MAJOR CHEMICAL CONSTITUENTS

Hypericin, pseudohypericin, isohypericin, hyperforin; flavonols including kaempferol and quercetin; flavones, glycosides, bioflavonoids, catechins; phenols including caffeic acid, p-coumaric acid, ferulic acid, and vanillic avid; volatile oils, carotenoids, nicotinic avid, isovalerinic acid, palmitic acid, and a number of volatile oils.

PRINCIPAL USES

TRADITIONAL AND HISTORICAL USES

St. John’s wort (SJW) has been a famed vulnerary and antidepressant herb since the Greco-Roman times. In ancient medical history, however, depression was not the likely diagnosis—a patient was said to have been afflicted by evil spirits or other psychic malady.

In our modern era, mounting evidence from clinical trials, especially those conducted in the 1980s and 1990s, established the efficacy and safety of standardized SJW extracts for treating mild to moderate depression, and practically overnight, SJW became a “household alternative” for the treatment of depression as well as a multi-million dollar boon for the natural products industry. Although SJW remains a top-selling herb, reports of potentially serious herb–drug interactions, as well as widely publicized but poorly conducted studies questioning its efficacy have led to some decline in its popularity as a treatment for depression.

CLINICAL INDICATIONS

SJW is indicated for mild to moderate depression. Herbalists also prescribe SJW as a mild sedative and nerve tonic for excitability, anxiety, and nervous irritability, for pain relief for neuralgia and sciatica, as an antiviral for both internal and topical prevention and treatment of Herpes simplex virus (HSV), and for neurovegetative menopausal complaints, particularly anxiety and sleep difficulties, typically in combination with other herbs. It is commonly included as a vulnerary—or

St. John’s wort (Hypericum perforatum).

Photo by Martin Wall.

wound healing herb—in formulae for the treatment of cuts, scrapes, and puncture wounds, as well as to soothe and heal the perineum with or without perineal lacerations after childbirth, to soothe and reduce hemorrhoids, and for the treatment of vaginal abrasions in vaginitis and those that can occur with perimenopausal vaginal atrophy and vaginal dryness. Herbal practitioners may also include SJW in formulae for the treatment of cystitis, urinary frequency and urgency, and interstitial cystitis.

MECHANISMS OF ACTION

The precise mechanisms of action for the antidepressant effects of SJW are not understood. In vitro studies using hyperforin have demonstrated significant binding of GABA A and GABA B, adenosine, MAO, and benzodiazepine receptors. Only GABA A and GABA B receptor activity is likely to be achieved in concentrations to elicit a biological effect after oral administration in humans. Early studies focused on the inhibitory activity of hypericin on MAO receptors; however, most studies have demonstrated only weak binding if at all. It appears that there might be some effects in inhibition of synaptosomal uptake of serotonin (5-HT), dopamine, and noradrenaline, with an upregulation of 5-HT in rat cortex, with some increase in dopamine and noradrenaline. Studies have shown possible decrease in tryptophan degradation; tryptophan is a 5-HT precursor. Another possible explanation for the antidepressant effect of SJW is via inhibition of interleukin-6 (IL-6) by hyperforin and via inhibition of substance P mediated effects on depression.

Antiviral effects of SJW are attributed in part to the flavonoid and catechin fractions of the herb. Both hypericin and psuedohypericin have demonstrated in vitro inhibition of HSV Types 1 and 2, Varicella zoster virus, and HIV type 1 via a photoactivation process that is not yet elucidated.