Serotonin modulating activities of plants used for menopause in Guatemala

Modulators of the serotonin (5HT) 1a and 7 receptors have been implicated as part of the pathophysiology of the menopausal hot flash. Some botanical extracts used to treat menopausal symptoms, (i.e. black cohosh) appear to modulate serotonin as part of their overall mechanism of action. As part of NIH grant AT002381–02 we have been investigating medicinal plants from Guatemala used to treat menopause. The plants were collected, air-dried and voucher specimens deposited at the Herbarium of the School of Biology at the University of San Carlos. Dried plant material was extracted with 95% ethanol and the extracts were tested in a range of serotonin receptor binding assays (5-HT-1A, 2A, 5A, and 7). Five plants from the Piperaceae namely Piper aeruginosibaccum Trelease, P. auritum HBK, P. diandrum C. DC., P. hispidum Swingle, P. tuerckheimii C.DC, and one plant from the Menispermiaceae, Cissampelos tropaeolifolia DC. were of interest due to their strong inhibition of radiolabeled ligand binding to the 5-HT1A, 2A and 7 receptors (activity deemed as >50% binding at 50µg/ml of the extract) and their insignificant binding to the estrogen receptors. Cissampelos tropaeolifolia exhibited significant binding to the 5-HT1A receptor (88%) and the 5-HT7 serotonin receptor (94%), Piper tuerckheimii (90 and 72%, respectively) and P aeruginosibaccum (81 and 82%, respectively) were followed by P. hispidum (63 and 96%, respectively), P. auritum (66 and 83%, respectively) and P. diandrum (56 and 76%, respectively). One new compound, 4,6-dioxypiperolide isolated from P. hispidum, bound to the 5HT-7 receptor.