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

PLoS One. 2014 Nov 25;9(11):e113834. doi: 10.1371/journal.pone.0113834. eCollection 2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclooxygenase 2 / genetics*
  • Gentiana / chemistry*
  • Iridoids / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • NF-kappa B / genetics*
  • Nitric Oxide Synthase Type II / genetics*
  • Promoter Regions, Genetic*
  • RNA, Messenger / genetics*
  • Tumor Necrosis Factor-alpha / genetics*


  • Iridoids
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • gentiolactone
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2

Grant support

This work was supported by a fund from the Basic Biotechnology Project of Iwate Prefecture, Japan, and the Adaptable and Seamless Technology Transfer Program through Target (A-STEP, 241FT0403). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.