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Tannins as Modulators in the Prevention of Mitochondrial Dysfunction

Abdulkhakova Gulnazira VakhobjonovnaInstitute of Biophysics and Biochemistry, The National University of Uzbekistan, Tashkent, UzbekistanKomilov Esokhon JurayevichInstitute of Biophysics and Biochemistry, The National University of Uzbekistan, Tashkent, UzbekistanAbdullaev Izzatullo Ziyoyiddin OgliA. S. Sadykov Institute of Bioorganic Chemistry, The Academy of Sciences of the Republic of Uzbekistan, Tashkent, UzbekistanErgashev Nurali AzamovichA. S. Sadykov Institute of Bioorganic Chemistry, The Academy of Sciences of the Republic of Uzbekistan, Tashkent, UzbekistanMakhmudov Rustamjon RasuljonovichA. S. Sadykov Institute of Bioorganic Chemistry, The Academy of Sciences of the Republic of Uzbekistan, Tashkent, UzbekistanAsrarov Muzaffar IslomovichInstitute of Biophysics and Biochemistry, The National University of Uzbekistan, Tashkent, Uzbekistan
Trends in Sciencesjournal2025en
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In this article, the effects of octagalloyl-glucose and nonagalloyl-glucose hydrolyzable tannins isolated from the leaves of Pistacia vera L., a plant of the Anacardiaceae family, on lipid peroxidation (LPO), mitochondrial permeability transition pore (mPTP) status, and ATP-dependent K+ (mitoKATP) channel activity in mitochondria, which are directly involved in various pathologies, as well as their antiradical properties were studied in vitro. In vitro experiments showed that octagalloyl-glucose and nonagalloyl-glucose tannins inhibited the Fe2+/ascorbate-induced LPO process in mitochondria by 86.7 ± 4.4% and 85.5 ± 4%, respectively, at a concentration of 10 μM, while they blocked mitochondrial mPTP by 88.2 ± 4.5% and 90.3 ± 5.1%, respectively, at a concentration of 15 μM in succinate + rotenone medium. MitoKATP-channel of rat liver mitochondria was activated by octagalloyl-glucose at 10 μM concentration by 90.9 ± 2.6%, nonagalloyl-glucose at 5 μM concentration by 84.2 ± 1.8%, but at 10 μM concentration, it was able to activate by 50.5 ± 5.3%. Octagalloyl-glucose and nonagalloyl-glucose tannins at a concentration of 15 μM neutralized DPPH radical by 91.7 ± 1.83% and 85.9 ± 3.5%, respectively. According to the obtained results, taking into account that the high antiradical and antioxidant activity of the studied hydrolyzable tannins (octagalloyl-glucose and nonagalloyl-glucose) at low concentrations have a stabilizing effect on the mitochondrial membrane, it is possible to conduct additional experiments that allow creating membrane-active preparations from them. HIGHLIGHTS Hydrolyzable tannins (octagalloyl- and nonagalloyl-glucose) were isolated from Pistacia vera L. leaves. Both compounds significantly inhibited Fe²⁺/ascorbate-induced mitochondrial lipid peroxidation in vitro. Octagalloyl- and nonagalloyl-glucose effectively blocked mitochondrial permeability transition pore (mPTP) opening. Activation of ATP-sensitive mitochondrial potassium (mitoKATP) channels was concentration-dependent. Both tannins exhibited high DPPH radical scavenging activity, indicating potent antioxidant properties. Results support their potential use as membrane-stabilizing, antioxidant therapeutic agents. GRAPHICAL ABSTRACT

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