Lithospermic acid as a novel xanthine oxidase inhibitor has anti-inflammatory and hypouricemic effects in rats.
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 microg/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.
Liu
Xiaoyu
X
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Second Military Medical University, and Changhai Hospital, Shanghai 200433, China.
Chen
Ruohua
R
Shang
Yanjun
Y
Jiao
Binghua
B
Huang
Caiguo
C
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015210:Arthritis, Gouty / Q000188:drug therapy; D001572:Benzofurans / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D053630:Depsides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D033461:Hyperuricemia / Q000139:chemically induced / Q000188:drug therapy*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008968:Molecular Conformation; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010094:Oxonic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014527:Uric Acid / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001572:Benzofurans; D053630:Depsides; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; C046833:lithospermic acid; D014527:Uric Acid; C489337:potassium oxonate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010094:Oxonic Acid; D000493:Allopurinol; D014969:Xanthine Oxidase; D013755:Tetradecanoylphorbol Acetate