Pharmacopsychiatry 2001; 34(Suppl1): 26-28
DOI: 10.1055/s-2001-15462
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Inhibition of Substance P-Induced Cytokine Synthesis
by St. John's Wort Extracts

B. L. Fiebich, A. Höllig, K. Lieb
  • Department of Psychiatry, University of Freiburg Medical School, Freiburg, Germany
Further Information

Publication History

Publication Date:
31 December 2001 (online)

We tested the hypothesis that extracts from St. John's wort interfere with protein synthesis induced by substance P (SP), a neuropeptide which has been implicated in the etiopathology of depression and anxiety. Using human astrocytoma cells, which express functional neurokinin (NK)-1-receptors, we investigated whether extracts from St. John's wort are able to inhibit SP-induced synthesis of the cytokine interleukin-6 (IL-6). We found a potent and dose-dependent inhibition of SP-induced IL-6 synthesis by various extracts from St. John's wort. These results do not only give further evidence of the anti-inflammatory effects of St. John's wort, but also lend support to the hypothesis that the antidepressant effect of St. John's wort is, at least in part, a result of its inhibitory effects on SP-induced protein synthesis.

References

  • 1 Bork P M, Bacher S, Schmitz M L, Kaspers U, Heinrich M. Hypericin as a non-antioxidant inhibitor of NF-kappa B.  Planta Med. 1999;  65 297-300
  • 2 Chatterjee S S, Bhattacharya S K, Wonnemann M, Singer A, Muller W E. Hyperforin as a possible antidepressant component of hypericum extracts.  Life Sci. 1998;  63 499-510
  • 3 Feuerstein T J, Gleichauf O, Landwehrmeyer G B. Modulation of cortical acetylcholine release by serotonin: the role of substance P interneurons.  Naunyn Schmiedebergs Arch Pharmacol. 1996;  354 618-626
  • 4 Fiebich B L, Heinrich M, Langosch J M, Kammerer N, Lieb K. Antibacterial activity of hyperforin from St. John's wort.  Lancet. 1999;  354 777
  • 5 Fiebich B L, Hofer T J, Lieb K, Huell M, Butcher R D, Schumann G, Schulze-Osthoff K, Bauer J. The non-steroidal anti-inflammatory drug tepoxalin inhibits interleukin-6 and alpha1-anti-chymotrypsin synthesis in astrocytes by preventing degradation of I kappaB-alpha.  Neuropharmacology. 1999;  38 1325-1333
  • 6 Frommberger U H, Bauer J, Haselbauer P, Fraulin A, Riemann D, Berger M. Interleukin-6-(IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur. Arch.  Psychiatry Clin Neurosci. 1997;  247 228-233
  • 7 Heuillet E, Menager J, Fardin V, Flamand O, Bock M, Garret C, Crespo A, Fallourd A M, Doble A. Characterization of a human NK1 tachykinin receptor in the astrocytoma cell line U 373 MG.  J Neurochem. 1993;  60 868-876
  • 8 Kramer M S, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek J J, Reines S A, Liu G, Snavely D, Wyatt-Knowles E, Hale J J, Mills S G, MacCoss M, Swain C J, Harrison T, Hill R G, Hefti F, Scolnick E M, Cascieri M A, Chicchi G G, Sadowski S, Williams A R, Hewson L, Smith D, Rupniak N M. Distinct mechanism for antidepressant activity by blockade of central substance P receptors.  Science. 1998;  281 1640-1645
  • 9 Lieb K, Fiebich B L, Berger M, Bauer J, Schulze-Osthoff K. The neuropeptide substance P activates transcription factor NF-kappa B and kappa B-dependent gene expression in human astrocytoma cells.  J Immunol. 1997;  159 4952-4958
  • 10 Lieb K, Schaller H, Bauer J, Berger M, Schulze-Osthoff K, Fiebich B L. Substance P and histamine induce interleukin-6 expression in human astrocytoma cells by a mechanism involving protein kinase C and nuclear factor-IL-6.  J Neurochem. 1998;  70 1577-1583
  • 11 Linde K, Ramirez G, Mulrow C D, Pauls A, Weidenhammer W, Melchart D. St. John's wort for depression - an overview and meta-analysis of randomised clinical trials.  BMJ. 1996;  313 253-258
  • 12 Maubach K A, Rupniak N M, Kramer M S, Hill R G. Novel strategies for pharmacotherapy of depression.  Curr Opin Chem Biol. 1999;  3 481-488
  • 13 Philipp M, Kohnen R, Hiller K O. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks.  BMJ. 2000;  319 1534-1538

PhD Bernd L. Fiebich

Department of Psychiatry
University of Freiburg Medical School

Hauptstraße 5

79104 Freiburg

Germany

Phone: (49)761/270-6501

Fax: (49)761/270-6917

Email: bernd_fiebich@psyallg.ukl.uni-freiburg.de