Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC6

Title: Protonophore properties of hyperforin are essential for its pharmacological activity.

Authors: Thomas S Sell, Thabet Belkacemi, Veit Flockerzi, Andreas Beck

Journal, date & volume: Sci Rep, 2014 , 4, 7500

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25511254

Abstract
Hyperforin is a pharmacologically active component of the medicinal plant Hypericum perforatum (St. John's wort), recommended as a treatment for a range of ailments including mild to moderate depression. Part of its action has been attributed to TRPC6 channel activation. We found that hyperforin induces TRPC6-independent H(+) currents in HEK-293 cells, cortical microglia, chromaffin cells and lipid bilayers. The latter demonstrates that hyperforin itself acts as a protonophore. The protonophore activity of hyperforin causes cytosolic acidification, which strongly depends on the holding potential, and which fuels the plasma membrane sodium-proton exchanger. Thereby the free intracellular sodium concentration increases and the neurotransmitter uptake by Na(+) cotransport is inhibited. Additionally, hyperforin depletes and reduces loading of large dense core vesicles in chromaffin cells, which requires a pH gradient in order to accumulate monoamines. In summary the pharmacological actions of the "herbal Prozac" hyperforin are essentially determined by its protonophore properties shown here.