Journal
PLANTA MEDICA
Volume 76, Issue 3, Pages 303-308Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0029-1186085
Keywords
rthritis; alpha-pinene; IL-1 beta; essential oil; NF-kappa B; nitric oxide
Categories
Funding
- Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/19763/2004, OSM/67936/2006]
- [C.E.F./POCI 2010/FEDER]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/19763/2004] Funding Source: FCT
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Nuclear factor-kappa B is a key transcription factor activated by pro-inflammatory signals, like interleukin-1 beta (IL-1), being required for the expression of many inflammatory and catabolic mediators, such as nitric oxide (NO), that play an important role in arthritic diseases. This work aimed at screening and identifying natural inhibitors of IL-induced NF-kappa B activation and NO production in human articular chondrocytes. Five essential oils obtained from four plants of the Iberian flora, Mentha x piperita L. (Lamiaceae), Origanum virens L. (Lamiaceae), Lavandula luiseri L. (Lamiaceae), and Juniperus oxycedrus L. subsp. oxycedrus (Cupressaceae), were screened for their ability to prevent IL-1-induced NO production. The oil showing higher inhibitory activity was fractionated, concentrated, analyzed for composition elucidation and prepared for further assays. For this purpose, the human chondrocytic cell line C-28/I2 was used to evaluate NF-kappa B activation by determining the cytoplasmic levels of the total and phosphorylated forms of the inhibitory protein, I kappa B-alpha, and the NF-kappa B-DNA binding activity. The essential oil from the leaves of J. oxycedrus in a concentration of 0.02% (v/v) achieved the greatest inhibition (80 +/- 8%) of IL-1-induced NO production. Chemical analysis showed that this essential oil is predominantly composed of monoterpene hydrocabons, being alpha-pinene [2,6,6-trimethyl-bicyclo(3.1.1) hept-3-ene] the major constituent (76%). Similarly to the effect of the whole oil, a fraction containing 93% alpha-pinene reduced significantly IL-1-induced I kappa B-alpha degradation. Moreover, alpha-pinene also decreased I kappa B-alpha phosphorylation, NF-kappa B-DNA binding activity, and NO production. Another fraction containing oxygenated mono- and sesquiterpenes was nearly as effective as alpha-pinene. The ability of the alpha-pinene-containing fraction to reduce IL-1-induced NF-kappa B activation and NO production warrants further studies to demonstrate the usefulness of alpha-pinene in the treatment of arthritic diseases and other conditions in which NF-kappa B and NO play pathological roles.
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