hyperforin

Hyperforin is a phloroglucinol derivative and the primary active constituent responsible for the antidepressant and anxiolytic properties of St. John's wort (Hypericum perforatum) extracts. It acts as a broad-spectrum reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, as well as GABA and glutamate. Unlike conventional antidepressants that target specific transporters, hyperforin inhibits neurotransmitter uptake by activating the transient receptor potential ion channel TRPC6, leading to increased intracellular sodium and calcium concentrations which in turn inhibit monoamine reuptake. Hyperforin also induces cytochrome P450 enzymes CYP3A4 and CYP2C9 via activation of the pregnane X receptor (PXR), contributing to significant drug interactions when St. John's wort is used concurrently with other medications. In addition to its antidepressant effects, hyperforin exhibits anxiolytic-like activity, cognition-enhancing effects in vivo, antioxidant properties in vitro, anticyclooxygenase-1 activity, and potential anticarcinogenic effects[1][2][5][6][8].