Protective properties of nanoparticles green-synthesized by plant on myocardial ischemia

Abstract

The formulation and characterization of novel cardiovascular supplements and drugs without any side effects are in both developed and developing countries research priority. Myocardial ischemia-reperfusion causes to an inflammatory response that leads more damage to apoptosis. Chronic and acute immune responses elicited by myocardial ischemia is in the heart functional deterioration. In this study, we formulated a modern cardioprotective protective drug by gold nanoparticles containing Silybum marianum on isoproterenol-induced myocardial ischemia mice by investigating the PPAR-Υ/NF-κB pathway. Determining the antioxidant capacities of gold nanoparticles was done with the conventional free radical scavenging test, i.e., DPPH in the presence of butylated hydroxytoluene as the positive control. The gold nanoparticles were characterized by standard physicochemical techniques, including FT-IR, FE-SEM, UV-Vis, and TEM. The nanoparticles inhibited half of the DPPH molecules in the concentration of 72 μg/mL. In the in vivo design, to induce myocardial ischemia in C57BL/6 mice, isoproterenol (40 mg/kg) was administered. The mice were randomly divided into five groups: (1) control; (2) isoproterenol; (3-5) isoproterenol + gold nanoparticles at different doses (10, 20 and 40 μg/ml) and timings. After treatment, cardiac function was evaluated by histochemical and biochemical analysis. Gold nanoparticles treatment decreased the inflammatory milieu in the myocardial ischemia mice heart, thereby blocking the proinflammatory cytokines upregulation (IL-1β, TNF-α and IL-6). Also, gold nanoparticles treatment significantly ameliorate ventricular wall ischemia, reduces the mortality incidence, and inhibits the myocardial injury markers levels. In addition, gold nanoparticles administration significantly prevents the typical ST segment depression. Treatment with gold nanoparticles significantly suppresses the inflammation cytokines expression and decrease cell death. The gold nanoparticles beneficial effects is related to the normalization in PPAR-Υ and PPAR-Υ/NF-κB/ΙκB-α/ΙΚΚα/β phosphorylation gene expression. Gold nanoparticles exert cardioprotective properties against isoproterenol-induced myocardial ischemia in mice, which may associated to the PPAR-γ activation and NF-κB signaling inhibition.