Cardioprotective Effect of Gedunin on Isoproterenol‑Induced Cardiotoxicity through the Attenuation of NF-κB‑Mediated Inflammatory Pathway in Rats

Abstract

Background: There is an increasing interest in new natural compounds for the treatment of myocardial infarction (MI). Gedunin is a tetranortriterpenoid extracted from the Indian neem tree (Azadirachta indica). The main objective of this study is to understand the cardioprotective effects of gedunin against MI through the suppression of NF‑κB‑mediated inflammatory pathways.Materials and Methods: Male Wistar rats were categorized into 4 groups of 6 each: control, inducer isoproterenol (ISO) alone, ISO + gedunin‑treated, and gedunin (50 mg/kg b.w.)‑pretreated rats followed by ISO induction. The infarct size, heart‑to‑body weight ratio, cardiac enzymes, ATP values, Ca2+ levels, and inflammatory and apoptotic markers were studied and compared in all these groups. Data were expressed as mean ± SD. One‑way analysis of variance (ANOVA) and post hoc Tukey–Kramer test were used for comparing multiple values.Results: Gedunin pre‑treatment caused a reduction in cardiac size, attenuated the levels of cardiac bio‑enzymes, and reduced immune cell infiltration and necrosis. It also enhanced the secretion of antioxidant enzymes glutathione‑S‑transferase (GST) and superoxide dismutase (SOD) and reduced glutathione (GSH) and glutathione peroxidase (GPx). Gedunin suppressed inflammation by down‑regulating the secretion of interleukin 10 (IL‑10), interleukin‑1β (IL‑1β), nuclear factor‑kappa B (NF‑κB), tumor necrosis factor‑α (TNF‑α), and apoptotic markers caspase‑3, caspase‑9, Bax, and Bcl‑2.Conclusion: Gedunin inhibited apoptosis in cardiotoxicity‑induced MI in rats by inhibiting inflammation and apoptosis markers. Thus, gedunin is a potential natural cardioprotective compound.

Keywords: Antioxidants; apoptosis; cardiotoxicity; gedunin; inflammation