Lu Jiaqi, Zhou Hang, Meng Danyang, Zhang Junjun, Pan Kailing, Wan Bo, Miao Zhigang
Institute of Neuroscience, Soochow University, Suzhou City, China.
Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou City, China.
Neuroscience. 2020 Mar 15;430:1-11. doi: 10.1016/j.neuroscience.2020.01.026. Epub 2020 Jan 31.
Depression is a serious global affective disorder and one of the most common neurological diseases. Tanshinone IIA (TSA) is the mainly active constituent of Salvia miltiorrhiza and has diverse biological effects, including anti-inflammatory and antioxidant effects and significant neuroprotective effects against cerebral ischemia and Alzheimer's disease. However, whether TSA has an antidepressant effect remains unknown. The present study attempted to explore the antidepressant effects and the mechanism of TSA by examining the brain-derived neurotrophic factor (BDNF) expression in the hippocampus of depressive mice. The tail suspension test (TST) and forced swim test (FST) showed that TSA can significantly reduce the immobility time of depressed mice. Chronic administration of TSA increased p-ERK and p-CREB, BDNF proteins in mice hippocampus. We further explored the potential mechanism of TSA' antidepressant effect. TSA significantly increased the expression of p-ERK, p-CREB and BDNF proteins in dexamethasone-treated PC12 cells, and this enhancement was suppressed by pretreatment with the extracellular signal-regulated kinase (ERK) inhibitor SL327. Moreover, we observed that SL327 treatment markedly suppressed the increased levels of p-ERK, p-CREB and BDNF in mice hippocampus induced by TSA, preventing the antidepressant effects of TSA. Taken together, our results suggest that the antidepressant-like effects of TSA were mediated by ERK-CREB-BDNF pathway in mice hippocampus.
抑郁症是一种严重的全球性情感障碍，也是最常见的神经疾病之一。丹参酮IIA（TSA）是丹参的主要活性成分，具有多种生物学效应，包括抗炎、抗氧化作用以及对脑缺血和阿尔茨海默病显著的神经保护作用。然而，TSA是否具有抗抑郁作用仍不清楚。本研究试图通过检测抑郁小鼠海马中脑源性神经营养因子（BDNF）的表达来探讨TSA的抗抑郁作用及其机制。悬尾试验（TST）和强迫游泳试验（FST）表明，TSA可显著缩短抑郁小鼠的不动时间。长期给予TSA可增加小鼠海马中p-ERK、p-CREB和BDNF蛋白的表达。我们进一步探讨了TSA抗抑郁作用的潜在机制。TSA显著增加了地塞米松处理的PC12细胞中p-ERK、p-CREB和BDNF蛋白的表达，而细胞外信号调节激酶（ERK）抑制剂SL327预处理可抑制这种增强作用。此外，我们观察到SL327处理显著抑制了TSA诱导的小鼠海马中p-ERK、p-CREB和BDNF水平的升高，从而阻止了TSA的抗抑郁作用。综上所述，我们的结果表明，TSA的抗抑郁样作用是由小鼠海马中的ERK-CREB-BDNF通路介导的。
