The Effects Of Estrogenic Components Of Licorice Root On Cognition

It is well established that estrogens modulate cognition in a task-dependent manner. Many dietary supplements contain estrogenic compounds, the efficacy and safety of which are poorly understood. This study investigated the efficacy of components of licorice root to alter performance on a hippocampus-sensitive metric change in object location (MCOL) task. We investigated isoliquiritigenin (ISL), Glycyrrhiza glabra root power (LRP), and an ethanol extract of Glycyrrhiza glabra root (LRE). We also explored whether a high fat diet (HFD) would impair performance on this task and whether the botanicals could mitigate any negative effects. Young adult (3-month old) Long-Evans female rats were ovariectomized and exposed to either a HFD (44.8% kcal from fat) or a LFD (17.2% kcal from fat) for five weeks prior to testing. A subset of rats on each diet were exposed to ISL, LRP or LRE at a concentration of 0.05%, 5% or 0.5% respectively of the diet for three weeks prior to testing. Estradiol improves performance on the MCOL task and thus was included as a positive control. Rats in the estradiol group were injected subcutaneously 48 and 24 hours prior to testing with 45 µg/kg of estradiol. In the MCOL task, rats were allowed to explore two objects in a black Plexiglas® chamber while object exploration time was recorded for three 5-min trials with a 3-min inter-trial interval in the rat's home cage. For the fourth 5-min trial, the objects were moved closer together and exploration time was again recorded. An increase in object exploration time in the final trial suggests that the rat detected the change in object locations. As expected, estradiol increased object exploration time on the final trial. ISL and LRE exposure also led to a significant increase in exploration time in the final trial relative to the third trial, indicating better performance on the task. Diet had no effect on its own and did not interact with botanical exposure.

Acknowledgements: This work was supported by funding from the NIH (NIH 5P50AT006268 – 05), a Neuroscience Program fellowship to Payel Kundu, as well as an Environmental Toxicology Scholar traineeship to Payel Kundu.