Comparative study of the effects of acetyl-tanghinin, tanghinin, and deacetyl tanghinin isolated from Tanghinia venenifera Poir. (Apocynaceae) on cardiac activity

This study aimed to compare the relationship between chemical structures and pharmacological activities of three cardiac glycosides isolated from Tanghinia venenifera (Apocynaceae): acetyl-tanghinin, tanghinin, and deacetyl-tanghinin, by evaluating their effects on myocardial contractility, heart rate, transmembrane permeability, and binding affinity toward Na⁺/K⁺-ATPase. Experiments were performed using an experimentally impaired isolated frog heart, complemented by transmembrane diffusion assays and in silico molecular docking analyses.
All three compounds exhibited positive inotropic and negative chronotropic effects. Acetyl-tanghinin showed the greatest inotropic activity (221.23 ± 0.90 %), followed by tanghinin (197.01 ± 1.18 %) and deacetyl-tanghinin (177.15 ± 1.01 %) (p < 0.05). They also decreased respectively the heart rate from 55 ± 0.06 beats/min to 27 ± 0.05 beats/min, 28.51 ± 2.1 beats/min and 28.99 beats/min (p < 0.05). Membrane permeation studies demonstrated that increasing the number of acetyl groups enhanced lipophilicity and facilitated transmembrane diffusion, thereby improving intracellular availability. Molecular docking revealed that deacetyl-tanghinin displayed the strongest binding affinity for Na⁺/K⁺-ATPase because of its higher polarity, although this greater affinity did not translate into superior pharmacological efficacy because of its low transmembrane diffusion.
These findings indicate that the cardiotonic activity of these glycosides is governed by a balance between lipophilicity, membrane permeability, and receptor binding affinity. Structural acetylation plays a critical role in optimizing biological activity by promoting transmembrane diffusion while maintaining interaction with the molecular target. Overall, this study highlights the importance of subtle structural modifications in determining their pharmacological properties and provides valuable insights for the rational design of cardiotonic agents with improved therapeutic potential