Cytoprotective Properties of a New Nanocomplex of Selenium with Taxifolin in the Cells of the Cerebral Cortex Exposed to Ischemia/Reoxygenation

Abstract

The neuroprotective effect of the natural antioxidant taxifolin (TAX) is well known for ischemic pathologies. However, the limitations of taxifolin application are described—poor solubility, low ability to penetrate the blood–brain barrier, and side effects from high doses for stroke therapy. We proposed the problem of targeted delivery of taxifolin and achievement effective concentrations could be solved by developing a nanocomplex of selenium nanoparticles (SeNPs) with taxifolin (Se–TAX). In this study, we developed a selenium–taxifolin nanocomplex based on selenium nanoparticles with a 100 nm size. It was shown that TAX, SeNPs, and Se–TAX were all able to suppress the production of ROS in neurons and astrocytes under exposure to exogenous H2O2 and ischemia-like conditions. However, the Se–TAX nanocomplex appeared to be the most effective, displaying a lower working concentration range and negligible pro-oxidant effect compared with pure SeNPs. The mechanism of Se–TAX beneficial effects involved the activation of some antioxidant enzymes and the suppression of ROS-generating systems during OGD/reoxygenation, while TAX and “naked” SeNPs were less effective in regulating the cellular redox status. Naked SeNPs inhibited a global increase in Ca2+ ions in cytosol, but not OGD-induced hyperexcitation of the neuroglial network, while Se–TAX suppressed both [Ca2+]i rise and hyperexcitation. The effect of TAX at similar doses appeared exclusively in inhibiting OGD-induced hyperexcitation. Analysis of necrosis and apoptosis after OGD/reoxygenation revealed the highest efficiency of the Se–TAX nanocomplex as well. Se–TAX suppressed the expression of proinflammatory and proapoptotic proteins with simultaneous activation of protective genes. We conclude that the Se–TAX nanocomplex combines the antioxidative features taxifolin and the antiapoptotic effect of nanoselenium, involving the regulation of Ca2+ dynamics.

Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis

“…Given that the NASH pathogenesis is heterogenous and diverse in humans, these pleiotropic effects of Taxifolin may be advantageous for clinical practice. In this respect, recent studies developed a novel nanocomplex of selenium with sorafenib [ 42 ] or Taxifolin [ 43 ], which exhibits more beneficial effects than those of single molecules in vitro in terms of anticancer or neuroprotective effects. Accordingly, the use of the nanocomplex would be a valuable therapeutic option for NASH.…”

A Review of the Antibacterial, Fungicidal and Antiviral Properties of Selenium Nanoparticles

“…Moreover, a study was conducted and published in our laboratory that showed that selenium nanoparticles can have a cytoprotective effect on neuroglial cells of the cerebral cortex during ischemia/reoxygenation [48]. At concentrations as low as 3 µg/mL, selenium nanoparticles inhibit the hyperproduction of ROS in cells.…”

“…At concentrations as low as 3 µg/mL, selenium nanoparticles inhibit the hyperproduction of ROS in cells. The experiments also used a complex of selenium NPs with taxifolin (a flavonoid that lacks the "high dosage effect" that occurs in selenium NPs), while at a concentration of 10 µg/mL, the Se-TAX complex inhibits ROS hyperproduction and does not have toxicity on brain cells [48].…”

“…The mechanism of action of this effect is based on the fact that nanoparticles regulate the expression of protective proteins in the cells of the cerebral cortex and reduce the total level of Ca 2+ ions. The combination of selenium nanoparticles with the flavonoid taxifolin makes it possible to increase the neuroprotective effect in the cells of the cerebral cortex under conditions of ischemia/reoxygenation [48]. Beyond the immunomodulatory and neuroprotective effects, selenium nanoparticles also demonstrate anticancer effects.…”

Synthesis of Taxifolin-Loaded Polydopamine for Chemo-Photothermal-Synergistic Therapy of Ovarian Cancer

“…However, TAX was able to counteract the toxicity of DEHP on cardiomyocytes by attenuating apoptosis [ 33 ].The low solubility and difficulty in absorption and digestion of this medication limit its bioavailability and effectiveness. To overcome these limitations, various nanoparticles, such as metal nanoparticles, liposomes, and inorganic nanoparticles, have been developed as tumor-targeting carriers for targeted drug delivery [ 34 , 35 , 36 , 37 ].…”