Sulforaphane reduces lipopolysaccharide-induced proinflammatory markers in hippocampus and liver but does not improve sickness behavior

Nutr Neurosci. 2017 Apr;20(3):195-202. doi: 10.1080/1028415X.2015.1103463. Epub 2015 Dec 7.

Abstract

Objectives: Acute peripheral infection is associated with central and peripheral inflammation, increased oxidative stress, and adaptive sickness behaviors. Sulforaphane (SFN) activates the transcription factor nuclear factor E2-related factor 2 (Nrf2), which upregulates antioxidant genes and lowers inflammation. The objectives of this study were to examine the effects of SFN on proinflammatory markers and Nrf2 target genes in hippocampus and liver of mice challenged with lipopolysaccharide (LPS), and to evaluate sickness response following the LPS immune challenge.

Methods: Adult Balb/c mice received SFN (50 mg/kg, i.p.) for 3 days before being injected i.p. with LPS (1 µg) to mimic an acute peripheral infection. Sickness behaviors were measured at baseline and 6 hours after LPS. Expression of proinflammatory mediators and antioxidant genes were analyzed in hippocampus and liver 6 hours after LPS.

Results: SFN elevated Nrf2 target genes and reduced expression of proinflammatory mediators in hippocampus and liver, but did not improve LPS-induced sickness response.

Discussion: The nutritional bioactive SFN displays potent anti-inflammatory properties against LPS-induced inflammation in vitro, but has not been previously assessed in vivo during peripheral infection as a potential treatment for sickness behavior. These data indicate that SFN has anti-inflammatory effects in both brain and periphery, but that longer exposure to SFN may be necessary to reduce sickness behavior.

Keywords: Lipopolysaccharide; Neuroinflammation; Peripheral infection; Sickness behavior; Sulforaphane.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Anticarcinogenic Agents / therapeutic use
  • Antioxidant Response Elements / drug effects
  • Antioxidants / therapeutic use
  • Behavior, Animal / drug effects
  • Biomarkers / metabolism
  • Disease Models, Animal*
  • Endotoxins / toxicity
  • Energy Intake / drug effects
  • Gene Expression Regulation / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / immunology
  • Hippocampus / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / immunology
  • Hypothalamus / metabolism
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Injections, Intraperitoneal
  • Isothiocyanates / administration & dosage
  • Isothiocyanates / therapeutic use*
  • Liver / drug effects
  • Liver / immunology
  • Liver / innervation
  • Liver / metabolism
  • Male
  • Mice, Inbred BALB C
  • Neurogenic Inflammation / immunology
  • Neurogenic Inflammation / prevention & control*
  • Neurons / drug effects*
  • Neurons / immunology
  • Neurons / metabolism
  • Organ Specificity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • Antioxidants
  • Biomarkers
  • Endotoxins
  • Inflammation Mediators
  • Isothiocyanates
  • endotoxin, Escherichia coli
  • sulforafan