Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 176, Issue 2-3, Pages 137-142Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2008.07.003
Keywords
Lithospermic acid; Xanthine oxidase; Superoxide scavenging; Competitive inhibitor; Neutrophilis; Gouty arthritis
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Lithospermic acid (LSA) was originally isolated from the roots of Salvia mitiorrhiza, a common herb of oriental medicine. Previous studies demonstrated that LSA has antioxidant effects. In this study, we investigated the in vitro xanthine oxidase (XO) inhibitory activity, and in vivo hypouricemic and anti-inflammatory effects of rats. XO activity was detected by measuring the formation of uric acid or superoxide radicals in the xanthine/xanthine oxidase system. The results showed that LSA inhibited the formation of uric acid and superoxide radicals significantly with an IC50 5.2 and 1.08 mu g/ml, respectively, and exhibited competitive inhibition. It was also found that LSA scavenged superoxide radicals directly in the system beta-NADH/PMS and inhibited the production of superoxide in human neutrophils stimulated by PMA and fMLP. LSA was also found to have hypouricemic activity on oxonate-pretreated rats in vivo and have anti-inflammatory effects in a model of gouty arthritis. These results suggested that LSA is a competitive inhibitor of XO, able to directly scavenge superoxide and inhibit superoxide production in vitro. and presents hypouricemic and anti-inflammatory actions in vivo. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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