Atractylenolide I and atractylenolide III inhibit lipopolysaccharide-induced TNF-α and NO production in macrophages

In order to clarify the mechanism involved in the antiinflammatory activity of atractylenolide I and atractylenolide III from the rhizomes of Atractylodes macrocephala Koidz, their effects on tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production in peritoneal macrophages were examined. Atractylenolide I and atractylenolide III decreased the TNF-alpha level in LPS-stimulated peritoneal macrophages in a dose-dependent manner, their IC50 values were 23.1 mu m and 56.3 mu m, respectively. RT-PCR analysis indicated that they inhibited TNF-alpha mRNA expression. Furthermore, they inhibited NO production in LPS-activated peritoneal macrophages, the IC50 value of atractylenolide 1 was 41.0 mu m, and the inhibition ratio of 100 mu m of atractylenolide III was 45.1% +/- 6.2%. The activity analysis of inducible nitric oxide synthase (iNOS) indicated that they could inhibit the activity of iNOS, their IC50 values were 67.3 mu m and 76.1 mu m, respectively. Western blot analysis showed that atractylenolide I and atractylenolide III attenuated LPS-induced synthesis of iNOS protein in the macrophages, in parallel. These results imply that the antiinflammatory mechanism of atractylenolide I and atractylenolide III may be explained at least in part, by the inhibition of TNF-alpha and NO production. Atractylenolide I showed more potent inhibition than atractylenolide III in the production of TNF-alpha and NO in LPS-activated peritoneal macrophages. So, atractylenolide I could be a candidate for the development of new drugs to treat inflammatory diseases accompanied by the overproduction of TNF-alpha and NO. Copyright (c) 2007 John Wiley & Sons, Ltd.