Sesquiterpene lactones from Arnica flowers down-regulate IL-1β stimulated matrix metalloproteinase genes in human and bovine chondrocytes

The major pathologic manifestations of rheumatoid arthritis and osteoarthritis are joint inflammation and articular cartilage degradation by proinflammatory cytokine-stimulated matrixmetalloproteinases (MMPs) and aggrecanases [1]. In a pilot clinical study phytomedicines from Arnica montana flowers have been proven to exert beneficial effects in patients suffering from mild to moderate osteoarthritis of the knees [2].

Here, we show that helenalin and dihydrohelenalin derivatives, sesquiterpene lactones (SLs) from Arnica flowers, were highly active in inhibiting IL-1β induced mRNA expression of matrixmetalloproteinase (MMP)-13 and MMP-1at micromolar concentrations in primary bovine articular chondrocytes and human articular chondrocytes using real time qPCR analyses. A similiar dose-dependent inhibition on DNA binding capacity of IL-1β-stimulating transcription factors AP-1 and NF-κB using the EMSA was also noted. Moreover, further experiments revealed that AP-1 was directly targeted. EMSA experiments were also carried out with different preparations from Arnica flowers. The strenght of DNA binding inhibition of both transcription factors was dependent on the type and content of SLs. In summary, besides its antiinflammatory activity SLs from Arnica may also be effective in blocking cartilage matrix degradation by MMPs by impairing AP-1 and NF-κB binding activities.

Acknowledgements: Financial support by Bioforce, Switzerland is gratefully acknlowledged

References: [1] Burrage, P.S. et al. (2006) Front. Bioscience 11: 529 [2] Knuesel, O. et al. (2002) Adv. Ther. 19: 209–218.