Antidepressant-Like Components of Hypericum perforatum Extracts: An Overview of Their Pharmacokinetics and Metabolism

Abstract

Extracts of Hypericum perforatum are becoming increasingly popular for the treatment of mild to moderate depression, despite the lack of consensus on their efficacy. Although the mechanism(s) of this action are still debated, several components, including the naphthodianthrones hypericin and pseudohypericin, the acylphloroglucinol hyperforin and some flavonols, are believed to play major roles in the antidepressant-like effects. Some of these also increase the expression of the P-glycoprotein transporter and others the expression of cytochrome P450 enzymes, possibly contributing to the interactions involving the extracts and conventional drugs. However, few pharmacokinetic studies of naphthodianthrones and hyperforin have appeared and none has yet evaluated the exposure to unchanged quercetin and its glycosides after intake of extracts. There are no formal pharmacokinetic studies in special populations. Bioavailability appears low, giving variable steady-state plasma concentrations, whose prediction may be complicated by non-linearity for hypericin and hyperforin. Data on tissue distribution are scarce, and it appears that hypericin and hyperforin do not reach the central nervous system in appreciable concentrations in animals. Clearance is low-intermediate, with little or no unchanged compounds excreted with urine. Although some potentially active conjugated metabolites have been identified for quercetin and its glycosides after intake of authentic compounds or flavonol-rich foods, these too have been characterised little with regard to their pharmacokinetics and central activities. Thus, further pharmacokinetic and pharmacodynamic studies of the main components and their metabolites are urgently needed to clarify the role of each constituent and provide more rational and safe regimens for people preferring "natural" drugs.

Liquid chromatography–tandem mass spectrometry of I3,II8-biapigenin, the major biflavone in Hypericum perforatum extracts

“…After the necessary correction for the contribution from residual blood [15,16], biapigenin brain concentrations approximated Table 1 Biapigenin plasma and brain concentrations in rodents given oral Hypericum perforatum extract Species a Plasma (ng mL −1 ) Brain (ng g −1 )…”

“…Most importantly, biapigenin total brain concentrations were low and mostly related to the residual biflavone in the circulation, as is possibly the case for other flavonoids found in rodent brain after intake of either pure compounds or flavonoidcontaining foods [15,16]. Poor brain-to-blood permeability is common to other polar components of H. perforatum, including hyperforin and hypericin, resulting in brain concentrations [19,20] generally too low for any direct interaction with neurotransmitter transporters and receptors, which are obviously important for the action of conventional antidepressants [15].…”

Hyperforin promotes mitochondrial function and development of oligodendrocytes

“…The pharmacokinetic studies of hyperforin in human are only feasible after the application of 14 C-labelled hyperforin and high-performance liquid chromatography tandem mass spectroscopy (HPLC/MS/MS) system which is a highly sensitive and selective method to detect hyperforin (Caccia, 2005). In rats, the maximum plasma level of hyperforin is approximately 690 nM 3 h after oral administration of 300 mg/kg of SJW extract containing 5% hyperforin.…”

Studies of Natural Products on Treating Neurological Disorders in China

“…Analgesic effects are possessed by sinomenine (Ye et al 2004) (extracted from Caulis sinomenii), vauquline (extracted from Semen strychni), total glucosides of astragalus, and total flavones from snow lotus extracts and Ginkgo biloba. Antidepressant efficacy is exhibited in Hypericin and hyperforin (Caccia 2005) (extracts from Hypericum perforatum (St. John's wort)), Radix morindae officinalis ethanol extracts, EGb761 (Gertz and Kiefer 2004) have been proved to contribute to the antidepressant efficacy. Extracts from Acanthopanax giraldii Harms, Hemerocallis fulva, schisandra chinensis (Turcz.)…”