Researching the antidepressant actions of Hypericum perforatum (St. John'swort) in animals and man

M. Franklin et Pj. Cowen, Researching the antidepressant actions of Hypericum perforatum (St. John'swort) in animals and man, PHARMACOPS, 34, 2001, pp. S29-S37
Citations number
Categorie Soggetti
Neurosciences & Behavoir
Journal title
ISSN journal
0176-3679 → ACNP
Year of publication
S29 - S37
SICI code
We have studied the effect of acute and sub-chronic treatments of a formula tion of a methanolic extract of hypericum perforatum (HP, also known as St John's wort) on plasma hormones and brain neurotransmitters in healthy huma n volunteers and rats. Also studied were the effects of equivalent acute do ses of two constituents of HP (with respect to LI 160 extract), hypericin a nd hyperforin in rats. In acute treatment studies in normal volunteers subj ects received 9 tablets of the finished product Jarsin (R) 300 and placebo in the pilot study (unblinded) and in the main study (a double blind, balan ced order, cross-over design). Results in normal volunteer studies show tha t HP caused significant increases of salivary cortisol and plasma growth ho rmone (GH) whereas it decreased plasma prolactin versus placebo. Plasma hor mone levels were associated with a rise in plasma hyperforin but not with h ypericin, however no significant correlation was found. In the animal studi es, acute treatment with LI 160, hyperforin and hypericin all caused signif icant increases in plasma corticosterone. This was associated with signific ant increases in brain cortical tissue 5-HT content. The corticosterone res ponses were attenuated by the 5-HT2 receptor antagonist, ketanserin but not by the 5-HT1A antagonist, WAY-100635. This suggests that the corticosteron e responses may be mediated via a 5-HT2 mechanism of action. When sub-chron ic and acute treatment using two different doses of LI 160 were compared, p lasma corticosterone level were significantly decreased. Thus suggesting a down-regulation or desensitisation of post-synaptic 5-HT2 receptors. Plasma prolactin was significantly reduced by acute treatment with Ll 160 and hyp erforin treatment but not by hypericin. This was associated with a concomit ant rise in brain cortical tissue DA. Both Ll 160 and hyperforin treatments decreased the plasma prolactin responses to the DA antagonist, haloperidol , suggesting that this may be associated with a DA-mediated mechanisn of ac tion. When acute and sub-chronic treatments were compared, plasma prolactin responses were increased in the sub-chronically treated animals. The studi es when taken together suggest that the LI 160 extract may effect plasma ho rmonal changes via both 5-HT and DA-mediated mechanisms but do not involve noradrenaline (NA). The data also suggests that hyperforin may be more impo rtant than hypericin for effecting these changes following acute treatment. Further studies investigating both acute and sub-chronic effects of these compounds are necessary.