Department of Psychiatry, Renmin Hospital of Wuhan University, Jiefang Road 238#, 430060, Hubei, People's Republic of China.
School of Healthcare Science, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, M156GX, UK.
Neurotox Res. 2022 Oct;40(5):1393-1404. doi: 10.1007/s12640-022-00553-z. Epub 2022 Aug 20.
Depression is a prevalent psychiatric disorder with a significant health impact and economic burden worldwide. Unfortunately, the exact pathogenesis of depression is not well understood. Neuroinflammation and microglial activation play an essential role in the pathogenesis of depression. Previous studies have shown that polydatin has anti-inflammatory and antioxidant properties. However, the link between polydatin and depression remains unclear. Therefore, the objective of this study was to investigate the antidepressant effect of polydatin in lipopolysaccharide (LPS)-induced depression in mice and its possible mechanism. Adult male C57BL/6 J mice were used in this study. The polydatin and LPS were injected intraperitoneally daily for 5 days. In addition, the EX527, an inhibitor of Sirt1, was injected intraperitoneally daily and 1 h before the polydatin injection. The behavior tests were performed to elucidate the depression-like behaviors. The Sirt1/HMGB1/NF-κB pathway expression was detected by western blot, ELISA, and immunofluorescence staining. Polydatin can significantly improve LPS-induced depression-like behavior in mice. Treatment with polydatin increased the expression of the Sirt1 but decreased the expression of the HMGB1, p-NF-κB, IL-1b, and TNF-α in the LPS-induced depression mice. In addition, the EX527 abolished the anti-depressive effects of the polydatin and the levels of Sirt1 protein. These findings suggested that the polydatin reversed the depressive effects through the Sirt1/HMGB1/NF-κB signaling in the LPS-induced depression mice. Therefore, polydatin can be used in the treatment of depression.
抑郁症是一种普遍存在的精神疾病，在全球范围内对健康和经济都有重大影响。不幸的是，抑郁症的确切发病机制尚未完全了解。神经炎症和小胶质细胞激活在抑郁症的发病机制中起着重要作用。先前的研究表明，白藜芦醇苷具有抗炎和抗氧化作用。然而，白藜芦醇苷与抑郁症之间的联系尚不清楚。因此，本研究旨在探讨白藜芦醇苷对脂多糖（LPS）诱导的抑郁小鼠的抗抑郁作用及其可能的机制。本研究采用成年雄性 C57BL/6J 小鼠。白藜芦醇苷和 LPS 每天腹腔注射，连续 5 天。此外，Sirt1 抑制剂 EX527 每天腹腔注射，并在白藜芦醇苷注射前 1 小时注射。通过行为测试来阐明抑郁样行为。通过 Western blot、ELISA 和免疫荧光染色检测 Sirt1/HMGB1/NF-κB 通路的表达。白藜芦醇苷可显著改善 LPS 诱导的抑郁样行为。白藜芦醇苷治疗可增加 LPS 诱导的抑郁小鼠 Sirt1 的表达，降低 HMGB1、p-NF-κB、IL-1b 和 TNF-α的表达。此外，EX527 消除了白藜芦醇苷的抗抑郁作用和 Sirt1 蛋白水平。这些发现表明，白藜芦醇苷通过 LPS 诱导的抑郁小鼠中的 Sirt1/HMGB1/NF-κB 信号通路逆转了抑郁作用。因此，白藜芦醇苷可用于治疗抑郁症。
