Pharmacology Division, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar-125001, Haryana, India.
Pharmacol Rep. 2011;63(3):660-9. doi: 10.1016/s1734-1140(11)70577-1.
The aim of the present study was to investigate the role of GABAergic and nitriergic modulation in the antianxiety effect of thymoquinone, a major constituent of Nigella sativa, in mice under unstressed and stressed conditions. Thymoquinone (10 and 20 mg/kg), methylene blue (1 mg/kg) and diazepam (2 mg/kg) were administered followed by behavioral testing using an elevated plus maze, the light/dark test and the social interaction test in both unstressed and stressed mice (mice subjected to 6 h immobilization). The effects of the above-mentioned drugs on plasma nitrite, a stable metabolite of nitric oxide (NO) and brain GABA content were also studied. Diazepam (2 mg/kg) produced significant anxiolytic-like effects only in unstressed mice. However, diazepam significantly increased the GABA content in both unstressed and stressed mice as compared with their respective control groups. Thymoquinone (10 and 20 mg/kg) produced significant antianxiety effects in unstressed mice without altering nitrite levels, but only the higher dose (20 mg/kg) of thymoquinone increased the GABA content in unstressed mice. In stressed mice, thymoquinone (20 mg/kg) showed anxiolytic effects, with a significant decrease in plasma nitrite and reversal of the decreased brain GABA content. Pre-treatment with methylene blue enhanced the antianxiety effect of thymoquinone in both unstressed and stressed mice. Therefore, the present study suggests an involvement of NO-cGMP and GABAergic pathways in the anxiolytic-like activity of thymoquinone.
本研究旨在探讨 GABA 能和氮能调制在百里香醌（黑种草的主要成分）抗焦虑作用中的作用，在无应激和应激条件下的小鼠中。给予百里香醌（10 和 20 mg/kg）、亚甲蓝（1 mg/kg）和地西泮（2 mg/kg），然后在无应激和应激小鼠（6 小时固定应激小鼠）中使用高架十字迷宫、明暗测试和社交互动测试进行行为测试。还研究了上述药物对血浆中亚硝酸盐（一氧化氮（NO）的稳定代谢物）和脑 GABA 含量的影响。地西泮（2 mg/kg）仅在无应激小鼠中产生明显的抗焦虑样作用。然而，与各自的对照组相比，地西泮显著增加了无应激和应激小鼠的 GABA 含量。百里香醌（10 和 20 mg/kg）在无应激小鼠中产生明显的抗焦虑作用，而不改变亚硝酸盐水平，但仅较高剂量（20 mg/kg）的百里香醌增加了无应激小鼠的 GABA 含量。在应激小鼠中，百里香醌（20 mg/kg）表现出抗焦虑作用，血浆中亚硝酸盐显著降低，大脑 GABA 含量降低得到逆转。亚甲蓝预处理增强了百里香醌在无应激和应激小鼠中的抗焦虑作用。因此，本研究表明 NO-cGMP 和 GABA 能途径参与了百里香醌的抗焦虑样活性。
