Article
The anti-inflammatory herbal drug, Devil’s Claw (Harpagophytum procumbens) (Allya®) inhibits TNFα gene expression via blockade of protein kinase Cε and AP-1
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Authors
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G. McGregor
- Pascoe Pharmaceutical Preparations GmbH, Medical Sciences Department, Giessen
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E. Munoz
- Cordoba
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B. Fiebich
- Freiburg
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A. Zimmermann
- Freiburg
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Y. Ibig
- Freiburg
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S. Orlikowski
- Freiburg
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M. Heinrich
- London
| Published: | June 13, 2005 |
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Outline
Text
Background
Extracts of the secondary roots of Harpagophytum procumbens (Devil´s Claw) are popular as adjunct treatment of osteoarthritis. The molecular mechanisms of its anti-inflammatory effects are unclear. We describe the effects of an ethanolic Devil´s Claw extract (that is the sole ingredient of the propreitory
drug, Allya®) (DC) on the expression and release of tumour necrosis factor α (TNFα), a key pro-inflammatory cytokine.
Materials and methods
TNFα-gene transcription and -release were quantified by northern blot analysis and ELISA respectively. Using western blot analysis and pharmacological inhibitors, those intracellular signalling pathways that are involved in the stimulated expression of TNFα were investigated in LPS-activated isolated human mononuclear cells and related cell-lines.
Results
DC inhibited LPS-induced TNFα gene expression and release in human monocytes. In the murine monocyte cell-line, RAW 264.7, the extract did not influence NFκB-dependent gene transcription or LPS-induced degradation of IκBα. LPS-induced activation of two mitogen activated protein kinases (MAPK), p38 MAPK and JNK, was also unaffected by DC. DC inhibited LPS-induced PKCε-activation. The transcriptional activation, in LPS-stimulated RAW cells, of AP-1, which is a downstream target of PKCε, was also inhibited by DC.
Discussion
These novel findings reveal that the traditional herbal drug, Devil´s Claw, exerts its anti-inflammatory effects by inhibiting TNFα gene expression through specific inhibition of the PKCε and AP-1 intracellular pathway. This finding is not only relevant for the anti-inflammatory effect of Devil´s Claw but also for its analgesic effects, since the PKCε and AP-1 pathway is also an intracellular mediator of nociception.
