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Equol, a Blood–Brain Barrier Permeable Gut Microbial Metabolite of Dietary Isoflavone Daidzein, Exhibits Neuroprotective Effects against Neurotoxins Induced Toxicity in Human Neuroblastoma SH-SY5Y Cells and Caenorhabditis elegans

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Abstract

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.

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Abbreviations

CNS:

central nervous system

CTG:

CellTiter-Glo 2.0 cell viability assay

DAI:

daidzein

EQL:

s-equol

ERβ:

estrogen receptor β

EST:

17β-estradiol

GEN:

genistein

LPS:

lipopolysaccharide

MPP+ :

1-methyl-4-phenylpyridinium

6-OHDA:

6-hydroxydopamine

PD:

Parkinson’s disease

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Acknowledgements

S.J. was supported by a fellowship from the George and Anne Ryan Institute for Neuroscience. Spectroscopic data were obtained from instruments located in the Rhode Island-IDeA Network for Excellence in Biomedical Research core facility supported by Grant # P20GM103430 from the National Institute of General Medical Sciences of the National Institutes of Health.

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Authors and Affiliations

  1. Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA

    Shelby L. Johnson, Hang Ma & Navindra P. Seeram

  2. George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI, 02881, USA

    Shelby L. Johnson, Paula Grammas, Hang Ma & Navindra P. Seeram

  3. Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA

    Hyun Y. Park & Dhiraj A. Vattem

  4. School of Applied Health Sciences and Wellness, Ohio University, Athens, OH, 45701, USA

    Hyun Y. Park & Dhiraj A. Vattem

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  1. Shelby L. Johnson
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Correspondence to Hang Ma or Navindra P. Seeram.

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Johnson, S.L., Park, H.Y., Vattem, D.A. et al. Equol, a Blood–Brain Barrier Permeable Gut Microbial Metabolite of Dietary Isoflavone Daidzein, Exhibits Neuroprotective Effects against Neurotoxins Induced Toxicity in Human Neuroblastoma SH-SY5Y Cells and Caenorhabditis elegans. Plant Foods Hum Nutr 75, 512–517 (2020). https://doi.org/10.1007/s11130-020-00840-0

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