Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of neuroinflammation

Abstract

Rationale

Major depressive disorder (MDD) is a highly prevalent illness that affects large populations across the world, and increasing evidence suggests that neuroinflammation and levels of brain-derived neurotrophic factor (BDNF) are closely related to depression. Dihydromyricetin (DHM) is a kind of flavonoid natural product that has been reported to display multiple pharmacological effects, including anti-inflammatory and anti-oxidative properties, and these may contribute to ameliorate MDD.

Objective

This study investigated the effect of DHM on depression-related phenotypes in various experimental animal models.

Methods

The antidepressant-like effect of DHM was validated via depression-related behavioral tests in naïve male C57BL/6 mice, as well as in the acute lipopolysaccharide-induced mouse model of depression. The chronic unpredicted mild stress (CUMS) mouse model of depression was also used to assess the rapid antidepressant-like effect of DHM by tail suspension test (TST), forced swimming test (FST), locomotor activity, and sucrose preference test (SPT). The expression of BDNF and inflammatory factors were determined through Western blotting and enzyme-linked immunosorbent assay, respectively.

Results

DHM reduced immobility time in the TST and FST both in mice and the acute LPS-induced mouse model of depression. Seven days of DHM treatment ameliorated depression-related behaviors induced by CUMS, whereas similar treatment with the typical antidepressant venlafaxine did not. DHM activated the ERK1/2-CREB pathway and increased glycogen synthase kinase-3 beta (GSK-3β) phosphorylation at ser-9, with upregulation of BDNF expression, in both hippocampal tissues and cultured hippocampal cells.

Conclusion

The present data indicate that DHM exerts a more rapid antidepressant-like effect than does a typical antidepressant, in association with enhancement of BDNF expression and inhibition of neuroinflammation.

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Acknowledgements

This work was supported by funds from the National Science Foundation of China (81130023, 30825042). Support provided from the Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD) and the Jiangsu key laboratory grant (BM2013003) is also appreciated.

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Correspondence to Xuechu Zhen.

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Ren, Z., Yan, P., Zhu, L. et al. Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of neuroinflammation. Psychopharmacology 235, 233–244 (2018). https://doi.org/10.1007/s00213-017-4761-z

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Keywords

  • Dihydromyricetin
  • Antidepressant activity
  • Brain-derived neurotrophic factor
  • ERK1/2
  • Glycogen synthase kinase-3β