Ginsenoside F1 suppresses astrocytic senescence-associated secretory phenotype

Chem Biol Interact. 2018 Mar 1;283:75-83. doi: 10.1016/j.cbi.2018.02.002. Epub 2018 Feb 3.

Abstract

Senescence is one of the hallmarks of aging and identified as a potential therapeutic target in the treatment of aging and aging-related diseases. Senescent cells accumulate with age in a variety of human tissues where they develop a complex senescence-associated secretory phenotype (SASP). SASP in brain could contribute to age-related inflammation and chronic neurodegenerative diseases. We confirmed that senescent astrocytes express a characteristic of SASP in vitro by human cytokine antibody array. Ginsenoside F1 suppresses the SASP from astrocytes induced by d-galactose via suppressing p38MAPK-dependent NF-κB activity. A specific inhibitor of p38MAPK, SB203580 significantly decreased the secretion of IL-6 and IL-8, the major components of SASPs. Additionally, treatment of senescent astrocytes with NF-κB inhibitor, BAY 11-7092, also suppressed the secretion of IL-6 and IL-8, suggesting NF-κB was required for SASP. Importantly, conditioned media from senescent astrocytes promoted the migration of glioblastoma cells, such as U373-MG, U251-MG and U87-MG assessed by scratch wound healing. This migration was significantly decreased by F1 treatment in senescent astrocytes. Interestingly, IL-8, the main mediator regulating glioblastoma cell invasion, was suppressed in both transcriptional and protein level. Herein, we propose ginsenoside F1 as a potential therapeutic strategy for reducing the deleterious contribution of senescent astrocytes in aged brain and related diseases.

Keywords: Astrocytic senescent; Ginsenoside F1; Glioblastoma; NF-κB; SASP; p38MAPK.

MeSH terms

  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cellular Senescence / drug effects*
  • DNA Repair / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Ginsenosides / pharmacology*
  • Humans
  • Imidazoles / pharmacology
  • Interleukin-6 / analysis
  • Interleukin-6 / metabolism
  • Interleukin-8 / analysis
  • Interleukin-8 / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Pyridines / pharmacology
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Ginsenosides
  • Imidazoles
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Pyridines
  • ginsenoside F1
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580