Resveratrol Prevents the Cellular Damages Induced by Monocrotophos via PI3K Signaling Pathway in Human Cord Blood Mesenchymal Stem Cells

Mol Neurobiol. 2018 Nov;55(11):8278-8292. doi: 10.1007/s12035-018-0986-z. Epub 2018 Mar 10.


The role of resveratrol (RV) as a neuroprotectant is well recognized, and cellular molecules involved in imparting the physiological effect have been well illustrated. However, some ambiguity still prevails as the specific receptor, and downstream signaling molecules are not yet clearly stated. So, we investigated the signaling pathway(s) involved in its cellular protection in the human umbilical cord blood mesenchymal stem cell (hUCB-MSC) derived neuronal cells. The mesenchymal stem cells were exposed to various concentrations (10, 100, 1000 μM) of monocrotophos (MCP), a known developmental neurotoxic organophosphate pesticide, for a period of 24 h. The MAPK signaling pathways (JNK, p38, and ERK) known to be associated with MCP-induced damages were also taken into consideration to identify the potential connection. The biological safe dose of RV (10 μM) shows a significant restoration in the MCP-induced alterations. Under the specific growth conditions, RV exposure was found to promote neuronal differentiation in the hUCB-MSCs. The exposure of cells to a specific pharmacological inhibitor (LY294002) of PI3K confirms the significant involvement of PI3K-mediated pathway in the ameliorative responses of RV against MCP exposure. Our data identifies the substantial role of RV in the restoration of MCP-induced cellular damages, thus proving to have a therapeutic potential against organophosphate pesticide-induced neurodegeneration.

Keywords: Human umbilical cord blood mesenchymal stem cells; Monocrotophos; Neuroprotection; PI3K; Resveratrol.

MeSH terms

  • Adult
  • Annexin A5
  • Antioxidants / pharmacology
  • Biomarkers / metabolism
  • Cell Death / drug effects
  • Cytoprotection / drug effects
  • Fetal Blood / cytology*
  • Fluorescein-5-isothiocyanate / metabolism
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology*
  • Mesenchymal Stem Cells / ultrastructure
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Models, Biological
  • Monocrotophos / toxicity*
  • Neurons / drug effects
  • Neurons / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Propidium / metabolism
  • Protective Agents / pharmacology
  • Reactive Oxygen Species / metabolism
  • Resveratrol / pharmacology*
  • Signal Transduction*


  • Annexin A5
  • Antioxidants
  • Biomarkers
  • Protective Agents
  • Reactive Oxygen Species
  • Propidium
  • Monocrotophos
  • Phosphatidylinositol 3-Kinases
  • Fluorescein-5-isothiocyanate
  • Resveratrol