Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP‑induced Parkinson's disease models in vitro and in vivo

Mol Med Rep. 2018 Dec;18(6):4913-4921. doi: 10.3892/mmr.2018.9509. Epub 2018 Sep 25.

Abstract

The pathological alterations of Parkinson's disease (PD) predominantly manifest as a loss of dopaminergic neurons in the substantia nigra, which may be caused by oxidative stress damage. Proanthocyanidins (PCs) are a class of compounds found in various plants, which have significant antioxidant and free radical‑scavenging activity. The present study investigated the protective effects and underlying mechanisms of PCs in a 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP)‑induced PD model in vitro and in vivo. MTT assays were used to detect cell viability, and flow cytometry and TUNEL assays were used to detect cell apoptosis. Mitochondrial membrane potential (MMP) alterations were investigated using a JC‑1 MMP Assay kit. The pole test was used to measure motor behavior in a mouse model of PD. Levels of reactive oxygen species (ROS) were measured using the fluorescent probe, 2',7'‑dichlorodihydrofluorescein diacetate. Immunohistochemistry and western blotting were performed to detect the expression levels of proteins associated with PD. In vitro, it was demonstrated that in MPTP‑treated PC12 cells, PCs increased cell viability and reduced cell apoptosis in a dose‑dependent manner. In vivo, it was revealed that PC treatment inhibited striatal dopamine depletion, which resulted in significant improvements in PD‑like movement impairment. Reactive oxygen species (ROS) production and MPTP‑induced apoptosis were also inhibited. Furthermore, the results demonstrated that the neuroprotective activity of PCs may be mediated via the inhibition of ROS generation, as well as modulation of c‑Jun N‑terminal kinase activation. Taken together, these data revealed that PCs may exert neuroprotective effects in in vivo and in vitro PD models, and may have potential in the prevention or treatment of PD.

Keywords: Parkinson's disease; proanthocyanidins; MPTP; reactiveoxygen species; apoptosis.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / adverse effects*
  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Male
  • Matrix Metalloproteinases / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Parkinson Disease / etiology*
  • Parkinson Disease / metabolism*
  • Proanthocyanidins / pharmacology*
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction*

Substances

  • Neuroprotective Agents
  • Proanthocyanidins
  • Reactive Oxygen Species
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • JNK Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinases