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Inhibition by gomisin C (a lignan from Schizandra chinensis) of the respiratory burst of rat neutrophils.

Abstract：

:1. The possible mechanisms of action of the inhibitory effect of gomisin C on the respiratory burst of rat neutrophils in vitro was investigated. 2. The peptide formyl-Met-Leu-Phe (FMLP) induced superoxide anion (O2-) formation and O2 consumption, which was inhibited by gomisin C in a concentration-dependent manner (IC50 21.5 +/- 4.2 micrograms ml-1 for O2- formation). Gomisin C also suppressed O2- formation and consumption at low concentrations of phorbol myristate acetate (PMA) with an IC50 value of 26.9 +/- 2.1 micrograms ml-1 for O2- formation. However, gomisin C did not affect the responses induced by a high concentration of PMA. 3. Gomisin C had no effect on O2- generation and uric acid formation in the xanthine-xanthine oxidase system, and failed to alter O2- generation during dihydroxyfumaric acid (DHF) autoxidation, indicating that it does not scavenge superoxide. 4. Like trifluoperazine (TFP), gomisin C attenuated the activity of PMA-activated neutrophil particulate NADPH oxidase in a concentration-dependent manner. 5. Gomisin C reduced the elevations of cytosolic free Ca2+ in neutrophils stimulated by FMLP in the presence or absence of EDTA. Cyclopiazonic acid (CPA) induced the release of Ca2+ from intracellular stores and this was also reduced by gomisin C. However, the Ca2+ influx pathway activated by CPA was not affected by gomisin C. 6. The cellular cyclic AMP level was markedly increased by forskolin, but not by gomisin C. Moreover, the inositol phosphate levels in FMLP-activated neutrophils were not affected by gomisin C. 7. These results show that the inhibitory action of gomisin C on the respiratory burst is not mediated by changes in cellular cyclic AMP or in inositol phosphates, or by scavenging O2- released from neutrophils, but may be mediated partly by the suppression of NADPH oxidase and partly by the decrease of cytosolic Ca2+ released from an agonist-sensitive intracellular store.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Wang JP,Raung SL,Hsu MF,Chen CC

doi

10.1111/j.1476-5381.1994.tb17084.x

subject

Has Abstract

pub_date

1994-11-01 00:00:00

pages

945-53

issue

eissn

0007-1188

issn

1476-5381

journal_volume

113

pub_type

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Inhibition by gomisin C (a lignan from Schizandra chinensis) of the respiratory burst of rat neutrophils.