Açaí (Euterpe oleracea Mart.) as a Potential Anti-neuroinflammatory Agent: NLRP3 Priming and Activating Signal Pathway Modulation

Mol Neurobiol. 2021 Sep;58(9):4460-4476. doi: 10.1007/s12035-021-02394-x. Epub 2021 May 22.

Abstract

Neurological disorders have been demonstrated to be associated with mitochondrial dysfunction. This impairment may lead to oxidative stress and neuroinflammation, specifically promoted by NLRP3 expression. Açaí (Euterpe oleracea Mart.) has been studied in this field, since it presents important biological activities. We investigated açaí extract's anti-neuroinflammatory capacity, through NLRP3 inflammasome modulation. Microglia (EOC 13.31) were exposed to LPS and nigericin, as agents of inflammatory induction, and treated with açaí extract. Additionally, we used lithium (Li) as an anti-inflammatory control. Three different experiment models were conducted: (1) isolated NLRP3 priming and activation signals; (2) combined NLRP3 priming and activation signals followed by açaí extract as a therapeutic agent; and (3) combined NLRP3 priming and activation signals with açaí extract as a preventive agent. Cells exposed to 0.1 µg/mL of LPS presented high proliferation and increased levels of NO, and ROS, while 0.1 µg/mL of açaí extract was capable to reduce cellular proliferation and recover levels of NO and ROS. Primed and activated cells presented increased levels of NLRP3, caspase-1, and IL-1β, while açaí, Li, and orientin treatments reversed this impairment. We found that açaí, Li, and orientin were effective prophylactic treatments. Preventative treatment with Li and orientin was unable to avoid overexpression of IL-1β compared to the positive control. However, orientin downregulated NLRP3 and caspase-1. Lastly, primed and activated cells impaired ATP production, which was prevented by pre-treatment with açaí, Li, and orientin. In conclusion, we suggest that açaí could be a potential agent to treat or prevent neuropsychiatric diseases related to neuroinflammation.

Keywords: Bioactive potential; Microglia cells; Natural product; Neuroinflammation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Caspase 1 / metabolism
  • Cell Proliferation / drug effects
  • Euterpe*
  • Inflammasomes / drug effects
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Nigericin / pharmacology
  • Nitric Oxide / metabolism
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Plant Extracts
  • Reactive Oxygen Species
  • Nitric Oxide
  • Caspase 1
  • Nigericin