Sorbus alnifolia protects dopaminergic neurodegeneration in Caenorhabditis elegans

Pharm Biol. 2017 Dec;55(1):481-486. doi: 10.1080/13880209.2016.1251468.

Abstract

Context: The twigs of Sorbus alnifolia (Sieb. et Zucc.) K. Koch (Rosaceae) have been used to treat neurological disorders as a traditional medicine in Korea. However, there are limited data describing the efficacy of S. alnifolia in Parkinson's disease (PD).

Objective: This study was conducted to identify the protective effects of the methanol extracts of S. alnifolia (MESA) on the dopaminergic (DA) neurodegeneration in Caenorhabditis elegans.

Materials and methods: To test the neuroprotective action of MESA, viability assay was performed after 48 h exposure to 1-methyl-4-phenylpyridine (MMP+) in PC12 cells and C. elegans (400 μM and 2 mM of MMP+, respectively). Fluorescence intensity was quantified using transgenic mutants such as BZ555 (Pdat-1::GFP) and and UA57 (Pdat-1::GFP and Pdat-1::CAT-2) to determine MESA's effects on DA neurodegeneration in C. elegans. Aggregation of α-synuclein was observed using NL5901 strain (unc-54p::α-synuclein::YFP). MESA's protective effects on the DA neuronal functions were examined by food-sensing assay. Lifespan assay was conducted to test the effects of MESA on the longevity.

Results: MESA restored MPP+-induced loss of viability in both PC12 cells and C. elegans (85.8% and 54.9%, respectively). In C. elegans, MESA provided protection against chemically and genetically-induced DA neurodegeneration, respectively. Moreover, food-sensing functions were increased 58.4% by MESA in the DA neuron degraded worms. MESA also prolonged the average lifespan by 25.6%. However, MESA failed to alter α-synuclein aggregation.

Discussion and conclusions: These results revealed that MESA protects DA neurodegeneration and recovers diminished DA neuronal functions, thereby can be a valuable candidate for the treatment of PD.

Keywords: Parkinson’s disease; food sensing; lifespan-extension; neurotoxicity; tyrosine hydroxylase.

MeSH terms

  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal / drug effects
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Survival / drug effects
  • Cytoprotection
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Dose-Response Relationship, Drug
  • Feeding Behavior / drug effects
  • Longevity / drug effects
  • Methanol / chemistry
  • Motor Activity / drug effects
  • Nerve Degeneration*
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Phytotherapy
  • Plant Components, Aerial
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Protein Aggregates
  • Rats
  • Solvents / chemistry
  • Sorbus / chemistry*
  • Time Factors
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Neuroprotective Agents
  • Plant Extracts
  • Protein Aggregates
  • Solvents
  • alpha-Synuclein
  • 1-Methyl-4-phenylpyridinium
  • Methanol