Identification of phytoconstituents of Memecylon sisparense gamble leaf and evaluation against cisplatin-induced oxidative renal damage in mice

Abstract

Background: Memecylon sisparense Gamble (MSG) belongs to Melastomataceae family, having a wide range of pharmacological activities such as antioxidant, hepatoprotective, and anti-inflammatory. Objective: The present study aimed for the first time toward the identification of biologically active compounds in MSG leaf ethyl acetate extract (MSGLEAE) by gas chromatography–mass spectrometry (GC-MS) analysis and compared with docking studies along with its nephroprotective activity against cisplatin (CP)-induced nephrotoxicity in mice. Materials and Methods: MSGLEAE was subjected to GC-MS analysis and molecular docking studies. Swiss albino male mice were treated with MSGLEAE (250, 500 mg/kg, PO) against CP 12 mg/kg IP evaluated for nephroprotective activity. The changes in renal tissue were assessed from serum biochemical renal toxicity, antioxidant stress markers along with histopathological studies. Results: Out of 41 compounds identified, 20 were found having biological activities such as nephroprotective, hepatoprotective, anticancer, antioxidant, and antimicrobial and inhibition of uric acid production. The nephroprotective active compounds (N,N,O-triacetylhydroxylamine, 2(4H)-benzofuranone, 5,6,7,7a-tetrahydro-4,4,7a-trimethyl-, N-{(4-hydroxy-3-methoxyphenyl) methyl}-8-methyl-6-nonenamide) had shown binding energy of −5.27, −5.98, −5.27 (ΔG(Kcal/mol)), respectively, in docking studies. MSGLEAE showed a significant protective effect against CP-induced nephrotoxicity because of the identified compounds by reducing the oxidative stress in renal tissue evident by histopathological studies. Conclusion: This is the first ever report in terms of identification of bioactive constituents in MSGLEAE. Pretreatment has a significant therapeutic benefit during CP therapy by inhibiting oxidative stress, enhancing nephroprotective activity. Abbreviations used: MSGLEAE: Memecylon sisparense Gamble leaf ethyl acetate extract; CP: Cisplatin; BUN: Blood urea nitrogen; SOD: Superoxide dismutase; CAT: Catalase; GSH: Glutathione; NO: Nitric oxide; MDA: Malondialdehyde; IAEC: Institutional Animal Ethics Committee; TCA: Trichloroacetic acid; DTNB: 5,51-dithiobis-2-nitrobenzoic acid; FC: Folin–Ciocalteu reagent; SNP: Sodium nitroprusside; H and E: Hematoxylin and eosin.