1. A Structure-Activity Relationship between the Veratrum Alkaloids on the Antihypertension and DNA Damage Activity in Mice.
- Author
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Cong Y, Wu Y, Shen S, Liu X, and Guo J
- Subjects
- Administration, Oral, Animals, Antihypertensive Agents pharmacology, Blood Pressure drug effects, Cerebral Cortex drug effects, Cerebral Cortex metabolism, Cluster Analysis, DNA Damage drug effects, Mice, Plant Extracts chemistry, Principal Component Analysis, Structure-Activity Relationship, Veratrum metabolism, Veratrum Alkaloids pharmacology, Antihypertensive Agents chemistry, Veratrum chemistry, Veratrum Alkaloids chemistry
- Abstract
Veratrum plant contains a family of compounds called steroidal alkaloids which have been previously reported to cause DNA damage and blood pressure decrease in vivo. In this study, the antihypertensive effects and DNA damage in brain cells of 12 steroidal alkaloids separated from Veratrum plant were all evaluated to develop a relationship among chemical structure, antihypertensive activity and neurotoxicity by utilization of chemical principal component analysis (PCA) and hierarchical cluster analysis (HCA). Twelve steroidal alkaloids markedly reduced high blood pressure of hypertensive mice and also similarly induced varying degrees of DNA single-strand breaks in mouse cerebellum and cerebral cortex after oral administration. On the basis of the PCA and HCA results, it was suggested that the 3-carboxylic esters and benzene group play a core role in the DNA damage of brain cells, while more hydroxy groups in the A-ring and B-ring structure of jervine-type alkaloid led to stronger antihypertensive activity. The primary structure, activity and neurotoxicity relationship were discussed briefly., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)
- Published
- 2020
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