Ginsenoside Rb1 attenuates microglia activation to improve spinal cord injury via microRNA-130b-5p/TLR4/NF-κB axis

J Cell Physiol. 2021 Mar;236(3):2144-2155. doi: 10.1002/jcp.30001. Epub 2020 Aug 6.

Abstract

Ginsenoside Rb1 (GRb1), a major ingredient of ginseng, has been found to be a potential protective agent in spinal cord injury (SCI) and in activated microglia-induced neuronal injury. This study discovered that GRb1 could facilitate miR-130b-5p expression in SCI rats and Toll-like receptor 4 (TLR4; a crucial player in inflammation) was a potential target of miR-130b-5p. Hence, we further investigated whether GRb1 could relieve SCI by reducing microglia-mediated inflammatory responses and neuronal injury via miR-130b-5p/TLR4 pathways. The results showed that GRb1 alleviated SCI through inhibiting neuronal apoptosis and proinflammatory factor expression via increasing miR-130b-5p.GRb1 weakened the damage of activated microglia to neurons through upregulating miR-130b-5p. miR-130b-5p attenuated activated microglia-induced neuron injury via targeting TLR4. GRb1 inactivated TLR4/nuclear factor-κB (NF-κB) activation and inhibited proinflammatory cytokine secretion by increasing miR-130b-5p in activated microglia. As a conclusion, GRb1 alleviated SCI through reducing activated microglia-induced neuronal injury via miR-130b-5p/TLR4/NF-κB axis, providing a deep insight into the molecular basis of GRb1 in the treatment of SCI.

Keywords: TLR4/NF-κB; ginsenoside Rb1; miR-130b-5p; microglia; neuron; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / drug effects
  • Animals
  • Apoptosis
  • Base Sequence
  • Cytokines / metabolism
  • Ginsenosides / pharmacology
  • Ginsenosides / therapeutic use*
  • Glucose / deficiency
  • Inflammation Mediators / metabolism
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology*
  • NF-kappa B / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxygen
  • Rats
  • Rats, Wistar
  • Signal Transduction*
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / genetics*
  • Toll-Like Receptor 4 / metabolism*
  • Up-Regulation / drug effects

Substances

  • 3' Untranslated Regions
  • Cytokines
  • Ginsenosides
  • Inflammation Mediators
  • MIRN130 microRNA, rat
  • MicroRNAs
  • NF-kappa B
  • Neuroprotective Agents
  • Toll-Like Receptor 4
  • ginsenoside Rb1
  • Glucose
  • Oxygen