A-51 as A Natural Calcium Channel Blocker: An Integrative Study Targeting Hypertension
DOI:
https://doi.org/10.48048/tis.2025.10760Keywords:
A-51, Vasorelaxation, Blood pressure, Calcium channels, Nitric oxide, Molecular dockingAbstract
This study investigates the vasorelaxant and antihypertensive potential of compound A-51 through an integrative approach involving in vitro, in vivo, and molecular docking analyses. A-51 induced concentration-dependent relaxation of rat aortic rings pre-contracted with 50 mM KCl, achieving 76.0% ± 2.7% relaxation at 60 μM, with an IC₅₀ of 31.54 μM. In phenylephrine (1 μM)-induced contractions, the effect was even stronger, with 80.0% ± 1.7% inhibition observed at 45 μM. Endothelium removal reduced the relaxant response by 25.0% ± 2.4%, indicating partial dependence on endothelial nitric oxide pathways. In vivo, A-51 administered at 25 mg/kg significantly lowered systolic blood pressure from 98.0 ± 8.9 mmHg to 84.3 ± 8.3 mmHg and diastolic pressure from 74.8 ± 7.3 mmHg to 58.0 ± 5.6 mmHg within 2 h. In adrenaline-induced hypertensive rats, A-51 at 50 mg/kg reduced systolic pressure from 160.3 ± 11.6 mmHg to 93.3 ± 9.2 mmHg within 3 h, demonstrating its antihypertensive efficacy under pathophysiological conditions. Molecular docking studies revealed strong binding affinities between A-51 and calcium-regulating proteins, including Ca²⁺-ATPase and the Na⁺/Ca²⁺ exchanger, with binding energies of −6.6 kcal/mol, supporting its role as a calcium modulator. Together, these findings highlight A-51’s multi-target mechanism of action involving vascular smooth muscle relaxation and endothelial support. Its notable efficacy, combined with natural origin, positions A-51 as a promising candidate for further development as a novel antihypertensive agent.
HIGHLIGHTS
- A51 was investigated for antihypertensive activity using integrated in vitro, in vivo, and in silico approaches.
- In vitro studies assessed A51’s effects on L-type and receptor-operated Ca²⁺ channels in isolated rat aortic rings.
- In vivo evaluation was conducted in an adrenaline-induced hypertension model in male Wistar rats.
- In silico molecular docking targeted key aortic ion channels involved in calcium regulation.
- The study aimed to elucidate the calcium-modulating mechanisms underlying A51’s vascular effects.
GRAPHICAL ABSTRACT
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