Department of Rehabilitation, Jinshan Hospital Affiliated to Fudan University, Shanghai, China.
Department of Neurology, Jinshan Hospital Affiliated to Fudan University, Shanghai, China.
J Biochem Mol Toxicol. 2020 Feb;34(2):e22424. doi: 10.1002/jbt.22424. Epub 2019 Nov 19.
Recent studies have shown that tricyclic antidepressants (TCAs) may have anti-inflammatory and anticonvulsant effects in addition to its antidepressant effects. So far, the nonantidepressant effects of TCAs and their molecular pharmacological mechanisms remain completely unclear. Chronic inflammation in the brain parenchyma may be related to the pathogenesis and progression of various neurodegenerative diseases. As a common antidepressant and anti-insomnia drug, doxepin also may be a potential anti-inflammatory and anticonvulsant drug, so the study on the anti-inflammatory protective effect of doxepin and its molecular mechanism has become a very important issue in pharmacology and clinical medicine. Further elucidating the anti-inflammatory and neuroprotective effects of doxepin and its molecular mechanism may provide the important theoretical and clinical basis for the prevention and treatment of neurodegenerative disease. This study was designed to understand the glio-protective mechanism of doxepin against the inflammatory damage induced by lipopolysaccharide (LPS) exposure in C6-glioma cells. We found the treatment of C6-glioma cells with LPS results in deleterious effects, including the augmentation of inflammatory cytokine levels (tumor necrosis factor-α, interleukin-1β), and suppresses the Akt phosphorylation. Furthermore, our outcomes demonstrated that doxepin was able to suppress these effects induced by LPS, through activation of the phosphatidylinositol-3-kinase-mediated protein kinase B (Akt) pathway. To sum up, these results highlight the potential role of doxepin against neuroinflammatory-related disease in the brain.
最近的研究表明，三环类抗抑郁药（TCAs）除了具有抗抑郁作用外，还可能具有抗炎和抗惊厥作用。到目前为止，TCAs 的非抗抑郁作用及其分子药理学机制仍完全不清楚。脑实质的慢性炎症可能与各种神经退行性疾病的发病机制和进展有关。作为一种常见的抗抑郁药和抗失眠药，多塞平也可能是一种潜在的抗炎和抗惊厥药物，因此，研究多塞平的抗炎保护作用及其分子机制已成为药理学和临床医学中的一个非常重要的问题。进一步阐明多塞平的抗炎和神经保护作用及其分子机制，可能为神经退行性疾病的预防和治疗提供重要的理论和临床依据。本研究旨在了解多塞平对脂多糖（LPS）暴露诱导的 C6 神经胶质瘤细胞炎症损伤的神经保护机制。我们发现 LPS 处理 C6 神经胶质瘤细胞会产生有害影响，包括炎症细胞因子水平（肿瘤坏死因子-α、白细胞介素-1β）的增加，并抑制 Akt 磷酸化。此外，我们的研究结果表明，多塞平通过激活磷脂酰肌醇-3-激酶介导的蛋白激酶 B（Akt）通路，能够抑制 LPS 诱导的这些作用。总之，这些结果强调了多塞平在大脑中对抗与神经炎症相关疾病的潜在作用。
