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Polydatin Prevents Neuroinflammation and Relieves Depression via Regulating Sirt1/HMGB1/NF-κB Signaling in Mice

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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.

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Tumor necrosis factor α


Interleukin β


High mobility group box 1


Silent information regulator 1


Open field test


Forced swim test


Phosphate-buffered saline


Polyvinylidene fluoride


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We thank Lucy McClellan, MIA, from Liwen Bianji (Edanz) (, for editing the English text of a draft of this manuscript.


This study was supported by grants from the CAMS Innovation Fund for Medical Science (2019-I2M-2–006); Natural Science Foundation of Tianjin (No. 19JCYBJC26600); and China Postdoctoral Science Foundation (No. 2019M660921 and 2020T130436). The funding organizations had no role in the study’s design and concept; the collection, management, analysis, and interpretation of the data; or the manuscript’s preparation, review, or approval.

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Drs. WG, TW, and SM contributed equally to this work. They had full access to all the data in the study and took responsibility for the integrity of the data and the data analysis accuracy. Study concept and design: all authors; acquisition of data: BH, XL, LL; analysis and interpretation of data: all authors; drafting of the manuscript: all authors; critical revision of the manuscript for important intellectual content: WG, TW, and SM; statistical analysis: BH; administrative, technical, or material support: all authors; obtained funding: TW; study supervision: WG.

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Correspondence to Mark Slevin, Wen-Jun Tu or Gaohua Wang.

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Bian, H., Xiao, L., Liang, L. et al. Polydatin Prevents Neuroinflammation and Relieves Depression via Regulating Sirt1/HMGB1/NF-κB Signaling in Mice. Neurotox Res 40, 1393–1404 (2022).

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