Maqola

Cardioprotective Effect of the F-36 Alkaloid and DKV-8 Conjugate

Sadriddin Nurilla Ugli BoboevDepartment of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, UzbekistanZhumaev Inoyat ZulfiqorovichDepartment of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, UzbekistanP. B. UsmanovDepartment of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, UzbekistanAbdisalim A. ZaripovDepartment of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, UzbekistanShavkat Yu. RustamovDepartment of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, UzbekistanShakhnoza B. QurbonovaDepartment of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, UzbekistanEldor B. IbragimovDepartment of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, UzbekistanSardor B. SobirovDepartment of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, UzbekistanAdilbay T. EsimbetovDepartment of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, UzbekistanShakhrizada Ajiniyazovna AbdikadirovaDepartment of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, UzbekistanDilbar Allaniyazovna PaluaniyazovaKarakalpak State University named after Berdakh. Ch.Abdirov str.1, Republic of Karakalpakstan 230100, UzbekistanSherzod Niyatqobulovich ZhurakulovDepartment of Alkaloids Chemistry, Institute of Chemistry of Plant Substances, Academy Sciences of Uzbekistan, Tashkent 100170, Uzbekistan

2026

Ochiq kirishOlmos

Litsenziya: cc-by-nc-nd

ABI

Annotatsiya

The search for new therapeutic strategies for cardiovascular diseases remains an urgent issue. This study investigated the effects of the natural compound 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (F-36) and its conjugate with dihydroquercetin, DKV-8, on the contractile activity of rat heart papillary muscle and their molecular mechanisms. In vitro mechanographic experiments showed that F-36 (5 - 100 µM) and DKV-8 (5 - 40 µM) dose-dependently increased contraction force by 75.7 ± 4.7 and 143.6 ± 5.4%, respectively. studies using specific inhibitors (lidocaine, nifedipine, NiCl₂, caffeine, and cyclopiazonic acid (CPA)) demonstrated that Na⁺ channels, L-type Ca²⁺ channels, and sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) play a key role in the observed positive inotropic effect. Overall, F-36 and its DKV-8 conjugate enhance cardiomyocyte Ca²⁺ homeostasis mainly through regulation of SERCA2a and plasma membrane ion channels. Their effects were also confirmed under in vitro hypoxic conditions. HIGHLIGHTS F-36 alkaloid and its DHQ-based conjugate DKV-8 produce a pronounced positive inotropic effect in isolated rat cardiac papillary muscle. The inotropic action is mediated by coordinated activation of Na⁺ and L-type Ca²⁺ channels, leading to increased intracellular Ca²⁺ availability. SERCA2a activation is a key mechanism underlying enhanced sarcoplasmic reticulum Ca²⁺ accumulation and stronger myocardial contraction. NCX and excessive RyR2 activation are not critically involved, indicating a selective and controlled Ca²⁺ regulation. This balanced modulation of Ca²⁺ homeostasis suggests low arrhythmogenic risk and highlights DKV-8 as a promising cardiotonic candidate. DKV-8 conjugate activates SERCA2a to a significant extent. GRAPHICAL ABSTRACT

Hali tarjima qilinmagan

Identifikatorlar

DOI: 10.48048/tis.2026.13312

Iqtiboslar va manbalar

0 ta iqtibos0 ta foydalanilgan manba