Hypericum perforatum : Pharmacokinetic, Mechanism of Action, Tolerability, and Clinical Drug-Drug Interactions

Abstract

Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP.

Arbuscular mycorrhizal fungi altered the hypericin, pseudohypericin, and hyperforin content in flowers of Hypericum perforatum grown under contrasting P availability in a highly organic substrate

“…John's Wort (Hypericum perforatum L.) is a perennial herb belonging to the Hypericaceae family (Ruhfel et al 2013), native to Europe, Asia, and North Africa, introduced and naturalized in North America and in temperate areas of the Southern hemisphere (Carrubba and Scalenghe 2012). H. perforatum and related species have been used since ancient times as a local resource for medicinal purposes, due to their wound healing, mild sedative, antiviral, and antidepressant properties (Russo et al 2014). These properties are associated with a group of hydrosoluble metabolites, mostly accumulated in flowers: the phenolic compounds naphthodianthrones, including hypericin and pseudohypericin, and the phloroglucinol derivative hyperforin (Lazzara et al 2015).…”

Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds

“…1A), an active ingredient of St. John's wort, which is a widely used and well investigated medicinal plant (Wolfle et al, 2014). Hyperforin is a multitarget compound that modulates various molecular functions and exerts various beneficial effects, showing antimicrobial, anti-inflammatory, anticancer, and antidepressant activity (Russo et al, 2014). It has been previously reported that hyperforin exerts antidepressant and neurotrophic effects via activation of TRPC6 in neurons (Leuner et al, 2007Griesi-Oliveira et al, 2015).…”

Applying evidence-based-medicine to the prescribing of herbal products

“…For most high quality products, the exact quantity of Hyperforin (which is the main chemical responsible for interactions) is known. Choosing a product with negligible amounts of Hyperforin is, therefore, recommended when a patient is using pharmaceutical medications that can potentially interact 19 .…”