Study on the antidepressant effect of panaxynol through the IκB-α/NF-κB signaling pathway to inhibit the excessive activation of BV-2 microglia

Yan Zhao; Xialin Sun; Tingwen Zhang; Shuangli Liu; Enbo Cai; Hongyan Zhu

doi:10.1016/j.biopha.2021.111387

Study on the antidepressant effect of panaxynol through the IκB-α/NF-κB signaling pathway to inhibit the excessive activation of BV-2 microglia

Biomed Pharmacother. 2021 Jun:138:111387. doi: 10.1016/j.biopha.2021.111387. Epub 2021 Mar 13.

Authors

Yan Zhao¹, Xialin Sun¹, Tingwen Zhang¹, Shuangli Liu², Enbo Cai¹, Hongyan Zhu¹

Affiliations

¹ College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, China.
² College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, China; National & Local Joint Engineering Research Center for Ginseng Breeding and Application, Jilin Agricultural University, Changchun, Jilin, China. Electronic address: liushuangli@jlau.edu.cn.

PMID: 33721753
DOI: 10.1016/j.biopha.2021.111387

Abstract

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-α (TNF-α) 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-κBp65) and phosphorylation of inhibitor of NF-κB (IκB-α). 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-κB/IκB-α 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.

Keywords: BV-2 microglia; LPS-induced depression; NF-κB/IκB-α pathway; Oxidative stress; Panaxynol.

MeSH terms

Animals
Antidepressive Agents / pharmacology*
Antidepressive Agents / therapeutic use
Cell Line
Depression / drug therapy
Depression / metabolism
Depression / psychology
Diynes / pharmacology*
Diynes / therapeutic use
Dose-Response Relationship, Drug
Fatty Alcohols / pharmacology*
Fatty Alcohols / therapeutic use
Immobilization / methods
Immobilization / physiology
Immobilization / psychology
Male
Mice
Mice, Inbred ICR
Microglia / drug effects*
Microglia / metabolism
NF-KappaB Inhibitor alpha / antagonists & inhibitors*
NF-KappaB Inhibitor alpha / metabolism
NF-kappa B / antagonists & inhibitors*
NF-kappa B / metabolism
Plant Extracts / pharmacology*
Plant Extracts / therapeutic use
Signal Transduction / drug effects
Signal Transduction / physiology
Treatment Outcome

Substances

Antidepressive Agents
Diynes
Fatty Alcohols
NF-kappa B
Plant Extracts
NF-KappaB Inhibitor alpha
falcarinol