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31.
The CHCl(3) -soluble fraction obtained from the MeOH extract of Peucedanum japonicum Thunb. inhibited phenylephrine-induced vasoconstriction in isolated rat thoracic aorta. We isolated a vasorelaxing compound, as one of the bioactive components, which was identified as (+)- cis-4'- O-acetyl-3'- O-angeloylkhellactone (1), a pyranocoumarin, and examined the mechanisms of vasorelaxant effect caused by 1. This compound (1) (10(-6)-10(-4) M) concentration-dependently relaxed the isolated rat thoracic aorta pre-contracted with phenylephrine (PE). This vasorelaxant potency was diminished by endothelial removal (by 20%), L- N(G)-nitro-arginine or methylene blue (MB), but not indomethacin treatment. These findings indicate that the vasorelaxant effect of 1 was partially endothelium dependent and mediated by nitric oxide and cyclic GMP pathway. To determine if the effect of 1 was mediated through the activation of some of the receptors known to lead to vascular relaxation, the effects of atropine, triprolidine and propranolol were determined. 1-induced vasorelaxation was not affected by atropine, triprolidine and propranolol. Compound 1 inhibited high potassium (80 mM)-induced, calcium-dependent contractions in a concentration-dependent manner. But it slightly relaxed the rat aorta precontracted with PE in the presence of nifedipine, a blocker of voltage-operated calcium channels. Tetraethylammonium (TEA, a non-specific (K+) channel blocker) did not affect the vasodilatory effect of 1 against PE-induced contraction. Mechanisms of the vasorelaxant effect of 1 were multiple, including endothelium dependence and Ca(2+) channel blockade. 相似文献
32.
Inhibitory activity of diacylglycerol acyltransferase by tanshinones from the root of Salvia miltiorrhiza 总被引:4,自引:0,他引:4
Ko JS Ryu SY Kim YS Chung MY Kang JS Rho MC Lee HS Kim YK 《Archives of pharmacal research》2002,25(4):446-448
The inhibitory activity of tanshinones from Salvia miltiorrhiza was tested on rat liver diacylglycerol acyltransferase (DGAT). Cryptotanshinone (1) and 15,16-dihydrotanshinone I (3) exhibited potent DGAT inhibitory activities dose-dependently with IC50 values of 10.5 microg/ml and 11.1 microg/ml. However, tanshinone IIA (2) and tanshinone I (4) showed very weak inhibition (IC50 value: > 250 microg/ml). A dihydrofuran moiety was seemed to be responsible for the stronger inhibitory activity. 相似文献
33.
PURPOSE: Previously we demonstrated that L-(+)-beta-hydroxybutyrate (L-BHB), acetoacetate (ACA), acetone, and dibenzylamine (DBA) were anticonvulsant in an audiogenic seizure-susceptible model, and that DBA was a bioactive contaminant identified in commercial lots of L-BHB. In the present study, we asked whether these effects could be mediated by ionotropic glutamate or gamma-aminobutyric acidA (GABAA) receptors. METHODS: We studied the effects of both stereoisomers of BHB (as well as the racemate), ACA, and DBA on N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5methyl-4-isoxazole-proprionic acid (AMPA), and GABAA receptors in cultured rodent neocortical neurons by using whole-cell voltage-clamp recording techniques. RESULTS: Only L-BHB and DBA exerted a concentration- and voltage-dependent block of NMDA-evoked currents, whereas none of the tested substrates affected AMPA- or GABA-activated currents. The kinetics of whole-cell block by L-BHB and DBA were similar, providing additional evidence that DBA is responsible for the anticonvulsant activity of L-BHB. CONCLUSIONS: BHB and ACA do not exert direct actions on GABAA or ionotropic glutamate receptors in cultured neocortical neurons. In addition, we provide additional evidence that DBA is responsible for the anticonvulsant activity of L-BHB, and that this action may be mediated in part by voltage-dependent blockade of NMDA receptors. 相似文献
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A comparative study on the expression of cyclooxygenase and 5-lipoxygenase during cerebral ischemia in humans 总被引:10,自引:0,他引:10
Prostaglandins and leukotrienes (eicosanoids), metabolites of the arachidonic acid pathway, are subjected to altered synthesis or relocation after an ischemic insult. Although cyclooxygenase (COX) expression has been reported in human cerebral ischemia, no information is available on the expression of 5-lipoxygenase (5-LO) and its topographical correlation to COX induction. The objective of this study was to elucidate the comparative distribution of eicosanoids in ischemic tissues. COX and 5- LO, key enzymes for the synthesis of prostaglandins and leukotrienes, respectively, were examined in autopsied brains. COX1 was expressed intensely in the microglia but weakly in the neurons in control brains. These COX1-immunoreactive microglia showed a more activated form following ischemic damage and hypoxemia. In contrast, COX2 was absent in the control brains, and was induced robustly in the neuronal cell bodies and dendrites during the acute stages of focal ischemic damage, and then subsided at the subacute stages. These COX2-immunoreactive neurons accumulated in the peri-infarct regions, but were absent from the distant regions. In focal ischemic damage and Binswanger's disease, COX2 was up-regulated in the microglia. Neuronal immunostaining for 5-LO was up-regulated occasionally during hypoxemia and focal ischemic damage. Glial cells immunoreactive for 5-LO appeared in the foci of the ischemic damage, with small blood vessels being infiltrated by 5-LO-immunoreactive mononuclear leukocytes. These findings indicate that the isozymes of COX are differentially regulated depending on the cellular source and the types of ischemic damage, and that vascular 5-LO may accelerate the migration of leukocytes and augment the blood-brain barrier permeability. The possibility of increased substrate availability for the other should be noticed in specific inhibition of either COX or 5-LO since these two enzymes are accumulated in parallel in ischemic tissues. 相似文献
36.
