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<p>The aim of the present study was to investigate the mechanism of <i>Syringa oblata</i> Lindl., Oleaceae extract in improving corticosterone-induced depressive symptoms in mice through alleviation of oxidative stress. A mouse model of depression was established by subcutaneous injection of corticosterone. Behavioral test results revealed that <i>S. oblata</i> extract co-treatment significantly increased sucrose water preference, increased open field voluntary activity, and shortened both tail suspension and forced-swimming immobility time. Pathological test results confirmed that <i>S. oblata</i> extract co-treatment attenuated hippocampal neuron damage and restored neuron density. Additionally, <i>S. oblata</i> extract co-treatment upregulated serum 5-hydroxytryptamine, dopamine, and norepinephrine levels, reduced malondialdehyde in brain tissue, and enhanced superoxide dismutase and glutathione activities. Using non-targeted metabolomics techniques, <i>S. oblata</i> co-treatment was demonstrated to differentially regulate 26 metabolites and to regulate glycerol phospholipid metabolism and other pathways. At the molecular level, <i>S. oblata</i> extract co-treatment upregulated BDNF, TrkB, Nrf2, HO-1, SLC7A11, GSH, and GPX4 mRNA expression levels and BDNF, TrkB, Nrf2, SLC7A11, and GPX4 protein expression levels. In summary, <i>S. oblata</i> extract improved corticosterone-induced depressive symptoms in a mouse model by regulating oxidative stress-related metabolic pathways, enhancing antioxidant capacity, and repairing neurotransmitter imbalances. We propose that the mechanism underlying the antidepressant effects of <i>S. oblata</i> may involve activation of the BDNF/Nrf2/GPX4 signaling pathway.</p> Graphical Abstract <p></p>

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Syringa oblata Extract Regulates Oxidative Stress Through the BDNF/Nrf2/GPX4 Pathway and Improves Depressive Behavior in a Mouse Model

  • 期刊论文

  • 发表日期：

    2025年10月16日

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  • Shuting Zhai,
  • Ruiyin Ye,
  • Ruhan A,
  • Yanjun Tuo,
  • Wei Xiao,
  • Yi Liu,
  • Li Li,
  • Jianan Sun,
  • Yulin Feng,
  • Mingzhen He

摘要

The aim of the present study was to investigate the mechanism of Syringa oblata Lindl., Oleaceae extract in improving corticosterone-induced depressive symptoms in mice through alleviation of oxidative stress. A mouse model of depression was established by subcutaneous injection of corticosterone. Behavioral test results revealed that S. oblata extract co-treatment significantly increased sucrose water preference, increased open field voluntary activity, and shortened both tail suspension and forced-swimming immobility time. Pathological test results confirmed that S. oblata extract co-treatment attenuated hippocampal neuron damage and restored neuron density. Additionally, S. oblata extract co-treatment upregulated serum 5-hydroxytryptamine, dopamine, and norepinephrine levels, reduced malondialdehyde in brain tissue, and enhanced superoxide dismutase and glutathione activities. Using non-targeted metabolomics techniques, S. oblata co-treatment was demonstrated to differentially regulate 26 metabolites and to regulate glycerol phospholipid metabolism and other pathways. At the molecular level, S. oblata extract co-treatment upregulated BDNF, TrkB, Nrf2, HO-1, SLC7A11, GSH, and GPX4 mRNA expression levels and BDNF, TrkB, Nrf2, SLC7A11, and GPX4 protein expression levels. In summary, S. oblata extract improved corticosterone-induced depressive symptoms in a mouse model by regulating oxidative stress-related metabolic pathways, enhancing antioxidant capacity, and repairing neurotransmitter imbalances. We propose that the mechanism underlying the antidepressant effects of S. oblata may involve activation of the BDNF/Nrf2/GPX4 signaling pathway.

Graphical Abstract