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Neuroprotective Effects of Bikaverin on H2O2-Induced Oxidative Stress Mediated Neuronal Damage in SH-SY5Y Cell Line

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Abstract

The generation of free radicals and oxidative stress has been linked to several neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Amyotrophic lateral sclerosis. The use of free radical scavenging molecules for the reduction of intracellular reactive oxygen species is one of the strategies used in the clinical management of neurodegeneration. Fungal secondary metabolism is a rich source of novel molecules with potential bioactivity. In the current study, bikaverin was extracted from Fusarium oxysporum f. sp. lycopersici and its structural characterization was carried out. Further, we explored the protective effects of bikaverin on oxidative stress and its anti-apoptotic mechanism to attenuate H2O2-induced neurotoxicity using human neuroblastoma SH-SY5Y cells. Our results elucidate that pretreatment of neurons with bikaverin attenuates the mitochondrial and plasma membrane damage induced by 100 µM H2O2 to 82 and 26 % as evidenced by MTT and LDH assays. H2O2 induced depletion of antioxidant enzyme status was also replenished by bikaverin which was confirmed by Realtime Quantitative PCR analysis of SOD and CAT genes. Bikaverin pretreatment efficiently potentiated the H2O2-induced neuronal markers, such as BDNF, TH, and AADC expression, which orchestrate the neuronal damage of the cell. The H2O2-induced damage to cells, nuclear, and mitochondrial integrity was also restored by bikaverin. Bikaverin could be developed as a preventive agent against neurodegeneration and as an alternative to some of the toxic synthetic antioxidants.

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Acknowledgments

The authors are grateful to UGC (University Grants Commission), New Delhi, India for providing the financial support under UGC-Major Research Project F. No. 34-244/2008 (SR). Authors are thankful to the Director DFRL, for providing necessary facilities for conducting the experiments.

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Authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Microbiology and Biotechnology, Bangalore University, Jnanabarathi Campus, Bangalore, Karnataka, India

    D. Nirmaladevi, A. Ramesha & C. Srinivas

  2. Defence Food Research Laboratory, Siddarthanagar, Mysore, Karnataka, India

    M. Venkataramana

  3. Biotechnology Division, University of Mysore, Manasagangothri, Mysore, Karnataka, India

    S. Chandranayaka & N. M. Jameel

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  1. D. Nirmaladevi
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  2. M. Venkataramana
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  3. S. Chandranayaka
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  4. A. Ramesha
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  5. N. M. Jameel
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  6. C. Srinivas
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Correspondence to C. Srinivas.

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D. Nirmaladevi and M. Venkataramana have contributed equally to this study.

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Nirmaladevi, D., Venkataramana, M., Chandranayaka, S. et al. Neuroprotective Effects of Bikaverin on H2O2-Induced Oxidative Stress Mediated Neuronal Damage in SH-SY5Y Cell Line. Cell Mol Neurobiol 34, 973–985 (2014). https://doi.org/10.1007/s10571-014-0073-6

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