Inhibition of nitric oxide by phenylethanoids in activated macrophages.
Nitric oxide (NO) is one of the pro-inflammatory molecules. Some phenylethanoids have been previously shown to possess anti-inflammatory effects. Seven phenylethanoids from the stems of Cistanche deserticola, viz. isoacteoside, tubuloside B, acteoside, 2'-O-acetylacteoside, echinacoside, cistanoside A and tubuloside A, were tested for their effect on NO radical generation by activated murine macrophages. At the concentration of 100-200 microM, all the phenylethanoids reduced (6.3-62.3%) nitrite accumulation in lipopolysaccharide (0.1 microgram/ml)-stimulated J774.1 cells. At 200 microM, they inhibited by 32.2-72.4% nitrite accumulation induced by lipopolysaccharide (0.1 microgram/ml)/interferon-gamma (100 U/ml) in mouse peritoneal exudate macrophages. However, these compounds did not affect the expression of inducible nitric oxide (iNOS) mRNA, the iNOS protein level, or the iNOS activity in lipopolysaccharide-stimulated J774.1 cells. Instead, they showed a clear scavenging effect (6.9-43.9%) at the low concentrations of 2-10 microM of about 12 microM nitrite generated from an NO donor, 1-propanamine-3-hydroxy-2-nitroso-1-propylhydrazino (PAPA NONOate). These results indicate that the phenylethanoids have NO radical-scavenging activity, which possibly contributes to their anti-inflammatory effects.
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630-Sugitani, 930-0194, Toyama, Japan.
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Xiong
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Tezuka
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Kaneko
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Li
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Tran
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Hase
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Namba
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Kadota
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D005419:Flavonoids; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010636:Phenols / Q000494:pharmacology*; D010946:Plants, Medicinal; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D012333:RNA, Messenger / Q000032:analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D010636:Phenols; D011108:Polymers; D059808:Polyphenols; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse