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ORIGINAL ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 61  |  Page : 309-316

Neuroprotective potential of methanolic extract of Saraca asoca bark against doxorubicin-induced neurotoxicity


1 Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India

Correspondence Address:
Nitesh Kumar
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal - 576 104, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pm.pm_79_18

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Background: Doxorubicin (DOX) is a widely used anthracycline-based anticancer agent, which causes a gradual decline in cognition on long-term usage in breast cancer patients that affect their quality of life negatively. Aim: The present study was designed to assess the neuroprotective potential of Saraca asoca bark against Dox-induced neurotoxicity, considering its previously reported anticlastogenic effect. Materials and Methods: Methanolic extract of bark was prepared by Soxhlet extraction and characterized by high-performance thin-layer chromatography (catechin-8.82%). In vitro studies were performed in IMR-32 neuroblastoma cells using cell viability and neurite growth assay to determine the neuroprotective potential of the extract against DOX-induced neurotoxicity. In vivo neuroprotection study of extract (100 and 200 mg/kg p. o) was performed by assessing episodic memory through novel object recognition test (NORT) in DOX-induced (10 cycles, 2.5 mg/kg, 5 days apart) memory deficit model. In addition, antioxidant markers and acetylcholinesterase activity in hippocampus and frontal cortex were evaluated. Results and Conclusion: The extract showed significant in vitro neuroprotection toward differentiated cells in morphological features and cell viability assessment against DOX (IC50-63.35 and 45.17 μg/ml against 1 μg/ml and 2 μg/ml DOX, respectively, and 0.46 μg/ml for DOX alone in 3-[4,5 dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay). DOX-treated animals showed depletion in episodic memory while extract at 100 mg/kg significantly prevented it. Similar changes were observed in antioxidant markers levels in the brain. DOX treatment elevated acetylcholinesterase activity which was significantly reversed by the treatment with extract. Thus, it can be stated that the neuroprotective and antioxidant potentials of extract possibly underlie the efficacy against the DOX-induced neurotoxicity. Abbreviations Used: DOX: Doxorubicin; S. asoca: Saraca asoca; DMEM: Dulbecco's Modified Eagle's Medium (DMEM); MTT: 3-[4,5 dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide; FBS: Fetal bovine serum; RA: Retinoic acid; CMC: Carboxymethyl cellulose; SOD: Superoxide dismutase; GSH: Reduced glutathione; HPTLC: High-performance thin-layer chromatography; NORT: Novel object recognition task; ITI: Intertrial interval; MPO: Myeloperoxidase; MDA: Malondialdehyde; RI: Recognition index; DI: Discrimination index.


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