Abstract
Neuroinflammation has emerged as a crucial factor in the development of depression. Despite the well-known anti-inflammatory properties of 6-gingerol, its potential impact on depression remains poorly understood. This study aimed to investigate the antidepressant effects of 6-gingerol by suppressing microglial activation. In vivo experiments were conducted to evaluate the effect of 6-gingerol on lipopolysaccharide (LPS)-induced behavioral changes and neuroinflammation in rat models. In vitro studies were performed to examine the neuroprotective properties of 6-gingerol against LPS-induced microglial activation. Furthermore, a co-culture system of microglia and neurons was established to assess the influence of 6-gingerol on the expression of synaptic-related proteins, namely synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), which are influenced by microglial activation. In the in vivo experiments, administration of 6-gingerol effectively alleviated LPS-induced depressive behavior in rats. Moreover, it markedly suppressed the activation of rat prefrontal cortex (PFC) microglia induced by LPS and the activation of the NF-κB/NLRP3 inflammatory pathway, while also reducing the levels of inflammatory cytokines IL-1β and IL-18. In the in vitro experiments, 6-gingerol mitigated nuclear translocation of NF-κB p65, NLRP3 activation, and maturation of IL-1β and IL-18, all of which were induced by LPS. Furthermore, in the co-culture system of microglia and neurons, 6-gingerol effectively restored the decreased expression of SYP and PSD95. The findings of this study demonstrate the neuroprotective effects of 6-gingerol in the context of LPS-induced depression-like behavior. These effects are attributed to the inhibition of microglial hyperactivation through the suppression of the NF-κB/NLRP3 inflammatory pathway.
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We thank anonymous reviewers whose constructive comments and suggestions would help improve the quality of our manuscript.
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The authors acknowledge funding sources from the National Natural Science Foundation of China (Grant No. 81171138), and Jiangsu Province Shuangchuang Talent Plan (Grant No. JSSCRC 2021533).
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C. L.: Methodology, Writing - original draft. Y. Z.: Methodology, Writing – review & editing. W. Z.: Writing – review & editing, Supervision, Funding acquisition.
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Liu, C., Zhao, Y. & Zhao, Wj. Positive Effect of 6-Gingerol on Functional Plasticity of Microglia in a rat Model of LPS-induced Depression. J Neuroimmune Pharmacol 19, 20 (2024). https://doi.org/10.1007/s11481-024-10123-z
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DOI: https://doi.org/10.1007/s11481-024-10123-z