Mezoneuron benthamianum attenuates indomethacin-induced toxicity: Design, synthesis, elemental analysis, in vivo and in silico studies

• The study examined the biochemical properties of Mezoneuron benthamianum , focusing on its potential role in mitigating liver damage and contributing to therapeutic interventions. • The in-silico analysis provided insights into the molecular interactions between the bioactive compounds of Mezoneuron benthamianum and the peroxisome proliferator-activated receptor alpha (PPAR-α). • The study revealed distinct hematological responses to different treatments in liver-damaged conditions. • The hepatoprotective and antioxidant effects of Mezoneuron benthamianum extract might be partially mediated through interactions with essential trace elements, such as iron (Fe), copper (Cu), and manganese (Mn). Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain relief and anti-inflammatory effects but can cause significant liver damage and oxidative stress. Mezoneuron benthamianum, a plant with medicinal properties, has been traditionally used for various treatments. This study evaluates the hepatoprotective and antioxidant effects of Mezoneuron benthamianum leaves extract against NSAID-induced toxicity in albino rats. Rats were divided into five groups: control, indomethacin-treated, Mezoneuron benthamianum extract-treated, indomethacin and Mezoneuron benthamianum co-treated, and indomethacin and methyl gallate co-treated. The extract’s biochemical composition was analyzed using GC–MS, and liver function biomarkers (ALT, AST, ALP) and biochemical markers (MDA, SOD, CAT, GSH) were measured. Results showed that indomethacin-treated group had significantly increased ALT, AST, and ALP levels, elevated MDA levels, and reduced SOD, CAT, and GSH activities, indicating liver damage and oxidative stress. Treatment with Mezoneuron benthamianum extract significantly reduced these biomarkers and restored antioxidant enzyme activities. Histopathological analysis confirmed reduced liver damage in extract-treated group, with similar protective effects observed in indomethacin and methyl gallate co-treated group. The concentration of Cd marginally exceeded WHO’s limit (0.3412 mg/kg vs. 0.3 mg/kg) whereas concentrations of Fe, Mn, and Cu were well below the thresholds. The hepatoprotective and antioxidant effects of Mezoneuron benthamianum extract might be partially mediated through interactions with essential trace elements, such as Fe, Cu, and Mn. The study reveals that Mezoneuron benthamianum extract attenuated liver damage by restoring antioxidant enzymes (SOD, CAT, GSH) and reducing oxidative stress markers (MDA). Molecular docking suggested PPAR-α activation as a potential mechanism, though further validation is needed. The study highlights its hepatoprotective potential but warrants dose–response studies for clinical translation.