Robinin decreases myocardial ischemia/reperfusion injury via Nrf2 anti-oxidative effects mediated by Akt/GSK3β/Fyn in hypercholesterolemic rats

Abstract

Robinin (RB) is an accepted antioxidant herbal product with known cardio-protective activity. To explore the anti-oxidative potential of RB in treating myocardial ischemia or reperfusion (MI/RI) damage in rats after inducing hypercholesterolemia (HC). HC was induced by administering cholesterol (2%) to rats for eight weeks. The rats were given RB (50 mg/kg bw) for the last two weeks. The rats were arbitrarily divided into four groups: (Group I) normal control, (Group II) hypercholesterolemic (HC) alone, (Group III) HC + RB (50 mg/kg body weight), and (Group IV) RB alone (50 mg/kg body weight). LV-developed pressure (LVDP), and left ventricular end-diastolic pressure (LVEDP) were recorded during the perfusion process. Histopathology staining was used to analyze liver and kidney damage in heart tissue (H&E, MT, and PAS stains), and in silico techniques, such as molecular docking and MD simulation, were employed. Results revealed that RB administration reduced MI/RI in HC rats due to Akt/GSK3β/Fyn-as facilitated Nrf2 anti-oxidative function. Administering RB to HC rats resulted in increased expression of Akt, whereas it reduced the Fyn and GSK3β levels, which activated Nrf2 activity. When RB is administered to HC rats. Glide (a Schrodinger module) was used to dock RB with NQO1, Nrf-2, HO-1, GSK-3β, and Akt to select the best interacting drug action on inflammatory markers for the therapeutic action of RB and followed OH-1 and Nrf2 MD simulation study were carried out. These results highlight how Nrf2 antioxidative effects are mediated by Akt/GSK3β/Fyn are enhanced by RB, protecting the HC heart from MI/RI.