Abstract
Opposing findings have been published on the regulation of the sperm-specific Ca 2+ channel CatSper (cation channel of sperm) in human sperm cells by the plant triterpenoids lupeol and pristimerin. While the original study on this topic found these triterpenoids to act as potent inhibitors of human CatSper, subsequent studies have failed to replicate such an inhibitory effect. It has been suggested that these issues could in part be due to purity issues and/or batch variation between the plant-derived extracts of lupeol and pristimerin obtained for the studies. The aim of this study was to elucidate this controversy by investigating the batches of lupeol and pristimerin used in our previous study with state-of-the-art 1H-, 13C- and 2D-nuclear magnetic resonance (NMR) methods to reveal potential purity and/or batch variation issues. When comparing the NMR-spectra obtained from 1H-NMR and 13C-NMR with previously published NMR-spectra for lupeol and pristimerin, we could confirm that both the lupeol and pristimerin batch were ≥95 % pure. These results confirm the validity of the findings in our previous study for lupeol and pristimerin, showing that lupeol and pristimerin do not inhibit activation of CatSper in human sperm. In conclusion, using 1H-, 13C- and 2D-NMR methods, we confirm that the lupeol and pristimerin batches used in our previous study were ≥95 % pure and thereby fail to identify any purity issues and/or batch variation that could explain the observed inability of lupeol and pristimerin to inhibit activation of CatSper in human sperm.
Highlights
Opposing findings have been published on the regulation of the sperm-specific Ca2+ channel CatSper in human sperm cells by the plant triterpenoids lupeol and pristimerin
The putative inhibitory action of the two plant triterpenoids lupeol and pristimerin on the activation of the human sperm CatSper Ca(2+)-channel has recently been debated in the scientific literature
The original study on this subject (Mannowetz et al, 2017) indicated that these triterpenoids act as very potent and efficacious inhibitors of progesterone-activated CatSper-currents in human sperm cells with IC -values in the lower nM range, and a follow-up study by the same research group confirmed the inhibitory action of pristimerin on progesterone-induced Ca(2+)-influxes via CatSper through measurements in the principal piece of the flagellum in single human sperm cells (Mannowetz et al, 2018)
Summary
Opposing findings have been published on the regulation of the sperm-specific Ca2+ channel CatSper (cation channel of sperm) in human sperm cells by the plant triterpenoids lupeol and pristimerin. The putative inhibitory action of the two plant triterpenoids lupeol and pristimerin on the activation of the human sperm CatSper Ca(2+)-channel has recently been debated in the scientific literature.
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