Osthole Protects Bone Marrow-Derived Neural Stem Cells from Oxidative Damage through PI3K/Akt-1 Pathway

Neurochem Res. 2017 Feb;42(2):398-405. doi: 10.1007/s11064-016-2082-y. Epub 2016 Oct 12.

Abstract

In recent years, neural stem cell (NSC) transplantation has been widely explored as a treatment for neurodegenerative diseases. NSCs are special cells that have some capacity for self-renewal and the potential to differentiate into multiple cell types. However, the inflammatory environment of diseased tissue is not conducive to the survival of transplanted cells. Osthole (Ost) is a principal bioactive component of Fructus Cnidii, Radix Angelicae Pubescentis and other traditional Chinese medicines. Ost has a wide range of pharmacological activities, such as anti-inflammation, immunomodulation, and neuroprotection. In the present study, we assessed the protective effects of Ost on bone marrow-derived-NSCs (BM-NSCs) against injury induced by hydrogen peroxide (H2O2). BM-NSCs were pre-treated with different doses of Ost and treated with H2O2. The cell counting kit-8 (CCK-8) method and lactate dehydrogenase (LDH) leakage assay were used to determine cell viability. Using the TUNEL assay and RT-PCR, we evaluated the effect of Ost on cell apoptosis. The results showed that Ost had protective effects against H2O2-induced cell damage, and the number of apoptotic cells was significantly decreased in the Ost pre-treated groups compared to the H2O2 group. The expression ratio of Bax/Bcl-2 mRNA was also decreased. Furthermore, western blotting was used to analyze levels of proteins related to PI3K/Akt-1 signaling pathway, and results indicated that ost can increase p-Akt and PI3K. Our findings suggested that Ost protects BM-NSCs against oxidative stress injury, and it can be used to improve the inflammatory environment of neurodegenerative diseases so and promote the survival rate of transplanted NSCs.

Keywords: Apoptosis; Neural stem cells; Osthole; Oxidative stress; Phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt-1) pathway.

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Coumarins / pharmacology*
  • Cytoprotection / drug effects
  • Cytoprotection / physiology*
  • Dose-Response Relationship, Drug
  • Hydrogen Peroxide / toxicity
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Coumarins
  • Hydrogen Peroxide
  • Phosphatidylinositol 3-Kinases
  • Akt1 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • osthol