Comparative effects of the herbal constituent parthenolide (Feverfew) on lipopolysaccharide-induced inflammatory gene expression in murine spleen and liver.

BACKGROUND: Parthenolide, a major sesquiterpene lactone present in extracts of the herb Feverfew, has been investigated for its inhibitory effects on mediators of inflammation, including the proinflammatory cytokines. Although parthenolide's anti-inflammatory effects have been investigated in vitro, little in vivo data are available. Moreover, the molecular mechanisms for these inhibitory effects are not fully understood. The objective of this study was to test the hypothesis that parthenolide suppresses lipopolysaccharide (LPS)-induced serum (interleukin) IL-6, tumor necrosis factor (TNF)-alpha, IL-1beta and cyclooxygenase (COX)-2 expression in mice as indicated by reduced splenic and liver mRNA levels. METHODS: Mice were co-treated i.p. with LPS (1 mg/kg bw) and parthenolide (5 mg/kg bw) and blood, spleen and liver collected. Serum was analyzed for IL-6, TNF-alpha and IL-1beta by ELISA. Total RNA was extracted from spleen and liver, and real-time RT-PCR was used to determine relative mRNA expression of IL-1beta, IL-6, TNF-alpha and COX-2. RESULTS: LPS induced increases in serum IL-6 and TNF-alpha concentrations with only IL-6 being suppressed in parthenolide-treated mice. Induction of IL-6 mRNA was reduced, TNF-alpha and COX-2 mRNAs unchanged, and IL-1beta mRNA increased in spleens of parthenolide plus LPS co-treated animals compared to LPS-only. No significant differences were observed in inflammatory gene expression between these two groups in liver samples. Overall, mRNA expression of each proinflammatory gene was much higher in spleen when compared to liver. CONCLUSION: In summary, only one gene, IL-6, was modestly suppressed by parthenolide co-exposure which contrasts with many in vitro studies suggesting anti-inflammatory effects of this compound. Also, LPS evoked greater effects in spleen than liver on expression of proinflammatory genes. Further study of the effects of parthenolide and other herbal constituents on inflammatory gene expression using model animal systems as described here are critical to evaluating efficacy of such supplements as well as elucidating their mechanisms of action.