• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.230-240
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• 2003

We investigated that Hwao-tang had various effects on stimulus-induced superoxide generation in human neutrophils. Hwao-tang significantly inhibited N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation in a concentration-dependent manner, but not that induced by arachidonic acid. Also, Hwao-tang significantly reduced mouse paw oedema induced by carrageenan. The results suggest that protein tyrosine kinase participates in fMLP-mediated superoxide generation by Hwao-tang-treated human neutrophils. Also, the results indicate that Hwao-tang exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and prostaglandin E2 production, which could be due to a decreased expression of iNOS and COX-2.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.83-92
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• 1988

Although the release of lysosomal enzymes from activated PMN leukocyte can be regulated by intracellular cyclic nucleotide levels, other responses of PMN leukocyte according to the binding of neurotransmitters to either ${\beta}$-adrenergic or muscarinic receptors are still not clarified. In addition, the function of PMN leukocyte mediated by ${\alpha}$-adrenergic receptors is uncertain. Atropine, phentolamine and propranolol inhibited calcium uptake, superoxide generation, NADPH oxidase activity and phagocytic activity in activated PMN leukocyte, whereas carbachol and isoproterenol slightly further stimulated the responses of activated cells. Either carbachol or isoproterenol stimulated superoxide generation was inhibited by their antagonists, atropine and propranolol, respectively. The response of activated PMN leukocyte was inhibited by chlorpromazine, verapamil and dantrolene but slightly stimulated by lithium. On the other hand, chlorpromazine and dibucaine did not affect NADPH oxidase activity. Atropine, phentolamine and propranolol suppressed the calcium dependent phagocytic activity. Thus, the results suggest that atropine, phentolamine and propranolol may inhibit superoxide generation in activated PMN leukocyte by the inhibition of calcium influx and by their direct action on the NADPH oxidase system which is associated with autonomic receptors.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.511-515
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• 2003

Quinazolinones, 2-substituted and 3-substituted, mainly synthesized by microwave irradiation, were subjected to anti-platelet aggregation and inhibition of superoxide anion generation assays. Interestingly, 2-phenyl-4-quinazolinone (4) exhibited significant inhibitory activities toward platelet aggregation and neutrophil activation, and it might therefore serve as a prototype lead compound.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.163-170
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• 1992

The present study was attempted to investigate the effect of cyclobuxine (a steroidal alkaloid) on generation of reactive oxygen metablite and myocardial damage promoted by an exogenous administeration of arachidonate in ischemic-reperfused hearts. Langendorff preparation of the isolated rat heart was made ischemic condition by reducing the flow rate to 0.5 ml/min for 45 min, and then followed by normal reperfusion (7 ml/min) for 5 min. The generation of superoxide anion was estimated by measuring the SOD-inhibitable ferricytochrome C reduction. The degree of lipid peroxidation in myocardial tissue was estimated from the tissue malondialdehyde (MDA) concentration using thiobarbituric acid method. The myocardial cell damage was observed by measuring LDH released into the coronary effluent. Sodium arachidonate $(0.1\;and\;1.0\;{\mu}g/ml)$ infused during the period of oxygenated reperfusion stimulated superoxide anion production dose-dependently. The rate of arachidonate-induced superoxide anion generation was markedly inhibited by cyclobuxine $(1.0\;and\;10\;{\mu}g/ml)$. The production of malondialdehyde was increased by infusion of arachidonate. This increase was prevented by superoxide dismutase (300 U/ml) and cyclobuxine $(1.0\;and\;10\;{\mu}g/ml)$. The release of LDH was increased by sodium arachidonate was also inhibited by superoxide dismutase and cyclobuxine. In conclusion, the present results suggest that cyclobuxine inhibits the production of reactive oxygen metabolite and myocardial damages which were promoted by an administeration of arachidonate during reperfusion of ischemic hearts.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.123-133
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• 1995

A number of tricyclic antidepressants appear to have inhibitory action on calmodulin. Although amitriptyline, imipramine and doxepine have been shown to inhibit calcium uptake, oxidative phosphorylation and ATPase activities, effects of amitriptyline, imipramine and doxepine on functional responses of human neutrophils have not been elucidated. In this study, effects amitriptyline, imipramine and doxepine on superoxide and hydrogen peroxide generation, myeloperoxidase release, leukocriene B4 formation and intracellular calcium level were investigated. Superoxide and hydrogen peroxide production in heat aggregated IgG-activated neutrophils were inhibited by amitriptyline, imipramine and doxepine. EDTA, EGTA, verapamil and bepredil inhibited heat aggregated IgG-induced superoxide production. Chlorpromazine, trifluoperazine, staurosporine and H-7 also inhibited it. PMA-induced superoxide production was inhibited by amitriptyline, imipramine, doxepine, chlorpromazine and H-7. Amitriptyline, imipramine, chlorpromazine and trifluoperazine inhibited the myeloperoxidase release by heat aggregated IgG. Productions of $LTB_4$, and 5-HETE in heat aggregated IgG-activated neutrophils were inhibited by amitriptyline, imipramine and doxepine. In neutrophils, elevation of intracellular calcium induced by heat aggregated IgG was inhibited by amitriptyline, imipramine, doxepine, chlorpromazine and EGTA, while verapamil slightly inhibited increase of intracellular calcium and H-7 did not inhibit it. These results suggest that the inhibitory effect of amitriptyline, imipramine and doxepine on respiratory burst, myeloperoxidase release and LTB4 production in heat aggregated IgG-activated neutrophils appears to be ascribed to the inhibition of calcium mobilization, calmodulin and protein kinase C.

• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.113-121
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• 1987

Local anesthetics were investigated for their effects on mitochondrial electron transport system, production of superoxide radical from submitochondrial particles and malondialdehyde production through lipid per oxidation. Local anesthetics had various effects on activities of enzymes in electron transport chain. The activities of NADH dehydrogenase, NADH oxidase and NADH-ubiquinone oxidoreductase were effectively inhibited by lidocaine, procaine and dibucaine but slightly influenced by cocaine. The activities of succinate dehydrogenase, succinate-cytochrome c oxidoreductase and succinate-ubiquinone oxidoreductase were inhibited by lidocaine and dibucaine, but the succinate oxidase activity was stimulated by local anesthetics. Both dihydroubiquinone-cytochrome c oxidoreductase and cytochrome c oxidase activities were inhibited by local anesthetics. In these reactions, the response of Complex I segment to local anesthetics was greater than other Complex segments. Local anesthetics inhibited both the superoxide production from submitochondrial particles supplemented with succinate or NADH and the enhanced production of superoxide radicals by antimycin. The malondialdehyde production by oxygen free radicals was inhibited by local anesthetics. These results suggest that the inhibition of superoxide and malondialdehyde production caused by local anesthetics may be brought by suppression of the electron transport in mitochondria at sites in or near complex I segment.

• Proceedings of the Korean Society of Sericultural Science Conference
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• 2003.10a
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• pp.66-70
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• 2003

The first line of antioxidant defense against reactive oxygen species includes the enzymatic activity of the superoxide dismutase (SOD) that catalyzes the disproportionation of superoxide to hydrogen peroxide and water. The SOD mainly removes highly toxic $O_2$$^{[-10]}$ and also prevents $O_2$$^{[-10]}$ mediated reduction of iron and subsequent OH$^{[-10]}$ generation. Along with an interest in SOD as a first line of defense against damage mediated by the superoxide anion, the SOD1 enzyme has been subjected to investigation in the molecular and cellular level. (omitted)

• Journal of Life Science
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• v.7 no.3
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• pp.180-185
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• 1997

Methylelaiophylin generated superoxide radicals in Bacillus subtilis and showed antibacterial activity against a broad range of gram positive bacteria. The inhibition of DNA synthesis was more sensitive than one of RNA synthesis. A recombination-deficient mutant strain of B. subtilis was 2-fold more sensitive than a wild strain, and this sensitivity was reduced in the presence of an antioxidant, dithiothreitol. Methylelaiophylin generated superoxide radicals in B. subtilis lysates, and this suggests that the antibacterial activity of methylelaiophylin is related to the generation of active oxygen species in the cells.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.2
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• pp.103-109
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• 2003

The cellular mechanisms that contribute to the acceleration of atherosclerosis in diabetes are poorly understood. Therefore, the potential mechanisms involved in the diabetes-dependent increase in vascular smooth muscle cell (VSMC) proliferation was investigated. Using primary culture of VSMC from streptozotocin-induced diabetic rat aorta, cell proliferation assay showed two-fold increase in cell number accompanied with enhanced superoxide generation compared to normal VSMC, 2 days after plating. Both the increased superoxide production and cell proliferation in diabetic VSMC were significantly attenuated by not only tiron (1 mM), a superoxide scavenger, but also by diphenyleneiodonium (DPI; $10{\mu}M$), an NAD(P)H oxidase inhibitor. NAD(P)H oxidase activity in diabetic VSMC was significantly higher than that in control cell, accompanied with increased mRNA expression of p22phox, a membrane subunit of oxidase. Furthermore, inhibition of p22phox expression by transfection of antisense p22phox oligonucleotides into diabetic VSMC resulted in a decrease in superoxide production, which was accompanied by a significant inhibition of cell proliferation. Based on these results, it is suggested that diabetes-associated increase in NAD(P)H oxidase activity via enhanced expression of p22phox contributes to augmented VSMC proliferation in diabetic rats.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.213-223
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• 2000

SD-994 was prepared from methanol extract of Artemisia argyi by stepwise purification of solvent partioning and silica gel chromatography. In the course of this purification, fractions obtained at each step were investigated for their cytotoxicities against L1210 cells. Fractions A~G prepared from chloroform fraction showed considerable cytotoxicities raging 40~90% against L1210 cells. Subfractions I~IX obtained from fraction A exhibited various cytotoxicities and subfraction I (SD-994) was found to be the most effective compound. $IC_{50}$ values of SD-994 were measured to be $0.5{\;}{\mu\textrm{g}}/ml and less than $0.05{\;}{\mu\textrm{g}}/ml against L1210 cells and normal lymphocytes, respectively: When SD-994 was added to L1210 cell as cytotoxic agent, significantly increased amount of superoxide ($O_2^-$) and dramatically augmented activities of superoxide dismutase (SOD), specially MnSOD and glutathione peroxidase (GPx) were observed according to the concentration and incubation time. Whereas, in case of normal lymphocytes under the same condition, cytotoxicities were not apparent and the generation of superoxide ($O_2^-$) or the activity changes of SOD and GPx were insignificant. These results together indicate that the cytotoxic action of SD-994 against L1210 cell may be achieved via necrosis and/or apoptosis induced by reaction oxygen species which could not probably be completely abolished even by drastically increased antioxidant enzymes, SOD and GPx activities.