Emerging data support that plant food based
isoflavones have ameliorating effects on a variety of
neurodegenerative diseases including
Parkinson's disease (PD). Our previous investigation revealed that dietary
isoflavones including
genistein (GEN),
daidzein (DAI), and
equol (EQL; a gut microbial metabolite of DAI) showed promising blood-brain barrier permeability and anti-neuroinflammatory activity in murine microglial BV2 cells. However, the
neuroprotective effects of EQL against
neurotoxins induced toxicity in PD related models remains unclear. Herein, EQL, along with GEN and DAI, were evaluated for their cytoprotective effect in a non-contact co-culture model with LPS-BV2-conditioned media and human
neuroblastoma SH-SY5Y cells. In addition, their
neuroprotective effects against PD related
neurotoxins including
6-hydroxydopamine (6-OHDA) and
1-methyl-4-phenylpyridinium (MPP+) induced cytotoxicity were evaluated in SH-SY5Y cells. Furthermore, EQL was evaluated for its
neuroprotective effects against MPP+ induced neurotoxicity using in vivo PD model including Caenorhabditis elegans lifespan assay. DAI (10 μM) and EQL (10 and 20 μM) showed cytoprotective effects by decreasing LPS-BV2-conditioned media induced cytotoxicity in SH-SY5Y cells by 29.2, 32.4 and 27.2%, respectively. EQL (10 and 20 μM) also showed
neuroprotective effects by decreasing
6-OHDA and MPP+ induced cytotoxicity in SH-SY5Y cells by 30.6-34.5 and 17.9-18.9%, respectively. Additionally, data from the in vivo assay supported EQL's
neuroprotective effect as it increases survival of C. elegans exposed to MPP+ from 72 to 108 h. Our findings support a growing body of evidence of the
neuroprotective effects of dietary
isoflavones and further studies are warranted to elucidate their mechanisms of action.