Metabolomic and Cardiotoxicity Analyses of American Aconitum Compared to Related Asian and European Species.

Abstract

Aconitum species have been used as traditional medicines in Asian countries for millennia, and contain well-characterized bioactive diterpenoid alkaloids. In contrast, American Aconitum species have been less studied, despite their close phylogenetical relationship to the important Asian medicinal species. This study aims to investigate the chemistry and bioactivity of American Aconitum, since they also produce diterpenoid alkaloids that possess toxicity. The chemical profiles of three American Aconitum species, A. delphiniifolium, A. columbianum, and A. uncinatum, and their four individual plant parts (roots, stems, leaves, and flowers) were studied using UPLC-qTof-MS^e technique, and compared to Asian and European species. Multivariate including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the chemical profiles. PCA suggests that American Aconitum is more chemically similar to Asian than European species. Using OPLS-DA, 29 unique marker compounds were found in American Aconitum, but not in the Asian or European species, we studied. Nineteen marker compounds were tentatively identified using Progenesis Qi and reference standards, including proved analgesic compounds such as talatisamine and 14-benzoyltalatisamine as well as other bioactive compounds. The results suggest that American Aconitum is a potential source for lead drugs. The cardiotoxicity of American Aconitum root extracts (200 μg/mL) was assessed using a zebrafish embryo model, and compared to the most widely used Asian species, A. carmichaelii. Aconitum delphiniifolium did not show any cardiotoxicity in this zebrafish model, as compared to A. carmichaelii and the control compound, aconitine. However, A. columbianum and A. uncinatum induced some morphological heart differences but not as profoundly as A. carmichaelii.