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The Antioxidant Effects of Thymoquinone in Activated BV-2 Murine Microglial Cells

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Abstract

Both neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. During chronic activation of the microglial cells, the induced release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines have been implicated in several neurodegenerative diseases such as Alzheimer’s disease. Thymoquinone (TQ), a major bioactive compound of the natural product Nigella sativa seed, has been shown to be effective against numerous oxidative stress-induced and inflammatory disorders as well as possess neuroprotective properties. In this study, we investigated the antioxidant effects of TQ on LPS/IFNγ or H2O2-activated BV-2 microglia by assessing the levels of specific oxidative stress markers, the activities of selected antioxidant enzymes, as well as profiling 84 key genes related to oxidative stress via real-time reverse transcription (RT2) PCR array. Our results showed that in the LPS/IFNγ-activated microglia TQ significantly decreased the cellular production of both superoxide and nitric oxide fourfold (p < 0.0001) and sixfold (p < 0.0001), respectfully. In the H2O2-activated microglia, TQ also significantly decreased the cellular production of superoxide threefold (p < 0.0001) and significantly decreased hydrogen peroxide levels ~20 % (p < 0.05). Moreover, ΤQ treatment significantly decreased the levels oxidative stress in the activated BV-2 as evidenced by the assessed levels of lipid hydroperoxides and glutathione. TQ significantly decreased the levels of lipid hydroperoxides twofold (p < 0.0001) and significantly increased the levels of antioxidant glutathione 2.5-fold (p < 0.0001) in the LPS/IFNγ-activated BV-2 cells. In the H2O2-activated microglia, TQ significantly decreased lipid hydroperoxides eightfold (p < 0.0001) and significantly increased glutathione 15 % (p < 0.05). Activities of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), in the TQ-treated microglial cells also reflected a reduced oxidative stress status in the cellular environment. SOD and CAT activities were sixfold (p < 0.0001) and fivefold (p < 0.0001) lower, respectfully, for the LPS/INFγ-activated microglia treated with TQ in comparison to those that were not. For the H2O2-activated microglia treated with TQ, SOD and CAT activities were fivefold (p < 0.0001) and threefold (p < 0.01) lower, respectfully, compared to the untreated. Furthermore, RT2 PCR array profiling of the selected 84 genes related to oxidative stress confirmed that TQ treatment in the LPS/IFNγ-activated microglia downregulates specific pro-oxidant genes, upregulates specific anti-oxidant genes, and enhances the up- or downregulation of specific genes related to the cells’ natural antioxidant defense against LPS/IFNγ activation. These findings suggest that TQ may be utilized as an effective therapeutic agent for delaying the onset and/or slowing/preventing the progression of microglia-derived neurodegeneration propagated by excessive oxidative stress in the CNS.

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Acknowledgments

This research was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health through Grant Number G12 MD007582 and Grant Number P20 MD006738.

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  1. College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Room 104 Dyson Pharmacy Building, 1520 ML King Blvd, Tallahassee, FL, 32307, USA

    Makini K. Cobourne-Duval, Equar Taka, Patricia Mendonca, David Bauer & Karam F. A. Soliman

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  1. Makini K. Cobourne-Duval
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  3. Patricia Mendonca
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  4. David Bauer
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  5. Karam F. A. Soliman
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Correspondence to Karam F. A. Soliman.

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Cobourne-Duval, M.K., Taka, E., Mendonca, P. et al. The Antioxidant Effects of Thymoquinone in Activated BV-2 Murine Microglial Cells. Neurochem Res 41, 3227–3238 (2016). https://doi.org/10.1007/s11064-016-2047-1

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  • DOI: https://doi.org/10.1007/s11064-016-2047-1

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