Planta Med 2004; 70(7): 680-682
DOI: 10.1055/s-2004-827194
Letter
© Georg Thieme Verlag KG Stuttgart · New York

In Vitro Effects of the Dicyclohexylammonium Salt of Hyperforin on Interleukin-6 Release in Different Experimental Models

Marco Gobbi1 , Manuela Moia1 , Marcella Funicello1 , Antonella Riva2 , Paolo Morazzoni2 , Tiziana Mennini1
  • 1Istituto di Ricerche Farmacologiche ”Mario Negri”, Milano, Italy
  • 2Indena S.P.A., Milano, Italy
This work was supported by Indena S.p. A.
Further Information

Publication History

Received: January 20, 2004

Accepted: March 20, 2004

Publication Date:
15 July 2004 (online)

Abstract

Cytokine hypersecretion might be involved in the onset and maintenance of depressive disorders and it has been suggested that St. John’s wort extracts (Hypericum perforatum, SJW) might exert their antidepressant-like effects by affecting peripheral interleukin-6 (IL6) expression. We found that hyperforin, one putative active principle of SJW, and its dicyclohexylammonium salt (hyperforin-DCHA), inhibited the substance P (SP)-induced IL6 release in human astrocytoma cells (U373MG) with an IC50 of 1.6 μM, indicating that hyperforin is likely to account for the inhibitory effect previously found in the same experimental model with SJW extracts. [3 H]SP binding experiments in parallel on the same intact cells indicate that hyperforin-DCHA does not interact with neurokinin-1 receptors but very likely interacts with some intracellular steps leading to the synthesis and/or release of IL6. Hyperforin-DCHA also inhibited, with a similar IC50, the IL6 release induced in U373MG cells by two other classic proinflammatory stimuli, IL1β and lipopolysaccharide (LPS), as well as the LPS-induced IL6 release in whole rat blood. Hyperforin-DCHA was less active in whole human blood. The concentrations required in vitro to inhibit LPS-induced IL6 release from rat and human whole blood are about one order of magnitude higher than the hyperforin levels measured in the plasma of rats or humans treated with pharmacologically active doses of SJW or hyperforin-DCHA.

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Dr. Marco Gobbi

Istituto di Ricerche Farmacologiche ”Mario Negri”

Via Eritrea 62

20157 Milano

Italy

Email: Gobbi@marionegri.it