A research team consisting of scientists located in Spain and Denmark have successfully proven that the formation of inclusion complexes between the alkaloid neurotoxin veratridine (VTD) and different cyclodextrins highly affect the toxicity of VTD.
Veratridine is a steroidal alkaloid found in plants of the lily family, specifically the genera Veratrum and Schoenocaulon (may be isolated from the seeds of Schoenocaulon officinale and from the rhizomes of Veratrum album). The following cyclodextrins were included in the study: native β-CD and γ-CD as well as the anionic β-CD derivative SBECD. The equilibrium constants of CD:VTD interactions were estimated to be 1500 M−1, 7200 M−1 and 8200 M−1 for β-CD, γ-CD and SBECD, respectively, making the γ-CD and the anionic SBECD the most stable hosts. In vitro studies showed that the three studied CDs have antidote-like effects against the VTD toxicity, protecting Neuro-2a cell viability to different extent, depending on the CD type as well as the CD and VTD concentrations. In the absence of CDs, the addition of 1 and 0.25 mM VTD caused around 100% cell mortality (0% cell viability). For 1 mM VTD, cell viabilities increased with increasing CD concentrations for γ-CD and SBECD, reaching around 100% of the cell viability and protecting the Neuro-2a cells from the VTD toxicity. The 1H-NMR and 1H-1H ROESY experiments confirmed the incorporation of VTD in each of the CDs’ cavities and the most stable orientation of the molecule inside the CDs was elucidated by performing docking and molecular dynamics simulations
Uribe, L.A.; Leonardo, S.; Nielsen, T.T.; Steinmann, C.; Campàs, M.; Fragoso, A. Supramolecular Complexes of Plant Neurotoxin Veratridine with Cyclodextrins and Their Antidote-like Effect on Neuro-2a Cell Viability. Pharmaceutics 2022, 14, 598. https://doi.org/10.3390/pharmaceutics14030598