4.7 Article

Study on the antidepressant effect of panaxynol through the I?B-?/NF-?B signaling pathway to inhibit the excessive activation of BV-2 microglia

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 138, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.111387

Keywords

Panaxynol; LPS-induced depression; Oxidative stress; NF-?B; I?B-? pathway; BV-2 microglia

Funding

  1. China National Key Research and Development Plan ProjectResearch on modernization of traditional Chinese Medicine [2019YFC1710700]

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Panaxynol (PAL) effectively alleviates LPS-induced depression behavior in mice by reducing the release of inflammatory factors in the brain, improving neurotrophic factors, inhibiting excessive activation of BV-2 microglia, and further inhibiting the depressive state of the mice.
Panaxynol (PAL) mainly comes from Umbelliferae plants, which has anti-inflammatory and neuroprotective activities. Lipopolysaccharide (LPS)-induced depression in mice was a classic model for studying the effects of drugs on depression in mice. The purpose of this study was to investigate the mechanism and effect of PAL on depression by LPS induced in mice. In the tail suspension test (TST) and forced swimming test (FST) results, PAL significantly reduced the immobility time of mice. In the result of the open field test (OFT) and the elevated plus maze test (EPM), improved their exploration ability. According to the results of ELISA, PAL could significantly reduce the tumor necrosis factor-? (TNF-?) and interleukin- 6 (IL-6) levels in serum. Increase the superoxide dismutase (SDO) level and decrease the malondialdehyde (MDA) level in hippocampus. According to Western blotting analysis results, PAL increased the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB), decreased the nuclear transport of nuclear factor kappa-Bp65 (NF-?Bp65) and phosphorylation of inhibitor of NF-?B (I?B-?). Meanwhile, PAL also inhibited the production of nitric oxide in BV-2 microglia and decreased the level of inflammatory factors. PAL also reduced levels of oxidative stress and inhibited protein expression in the NF-?B/I?B-? inflammatory pathway and increased the protein expression of BDNF/TrkB, thereby inhibiting the over-activation of BV-2 microglia. In conclusion, according to the results of the behavioral text, it is proved that PAL could effectively alleviate LPS induced depression behavior in mice. The mechanism may be that the anti-inflammatory and anti-oxidative stress effects of PAL reduce the release of inflammatory factors in the mouse brain. Meanwhile, PAL could improve brain neurotrophic factors, inhibit the excessive activation of BV-2 microglia, and further inhibit the depressive state of the mice.

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