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排序方式: 共有239条查询结果,搜索用时 15 毫秒
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Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation 总被引:1,自引:0,他引:1
Bustanji Y Taha MO Almasri IM Al-Ghussein MA Mohammad MK Alkhatib HS 《Journal of enzyme inhibition and medicinal chemistry》2009,24(3):771-778
Curcumin was investigated as an inhibitor of glycogen synthase kinase-3beta (GSK-3beta) in an attempt to explain some of its interesting multiple pharmacological effects, such as its anti-diabetic, anti-inflammatory, anti-cancer, anti-malarial and anti-alzheimer's properties. The investigation included simulated docking experiments to fit curcumin within the binding pocket of GSK-3beta followed by experimental in vitro and in vivo validations. Curcumin was found to optimally fit within the binding pocket of GSK-3beta via several attractive interactions with key amino acids. Experimentally, curcumin was found to potently inhibit GSK-3beta (IC50 = 66.3 nM). Furthermore, our in vivo experiments illustrated that curcumin significantly increases liver glycogen in fasting Balb/c mice. Our findings strongly suggest that the diverse pharmacological activities of curcumin are at least partially mediated by inhibition of GSK-3beta. 相似文献
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The adverse effects of either NaCl or mannitol on growth, nitrogen content, and antioxidant system in Vicia faba seedlings were investigated. The role of exogenous ascorbic acid in increasing resistance to these stressors was also evaluated. Thus, with an increase in concentration of either NaCl or mannitol in culture media, a progressively greater significant decrease in percentage germination, in growth parameters, and in nitrogen constituents of the germinating beans, was observed. On the other hand, amide-, nitrate-, and total soluble-N contents appeared to show a progressive significant increase. Exogenous addition of ascorbic acid (4 mM) to the stressful media induced a pronounced significantly increased percentage germination and the growth attributes, whereas nitrogen constituents were variably changed in relation to values maintained in beans treated with either NaCl or mannitol. Furthermore, exogenous addition of ascorbic acid to NaCl or mannitol media induced a significant increase in the contents of ascorbate and glutathione and enzymatic antioxidant activities, in particular, in beans treated with the three highest concentrations of NaCl or mannitol, throughout the period of the experiments (12 days). Thus, ascorbic acid ameliorates the adverse effects of the stressful media; the magnitude of amelioration being a function of the type and the concentration of the stressful agent as well as of the duration of treatment. The importance of the above-mentioned changes in growth and metabolism to stress tolerance in broad bean is discussed. 相似文献
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In vitro fertilization of goat oocytes 总被引:8,自引:0,他引:8
A I Younis K A Zuelke K M Harper M A Oliveira B G Brackett 《Biology of reproduction》1991,44(6):1177-1182
Experiments were carried out to achieve fertilization (IVF) and initial embryonic development of goat oocytes in vitro. Oocyte/cumulus complexes were recovered from large follicles (greater than 7 mm) of hormonally treated doses and from 1-6-mm follicles of ovaries from hormonally superstimulated and nontreated goats. Three different sperm treatment/IVF media were used: defined medium (Brackett and Oliphant, Biol Reprod 1975; 12:260-274) with modifications (mDM); TALP (Bavister and Yanagimachi, Biol Reprod 1977; 16:228-237), as modified by Parrish et al. (Theriogenology 1986; 25:591-600), i.e. modified TALP (mTALP); and HEPES-buffered M199 with modifications (mH-M199). Immature oocytes (from 1-6 mm, small antral follicles) were cultured for in vitro maturation (IVM) in M199 buffered with bicarbonate and with modifications including supplementation with 20% (v/v) goat serum (mB-M199) with either (a) 100 micrograms LH/ml, (b) 5 micrograms FSH/ml, or (c) no added gonadotropin control. Insemination of (in vivo or in vitro) matured oocytes was performed with swim-up separated and heparin-treated freshly ejaculated sperm; additionally, caffeine was included in the mDM treatment. Use of mDM yielded better results than mTALP or mH-M199 (p less than .05). Results with oocytes after IVM were significantly better than those obtained with oocytes matured in vivo (68.4% vs. 45.5%, p less than 0.05). Presence of LH or FSH during oocyte maturation improved both the IVM and IVF results over those of the control (p less than 0.05). The highest proportion of fertilized oocytes (fertilization rate) was achieved by combining the use of mDM for sperm and IVF with IVM in the presence of LH.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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(1) Photophosphorylation, fCa2+-ATPase and Mg2+-ATPase activities of isolated chloroplasts were inhibited 55–65% when the chemical potential of water was decreased by dehydrating leaves to water potentials (ψw) of ?25 bars before isolation of the plastids. The inhibition could be reversed in vivo by rehydrating the leaves.(2) These losses in activity were reflected in coupling factor (CF1) isolated from the leaves, since CF1 from leaves with low ?w had less Ca2+-ATPase activity than control CF1 and did not recouple phosphorylation in CF1-deficient chloroplasts. In contrast, CF1 from leaves having high ?w only partially recoupled phosphorylation by CF1-deficient chloroplasts from leaves having low ?w. This indicated that low ?w affected chloroplast membranes as well as CF1 itself.(3) Coupling factor from leaves having low ψw had the same number of subunits, and the same electrophoretic mobility, and could be obtained with the same yields as CF1 from control leaves. However, direct measurements of fluorescence polarization, ultraviolet absorption, and circular dichroism showed that CF1 from leaves having low ?w differed from control CF1. The CF1 from leaves having low ?w also had decreased ability to bind fluorescent nucleotides (?-ATP and ?-ADP).(4) Exposure of isolated CF1 to low ?w in vitro by preincubation in sucrose-containing media inhibited the Ca2+-ATPase activity of the protein in subsequent assays without sucrose. Inclusion of 5 or 10 mM Mg2+ in the preincubation medium markedly inhibited Ca2+-ATPase activity.(5) These results show that CF1 undergoes changes in cells which alter its phosphorylating ability. Since low cell ?w changed the spectroscopic properties but not other protein properties of CF1, the changes were most likely caused by altered conformation of the protein. This decreased the binding of nucleotides and, in turn, photophosphorylation. The inhibition of ATPase activity in CF1 in vitro at low ?w and high ion concentration mimicked the change in activity seen in vivo. 相似文献
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Steroid derivatives V, VI, VII and VIII reacted with Lawesson's reagent (LR) to produce spiro-oxazaphosphole-4',17-androstene derivative XI, diazaphospholoandrostane XIV and the thionated derivatives XVI and XVII, respectively. The structures of the new compounds were confirmed by analytical and spectroscopic evidence. A mechanism accounting for the formation of the new compounds was given. The in vitro antimicrobial activity of the new compounds were tested. 相似文献