Hypericin pharmacological effects

Hypericin and pseudohypericin (Fig. 21) are naphthodianthrones and occur in St. John s wort Hypericum perforatum, Clusiaceae). These dark-red compounds are accumulated in glands on the margin oiK perforatum leaves and petals. It was assumed for a long time that they represent the antidepressant principle in extracts of St. John s wort. Recently, however, it became evident that the prenylated acylphloroglucinols hyperforin and adhyperforin are responsible for most of the pharmacological effects. 

This herbal product has the most data available to support its usefulness as an antidepressant. Nevertheless, only minimal information is available about its pharmacology and its relative risk-benefit ratio. At least seven different biologically active chemicals have been isolated from crude extracts of hypericum. Several are ubiquitous in the plant kingdom. The exceptions are hypericin and pseudohypericin, which have been assumed to be responsible for any antidepressant activity of this product. Nevertheless, there is the potential for one or more of these seven compounds and their metabolites to mediate desired or undesired effects, particularly when used in combination with other medications (i.e., herb-drug interactions). 

Butterweck V, Korte B, Winterhoff H. Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment. Pharmacos-pychiatry 2001 34 S2-S7. 

COMT hypothesis. According to this hypothesis. St. John s wort increases the levels of catecholamines at the brain synapses by inhibiting their inactivation by oxidative deamination (MAOl) and by catechol functionalization (catechol-0-methyltransferase [COMTl). Recent studies have shown that hypericins possess such activities only at pharmacologically excessive concentrations. If true, these effects at normal doses are small and do nothing to alleviate depression. Other hypotheses suggest hormonal effects or effects on the dopaminergic system. Hyperforin has become a candidate for the major antidepressant constituent of St. John s wort. 

The pharmacological activities of the various constituents of St.John s wort have been studied extensively. Hyperforin appears to be the major bioactive constituent and it acts in several ways serving as a neurotransmitter reuptake inhibitor with a broad selectivity, as a ligand for the pregnane X receptor, and as an antibacterial and antitumor agent. It also has a rapid effect on amyloid precursor protein processing, indicating a possible role in the prevention of Hypericin and the flavonoid constituents may have... 

Other pharmacological activities described for Hypericum extracts include diuretic [185]. antioedematous [186] and anthelminthic properties [187]. In yeast cells highly diluted hypericin 1 has been reported to stimulate respiratory activity [1]. Moreover, general roborant and tonic effects of small doses of hypericin 1, reflected in an increased vitality and growth rate of farm and laboratory animals, have repeatedly been described [1]. 

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