Suppression of bone resorption by madindoline A,a novel nonpeptide antagonist to gp130 总被引:7,自引:0,他引:7
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Hayashi M Rho MC Enomoto A Fukami A Kim YP Kikuchi Y Sunazuka T Hirose T Komiyama K Omura S 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(23):14728-14733
IL-6 is a multifunctional cytokine involved in regulation of differentiation, antibody production, and growth of certain types of tumor cells. Its excessive production plays a major role in pathogenesis of multiple myeloma and postmenopausal osteoporosis. In the course of a screening program aimed at IL-6 inhibitor from microbial products, we found madindoline A (MDL-A) and madindoline B, which have a fuloindoline structure with diketocyclopentene bound to the methyl group. MDL-A has no cytotoxic activities. It inhibited only activities of both IL-6 and IL-11 without affecting the IL-6-specific signal transduction cascade, JAK2/STAT3. In a dose-dependent manner [(3)H]MDL-A binds to gp130, which is a signal transducing 130-kDa glycoprotein, but formation of the trimeric complex IL-6/IL-6 receptor/gp130 was not inhibited, suggesting that MDL-A suppresses dimerization of trimeric complexes. Not only did MDL-A markedly inhibit IL-6- and IL-11-induced osteoclastogenesis in vitro, but it also inhibited IL-6-stimulated serum amyloid A production and bone resorption in an experimental model of postmenopausal osteoporosis in vivo by a different mechanism from that of 17beta-estradiol. Here we show that MDL-A has a highly selective inhibitory effect on IL-6 and IL-11 activities by inhibiting a gp130 activity while suppressing bone loss in ovariectomized mice. MDL-A is anticipated as a lead compound for treatment of hormone-dependent postmenopausal osteoporosis, which has no serious side effects, and as a new mechanism of action, gp130 blocking. 相似文献
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39.
Jee CD Lee HS Bae SI Yang HK Lee YM Rho MS Kim WH 《International journal of oncology》2005,26(5):1265-1271
The caspases are a family of aspartic acid-specific proteases that fulfill varied and often critical roles in mammalian apoptosis or in the proteolytic activation of cytokines. Caspase-1 (interleukin-1beta-converting enzyme) is a member of the cysteine protease family, which cleaves target proteins following aspartic acid residues. We investigated caspase-1 expression in stomach cancer, tissues and cell lines. Of 301 consecutive gastric carcinomas, 58 cases (19.3%) showed the expressional loss of caspase-1. Loss of caspase-1 expression was significantly associated with pTNM stage (p=0.03), lymph node metastasis (p=0.01) and patient survival (p<0.01). Caspase-1 expression was also significantly correlated in an inverse manner with p53 expression (p<0.01). Among the 11 gastric cancer cell lines examined, three cell lines showed loss of expression at the protein and mRNA levels. On treatment with 5-aza-2'-deoxycytidine (5-aza-C), and/or trichostatin A (TSA), all three cell lines re-expressed caspase-1 mRNA. The above findings suggest that epigenetic events such as DNA methylation and histone deacetylation play important roles in the regulation of caspase-1, and that loss of caspase-1 expression is associated with poor survival in gastric carcinoma. 相似文献
40.
Sunwoo S Kim YS Cho BL Cheon KS Seo HG Rho MK Cheong YS Hong MH Kim SW Kim DH;Korea Post-Marketing Surveillance Research Group 《International journal of impotence research》2005,17(1):71-75
In order to investigate the safety and efficacy of sildenafil prescribed in primary care, a post-marketing surveillance study was undertaken. A total of 651 men with erectile dysfunction (ED) were enrolled from 31 family physicians in Korea from December 1999 to July 2002. Patients were regularly followed up to ascertain the safety and efficacy of sildenafil. Of the 651 patients enrolled, 572 (87.9%) returned for safety evaluation and efficacy assessment. In all, 458 (80.1%) of 572 patients reported improved erectile function with sildenafil. Hypertension, diabetes and low-dose sildenafil were associated with poor efficacy. A total of 71 adverse events were reported among 56 patients (8.6%), with the most frequent being hot flushes (5.6%), followed by headache (2.6%), palpitation (1.0%), anxiety (0.5%) and elevated ALT (0.5%). Only six patients (1.0%) discontinued sildenafil as a direct result of adverse events. These results suggest that sildenafil prescribed by primary care physicians was well tolerated and improved erectile function in patients with ED. 相似文献