Anti-α-synuclein Toxicity and Anti-neurodegenerative Role of Chrysin in Transgenic Caenorhabditis elegans Models of Parkinson's Disease

ACS Chem Neurosci. 2022 Feb 16;13(4):442-453. doi: 10.1021/acschemneuro.1c00548. Epub 2022 Feb 4.

Abstract

Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the central nervous system in the elderly, causing motor impediments and cognitive dysfunctions. Dopaminergic (DA) neuron degeneration and α-synuclein (α-Syn) accumulation in substantia nigra pars compacta are the major contributors to this disease. At present, PD remains untreatable with a huge burden on the quality of life. Therefore, we attempt to explore novel treatment strategies by detecting effective drugs that stop or arrest PD's progression via modifying disease-specific pathways. Chrysin is a flavonoid derived from passion flowers and possesses anti-cancer, anti-inflammatory, anti-oxidant, and anti-depression properties. In the present study, we assessed the neuroprotective potential of chrysin in transgenic Caenorhabditis elegans models of PD. We observed that chrysin reduced the aggregative toxicity of α-Syn and diminished DA neuron degeneration induced by 6-hydroxydopamine (6-OHDA), reduced food-sensing behavioral disabilities, and expanded the nematodes' lifespan. Moreover, chrysin augmented the ubiquitin-like proteasome and superoxide dismutase activities in transgenic C. elegans models. Further, we observed the anti-oxidative role of chrysin by reducing the internal cellular reactive oxygen species levels in 6-OHDA-intoxicated C. elegans. Together, these findings supported chrysin as a possible treatment for PD and encouraged further investigation of chrysin's mechanism of action as a neuroprotective medicine in the future.

Keywords: 6-hydroxydopamine; Caenorhabditis elegans; Parkinson’s disease; chrysin; oxidative stress; proteasome; α-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Disease Models, Animal
  • Dopaminergic Neurons / metabolism
  • Flavonoids* / pharmacology
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / metabolism
  • Quality of Life
  • alpha-Synuclein* / metabolism

Substances

  • Flavonoids
  • alpha-Synuclein
  • chrysin