Visnagin prevents isoproterenol-induced myocardial injury by attenuating oxidative stress and inflammation and upregulating Nrf2 signaling in rats

Oxidative tissue injury and inflammatory responses play major roles in cardiovascular diseases and heart failure. Visnagin (VIS) is a natural bioactive component of Ammi visnaga, with promising radical scavenging and anti-inflammatory activities. This study explored the protective effect of VIS against isoproterenol (ISO)-induced acute myocardial injury and oxidative stress in rats. VIS was supplemented for 14 days, and the rats received ISO (100 mg/kg) twice at an interval of 24 h. ISO-induced myocardial injury was characterized by elevated serum CK-MB, LDH, and troponin-I associated with increased heart weight and several histopathological changes. ISO increased reactive oxygen species (ROS), malondialdehyde (MDA), NF-kappa B p65, TNF-alpha, IL-6, and decreased glutathione and antioxidant enzymes in rats' hearts. VIS prevented myocardial injury and ameliorated the cardiac function markers, ROS, MDA, NF-kappa B p65, and pro-inflammatory cytokines in ISO-intoxicated rats. In addition, VIS decreased Bax mRNA and caspases, and upregulated Nrf2, HO-1, Bcl-2, and PPAR gamma. Molecular docking simulations revealed the binding method of VIS to NF-kappa B, Keap1, and PPAR gamma. In conclusion, VIS protects against ISO-induced acute myocardial injury by attenuating oxidative tissue injury and reducing key inflammatory and apoptosis markers. In vivo and in silico results showed that activation of Nrf2/HO-1 signaling and PPAR gamma mediates the cardioprotective effect of VIS.

Automated summary

Visnagin protects against ISO-induced acute myocardial injury by attenuating oxidative tissue injury and reducing key inflammatory and apoptosis markers. In vivo and in silico results showed that activation of Nrf2/HO-1 signaling and PPAR gamma mediates the cardioprotective effect of VIS.