Tannins as Modulators in the Prevention of Mitochondrial Dysfunction
Abstract
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