AI Article Synopsis

  • Atherosclerosis leads to various cardiovascular diseases, and nutraceuticals are gaining attention for their potential to improve vascular health, but their complex ingredients complicate efficacy evaluation.
  • Researchers created a coculture system using human pluripotent stem cell-derived endothelial cells and hepatocytes to study the vascular-protective effects of nutraceuticals like quercetin and genistein.
  • While quercetin and genistein alone didn’t reduce inflammation, the combination with hepatocytes helped generate bioactive metabolites that reduced inflammatory responses, demonstrating the coculture model's ability to predict nutraceutical efficacy and metabolic interactions.

Article Abstract

Atherosclerosis underlies many cardiovascular and cerebrovascular diseases. Nutraceuticals are emerging as a therapeutic moiety for restoring vascular health. Unlike small-molecule drugs, the complexity of ingredients in nutraceuticals often confounds evaluation of their efficacy in preclinical evaluation. It is recognized that the liver is a vital organ in processing complex compounds into bioactive metabolites. In this work, we developed a coculture system of human pluripotent stem cell-derived endothelial cells (hPSC-ECs) and human pluripotent stem cell-derived hepatocytes (hPSC-HEPs) for predicting vascular-protective effects of nutraceuticals. To validate our model, two compounds (quercetin and genistein), known to have anti-inflammatory effects on vasculatures, were selected. We found that both quercetin and genistein were ineffective at suppressing inflammatory activation by interleukin-1β owing to limited metabolic activity of hPSC-ECs. Conversely, hPSC-HEPs demonstrated metabolic capacity to break down both nutraceuticals into primary and secondary metabolites. When hPSC-HEPs were cocultured with hPSC-ECs to permit paracrine interactions, the continuous turnover of metabolites mitigated interleukin-1β stimulation on hPSC-ECs. We observed significant reductions in inflammatory gene expressions, nuclear translocation of nuclear factor κB, and interleukin-8 production. Thus, integration of hPSC-HEPs could accurately reproduce systemic effects involved in drug metabolism in vivo to unravel beneficial constituents in nutraceuticals. This physiologically relevant endothelial-hepatic platform would be a great resource in predicting the efficacy of complex nutraceuticals and mechanistic interrogation of vascular-targeting candidate compounds. Stem Cells Translational Medicine 2017;6:851-863.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442778PMC
http://dx.doi.org/10.5966/sctm.2016-0129DOI Listing

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