Maqola

Pharmacological Evaluation of F45 on the Cardiovascular System Using In Vitro, In Vivo Models and Molecular Dockings

Ikbolkhon AbdurazakovaFergana Medical Institute of Public Health, Fergana Region, UzbekistanAnvar ZaynabiddinovAndijan State University, Andijan Region, UzbekistanIzzatullo AbdullaevA. S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan, Plant Cytoprotectors Laboratory and Pharamacology, Tashkent, UzbekistanЛ. У. МахмудовA. S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan, Plant Cytoprotectors Laboratory and Pharamacology, Tashkent, UzbekistanUlugbek GayibovA. S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan, Plant Cytoprotectors Laboratory and Pharamacology, Tashkent, UzbekistanSirojiddin OmonturdievA. S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan, Plant Cytoprotectors Laboratory and Pharamacology, Tashkent, UzbekistanGafurjon AbdullayevNamangan State University, Namangan Region, UzbekistanMadina XolmirzayevaAndijan State University, Andijan Region, UzbekistanSherzod ZhurakulovInstitute of the Chemistry of Plant Substances, Uzbekistan Academy of Sciences, Tashkent, Uzbekistan

Trends in Sciencesjournal2025

ABI

Annotatsiya

The current study investigated the vasorelaxant and antihypertensive potential of the novel compound F-45 through a combination of in vitro, in vivo, and in silico approaches. F-45 demonstrated significant relaxation of rat aortic rings pre-contracted with KCl and phenylephrine, suggesting its capacity to inhibit both voltage-dependent L-type Ca2+ channels and receptor-operated calcium entry mechanisms. At 70 μM, F-45 reduced KCl-induced contraction by 84.0% ± 1.3%, while 45 μM of F-45 inhibited phenylephrine-induced contraction by 78.0% ± 2.2%. Endothelium-denuded experiments confirmed that nitric oxide signaling contributes significantly to F-45-mediated vasorelaxation, with a 35.0% ± 2.4% reduction in relaxation observed after endothelial removal. Molecular docking studies revealed high binding affinities of F-45 for Ca2+-ATPase (−8.6 kcal/mol) and Sodium\Calcium Exchanger (−6.8 kcal/mol), supporting its role in modulating calcium transport. In vivo experiments using tail-cuff plethysmography showed that 50 mg/kg of F-45 reduced SBP and DBP from 132.5 ± 12.3 and 94.3 ± 9.1 to 96.8 ± 9.4 and 65.3 ± 6.4 mmHg, respectively. In the adrenaline-induced hypertension model, F-45 decreased elevated SBP and DBP from 140.8 ± 14.2 and 104.3 ± 10.3 to 90.0 ± 8.7 and 61.5 ± 6.0 mmHg within 2 h. These findings suggested that F-45 is a promising candidate for further development as a natural antihypertensive agent with multimodal action. HIGHLIGHTS F45 demonstrated potent vasorelaxant activity in isolated rat aortic rings, primarily through inhibition of L-type and receptor-operated calcium channels. Endothelium-dependent mechanisms, especially nitric oxide (NO) signaling, significantly contributed to the vascular relaxation induced by F-45. Molecular docking analysis revealed high binding affinities of F-45 to Ca2+-ATPase (−8.6 kcal/mol) and NCX (−6.8 kcal/mol), supporting its role in calcium homeostasis modulation. In vivo experiments confirmed a dose-dependent antihypertensive effect, with 50 mg/kg of F-45 significantly reducing systolic and diastolic blood pressure. In an adrenaline-induced hypertension model, F-45 rapidly normalized elevated blood pressure, suggesting its potential as a fast-acting antihypertensive agent. GRAPHICAL ABSTRACT

Mavzular

Cardiac Imaging and Diagnostics Cancer Treatment and Pharmacology HER2/EGFR in Cancer Research

Identifikatorlar

DOI: 10.48048/tis.2025.10924

Iqtiboslar va manbalar

2 ta iqtibos0 ta foydalanilgan manba

Koʻrsatkichlar — AkademScholar · Tez orada