From Ms J. Barnes, MRPharmS and Dr L. Williamson, MRPharmS
SIR,-"Onlooker" (PJ, June 17, p896) refers to hypericin being the active principle of St John's wort (Hypericum perforatum) and its effects as an inhibitor of monoamine oxidase. However, while attention was focused initially on hypericin as the constituent of St John's wort believed to be responsible for the herb's antidepressant effects, and while inhibition of monoamine oxidase (MAO) type A and B in rat brain mitochondria in vitro has been described for hypericin,1 other studies have demonstrated only weak or no MAO inhibition.2,3,4
Thus, it is now generally accepted that MAO inhibition plays little or no part in St John's wort's antidepressant activity. Furthermore, experimental5,6 and clinical7 evidence has now emerged to indicate that hyperforin is one of the major constituents required for St John's wort's antidepressant activity. Hyperforin has been shown to be an uptake inhibitor of 5-HT, dopamine, norepinephrine, GABA and L-glutamate in synaptosomal preparations,5 and to inhibit 5-HT uptake in rat peritoneal cells in a dose-dependent manner.6 A study involving healthy volunteers suggested that St John's wort extract may increase aspects of brain dopamine function, although further studies are required to confirm this, to assess dose response relationships, and to determine whether there is evidence for effects on dopaminergic systems in patients with depression treated with St John's wort.8
In summary, hyperforin rather than hypericin, as originally thought, has emerged as one of the major constituents responsible for St John's wort's antidepressant activity. However, further research is required to determine which other constituents contribute to the antidepressant effect, and to elucidate the precise mechanism(s) of action for St John's wort's antidepressant effects.
Jo Barnes Teaching and Research Fellow Liz Williamson Lecturer The School of Pharmacy, University of London
References
1. Suzuki O et al. Inhibition of monoamine oxidase by hypericin. Planta Med 1984;50:272-4.
2. Bladt S, Wagner H. Inhibition of MAO by fractions and constituents of Hypericum extract. J Geriatric Psychiatry Neurology 1994; 7:S57-9
3. Demisch L et al. Identification of MAO-type-A inhibitors in Hypericum perforatum L (Hyperforat). Pharmacopsychiatry 1989; 22:194.
4. Thiede HM, Walper A. Inhibition of MAO and COMT by Hypericum extracts and hypericin. J Geriatric Psychiatry Neurology 1994;7:S54-6.
5. Chatterjee SS et al. Hyperforin as a possible antidepressant component of hypericum extracts. Life Sci; 1998; 63(6):499-510.
6. Chatterjee SS et al. Antidepressant activity of Hypericum perforatum and hyperforin: the neglected possibility. Pharmacopsychiatry 1998;31 (Suppl): 7-15.
7. Laakman G et al. St John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry 1998;31(Suppl):54-9.
8. Franklin M et al. Neuroendocrine evidence for dopaminergic actions of hypericum extract (L1 160) in healthy volunteers. Biol Psychiatry 1999;46:581-4.