Polydatin prevents neuroinflammation and relieves depression via regulating Sirt1/HMGB1/NF-κB signaling in mice

Bian, H, Xiao, L, Liang, L, Xie, Y, Wang, H, Slevin, M ORCID: https://orcid.org/0000-0003-3767-4861, Tu, WJ and Wang, G (2022) Polydatin prevents neuroinflammation and relieves depression via regulating Sirt1/HMGB1/NF-κB signaling in mice. Neurotoxicity Research, 40 (5). pp. 1393-1404. ISSN 1029-8428

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Abstract

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.