Atractylenolide I and atractylenolide III inhibit Lipopolysaccharide‐induced TNF‐α and NO production in macrophages

Abstract 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‐ α (TNF‐ α ) and nitric oxide (NO) production in peritoneal macrophages were examined. Atractylenolide I and atractylenolide III decreased the TNF‐ α level in LPS‐stimulated peritoneal macrophages in a dose‐dependent manner, their IC 50 values were 23.1 µ m and 56.3 µ m , respectively. RT‐PCR analysis indicated that they inhibited TNF‐ α mRNA expression. Furthermore, they inhibited NO production in LPS‐activated peritoneal macrophages, the IC 50 value of atractylenolide I was 41.0 µ m , and the inhibition ratio of 100 µ 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 IC 50 values were 67.3 µ m and 76.1 µ 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‐ α and NO production. Atractylenolide I showed more potent inhibition than atractylenolide III in the production of TNF‐ α 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‐ α and NO. Copyright © 2007 John Wiley & Sons, Ltd.