Effect of Talatisamine and its Derivate 14-O-Benzoyltalatisamine on Functional State of Rat Liver and Heart Mitochondria
Dilnoza Kh. Muratova1*, Nurali A. Ergashev2 and Muzaffar I. Asrarov

1Department of Biophysics, National University of Uzbekistan named after Mirzo Ulugbek., Tashkent, Uzbekistan.

2Institute of Biophysics and Biochemistry, National University of Uzbekistan named after Mirzo Ulugbek., Tashkent, Uzbekistan.

Corresponding Author E-mail: dilnozaxasanovnam@gmail.com

Abstract: Dysfunction of the mitochondria of various tissues causes the development of most pathological processes, including ischemia. In recent years, great attention has been paid to the use of plant biologically active substances in the prevention and treatment of pathological processes related to mitochondrial dysfunction. This is very relevant in relation to ischemic diseases and is of scientific and practical importance in the search for new pharmacological agents that correct the functions of damaged mitochondria for their treatment. The mitochondrial permeability transition pore (mPTP) actively participates in the regulation of mitochondrial functions, in the development of various pathological conditions and, at the same time, targets for various drugs and some biologically active substances. In vitro experiments evaluated the effects of alkaloids talatisamine and 14-O-benzoyltalatisamine on rat liver and heart Ca2+-dependent mPTP and lipid peroxidation (LPO) induced by Fe2+/ascorbate system. The investigated diterpenealkaloids inhibited the opening of the Ca2+-dependent mPTP in the membranes of rat liver and heart mitochondria. It was found that 14-O-benzoyltalatizamine inhibits the Ca2+-dependent conductance pore of rat liver and heart mitochondria more strongly than talatisamine. To compare the effects of 14-O-benzoyltalatisamine on rat liver and heart mPTP, concentrations from 1 μM to 200 μM were investigated. At these concentrations, liver mPTP was reliably inhibited by 10% to 81% and heart mPTP by 3.6% to 71.5% relative to control. The high sensitivity of diterpene alkaloids to the Ca2+-dependent permeability transition pore of liver mitochondria compared to heart mitochondria indicates their tissue specificity. The investigated alkaloids exhibited antioxidant properties by inhibiting Fe2+/ascorbate-induced mitochondrial suppression (LPO process) and MDA formation in membranes. LPO induced by Fe2+/ascorbate system in mitochondrial membranes was more actively inhibited by 14-O-benzoyltalatisamine. According to the results of the research, acylation of the hydroxyl group at the C-14 position of talatisamine by benzoyl chloride caused a rise in molecular activity  of the derivative due to the introduction of the benzoyl group.

Keywords: lipid peroxidation; mitochondria; 14-О-benzoyltalatisamine; permeability transition pore; talatisamine .

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