal standard. The ropivacaine and internal standard separated on ODS column were detected by an ultra violet (UV) detector set at 215 nm. The mobile phase solvent consisted of acetonitrile, methanol and 0.05 M phosphate buffer adjusted to pH 4.0 (10 : 30 : 60, v/v) was pumped at a flow rate of 0.8 ml/min. The calibration curve of ropivacaine was linear at the concentration of 25—1000 ng/ml (r=0.9998). The recoveries of ropivacaine from plasma were greater than 87.9% with the coefficient of variations (CVs) less than 6.1%. The CVs for intra- and inter-day assay of ropivacaine were 2.0—12.0% and 1.7—14.8%, respectively. This HPLC method was applied to determining plasma ropivacaine in two healthy subjects after receiving 0.5% ropivacaine viscous preparation, which was prepared in our hospital. Our preliminary pharmacokinetic data showed that ropivacaine viscous could be used safely based on the plasma ropivacaine concentrations (Cmax: 89—125 ng/ml) for pain relief in oral mucosa.
  • Shuji Kitagawa, Tomohiro Nabekura, Tomoharu Takahashi, Yutaka Nakamura ...
    2005 年 28 巻 12 号 p. 2274-2278
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    We studied the effects of flavonoids, naringenin (flavanone), baicalein (flavone), kaempferol, quercetin, myricetin, morin, and fisetin (flavonols) as well as two glycosides of quercetin on P-glycoprotein (P-gp) function in multidrug-resistant P-gp overexpressing KB-C2 cells. Flavonoids such as kaempferol and quercetin increased the accumulation of rhodamine-123 dependent on their chemical structure. Analysis by flow cytometry indicated that the increase in substrate accumulation was due to the inhibition of substrate efflux. Naringenin, which lacks the 2,3-double bond in the C ring, had no effect, although it was more hydrophobic than myricetin, fisetin and morin. Therefore, the planar structure of the flavonoids seemed to be important for their interaction with P-gp. The effects of other flavonoids on the accumulation of daunorubicin were in the order of kaempferol>quercetin, baicalein>myricetin>fisetin, morin. Quercetin-3-O-glucoside and rutin had no effect. The order of the effects corresponded with that of the partition coefficients. Difference in the number and position of hydroxyl groups in flavonoid molecules by themselves seemed to have little effect. These results suggested that hydrophobicity as well as planar structure is important for the inhibitory effects of flavonoids on P-gp-mediated transport.
  • Chun-Ying Cui, Wan-Liang Lu, Lan Xiao, Shuang-Qing Zhang, Yan-Bei Huan ...
    2005 年 28 巻 12 号 p. 2279-2288
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    The purposes of this study were to evaluate effects of enhancers for sublingual delivering insulin on the mucosal lipid fluidity and protein conformation, transport, and in vivo hypoglycemic activity in normal rats. The effects on sublingual mucosa, and aggregation states of insulin were estimated using fluorescence polarization, and circular dichroism method, respectively. The human immortalized oral epithelial cell monolayer was used for evaluating transport of insulin. Hydroxylpropyl-β-cyclodextrin (HP-β-CD), chitosan, polyethylene–polypropylene glycol, polyoxyethylene lauryl ether, polysorbate 80, egg lecithin, or oleic acid, was used as a penetration enhancer, respectively. The fluidity of sublingual mucosal lipid was markedly reduced by these enhancers excluding polysorbate 80, and the secondary structure of the mucosal proteins was also influenced by these enhancers. The hexamers of insulin were dissociated to monomers only by chitosan, polyoxyethylene lauryl ether, and egg lecithin. Nonetheless, plasma glucose levels in normal rats were significantly lowered after sublingual administration of insulin with an enhancer compared with those without an enhancer at the same time-point. The enhancing effects may be due to one or multiple factors: increasing the mucosal lipid fluidity, directly loosing the tight junction of epithelia, and dissociating the hexamers of insulin to monomers. Among these, the opened tight junction may correlate most with the enhancing effect in the mucosal permeability. Because the aggregates of insulin exist, the dissociation of the aggregates by an enhancer would benefit the permeability.
Notes
  • Mayuko Ujibe, Syu-ichi Kanno, Yu Osanai, Kimiko Koiwai, Takaharu Ohtak ...
