Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
Provincial Key Laboratory of Inflammation and Molecular Drug Target, Jiangsu, China.
Int J Neuropsychopharmacol. 2019 Sep 1;22(9):585-600. doi: 10.1093/ijnp/pyz032.
Major depressive disorder is a worldwide neuropsychiatric disorder associated with various symptoms, but current antidepressants used in clinical practice have various side effects and high failure rates. Andrographolide is the main bioactive ingredient of Andrographis paniculata and exhibits numerous pharmacological actions. This study aimed to evaluate the antidepressant-like effects of andrographolide in male C57BL/6J mice.
The antidepressant-like effects of andrographolide in mice were explored in a forced swim test, tail suspension test, and chronic unpredictable mild stress model of depression. Western blotting and immunofluorescence were further performed to assess the effects of chronic unpredictable mild stress and andrographolide on the brain-derived neurotrophic factor signalling cascade and hippocampal neurogenesis. Moreover, a pharmacological inhibitor (K252a) and a lentiviral-short hairpin RNA (LV-TrkB-shRNA) were used to clarify the antidepressant-like mechanism of andrographolide.
Andrographolide exhibited antidepressant-like potential in the forced swim test and tail suspension test without influencing the locomotor activity of mice. Repeated andrographolide treatment not only produced significant antidepressant-like effects in the chronic unpredictable mild stress model but also prevented the decreasing effects of chronic unpredictable mild stress on hippocampal brain-derived neurotrophic factor signalling and neurogenesis in mice. Importantly, blockade of the hippocampal brain-derived neurotrophic factor system by K252a and TrkB-shRNA fully abolished the antidepressant-like effects of andrographolide in mice.
Andrographolide exerts antidepressant-like effects in mice via promoting the hippocampal brain-derived neurotrophic factor signalling cascade.
重度抑郁症是一种全球性的神经精神疾病，与各种症状相关，但目前临床实践中使用的抗抑郁药具有各种副作用和高失败率。穿心莲内酯是穿心莲的主要生物活性成分，具有多种药理作用。本研究旨在评估穿心莲内酯在雄性 C57BL/6J 小鼠中的抗抑郁样作用。
通过强迫游泳试验、悬尾试验和慢性不可预测轻度应激抑郁模型，探讨了穿心莲内酯在小鼠中的抗抑郁样作用。进一步进行了 Western blot 和免疫荧光检测，以评估慢性不可预测轻度应激和穿心莲内酯对脑源性神经营养因子信号级联和海马神经发生的影响。此外，使用药理学抑制剂（K252a）和慢病毒短发夹 RNA（LV-TrkB-shRNA）来阐明穿心莲内酯的抗抑郁样机制。
穿心莲内酯在强迫游泳试验和悬尾试验中表现出抗抑郁样作用，而不影响小鼠的运动活性。重复穿心莲内酯治疗不仅在慢性不可预测轻度应激模型中产生了显著的抗抑郁样作用，而且防止了慢性不可预测轻度应激对小鼠海马脑源性神经营养因子信号和神经发生的降低作用。重要的是，K252a 和 TrkB-shRNA 阻断海马脑源性神经营养因子系统完全消除了穿心莲内酯在小鼠中的抗抑郁样作用。
穿心莲内酯通过促进海马脑源性神经营养因子信号级联在小鼠中发挥抗抑郁样作用。
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