Gisenoside Rg1 attenuates cadmium-induced neurotoxicity in vitro and in vivo by attenuating oxidative stress and inflammation

Inflamm Res. 2021 Dec;70(10-12):1151-1164. doi: 10.1007/s00011-021-01513-7. Epub 2021 Oct 18.

Abstract

Objective: Gisenoside Rg1 is a potent neuroprotectant in ginseng. The aim of this study was to investigate the elimination effect of Rg1 on cadmium (Cd)-induced neurotoxicity.

Materials and methods: A cumulative Cd exposure mouse model was established. Also, the toxicity of Cd and the protective effect of Rg1 were examined in vitro using cultured neurons and microglia.

Results: We found that Cd-intoxicated mice exhibited significant injury in the liver, kidney, small intestine, and testis, along with cognitive impairment. Antioxidant enzymes such as SOD, GSH-Px and CAT were reduced in the blood and brain, and correspondingly, the lipid peroxidation product MDA was elevated. In the brain, astrocytes and microglia were activated, characterized by an increase in inflammatory factors such as TNF-α, IL-1β and IL-6, as well as their protein markers GFAP and IBA1. However, Rg1 eliminated Cd-induced toxicity and restored oxidative stress and inflammatory responses, correspondingly restoring the behavioral performance of the animals. Meanwhile, the BDNF-TrkB/Akt and Notch/HES-1 signaling axes were involved in the Rg1-mediated elimination of Cd-induced toxicity.

Conclusion: Rg1 is a promising agent for the elimination of Cd-induced toxicity.

Keywords: Cd neurotoxicity; GFAP; HES-1; IBA1; Rg1; TNF-α.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects
  • Brain / drug effects
  • Brain / immunology
  • Brain / pathology
  • Cadmium*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / immunology
  • Ginsenosides / pharmacology
  • Ginsenosides / therapeutic use*
  • Intestine, Small / drug effects
  • Intestine, Small / pathology
  • Kidney / drug effects
  • Kidney / pathology
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Microglia / pathology
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Neurotoxicity Syndromes / drug therapy*
  • Neurotoxicity Syndromes / immunology
  • Neurotoxicity Syndromes / pathology
  • Oxidative Stress / drug effects
  • Oxidoreductases / immunology
  • Testis / drug effects
  • Testis / pathology

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Ginsenosides
  • Neuroprotective Agents
  • Cadmium
  • Oxidoreductases
  • ginsenoside Rg1