Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment

Clinical studies have demonstrated the antidepressant efficacy of Hypericum (St. John's wort) extracts comparable to tricyclic antidepressants such as imipramine. We examined the effects of Hypericum extract and hypericin, one active constituent, in the forced swimming test (FST) after treatment repeated for 14 days. It has recently been shown that hypericin was inactive in the FST after acute treatment, but remarkably active when solubilized by subfraction IIIc1 containing mainly procyanidin B2. Therefore, we investigated the cooperative effects of hypericin and procyanidin B2 after repeated treatment. Imipramine (15 mg/kg), Hypericum extract (500 mg/kg) and hypericin (0.1 mg/kg) given daily for 2 weeks significantly reduced immobility time in the FST. No differences were observed between animals receiving pure hypericin and those receiving hypericin in combination with procyanidin B2. As several antidepressants act on the neuroendocrine axis resulting in altered hormone concentrations, selected endocrine parameters were investigated after repeated treatment. Daily treatment with either imipramine, Hypericum extract or hypericin alone or in combination with procyanidin B2 for 14 days significantly decreased plasma ACTH and corticosterone levels. None of the substances had pronounced effects on plasma prolactin or LH levels. From our present data, we propose that cooperative effects of hypericin and procyanidin B2 are of important relevance for the acute, but not for the chronic effects of this polycylic quinone.