Abstract
Nortrachelogenin is a pharmacologically active lignan found in knot extracts of Pinus sylvestris. In previous studies, some lignans have been shown to have anti-inflammatory properties,
which made nortrachelogenin an interesting candidate for our study. In inflammation,
bacterial products and cytokines induce the expression of inducible nitric oxide synthase,
cyclooxygenase-2, and microsomal prostaglandin E synthase-1. These enzymes synthesize
factors, which, together with proinflammatory cytokines, are important mediators and
drug targets in inflammatory diseases.
The effects of nortrachelogenin on the expression of inducible nitric oxide synthase,
cyclooxygenase-2, and microsomal prostaglandin E synthase-1 as well as on the production
of nitric oxide, prostaglandin E2, and cytokines interleukin-6 and monocyte chemotactic protein-1 were investigated
in the murine J774 macrophage cell line. In addition, we examined the effect of nortrachelogenin
on carrageenan-induced paw inflammation in mice.
Interestingly, nortrachelogenin reduced carrageenan-induced paw inflammation in mice
and inhibited the production of inflammatory factors nitric oxide, prostaglandin E2, interleukin-6, and monocyte chemotactic protein-1 in J774 macrophages in vitro. Nortrachelogenin inhibited microsomal prostaglandin E synthase-1 protein expression
but had no effect on cyclooxygenase-2 protein levels. Nortrachelogenin also had a
clear inhibitory effect on inducible nitric oxide synthase protein expression but
none on its mRNA levels, and the proteasome inhibitor lactacystin reversed the effect
of nortrachelogenin on inducible nitric oxide synthase expression, suggesting a post-transcriptional
mechanism of action.
The results revealed hitherto unknown anti-inflammatory properties of nortrachelogenin,
which could be utilized in the development of anti-inflammatory treatments.
Key words
nortrachelogenin - lignan - iNOS - inflammation -
Pinus sylvestris
- Pinaceae
