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J Pharm Pharmacol. 2014 Nov;66(11):1606-14. doi: 10.1111/jphp.12242. Epub 2014 Aug 31.

Alteration of anti-inflammatory activity of Harpagophytum procumbens (devil's claw) extract after external metabolic activation with S9 mix.

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  • 1Institute for Complementary Medicine, University Hospital Zurich, Zurich, Switzerland.

Abstract

OBJECTIVES:

Extracts of the tubers of Harpagophytum procumbens (devil's claw, DC) inhibit different proinflammatory mediators important in the pathophysiology of osteoarthritis. Many plant-derived preparations interfere with cytochrome P450 liver enzymes, which influence their different biological activities. Therefore, the present study was designed to investigate the influence of an external metabolic activation of a DC extract on the cytotoxicity and the release of proinflammatory cytokines.

METHODS:

A screening experiment with a panel of 12 inflammatory cytokines identified three as suitable for the study: tumour necrosis factor-α (TNF-α), interleukin (IL) IL-6 and IL-8. They were determined using enzyme-linked immunosorbent assays in lipopolysaccharide (LPS)-stimulated monocytic THP-1 cells, which were treated with rat liver S9 mix metabolically activated DC extract (DCm). For the cytotoxity experiments, a WST-1 assay was used.

KEY FINDINGS:

DC dose-dependently suppressed the release of TNF-α, IL-6 and IL-8 in LPS-stimulated monocytic THP-1 cells at non-cytotoxic concentrations (50-250 μg/ml). The metabolic activation of the DC extract by S9 mix did not alternate its cytotoxicity and did not diminish its inhibitory effect. This effect was improved in the case of TNF-α inhibition as reflected by their EC50 values of 116 ± 8.2 μg/ml and 49 ± 3.5 μg/ml for DC and DCm (P < 0.01).

CONCLUSIONS:

Cytokines inhibitory activity of DC was not affected after its external metabolic activation. However, the amount of harpagoside and caffeic acid derivates was decreased. Other components of the extract might have contributed to its anti-inflammatory effect.

KEYWORDS:

S9 mix; THP-1 cells; devil's claw extract; proinflammatory cytokines

PMID:
25175765
DOI:
10.1111/jphp.12242
[PubMed - indexed for MEDLINE]
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