    2005 年 28 巻 12 号 p. 2338-2341
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    We found that octylcaffeate, a semisynthetic caffeic acid derivative, strongly inhibited the growth of human histiolytic lymphoma U937 cells in a dose- and time-dependent manner via apoptosis. Octylcaffeate induced the fragmentation of DNA into multiples of 180 bp (an apoptotic DNA ladder) and condensation of chromatin, and increased the percentage of hypodiploid cells detected with a flow cytometer. DNA fragmentation induced by octylcaffeate was inhibited by pretreatment with Z-DEVD-FMK and Z-Asp-CH2D-CB, an inhibitor of caspase, clearly showing that the mode of cell death is apoptotic. These findings suggest that the cytotoxicity of octylcaffeate involves the induction of apoptosis.
Miscellaneous
Regular Articles
  • Takuji Nakashima, Tadashi Tamura, Maki Kurachi, Kenichi Yamaguchi, Tat ...
    2005 年 28 巻 12 号 p. 2289-2295
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Recently we discovered a bacterial strain (MS-02-063) that produces large amounts of red pigment (PG-L-1). Among the cell lines tested, U937 cells showed the highest susceptibility to PG-L-1 toxicity. PG-L-1 induced typical apoptotic nuclear morphological changes, and single cell gel electrophoresis revealed that PG-L-1 caused DNA fragmentation in U937 cells. In PG-L-1 treated U937 cells, the acidic compartment such as lysosomes disappeared, suggesting that PG-L-1-induced disorder of intracellular pH compartmentalization might trigger apoptotic signal. Since p38 MAP kinase inhibitor specifically prevented the PG-L-1 mediated cell death, p38 MAP kinase may be involved in the cytotoxic mechanism. In fact, immunoblot analysis of p38 MAP kinase revealed that phosphorylation of p38 MAP kinase occurred in PG-L-1-treated U937 cells. In addition to the activity to induce apoptotic cell death as reported in several PG family members, our chemiluminescence analysis suggested that PG-L-1 inhibited superoxide generation by 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated U937 cells in a dose-dependent manner. Since PG-L-1 had no effect on the chemiluminescence response caused by xanthine oxidase/hypoxanthine system, PG-L-1 acts on the enzyme system responsible for O2 generation rather than direct scavenging toward O2. Our results suggest that PG-L-1 causes multiple biochemical effects on the target cells such as increase in pH in acidic intracellular compartment, activation of p38 MAP kinase, inhibition of O2 generation, and eventually induces apoptotic cell death.
  • Ying Ling Lai, Masayoshi Yamaguchi
    2005 年 28 巻 12 号 p. 2296-2301
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    The effects of copper on biochemical components in the femoral-diaphyseal (cortical bone) and -metaphyseal (trabecullar bone) tissues of rats in vivo and in vitro were investigated. Rats were orally administered copper sulfate (50, 100, or 200 μg Cu/100 g body weight) once daily for 7 d. Calcium content in the diaphyseal and metaphyseal tissues was significantly decreased with the administration of copper (200 μg/100 g), while alkaline phosphatase activity in these tissues was not significantly changed by copper administration. The diaphyseal DNA content was significantly decreased with the administration of copper (50, 100, or 200 μg/100 g). Moreover, the femoral-diaphyseal and -metaphyseal tissues were cultured for 48 h in serum-free medium containing either vehicle or copper (10−7—10−4 M). Culture with copper (10−7—10−4 M) caused a significant decrease in alkaline phosphatase activity in the diaphyseal and metaphyseal tissues, while calcium and DNA contents in these tissues were not significantly changed. Culture with parathyroid hormone [PTH (1-34); 10−7 M], a bone-resorbing factor, caused a significant decrease in calcium content in the diaphyseal and metaphyseal tissues. This decrease was completely inhibited in the presence of copper (10−6 or 10−5 M). Culture with zinc sulfate (10−4 M) caused a significant increase in calcium content and alkaline phosphatase activity in the diaphyseal and metaphyseal tissues. The effects of zinc (10−4 M) in increasing femoral calcium content and alkaline phosphatase activity were not seen in the presence of cycloheximide (10−6 M), an inhibitor of protein synthesis, suggesting that the effects of zinc are involved in newly synthesized protein components. The effects of zinc in increasing calcium content and alkaline phosphatase activity in the diaphyseal and metaphyseal tissues were significantly weakened in the presence of copper (10−4 M). The inhibitory effects of copper were further enhanced in the presence of cycloheximide. This study demonstrates that supplementation with copper in adequate copper nutrition does not have anabolic effects on bone components in vivo and in vitro and that copper weakens the anabolic effects of zinc in vitro.
