Abstract
Considered an antidepressant and anti-anxiety agent, Hypericum perforatum affects multiple neurotransmitters in a non-competitive synergistic manner, and may have nootropic potential. We quantitatively reviewed the pre-clinical literature to examine if there is a cognitive-enhancing effect of H. perforatum in healthy rodents. Additionally, within these studies, we compared the effects observed in intact rodents versus those whose performance has been impaired, mostly through stress manipulations. The meta-analysis incorporated studies that examined the effect of H. perforatum versus placebo on memory indices of task performance. All analyses were based on weighting different studies according to their inverse variance. Thirteen independent studies (published 2000–2014) involving 20 experimental comparisons met our inclusion criteria. The results showed a large positive effect of H. perforatum on cognitive performance for intact, healthy rodents (d = 1.11), though a larger effect emerged for stress-impaired rodents (d = 3.10 for restraint stress). The positive effect on intact rodents was observed in tasks assessing reference memory as well as working memory, and was not moderated by the type of memory or motivation (appetitive versus aversive). Thus, while primarily considered as a medication for depression, H. perforatum shows considerable nootropic potential in rodents.
Highlights
H. perforatum includes at least seven different active ingredients[16], among them hypericin and hyperforin are considered the primary constituents[7,17]
We included studies fulfilling the following two criteria: random assignment of animals to groups, and a complete design with at least one healthy, intact, control group treated with placebo and a healthy intact rodent group treated with H. perforatum
The literature search provided a total of 792 citations, of which 13 studies met the criteria and were included in the review
Summary
H. perforatum includes at least seven different active ingredients[16], among them hypericin and hyperforin are considered the primary constituents[7,17]. Upregulation of 5-HT in these areas reduces negative affect from impinging into memory processes[22,23], while upregulation of dopamine reduces background firing rate of neurons, decreasing non-task related activity and improving signal to noise ratio[24]. These monoaminergic effects are considered quite weak[8,16,18]; they are relatively broad in that the expression of 5-HT1A receptors is upregulated as in most SSRIs, and of 5-HT2 receptors[17,18]. The existence of these neuropharmacological pathways suggests that H. perforatum can enhance the cognitive performance of healthy intact animals, either because of its anti-anxiolytic effects which may alleviate task stress or through its effects on memory and task-related attention
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