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

Abstract

Introduction

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.

Methods

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 and discussion

Results showed that the 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 the extract-treated group, with similar protective effects observed in the 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.

Conclusion

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.