St. John's Wort (Hypericum perforatum)

St. John's Wort (Hypericum perforatum) is primarily valued as a medicinal herb rather than a nutritional food source. Its key bioactive compounds dominate its profile: Hypericin and pseudohypericin (naphthodianthrone derivatives) at 0.0095–0.466% dry weight, serving as marker compounds for standardization; Hyperforin and adhyperforin (phloroglucinol derivatives) at 2–4.5% dry weight, considered primary active constituents for neuromodulatory effects. Flavonoids constitute 2–12% total dry weight, including hyperoside (quercetin-3-galactoside, ~0.5–2%), quercitrin (~0.3–1%), rutin (~0.3–0.8%), isoquercitrin, kaempferol, and luteolin glycosides; these exhibit moderate oral bioavailability (20–50%) influenced by gut microbiota metabolism and efflux transporters. Phenolic acids include chlorogenic acid, caffeic acid, and protocatechuic acid at trace to minor levels (~0.1–0.5%). Tannins (condensed and hydrolysable) range from 3–16% dry weight, contributing astringent properties but potentially reducing absorption of co-administered compounds. Essential oils comprise approximately 0.05–0.9%, containing caryophyllene, humulene, and pinene. Macro/micronutrient content is nutritionally insignificant; the herb provides negligible protein (<5% DW), minimal lipids (<3% DW), and modest carbohydrates. Bioavailability notes: Hyperforin is highly lipophilic (LogP ~7), requiring micellar solubilization for absorption; peak plasma concentrations observed 3–4 hours post-ingestion. Hypericin bioavailability is low (~14%) due to poor aqueous solubility. Flavonoid glycosides require intestinal hydrolysis to aglycone forms prior to absorption. CYP3A4 and CYP1A2 induction by hyperforin significantly alters co-administered drug pharmacokinetics, reducing systemic exposure of numerous medications.