1. Academic Validation
  2. Geniposide protects depression through BTK/JAK2/STAT1 signaling pathway in lipopolysaccharide-induced depressive mice

Geniposide protects depression through BTK/JAK2/STAT1 signaling pathway in lipopolysaccharide-induced depressive mice

  • Brain Res Bull. 2021 May;170:65-73. doi: 10.1016/j.brainresbull.2021.02.008.
Menglin Zheng 1 Ke Li 1 Tong Chen 1 Shengnan Liu 1 Ling He 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, China Pharmaceutical University, 639, Longmian Avenue, Nanjing, 211198, China.
  • 2 Department of Pharmacology, China Pharmaceutical University, 639, Longmian Avenue, Nanjing, 211198, China. Electronic address: hexyz@163.com.
Abstract

The purpose of this study was to investigate the antidepressant mechanism of GEN (geniposide) on depression mice induced by LPS. The mice were intragastrically treated with GEN (10 mg/kg/d or 40 mg/kg/d) or ibrutinib for continuous 7 days prior to LPS injection. The anxiety- and depression-like behaviors of mice were assessed via behavioral tests (sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open-field test (OFT)). Microglial BV2 cells were treated with GEN or/and ibrutinib and stimulated with LPS. The productions of pro-inflammatory cytokines IL-6 and TNF-α in hippocampus, serum, and supernatant were detected by ELISA. The correlative proteins Btk, p-BTK, JAK2, p-JAK2, STAT1, p-STAT1, BDNF, TrkB, and p-TrkB were assessed through western blot. As a result, GEN ameliorated the anxiety- and depression-like behaviors of mice in behavioral tests. GEN treatment also regulated microglia polarization towards anti-inflammatory phenotype M2 and inhibited the production of pro-inflammatory cytokines IL-6 and TNF-α. In addition, with the application of ibrutinib, the selective inhibitor of Btk, it was proclaimed that the administration of GEN restrained the activation of JAK2/STAT1 pathway via attenuating the hyperphosphorylation of Btk both in mice and BV2 cells. Furthermore, it was also found that GEN activated BDNF/TrkB neuroprotective signaling pathway through the reduction of Btk phosphorylation. From the overall results, we suggested that GEN exerted a beneficial effect on LPS-induced depression in mice possibly through the modulation of Btk/JAK2/STAT1 signaling.

Keywords

BTK; Depression; Geniposide; Inflammation; JAK2/STAT1; LPS.

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