Date of Award
Ph.D. in Pharmaceutical Sciences
Pharmaceutics and Drug Delivery
Nicole M. Ashpole
Female Sexual Dysfunction (FSD) affects nearly 40% of women in the United States. While males have five FDA approved drugs for ED, there is only one FDA-approved as-needed treatment for premenopausal women with acquired, generalized Hypoactive Sexual Desire Disorder (HSDD), the most prevalent FSD. The lack of approved drugs is largely due to the biopsychosocial complexity of HSDD; however, there are neurobiological underpinnings evident. Due to the lack of safe efficacious treatment options, we hypothesize that botanical species traditionally used as aphrodisiacs may be promising leads, and exert their effects via activation of melanocortin’s, an excitatory circuit implicated in sexual function, specifically at MC4R, and later the MC3R. We conducted a review of the aphrodisiac products in the U.S. dietary supplement market to determine their levels of ethnobotanical and clinical evidence and narrow species selection. Utilizing market data, we found that 53 species were used for female specific sexual complaints; concluding that there is little to no clinical evidence from the literature to substantiate their use. We selected six species for further evaluation, Corynanthe johimbe, Labisia pumila, Asparagus racemosus, Tribulus terrestris, Eurycoma longifolia, and Trigonella foenum-graecum. Species were sequentially extracted, concentrated, dried, and tested to determine an MTC before subjection to melanocortin assays. While T. foenum-graecum initially demonstrated activation, replication experiments did not. C. johimbe, L. pumila, demonstrated activation of both the MC4R and MC3R over control (p < .05); however further fractionation of L. pumila resulted in a loss of activity. Select isolated and pure secondary metabolites of these species were also assessed, however no activation was observed. Both species were then assessed for their ability to secrete GnRH from a GT1-7 cell line, as well as ability to cause transcriptional changes in four genes of interest. Due to high secretion variability we cannot conclude the effects of our species on GnRH secretion; however, we observed significant transcriptional changes at GNRH1 and AGRP. This study is the first to evaluate botanical aphrodisiacs at the melanocortin receptors and provides preliminary insight into a mechanistic reasoning for their persistence as such.
Prescott, Hayley N., "Botanical Aphrodisiacs for Women's Health" (2022). Electronic Theses and Dissertations. 2267.
Available for download on Thursday, August 15, 2024