Ginkgo Biloba L. Extract Reduces H2O2-Induced Bone Marrow Mesenchymal Stem Cells Cytotoxicity by Regulating Mitogen-Activated Protein Kinase (MAPK) Signaling Pathways and Oxidative Stress

Med Sci Monit. 2018 May 14:24:3159-3167. doi: 10.12659/MSM.910718.

Abstract

BACKGROUND The oxidative stress environment of pathological tissue has an adverse effect on the survival of bone marrow mesenchymal stem cells (BMSCs) transplantation. Ginkgo biloba L. extract (EGB) has a potent antioxidant effect. In this research, we assessed the protective effects of EGB and EGB-Containing Serum (EGB CS) on BMSCs against injury induced by hydrogen peroxide (H2O2). MATERIAL AND METHODS BMSCs were pretreated with EGB or EGB CS and treated with H2O2. The cell counting kit-8 (CCK-8) method was utilized to detect cell viability. The DCFH-DA Fluorescent Kit method was used to detect intracellular ROS level. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and (CAT) were determined. The Hoechst staining assay and qRT-PCR assay were utilized to evaluate the effect of EGB on cell apoptosis. Mitogen-activated protein kinases (MAPKs) signaling pathway were detected by western blot analysis. RESULTS Compared to the H2O2 group, the number of apoptotic cells in the EGB and EGB CS pretreated groups significantly decreased. The mRNA expression ratio of Bax/Bcl-2 was also decreased. EGB and EGB CS can reduce the production of ROS in BMSCs exposed to H2O2. SOD, GSH-Px and CAT activities were significantly higher compared with those with H2O2 group. Furthermore, EGB or EGB CS pretreatment decreased the protein levels of p-p38MAPK and p-JNK in BMSCs compared to the H2O2 group. CONCLUSIONS Our findings suggested that EGB and EGB CS have protective effect on BMSCs against oxidative stress injury and increase the survival rate of BMSCs transplantation by regulating p38MAPK and JNK signaling.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Ginkgo biloba
  • Hydrogen Peroxide / toxicity*
  • Intracellular Space / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / enzymology*
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology*
  • Oxidative Stress / drug effects*
  • Plant Extracts / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Serum
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Biomarkers
  • Plant Extracts
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • Ginkgo biloba extract
  • Hydrogen Peroxide