Thymoquinone Protects Dopaminergic Neurons against MPP+ and Rotenone

Thymoquinone is the main active constituent of Nigella sativa seeds with antioxidant and antiinflammatory properties. In the present study, primary dopaminergic cultures from mouse mesencephala were used to investigate the neuroprotective effects of thymoquinone against MPP+ and rotenone toxicities. MPP+ (10 gin on day 10 in vitro (i.v.) for 48 h) significantly decreased the number of THir by 40% compared with untreated control cultures. Rotenone at both short (20 nM on day 10 i.v. for 48 h) and long-term (1nM on day 6 i.v. for 6 consecutive days) toxicities reduced the number of THir neurons by 33% and 24%, respectively. Treatment of cultures with thymoquinone (0.01, 0.1, 1, 10 mu Mm on day 8 i.v. for 4 days) rescued about 25% of THir neurons at concentrations of 0.1 mu M and 1 mu M against MPP+-induced cell death. Against rotenone, thymoquinone afforded significant protection in both short- and long-term models. In short-term rotenone toxicity, thymoquinone (from days 8-12 i.v.) saved about 65%, 74% and 79% of THir neurons at concentrations of 0.01, 0.1 and 1 mu M, respectively, compared with cell loss induced by rotenone. In long-term rotenone toxicity, concomitant treatment of cultures with thymoquinone significantly rescued about 83-100% of THir neurons compared with rotenone-treated cultures. In conclusion, the current study presents for the first time the potential of thymoquinone to protect primary dopaminergic neurons against MPP+ and rotenone relevant to Parkinson's disease. Copyright (C) 2008 John Wiley & Sons, Ltd.