Abstract
BACKGROUND: Paracetamol is a widely used over-the-counter drug for pain relief and fever management. However, its misuse through chronic overuse or acute overdose presents significant risks to human health, primarily causing hepatotoxicity and systemic oxidative stress. METHODOLOGY: This study evaluated the hepatoprotective, antioxidant, and anti-inflammatory effects of aqueous leaf extracts of Celosia trigyna and Euphorbia hirta in mitigating paracetamol-induced liver damage in male Wistar rats. RESULTS: Paracetamol administration (150 mg/kg) significantly elevated liver function markers (ALT, AST, ALP, and bilirubin), oxidative stress parameters (MDA), and inflammatory cytokines (IL-6 and TNF-α), while depleting antioxidant defenses (SOD and GSH). Disrupted lipid profiles were also observed in the paracetamol-only group. Pretreatment with Celosia trigyna and Euphorbia hirta extracts (125 mg/kg and 250 mg/kg) effectively ameliorated these effects by normalizing liver function markers, reducing oxidative stress and inflammation, and restoring lipid profiles. Molecular docking identified bioactive compounds such as rutin, quercetin, and kaempferol as potent inhibitors of Glutathione-S-Transferase, Tumor Necrosis Factor-alpha, and Cytochrome P450, with binding affinities of -9.3, -7.2, and -8.3 kcal/mol, respectively. These interactions underpin the antioxidant and anti-inflammatory activities observed in vivo. CONCLUSION: These findings suggest that Celosia trigyna and Euphorbia hirta have the potential to serve as natural prophylactic or therapeutic agents for mitigating paracetamol toxicity. Further research is required to isolate their active compounds and explore their synergistic potential with conventional treatments. This study bridges traditional medicine and modern pharmacology, offering innovative approaches to managing drug-induced liver.