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71.
We investigated the cell death effects of eight xanthones on PC12 rat pheochromocytoma cells. Among these compounds, alpha-mangostin, from the fruit hull of Garcinia mangostana L., had the most potent effect with the EC(50) value of 4 microM. Alpha-mangostin-treated PC12 cells demonstrated typical apoptotic DNA fragmentation and caspase-3 cleavage (equivalent to activation). The flow cytometric analysis indicated that this compound induced apoptosis in time-and concentration-dependent manners. Alpha-mangostin showed the features of the mitochondrial apoptotic pathway such as mitochondrial membrane depolarization and cytochrome c release. Furthermore, alpha-mangostin inhibited the sarco(endo)plasmic reticulum Ca(2+)-ATPase markedly. There was a correlation between the Ca(2+)-ATPase inhibitory effects and the apoptotic effects of the xanthone derivatives. On the other hand, c-Jun NH(2)-terminal kinase (JNK/SAPK), one of the signaling molecules of endoplasmic reticulum (ER) stress, was activated with alpha-mangostin treatment. These results suggest that alpha-mangostin inhibits Ca(2+)-ATPase to cause apoptosis through the mitochondrial pathway. 相似文献
72.
Neamphamide A, a new HIV-inhibitory depsipeptide from the Papua New Guinea marine sponge Neamphius huxleyi 总被引:2,自引:0,他引:2
Oku N Gustafson KR Cartner LK Wilson JA Shigematsu N Hess S Pannell LK Boyd MR McMahon JB 《Journal of natural products》2004,67(8):1407-1411
A new HIV-inhibitory cyclic depsipeptide, neamphamide A (2), was isolated from a Papua New Guinea collection of the marine sponge Neamphius huxleyi. Its structure was established through interpretation of spectroscopic data and by acid hydrolysis, derivatization of the free amino acids, and LC-MS analysis of the derivatives. Neamphamide A (2) contains 11 amino acid residues and an amide-linked 3-hydroxy-2,4,6-trimethylheptanoic acid moiety. The amino acid constituents were identified as L-Leu, L-NMeGln, D-Arg, D- and L-Asn, two residues of D-allo-Thr, L-homoproline, (3S,4R)-3,4-dimethyl-L-glutamine, beta-methoxytyrosine, and 4-amino-7-guanidino-2,3-dihydroxyheptanoic acid. In a cell-based XTT assay, 2 exhibited potent cytoprotective activity against HIV-1 infection with an EC50 of approximately 28 nM. 相似文献
73.
Antiangiogenic photodynamic therapy (PDT) using Visudyne causes effective suppression of tumor growth 总被引:1,自引:0,他引:1
Ichikawa K Takeuchi Y Yonezawa S Hikita T Kurohane K Namba Y Oku N 《Cancer letters》2004,205(1):39-48
We previously observed that antiangiogenic photodynamic therapy (PDT), namely, laser irradiation at 15 min after administration of photosensitizer, by using stable liposomal benzoporphyrin derivative monoacid ring A (BPD-MA), in which the liposomes were composed of dipalmitoylphosphatidylcholine, palmitoyloleoylphosphatidylcholine, cholesterol, and dipalmitoylphosphatidylglycerol (10:10:10:2.5 as a molar ratio), was quite effective for cancer treatment. On the other hand, Visudyne, a commercialized liposomal formulation of BPD-MA, is based on more fluid lipids, namely, dimyristoylphosphatidylcholine and egg yolk phosphatidylglycerol, and is thought to be less stable in the presence of serum. The data of spin column chromatography indicated a little faster transfer of BPD-MA from Visudyne to lipoprotein fraction when Visudyne was incubated with serum than when the stable liposomal BPD-MA was used. The phototoxicity of Visudyne against a human endothelial cell line, ECV304, was almost the same as that of stable liposomal BPD-MA after PDT treatment. Therefore, we examined the antiangiogenic scheduling of PDT with Visudyne. Tumor growth of Meth-A sarcoma-bearing mice was strongly suppressed when the antiangiogenic scheduling was performed with Visudyne, namely, irradiation at 15 min after injection of the drug, in comparison with the conventional scheduling in which laser irradiation is done at 3 h post-injection. This greater effectiveness of PDT at 15 min was suggested to be caused by hemostasis, based on observations made in a dorsal air sac angiogenesis model. Visudyne-mediated antiangiogenic PDT cured 40 or 60% of Meth-A-bearing mice completely when 0.25 or 0.5 mg/kg BPD-MA, respectively, was used. These data suggest that the antiangiogenic scheduling is effective in Visudyne-mediated cancer PDT despite the transferring of BPD-MA from the liposomal fraction to lipoproteins in the bloodstream. 相似文献
74.
