Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2875-2881. doi: 10.1080/21691401.2019.1626406.

Abstract

Geniposide is an active ingredient with anti-apoptotic and anti-inflammatory properties. This study was to examine the effects of geniposide on a cell model of spinal cord injury (SCI). PC12 cells were administrated with geniposide before subjected to LPS. The effects of geniposide were analyzed by utilizing CCK-8 assay, apoptosis assay, ELISA, RT-qPCR and Western blot. We found that PC12 cells viability was unchanged by treating with geniposide. However, geniposide with concentrations of 200 or 300 μg/mL significantly mitigated LPS-evoked viability loss. Meanwhile, apoptosis driven by LPS was mitigated by geniposide, which accompanied with p53, Bax and cleaved caspase-3 down-regulation, and Bcl-2 up-regulation. Besides this, the expression and release of IL-1β, IL-6, IL-8 and TNF-α evoked by LPS were mitigated by geniposide. miR-145-5p was a target of geniposide. miR-145-5p expression was up-regulated by geniposide, and geniposide did not protect PC12 cells against LPS injury when miR-145-5p was silenced. Moreover, geniposide inhibited NF-κB and JNK pathways via up-regulating miR-145-5p. In short, the present work described the neuroprotective effects of geniposide by targeting miR-145-5p. Further mechanisms involved in geniposide's beneficial effects are correlated with the inhibited NF-κB and JNK pathways. Highlights Geniposide prevents LPS-induced injury in PC12 cells; Geniposide up-regulates miR-145-5p; Geniposide protects PC12 cells via up-regulation of miR-145-5p; Geniposide inhibits NF-κB and JNK pathways via up-regulation of miR-145-5p.

Keywords: Geniposide; PC12 cell; lipopolysaccharide (LPS); miR-145-5p; spinal cord injury (SCI).

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Cytoprotection / drug effects*
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Iridoids / pharmacology*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / adverse effects*
  • MicroRNAs / genetics*
  • NF-kappa B / metabolism
  • PC12 Cells
  • Rats
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects*

Substances

  • Cytokines
  • Iridoids
  • Lipopolysaccharides
  • MIRN145 microRNA, rat
  • MicroRNAs
  • NF-kappa B
  • geniposide
  • JNK Mitogen-Activated Protein Kinases