Deng Xue-Yang, Li Hong-Yan, Chen Jun-Jun, Li Rui-Peng, Qu Rong, Fu Qiang, Ma Shi-Ping
Department of Pharmacology of Chinese Materia, China Pharmaceutical University, Nanjing 210009, China.
Department of Pharmacology of Traditional Chinese Medical Formulae, Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
Behav Brain Res. 2015 Sep 15;291:12-19. doi: 10.1016/j.bbr.2015.04.052. Epub 2015 May 6.
Thymol, a bioactive monoterpene isolated from Thymus vulgaris, has displayed inspiring neuroprotective properties. The present study was designed to evaluate the antidepressant-like effects of thymol on a chronic unpredictable mild stress (CUMS) model of depression in mice and explore the underlying mechanisms. It was observed that thymol treatment (15 mg/kg and 30 mg/kg) significantly reversed the decrease of sucrose consumption, the loss of body weight, the reduction of immobile time in the tail suspension tests (TST) and forced swimming tests (FST) induced by CUMS paradigm. The levels of norepinephrine (NE) and serotonin (5-HT) in the hippocampus decreased in the CUMS-treated mice. Chronic treatments with thymol significantly restored the CUMS-induced alterations of monoamine neurotransmitters in the hippocampus. Our results further demonstrated that thymol administration negatively regulated the induction of proinflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in CUMS mice. Furthermore, thymol inhibited the activation of nod-like receptor protein 3 (NLRP3) inflammasome and its adaptor, and subsequently decreased the expression of caspase-1. In sum, our findings suggested that thymol played a potential antidepressant role in CUMS mice model through up-regulating the levels of central neurotransmitters and inhibiting the expressions of proinflammatory cytokines, which might provide potential for thymol in the light of opening up new therapeutic avenues for depression.
百里香酚是一种从百里香中分离出的具有生物活性的单萜，已显示出令人鼓舞的神经保护特性。本研究旨在评估百里香酚对小鼠慢性不可预测轻度应激（CUMS）抑郁模型的抗抑郁样作用，并探讨其潜在机制。观察到百里香酚治疗（15毫克/千克和30毫克/千克）显著逆转了由CUMS范式诱导的蔗糖消耗减少、体重减轻、尾悬测试（TST）和强迫游泳测试（FST）中不动时间的减少。在接受CUMS治疗的小鼠中，海马中的去甲肾上腺素（NE）和5-羟色胺（5-HT）水平降低。百里香酚的长期治疗显著恢复了CUMS诱导的海马中单胺类神经递质的改变。我们的结果进一步表明，给予百里香酚可负向调节CUMS小鼠中促炎细胞因子白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α的诱导。此外，百里香酚抑制了NOD样受体蛋白3（NLRP3）炎性小体及其接头的激活，随后降低了半胱天冬酶-1的表达。总之，我们的研究结果表明，百里香酚通过上调中枢神经递质水平和抑制促炎细胞因子的表达，在CUMS小鼠模型中发挥了潜在的抗抑郁作用，这可能为百里香酚开辟治疗抑郁症的新途径提供潜力。