Takanashi K Takahashi M Miyanishi K Hayashi T Takada K Oku T Ishiwatari H Kogawa T Takayama T Kato J Niitsu Y 《Gan to kagaku ryoho. Cancer & chemotherapy》2004,31(9):1415-1417
The patient was a 78-year-old male with a history of colon cancer. After surgical resection of colon cancer, he suffered a multiple liver metastasis. We treated him by arterial infusion chemotherapy with the catheter edge embedded at the common hepatic artery. For a long period, the lesions were defined as partial response on WHO-criteria, but a wide area of the common hepatic artery was shrunk. After changing the treatment to systemic intravenous chemotherapy, the metastatic lesions began to enlarge. Then, we somehow were able to put a microcatheter into the replaced right hepatic artery (rRHA), and could restart arterial infusion chemotherapy. We continued this procedure for over a year without any complication. 相似文献
75.
Osaki Y Doi K Takasawa M Noda K Nishimura H Ihara A Iwaki T Imaizumi M Yoshikawa T Oku N Hatazawa J Kubo T 《Neuroreport》2004,15(2):287-291
We compared neural activation detected by magnetoencephalography (MEG) during tactile presentation of words and non-words in a postlingually deaf-blind subject and six normal volunteers. The left postcentral gyrus, bilateral inferior frontal gyri, left posterior temporal lobe, right anterior temporal lobe, bilateral middle occipital gyri were activated when tactile words were presented to the right hand of the deaf-blind subject. This set of activated regions was not observed in the normal volunteers, although activation of several combinations of these regions was detected. Positron emission tomography confirmed the location of the MEG-activated areas in the deaf-blind subject. Our results demonstrated that the deaf-blind subject is heavily involved in interpreting tactile language by enhancing cortical activation of cognitive and semantic processing. 相似文献
76.
Multiple modes of action of tacrolimus (FK506) for neuroprotective action on ischemic damage after transient focal cerebral ischemia in rats 总被引:9,自引:0,他引:9
Furuichi Y Noto T Li JY Oku T Ishiye M Moriguchi A Aramori I Matsuoka N Mutoh S Yanagihara T 《Brain research》2004,1014(1-2):120-130
While the immunosuppressant tacrolimus (FK506) is known to be neuroprotective following cerebral ischemia, the mechanisms underlying its neuroprotective properties are not fully understood. To determine the mode of action by which tacrolimus ameliorates neurodegeneration after transient focal ischemia, we therefore evaluated the effect of tacrolimus on DNA damage, release of cytochrome c, activation of microglia and infiltration of neutrophils following a 60-min occlusion of the middle cerebral artery (MCA) in rats. In this model, cortical brain damage gradually expanded until 24 h after reperfusion, whereas brain damage in the caudate putamen was fully developed within 5 h. Tacrolimus (1 mg/kg) administered immediately after MCA occlusion significantly reduced ischemic damage in the cerebral cortex, but not in the caudate putamen. Tacrolimus decreased both apoptotic and necrotic cell death at 24 h and reduced the number of cytochrome c immunoreactive cells at 8 h after reperfusion in the ischemic penumbra in the cerebral cortex. In contrast, tacrolimus did not show significant neuroprotection for necrotic cell death and reduction of cytochrome c immunoreactive cells in the caudate putamen. Tacrolimus also significantly decreased microglial activation at 8 h and inflammatory markers (cytokine-induced neutrophil chemoattractant and myeloperoxidase [MPO] activity) at 24 h after reperfusion in the ischemic cortex but not in the caudate putamen. These results collectively suggest that tacrolimus ameliorates the gradually expanded brain damage by inhibiting both apoptotic and necrotic cell death, as well as suppressing inflammatory reactions. 相似文献
77.
