Article

Channelopathy Activity Of A-41(Propyl Ester of Gallic Acid): Experimental and Computational Study of Antihypertensive Activity

Shodiyakhon SodiqovaAndijan State University, Andijan, Andijan Region, UzbekistanShokhida KadirovaNational University of Uzbekistan, Gulistonуй, Universitet Ko'chasi 4, Toshkent, UzbekistanAnvar ZaynabiddinovAndijan State University, Andijan, Andijan Region, UzbekistanIzzatullo AbdullaevA.S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan “Plant Cytoprotectors Laboratory” and “Pharamacology”, Tashkent, UzbekistanЛ. У. МахмудовTashkent Medical Academy, Farabi 2 Tashkent UZ, UzbekistanUlugbek GayibovA.S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan “Plant Cytoprotectors Laboratory” and “Pharamacology”, Tashkent, UzbekistanMukhabbat YuldashevaNational University of Uzbekistan, Gulistonуй, Universitet Ko'chasi 4, Toshkent, UzbekistanMadina XolmirzayevaAndijan State University, Andijan, Andijan Region, UzbekistanR. N. RakhimovTashkent State Transport University, 25 Sairam Street, Tashkent, UzbekistanAzizbek MutalibovAndijan State University, Andijan, Andijan Region, UzbekistanHayotbek KarimjonovAndijan State University, Andijan, Andijan Region, Uzbekistan

Trends in Sciencesjournal2025en

ABI

Abstract

This study aimed to evaluate the antihypertensive potential of the natural compound A41, a bioactive molecule, using integrated in vitro, in vivo, and in silico approaches. The rationale for selecting A41 is based on preliminary screening that suggested its strong calcium-modulating activity, a key factor in vascular tone regulation. In vitro experiments were performed on isolated rat aortic rings to investigate A41’s effect on vascular smooth muscle ion channels, particularly voltage-operated L-type Ca²⁺ channels and receptor-operated Ca²⁺ channels. The study also explored endothelium-dependent pathways. Selective ion channel blockers were applied to confirm the involvement of specific mechanisms. A41 significantly inhibited Ca²⁺ entry through L-type Ca²⁺ channels under hypertensive conditions, achieving 82.2 ± 2.0 % relaxation at 35 μM, with an IC₅₀ of 22.10 μM. Additionally, receptor-operated Ca²⁺-induced contractions were reduced by 87.0 ± 2.7 % at 50 μM. Molecular docking simulations demonstrated high binding affinity of A41 to calcium-regulating proteins, including the sodium-calcium exchanger (NCX) and plasma membrane Ca²⁺ ATPase, with binding free energies of −6.6 kcal/mol and estimated inhibitory constants (Kᵢ) of 14.558 μM. In vivo studies were conducted using male Wistar rats (n = 6) in an adrenaline-induced hypertension model. Intravenous administration of A41 (dose: 50 mg/kg) produced a marked antihypertensive effect, lowering systolic blood pressure to 82.8 ± 8.3 mmHg and diastolic pressure to 61.3 ± 5.9 mmHg within 3 h. Together, these findings demonstrate that A41 exerts antihypertensive effects by modulating calcium transport mechanisms in vascular smooth muscle, involving both ion channels and calcium-handling proteins, supporting its potential as a candidate for hypertension therapy. HIGHLIGHTS A41 was investigated for antihypertensive activity using integrated in vitro, in vivo, and in silico approaches. In vitro studies assessed A41’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 A41’s vascular effects. GRAPHICAL ABSTRACT

Topics

Computational Drug Discovery Methods

Identifiers

DOI: 10.48048/tis.2025.10496

Citations and references

Cited by 20 references

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