PHYTO-PHARMACOLOGICAL EVALUATIONS OF NELUMBO NUCIFERA (GAERTN) IN CYCLOPHOSPHAMIDE-INDUCED NEPHROTOXITY IN RATS

Objectives: Nelumbo nucifera (Gaertn) (Sacred Lotus) is a medicinally important plant conventionally used for the treatment of inflammatory and oxidative stress-related disorders. The present study aimed to evaluate the phytochemical profile, antioxidant potential, and protective effects of methanolic and aqueous extracts of N. nucifera against cyclophosphamide (CP)-induced toxicity. Methods: Extractive values of methanolic and aqueous extracts were determined, followed by preliminary phytochemical screening and quantification of total phenolic and flavonoid contents. Antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Cytotoxicity and growth curve studies were performed using wild-type and Δtrx2 yeast strains to assess biocompatibility and stress response. In vivo nephroprotective effect was evaluated in CP-induced nephrotoxicity models by measuring serum creatinine, urea, uric acid, protein, globulin, alanine aminotransferase, aspartate aminotransferase, glutathione, catalase, and malondialdehyde levels, along with pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin-1 beta. Results: The aqueous extract yielded higher extractive value (13.0% w/w), whereas the methanolic extract exhibited higher phenolic (1.50 mg/100 mg) and flavonoid (2.33 mg/100 mg) content. DPPH assay revealed potent free-radical scavenging activity for methanolic extract (IC50=42.32 μg/mL), closer to ascorbic acid. Yeast cytotoxicity studies confirmed the safety of the extracts and demonstrated their membrane-protective effects. In vivo studies showed that both extracts significantly (p<0.05–p<0.001) attenuated CP-induced alterations in renal and oxidative stress biomarkers, with methanolic extract (200 mg/kg) showing maximal protective effects. Conclusion: N. nucifera extracts, particularly the methanolic fraction, possess strong antioxidant, nephroprotective, hepatoprotective, and anti-inflammatory activities. These findings support its potential therapeutic application in managing CP-induced nephrotoxity and oxidative stress-related disorders.