Shigeta Y Imanaka H Yonezawa S Oku N Baba N Makino T 《Biological & pharmaceutical bulletin》2004,27(6):879-882
Since the liposomal formulation of linoleic acid (LA) exhibited an enhanced skin-whitening effect, the influence of liposomalization on the cutaneous absorption of LA was examined using a three-dimensional (3D) reconstructed skin model. Liposome entrapped [(14)C]-LA was applied on the skin model, and the permeation of LA through the skin was monitored. The permeation rate of LA in the liposomal formulation was found to be lower than that in the conventional formulation without liposomes, suggesting the increased retention time of LA in the skin by the liposomal formulation. Next, to investigate the dependence of the LA permeation on melanocyte conditions and intactness of the reconstructed skin model, the effect of UV irradiation on LA permeation was examined. Low-dose UVB irradiation (0.03 J/cm(2) for 3 times), which activated melanocytes in the skin, did not influence the extent of LA permeation, while high-dose irradiation (0.30 J/cm(2) for 3 times) enhanced the permeation of LA in both the conventional and liposomal formulation. The present results suggest the importance of skin intactness for LA permeation and that the 3D reconstructed skin model would be useful for evaluating the characteristics of skin-oriented cosmetics and drugs. 相似文献
78.
Eight 2-arylbenzofurans and an isoflavone isolated from medicinal plants were tested for their antimicrobial activities against vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Among these compounds, six hydrophobic 2-arylbenzofurans (log P = 4.4-8.7) exhibited considerable antibacterial activity against five VRE strains(VanA-, VanB-, and VanC-phenotypes) (MICs = 3.13-6.25 microg/mL). Five compounds also showed antibacterial activity against ten MRSA strains (MIC80 = 3.13 microg/mL). 相似文献
79.
A 35% EtOH extract of the fruits of Chaenomeles sinensis, long utilized as a folk medicine for cough, significantly inhibited the pruritogenic agent compound 48/80 (COM)-induced scratching behavior in mice. Antipruritic activity-guided fractionation and purification yielded active quercetin, apigenin, and catechin derivatives, which exhibited significant inhibitory effects on COM-induced scratching behavior. To the best of our knowledge, apigenin (5), apigenin 7-glucronide (6), and apigenin 4'-methoxy-7-glucronide (acacetin 7-glucronide) (7) were isolated from the fruits of C. sinensis for the first time. The active fraction and these compounds also inhibited serotonin-, platelet activating factor-, and prostaglandin E(2)-induced scratching behavior, but did not inhibit histamine-induced scratching behavior or locomotive behavior. This study also showed that the fruits of C. sinensis could be used to treat allergic itching sensation. 相似文献
80.
A 35% EtOH extract of flowers of Impatiens textori MIQ. showed an inhibitory effect on blood pressure decrease in response to platelet activating factor (PAF) measured with a blood pressure monitoring system. Bioassay-guided fractionation of the 35% EtOH extract (IT) led to isolation of the flavones apigenin (1) and luteolin (3), which significantly inhibited blood pressure decrease in response to PAF. Their compounds and apigenin 7-glucoside (2), chrysoeriol (4), quercetin (5), quercetin 3-glucoside (6), kaempferol (7), kaempferol 3-glucoside (8) and kaempferol 3-rhamnosyldiglucoside (9) were also isolated from the flowers of I. textori for the first time. This study revealed that the flowers of I. textori might be a possible anti-allergy agent. 相似文献