Preclinical data supporting/refuting the use of Hypericum perforatum in the treatment of depression

Extracts of Hypericum perforatum (St. John's wort) have gained popularity as an alternative to synthetic antidepressants or behavioural therapy in the treatment of mild to moderate forms of depressive disorders. The present article reviews and discusses the available preclinical data that are in favour of or against the use of Hypericum perforatum as an antidepressant. Multiple chemical entities constitute extracts from Hypericum perforatum. The effects of Hypericum perforatum extracts have been compared with those of conventional antidepressants in different in vitro and in vivo biochemical studies of antidepressant-like activity and in behavioural pharmacology studies using animal models of depression. Recent investigations have indicated that Hypericum perforatum, like conventional antidepressants, is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function and influence, at least in part, stress-induced effects on neuroplasticity and neurogenesis. From the available evidence it can be concluded that data supporting the use of Hypericum perforatum for the treatment of depression are present in literature. However, results from experiments carried out with extracts or pure compounds do not always resemble biochemical and pharmacological profile characteristic of synthetic antidepressants. In particular, the majority of findings in preclinical studies have been obtained with high doses of pure compounds and extracts that are not comparable to the concentrations of single active constituents after oral administration in humans.