Podophyllum hexandrum ameliorates endosulfan-induced genotoxicity and mutagenicity in freshwater cyprinid fish crucian carp

Context: Medicinal plants continue to act as a repository for novel drug leads with novel mechanisms of action. Podophyllum hexandrum Royale (Berberideceae) treats diverse conditions in folk medicine. Objective: The antimutagenic potential of P. hexandrum was evaluated against endosulfan-induced clastogenicity in a piscine model by cytogenetic endpoints. Materials and methods: Podophyllum hexandrum rhizomes were subjected to successive solvent extraction. Fish were exposed to hexane, chloroform, ethyl acetate, methanol and aqueous extracts (15 mg/L each) of plant and endosulfan (0.05 mg/L) alone followed by their combination for antimutagenicity estimates. Chromosomal aberrations (CA) were made from kidney cells and micronuclei (MN) slides from peripheral blood erythrocytes at 48, 72 and 96 h. Antioxidant activity was analyzed by the DPPH assay. Phytochemical analyses were carried out using chromatographic and spectroscopic techniques. Results: Endosulfan induced significant (p < .05) MN, authenticated by scanning electron microscopy, and CA in a time-dependent manner. However, methanol and ethyl acetate extracts revealed ameliorating effects. The column eluted methanolic fraction-2 (ME-F2) showed highest reduction profile of 83 and 84% in CA and MN, followed in its extent (73 and 72%) by ethyl acetate fraction-4 (EE-F4). ME-F2 and EE-F4 showed three and six major peaks when analyzed by GC-MS. To explore possible mechanism of action, ME-F2 showed potent antioxidant potential and strong correlation (R(2 )=( ).900) with antimutagenic activity, whereas EE-F4 seemed to act through a different mechanism. Discussion and conclusion: This study confirms the antimutagenic potential of the subject plant with the identification of some novel compounds, justifying their use in folk medicine, and their corresponding benefit to mankind.