Sex Differences in the In Vivo Exposure Process of Multiple Components of Gelsemium elegans in Rats

Abstract

Asian Gelsemium elegans (G. elegans) has a wide range of pharmacological activities. However, its strong toxicity limits its potential development and application. Interestingly, there are significant gender differences in G. elegans toxicity in rats. This work aimed to elucidate the overall absorption, distribution, metabolism, and excretion (ADME) of whole G. elegans crude extract in female and male rats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS), which facilitates determining the reasons for the gender differences in toxicity. A total of 25 absorbed bioactive components and 3 related produced metabolites were tentatively identified in female rats, while only 17 absorbed bioactive components and 3 related produced metabolites were identified in male rats. By comparison of peak intensities, most compounds were found to be more active in absorption, distribution and excretion in female rats than in male rats, which showed that female rats were more sensitive to G. elegans. This study was the first to investigate the multicomponent in vivo process of G. elegans in rats and compare the differences between sexes. It was hypothesized that differences in the absorption of gelsedine-type alkaloids were one of the main reasons for the sex differences in G. elegans toxicity.

The antianxiety effects of koumine and gelsemine, two main active components in the traditional Chinese herbal medicine Gelsemium: A comprehensive review

“…The uptake, distribution, and excretion of Gelsemium alkaloids are more active in females than in males, especially gelsedine alkaloids. [83] Furthermore, gelsemine and koumine are slowly eliminated in humans and differ in their metabolic rate, metabolic species, and metabolite production. [20] Therefore, it remains unknown whether the anxiolytic effects of Gelsemium alkaloids are consistent between humans and animals and whether there are differences in the effects of Gelsemium alkaloids between species or sexes, which are questions worth considering in the future medicine of Gelsemium plants.…”

“…In addition, there are significant sex differences in the course of Gelsemium alkaloids in animals. The uptake, distribution, and excretion of Gelsemium alkaloids are more active in females than in males, especially gelsedine alkaloids [83] . Furthermore, gelsemine and koumine are slowly eliminated in humans and differ in their metabolic rate, metabolic species, and metabolite production [20] .…”