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Influence of Saint John's wort (Hypericum perforatum) constituent hyperforin on phagocytosis and inducible nitric oxide synthase (iNOS) in microglia
Extracts of the flowering upper parts of St. John's wort (Hypericum perforatum L.) are used effectively for the treatment of mild to moderate depression, and there is already broad knowledge about the mode of action of extracts and constituents thereof on neurons [1, 2]. However, there is still considerable lack in scientific knowledge about the impact on microglia, the immunocompetent cells of the brain. We investigated the effects of St. John's wort extract and its constituent hyperforin on nitric oxide (NO) production via iNOS in N11 and BV2 mouse microglia. Moreover, the influence on transcription factor activation and phagocytosis was analyzed. We found that extracts of St. John's wort efficiently suppress LPS-induced NO release and identified hyperforin as the responsible compound, being effective at concentrations between 0.25 and 0.75µM. Reduced NO production was mediated by diminished iNOS expression on the mRNA- and protein-level. In addition, at similar hyperforin concentrations, zymosan phagocytosis was reduced to 20–40% and CD206 macrophage mannose receptor expression was down regulated. The observed effects correlated with a suppression of the activated state of Nf-kappaB and phospho-CREB, while c-JUN, STAT1 and HIF-1alpha activity as well as COX-2 expression remained unaffected by hyperforin .
Acknowledgements: We thank Steigerwald Arzneimittel GmbH (Darmstadt, Germany) for financial support.
References: 1. Barnes J. et al. (2001)J Pharm Pharmacol 53:583–600.
2. Butterweck V. (2003) CNS Drugs 17:539–562.
3. Kraus B. et al. (2010) Naunyn Schmiedebergs Arch Pharmacol. 2010 Apr 6. [Epub ahead of print]; doi: 10.1007/s00210–010–0512-y.