Gentiolactone, a Secoiridoid Dilactone from Gentiana triflora, Inhibits TNF-α, iNOS and Cox-2 mRNA Expression and Blocks NF-κB Promoter Activity in Murine Macrophages

BACKGROUND: Gentian roots have been used as a herbal medicine because of their anti-inflammatory activities. However, the molecular mechanisms of these anti-inflammatory effects remain to be completely explained. METHODS AND FINDINGS: Here, we investigated anti-inflammatory effects of gentian roots and showed that root extracts from Gentiana triflora inhibited lipopolysaccharide (LPS)-induced expression of TNF-α in RAW264.7 cells. The extracts also contained swertiamarin and gentiopicroside, which are the major active compounds of gentian roots; however, neither compound had any effect on LPS-induced TNF-α production in our test system. We isolated gentiolactone as an inhibitor of TNF-α production from the extracts. Gentiolactone also inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) expression at the mRNA level. Moreover, gentiolactone suppressed NF-κB transcriptional activity without inhibition of IκB degradation or NF-κB nuclear transport. CONCLUSIONS: Our results indicate that inhibition of TNF-α, iNOS and Cox-2 expression by gentiolactone is one of the mechanisms of the anti-inflammatory properties of gentian roots.