Memory and cognition enhancing activities of an ethanolic extract from Calendula officinalis flowers after oral administration in rats and mice

Pharmaceutical preparations containing Calendula officinalis have a long tradition in the treatment of wounds and other skin irritations. Beside topical application, internal administration is also employed to treat gastro-intestinal disorders, amenorrhoea or epistaxis. During a systematic evaluation of oral uses of C. officinalis in folk medicine, we gained information suggesting that such extracts cause sedation. Based on these observations, we investigated if an ethanolic (60% m/m) extract prepared from the flowers of C. officinalis (CoE) has pharmacological effects on the CNS. Surprisingly, we obtained data indicating clinically relevant improvement of cognitive functions.

Behavior of young and old mice was tested in the T-maze which is a suitable animal model to study spatial working memory. Oral administration of CoE at doses of 150 and 300 mg/kg antagonized scopolamine-induced or age-dependent cognitive impairment comparable to the 0.3 mg/kg of the positive reference drug donepezil (73%, 90%, 77%) respectively. In addition, rats were tested in the Morris water maze and the passive avoidance test. Both models are often used to investigate learning behavior of rodents. Cognitive impairment was induced by the mitochondrial poison sodium azide (NaN₃) which was administered via subcutaneously implanted osmotic minipumps. Daily administration of CoE at doses of 50, 100 and 200 mg/kg/day for 30 days prevented NaN₃-induced deficits in the Morris maze in a dose-dependent manner by 68%, 85% and 88%, respectively. In the passive avoidance model all three doses completely reversed the NaN₃-induced impairments. Initial studies on the mechanism of action showed that administration of CoE modulates the plasma ratio of dehydroepiandrosterone (DHEA) to DHEA sulfate which was accompanied by a moderately increased hippocampal acetylcholine concentration. These results indicate that CoE enhances brain cholinergic function and improves memory, learning and attention in rodents.