The Mechanism of Action of St. John's wort (Hypericum perforatum) in the Treatment of Depression. The molecular mechanism of action of hyperforin is still under investigation. Mechanisms of Action St. John’s wort is a mixture of biologically active compounds. This makes hyperforin the first member of a new class of compounds with a preclinical antidepressant profile due to a completely novel mechanism of action. The St John Wort extract and hyperforin attenuated symptoms of mild to moderate depression in a few clinical trials. Specifically, naphthodianthrone hypericin and the phloroglucinol derivative hyperforin … Whole cell patch clamp studies showed that hyperforin at 0.5 μM concentration did not change cortical NMDAR currents. Hyperforin has been shown to inhibit, like conventional antidepressants, the neuronal uptake of serotonin, norepinephrine and dopamine. DGIdb, The Drug Gene Interaction Database, is a research resource that can be used to search candidate genes or drugs against the known and potentially druggable genome. However, hyperforin inhibits also the uptake of gamma-aminobutyric acid and L-glutamate. Second possible hyperforin's antidepressant mechanism of action reported previously is related to blockade of NMDAR (Kumar et al., 2006). From molecular perspective, hyperforin has multidirectional mechanisms of action. The mechanisms of hyperforin actions are not yet understood, but may include inhibition of 5-lipoxygenase 10, high affinity binding to the pregnane X … However, if the primary mechanism of hyperforin is activation of NSCC2, its pharmacological effects may extend beyond those of typical antidepressant drugs and could explain hyperforin's beneficial effects on cognition (Klusa et al., 2001) and amyloid precursor protein processing (Froestl et al., 2003). Hyperforin is the primary active constituent responsible for the antidepressant and anxiolytic properties of extracts of St. John′s Wort. Hyperforin has been shown to inhibit, like conventional antidepressants, the neuronal uptake of serotonin, norepinephrine and dopamine. Although the mode of action of hyperforin seems to be associated with elevated [Na(+)](i) similar to those levels found with monensin, the molecular mechanism might be different, as even at high concentrations, hyperforin does not elevate free intracellular sodium concentration ([Na(+)](i)) up to the extracellular level, as monensin does. It is used in the synthesis of pharmaceuticals and explosives.Phloroglucinol is one of three isomeric benzenetriols.The other two isomers are hydroxyquinol (1,2,4-benzenetriol) and pyrogallol (1,2,3-benzenetriol). It Hyperforin acts as a reuptake inhibitor of serotonin and other monoamines including norepinephrine, dopamine, and GABA and glutamate by activating the transient receptor potential ion channel TRPC6. Phloroglucinol is an organic compound with the formula C 6 H 3 (OH) 3.It is a colorless solid. Our laboratory is currently investigating the means by which St-John's wort extract, or its constituent hyperforin, develops its antidepressant action. Both extract and hyperforin displayed antidepressant-like activity in preclinical studies (27, 28). The molecular mechanism of action of hyperforin is still under investigation. However, hyperforin inhibits also the uptake of gamma-aminobutyric acid (GABA) and L … Although hyperforin shows similar properties to classical antidepressants, there are indications of a novel mechanism of action. 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