Cardioprotective role of wedelolactone in restraint stress-triggered myocardial damage and cardiac arrhythmias in Wistar rats.
Restraint stress is a well-established model for inducing psychological and physiological stress that triggers oxidative damage, inflammation, and apoptosis in cardiac tissue. Wedelolactone, a bioactive coumestan derived from Eclipta alba, possesses known antioxidant and anti-inflammatory properties, but its cardioprotective effects under restraint stress have not been well elucidated. The present study aimed to evaluate the cardioprotective potential of Wedelolactone against restraint stress-induced myocardial injury through biochemical, molecular, and histopathological assessments. Male Wistar rats were divided into four groups: Control, Restraint Stress (RS), RS + wedelolactone (10 mg/kg, orally), and wedelolactone-alone. Electrocardiographic parameters, serum cardiac biomarkers (creatine kinase MB (CK-MB), lactate dehydrogenase, aspartate aminotransferase, cardiac troponin I), oxidative stress markers (malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione), inflammatory mediators (tumor necrosis factor-α, interleukin-6, C-reactive protein, nuclear factor-κB), and apoptotic gene expression (Bax, Bcl-2, caspase-3 and caspase-9) were analyzed. Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway activation was evaluated by western blot, and myocardial histology was assessed using hematoxylin and eosin staining. Restraint stress caused significant increases in oxidative stress, inflammation, and apoptotic gene expression, along with histological evidence of myocyte necrosis and vascular congestion. Wedelolactone treatment markedly normalized cardiac biomarkers, restored antioxidant enzyme levels, reduced inflammatory cytokines, and downregulated pro-apoptotic genes while enhancing Nrf2/HO-1 signaling and anti-apoptotic gene expression. We found that Wedelolactone exhibits potent cardioprotective, antioxidant, anti-inflammatory, and anti-apoptotic properties against restraint stress-induced myocardial damage, primarily through activation of the Nrf2/HO-1 pathway and suppression of nuclear factor-κB signaling.