Anti-inflammatory activity of omphalocarpin isolated from Radix Toddaliae Asiaticae

Radix Toddaliae Asiaticae has long been used as a traditional ethnic Chinese medicine for the treatment of inflammation and rheumatism. In our earlier communication we have reported the anti-arthritic activity of the ethyl alcohol extract and ethyl acetate fraction from Radix Toddaliae Asiaticae. This study was to examine the anti-inflammatory activity of prenylcoumarin omphalocarpin isolated from the ethyl acetate extract with the bioassay-guided methods.

Cultured macrophage RAW 264.7 cells were used for the experiments. The ability of omphalocarpin to modulate the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was evaluated. Western blot was used to detect the expression of iNOS and COX-2 and the translocation of nuclear factor kappa B (NF-κB) to the nucleus. Meanwhile, the anti-inflammatory activity of omphalocarpin in vivo was also assayed by xylene induced ear edema in mice.

It has been shown that omphalocarpin inhibited lipopolysaccharide (LPS)-stimulated NO production and pro-inflammatory mediators secretion, including TNF-α, IL-6 in a dose-dependent manner. Omphalocarpin also strongly suppressed the expression and enzymatic activity of iNOS and COX-2 and the translocation of NF-κB to the nucleus. In vivo assays omphalocarpin exhibited anti-inflammatory activity for alleviation of the ear swelling in xylene induced ear edema test.

These results obtained in vitro and in vivo showed that the anti-inflammatory mechanism of omphalocarpin might be attributed to the inhibition of pro-inflammatory mediators including nitric oxide, IL-6 and TNF-α. Omphalocarpin decreased the overproduction of NO through down-regulation of the expression and enzymatic activity of iNOS and COX-2 in LPS-stimulated macrophage, which was due to the suppression of NF-κB activation in the transcriptional level. This is the first report of the anti-inflammatory activity of omphalocarpin.