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

Authors

  • Sadriddin Nurilla Ugli Boboev Department of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan
  • Inoyat Zulfiqorovich Zhumaev Department of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan
  • Pulat Bekmuratovich Usmanov Department of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan
  • Abdisalim Abdikarimovich Zaripov Department of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan
  • Shavkat Yusubovich Rustamov Department of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan
  • Shakhnoza Bakhtiyorovna Qurbonova Department of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan
  • Eldor Bakhtiyor Ugli Ibragimov Department of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan
  • Sardor Bakhtiyor Ugli Sobirov Department of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan
  • Adilbay Tlepovich Esimbetov Department of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan
  • Shakhrizada Ajiniyazovna Abdikadirova Department of Cell Biophysics, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan
  • Dilbar Allaniyazovna Paluaniyazova Karakalpak State University named after Berdakh. Ch.Abdirov str.1, Republic of Karakalpakstan 230100, Uzbekistan
  • Sherzod Niyatqobulovich Zhurakulov Department of Alkaloids Chemistry, Institute of Chemistry of Plant Substances, Academy Sciences of Uzbekistan, Tashkent 100170, Uzbekistan

DOI:

https://doi.org/10.48048/tis.2026.13312

Keywords:

Ca2 homeostasis, Cardioprotection, Conjugate, Isoquinoline alkaloid, Papillary muscle, Positive inotropy, SERCA2a

Abstract

               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

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Published

2026-05-30

How to Cite

Boboev, S. N. U., Zhumaev, I. Z., Usmanov, P. B., Zaripov, A. A., Rustamov, S. Y., Qurbonova, S. B., Ibragimov, E. B. U., Sobirov, S. B. U., Esimbetov, A. T., Abdikadirova, S. A., Paluaniyazova, D. A., & Zhurakulov, S. N. (2026). Cardioprotective Effect of the F-36 Alkaloid and DKV-8 Conjugate. Trends in Sciences, 23(11), 13312. https://doi.org/10.48048/tis.2026.13312

Issue

Vol. 23 No. 11 (2026): Trends in Sciences, Volume 23, Number 11, November 2026

Section

Research Articles

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