Lepidiline A Improves the Balance of Endogenous Sex Hormones and Increases Fecundity by Targeting HSD17B1.

SCOPE: Maca (Lepidium meyenii), a well-known plant from the Andean highlands of Peru, has been used widely as a nutritional supplement to increase sexual function and fecundity. However, the identity of its active ingredients and how they function remain unknown. METHODS AND RESULTS: Chemical substances in maca were identified by UPLC-Q-TOF, and the active ingredients were screened through HotMap coupled with an artificial neural network (ANN). Lepidiline A (LA), an imidazole alkaloid, was identified as the key active compound. LA affected the balance of endogenous sex hormones in mice and improved fecundity in Drosophila. Using a molecular LA probe, HSD17B1 was revealed to be the potential target of LA using a fishing-rod strategy. We demonstrated with experimental data that LA targets HSD17B1 to enhance the enzyme's activity and increase its bioconversion efficiency of actively formed sex hormones including estrogen to 17beta-estradiol and 4-androsten-3,7-dione to testosterone which ultimately improved reproductive activity. CONCLUSION: LA improved the balance of endogenous sex hormones and increased fecundity by targeting HSD17B1. This underlying mechanism of action provides a useful insight into the application of maca in the regulation of dietary nutrition and healthy fertility. This article is protected by copyright. All rights reserved.