Hypericaceae

Around 9 genera and 700 species, most of them in the genus Hypericum, distributed through temperate and subtropical regions. The field character is excellent: hold a leaf to the light and it appears perforated by translucent dots — schizogenous oil glands, which give H. perforatum its species name — while the petal margins carry black dots of hypericin-containing pigment that stain the fingers red when crushed.

St John’s wort (Hypericum perforatum) is the best-evidenced herbal antidepressant in existence, and simultaneously the most dangerous common herb for drug interactions. Both facts trace to the same molecule.

Efficacy is not in serious doubt. Cochrane reviews and multiple meta-analyses find standardised extract superior to placebo in mild to moderate depression and comparable to standard antidepressants, with fewer side effects and better tolerability. Evidence in severe depression is weaker. The active principle is chiefly hyperforin, a prenylated phloroglucinol that inhibits reuptake of serotonin, noradrenaline, dopamine, GABA and glutamate — an unusually broad, non- selective profile arising from a mechanism (sodium-conductance-dependent) quite unlike an SSRI’s. Hypericin, the red pigment, contributes photosensitivity more than antidepressant activity.

The interaction problem is the reason this herb requires care. Hyperforin is a potent activator of the pregnane X receptor, which induces CYP3A4 and P-glycoprotein. The consequence is that St John’s wort accelerates the clearance of a very large fraction of prescription medicine — including oral contraceptives (documented contraceptive failure and pregnancy), ciclosporin (documented transplant rejection), warfarin, antiretrovirals, some chemotherapy agents, statins and anticonvulsants. Combined with SSRIs or triptans it can also precipitate serotonin syndrome. This is not a theoretical caution: it is among the best-documented herb–drug interaction profiles in pharmacology, with real clinical harm behind it.

Photosensitivity is the other characteristic effect, well established in grazing livestock and reported in fair-skinned people at higher doses.

Prenylated phloroglucinols (hyperforin, adhyperforin) and naphthodianthrones (hypericin, pseudohypericin) are the family markers. Alongside them: flavonoids (hyperoside, rutin, quercitrin), biflavones (amentoflavone), tannins and xanthones.