hyperforin and Cognition-Disorders

St. John's Wort (SJW) has been used medicinally for over 5,000 years. Relatively recently, one of its phloroglucinol derivatives, hyperforin, has emerged as a compound of interest. Hyperforin first gained attention as the constituent of SJW responsible for its antidepressant effects. Since then, several of its neurobiological effects have been described, including neurotransmitter re-uptake inhibition, the ability to increase intracellular sodium and calcium levels, canonical transient receptor potential 6 (TRPC6) activation, N-methyl-D-aspartic acid (NMDA) receptor antagonism as well as antioxidant and anti-inflammatory properties. Until recently, its pharmacological actions outside of depression had not been investigated. However, hyperforin has been shown to have cognitive enhancing and memory facilitating properties. Importantly, it has been shown to have neuroprotective effects against Alzheimer's disease (AD) neuropathology, including the ability to disassemble amyloid-beta (Abeta) aggregates in vitro, decrease astrogliosis and microglia activation, as well as improve spatial memory in vivo. This review will examine some of the early studies involving hyperforin and its effects in the central nervous system (CNS), with an emphasis on its potential use in AD therapy. With further investigation, hyperforin could emerge to be a likely therapeutical candidate in the treatment of this disease.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antidepressive Agents; Bridged Bicyclo Compounds; Cognition Disorders; Hypericum; Mice; Mice, Transgenic; Neuroprotective Agents; Phloroglucinol; Receptors, N-Methyl-D-Aspartate; Terpenes; TRPC Cation Channels; TRPC6 Cation Channel

An increasing number of researches have focused on the cognitive changes in depression patients. Here, we observed impaired cognitive ability in a rat depression model along with down-regulated expression of canonical transient receptor potential 6 (TRPC6) protein. The cognitive defect could be rescued by treatment with hyperforin, which can invoke TRPC6 activation. This study was designed as following: rats were randomly divided into control, stressed and stressed+hyperforin groups. Chronic unpredictable stress combined with isolation rearing was applied on rats for three weeks, except for control group. Morris water maze was applied to evaluate spatial cognitive ability while long-term potentiation (LTP) was recorded to test the synaptic plasticity. Results showed that both spatial cognition and synaptic plasticity were impaired in stress group while improved after hyperforin treatment in stressed+hyperforin group, meanwhile, Western blot assay showed that TRPC6 expression was decreased in stressed group. The histological data also presented the decline of dendritic length, dendritic spine density and the number of excitatory synapses in stress group while they were increased in stressed+hyperforin group. These results suggest that there is a well potential of TRPC6 to become a new target for selecting promising new candidates as antidepressants with therapeutically effect on impaired cognition.

Topics: Animals; Body Weight; Central Nervous System Agents; Cognition; Cognition Disorders; Dendrites; Depressive Disorder; Dietary Sucrose; Disease Models, Animal; Down-Regulation; Feeding Behavior; Long-Term Potentiation; Male; Maze Learning; Phloroglucinol; Rats, Wistar; Reversal Learning; Social Isolation; Stress, Psychological; Terpenes; TRPC Cation Channels; Uncertainty