  • Kazue Tsukahara, Shigeru Moriwaki, Mitsuyuki Hotta, Tsutomu Fujimura, ...
    2005 年 28 巻 12 号 p. 2302-2307
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    It has been reported that application of sunscreens prevents the photoaging of skin in animal models and in humans. We irradiated the dorsal skin of hairless mice with ultraviolet-A (UVA), and investigated the effects of sunscreens on skin elastase activity and on skin properties. Six-week-old female HR/ICR hairless mice were used in these experiments. After being treated with either a UVA sunscreen (also containing ultraviolet-B (UVB) sunscreen to eliminate any slight UVB in the UVA lamps; Protection Factor of UVA (PFA)=6, Sun Protection Factor (SPF)=20) or a vehicle, the dorsal skins of mice were irradiated with the UVA lamps at 22.3 J/cm2/d, 5 times a week. At the end of 15 weeks skin properties were evaluated and elastase activities were measured. In the vehicle control group, UVA irradiation increased the brightness and yellowing of the skin, decreased the water content of the stratum corneum, increased skin thickness, decreased skin elasticity, increased skin elastase activity, and decreased the ability of the skin to recover in a pinch test, as compared to an unirradiated group. All these differences were statistically significant. In the UVA sunscreen group, both the UVA induced skin damage and the increase in skin elastase activity were significantly inhibited, as compared to the vehicle group. However, as compared to the unirradiated group, skin elastase activity was significantly increased and immediate extensibility of skin (Ue) was significantly decreased, thereby indicating that the UVA sunscreen did not prevent photoaging to the same level as the unirradiated group. These results suggest the partial efficacy of the topical photoprotection from UVA by the sunscreen in inhibiting elastase activation, and also suggest the possibility of reducing photoaging.
  • Tatsumi Adachi, Manabu Kunimoto
    2005 年 28 巻 12 号 p. 2308-2311
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    We investigated acute cytotoxic effects and Hg accumulation after exposure to methylmercury (MeHg) or Hg2+ in the presence or absence of serum in cultured astrocytes prepared from the cerebral hemisphere or cerebellum of newborn rats. Dose-related changes in viable cell numbers after exposure to mercuric compounds were not different between astrocytes from both regions under the specified conditions. Accumulation of each compound for 3 h was similar in both astrocytes but that for 24 h became different, especially that of Hg2+. In both astrocytes, susceptibility to the respective compounds was higher in the order of those exposed immediately after, without, and 24 h after changing the serum-containing medium to a serum-free defined medium (SFDM). Accumulation for 3 h was higher in the respective astrocytes exposed to MeHg or Hg2+ immediately after being maintained in SFDM than in those exposed 24 h after. These results suggest that accumulation of mercuric compounds up to 3 h strongly correlates with susceptibility, at least when maintained in SFDM. Astrocytic morphology changed to a satellite shape after the medium change to SFDM particularly in cerebellar astrocytes but only a few in cerebral hemisphere astrocytes, and it was reverted to a polygonal shape by MeHg but not Hg2+ at 3 μM. The present results suggest that although some properties such as morphological changes and Hg accumulation are different between cerebral hemisphere and cerebellar astrocytes, these differences are not simply reflected by susceptibility to the acute cytotoxicity of mercuric compounds.
Notes
  • Toshie Harada, Susumu Masuda, Masayuki Arii, Yoshiyuki Adachi, Mitsuhi ...
    2005 年 28 巻 12 号 p. 2342-2345
    発行日: 2005年
    公開日: 2005/12/01
    ジャーナル フリー
    Soy isoflavone aglycones (IFAs) have a wide range of biological actions that suggest they may be of use in cancer prevention. On the other hand, a branched β-glucan from Sparassis crispa (SCG) is a major 6-branched 1,3-β-D-glucan in an edible/medicinal mushroom: Sparassis crispa showing antitumor activity. We have previously reported that both oral and intraperitoneal administration of SCG enhanced the hematopoietic response in cyclophosphamide (CY)-induced leukopenic mice. In this study, we investigated the hematopoietic response due to IFA in combination with SCG in CY-induced leukopenic mice. The oral administration of IFA in combination with SCG synergistically enhanced the number of white blood cells, and increased spleen weight. Analyzing the leukocyte population by flow cytometry, the combination of IFA and SCG increased the number of monocytes and granulocytes in the spleen. Taken together, the combination of IFA and SCG synergistically provides the hematopoietic responses that are enhanced over IFA or SCG alone.
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