Solanaceae glycoalkaloids: α-solanine and α-chaconine modify the cardioinhibitory activity of verapamil

• Published in: Pharmaceutical biology 2022-12, Vol.60 (1), p.1317-1330
• Main Authors: Chowański, Szymon, Winkiel, Magdalena, Szymczak-Cendlak, Monika, Marciniak, Paweł, Mańczak, Dominika, Walkowiak-Nowicka, Karolina, Spochacz, Marta, Bufo, Sabino A., Scrano, Laura, Adamski, Zbigniew
• Format: Article
• Language: English
• Subjects: Biological activity; Calcium channels; Calcium channels (L-type); Developmental biology; Food products; Heart; Insects; L-type calcium channels; Myocardium; Physiology; Solanaceae; Stem cells; Verapamil
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2022.2094966

Solanaceae glycoalkaloids (SGAs) possess cardiomodulatory activity. This study investigated the potential interaction between verapamil and glycoalkaloids. The cardioactivity of verapamil and glycoalkaloids (α-solanine and α-chaconine) was tested in adult beetle (Tenebrio molitor) myocardium in vitro using microdensitometric methods. The myocardium was treated with pure substances and mixtures of verapamil and glycoalkaloids for 9 min with saline as a control. Two experimental variants were used: simultaneous application of verapamil and glycoalkaloids or preincubation of the myocardium with one of the compounds followed by perfusion with a verapamil solution. We used 9 × 10 −6-5  × 10 −5 M and 10 −9 -10 −5 M concentration for verapamil and glycoalkaloids, respectively. Verapamil, α-solanine and α-chaconine showed cardioinhibitory activity with IC 50 values equal to 1.69 × 10 −5 , 1.88 × 10 −7 and 7.48 × 10 −7 M, respectively. When the glycoalkaloids were applied simultaneously with verapamil, an antagonistic effect was observed with a decrease in the maximal inhibitory effect and prolongation of t 50 and the recovery time characteristic of verapamil. We also confirmed the expression of two transcript forms of the gene that encodes the α1 subunit of L-type calcium channels in the myocardium and brain with equal transcription levels of both forms in the myocardium and significant domination of the shorter form in the brain of the insect species tested. The results show that attention to the composition of the daily diet during therapy with various drugs is particularly important. In subsequent studies, the nature of interaction between verapamil and SGAs on the molecular level should be checked, and whether this interaction decreases the efficiency of cardiovascular therapy with verapamil in humans.