Protective Role of Gallic Acid Against Corticosterone-Induced Hepatic Toxicity: Modulation of Oxidative Stress and Inflammatory Pathways in Wistar Rats

Corticosterone (CORT), a key stress hormone, is vital for energy balance, but prolonged exposure causes hyperglycemia, obesity, and hepatotoxicity. Gallic acid (GA), a natural polyphenol with antioxidant and anti-inflammatory properties, was evaluated for its hepatoprotective effects in Wistar rats. This study aimed to assess how GA protects against CORT-induced liver toxicity in Wistar rats and to explore its molecular interactions through in silico docking studies. Animals received CORT (15 and 30 mg kg^-1 body weight) orally for 21 days, with GA pretreatment in selected groups. Hepatic status was assessed via biochemical assays, molecular markers, histopathology, and in silico docking. CORT significantly increased body weight (15%), blood glucose (1.5-fold), malondialdehyde (MDA; 28%), and protein carbonyls (34%,) with a statistical significance, <i>p</i> < 0.05 and <0.01, while glutathione (41.4% to 52.1%) and antioxidant enzymes were significantly reduced (statistical <i>p</i>-value significance at levels of <0.05, <0.01, and <0.001). GA pretreatment restored glucose MDA, and GSH toward control (<i>p</i> < 0.01), and protected histological injury. Docking studies showed strong GA binding to Keap1 (-6.9 kcal/mol), IKKβ (-6.0 kcal/mol), and COX-1 (-6.2 kcal/mol), supporting its antioxidant and anti-inflammatory action. GA confers significant protection against CORT-induced hepatotoxicity, validated by both in vivo and in silico analyses.