Falcarinol Is a Potent Inducer of Heme Oxygenase-1 and Was More Effective than Sulforaphane in Attenuating Intestinal Inflammation at Diet-Achievable Doses

Oxid Med Cell Longev. 2018 Oct 21;2018:3153527. doi: 10.1155/2018/3153527. eCollection 2018.

Abstract

Nuclear factor- (erythroid-derived 2) like 2 (Nrf2) is a transcription factor that regulates the expression of a battery of antioxidant, anti-inflammatory, and cytoprotective enzymes including heme oxygenase-1 (Hmox1, Ho-1) and NADPH:quinone oxidoreductase-1 (Nqo1). The isothiocyanate sulforaphane (SF) is widely understood to be the most effective natural activator of the Nrf2 pathway. Falcarinol (FA) is a lesser studied natural compound abundant in medicinal plants as well as dietary plants from the Apiaceae family such as carrot. We evaluated the protective effects of FA and SF (5 mg/kg twice per day in CB57BL/6 mice) pretreatment for one week against acute intestinal and systemic inflammation. The phytochemical pretreatment effectively reduced the magnitude of intestinal proinflammatory gene expression (IL-6, Tnfα/Tnfαr, Infγ, STAT3, and IL-10/IL-10r) with FA showing more potency than SF. FA was also more effective in upregulating Ho-1 at mRNA and protein levels in both the mouse liver and the intestine. FA but not SF attenuated plasma chemokine eotaxin and white blood cell growth factor GM-CSF, which are involved in the recruitment and stabilization of first-responder immune cells. Phytochemicals generally did not attenuate plasma proinflammatory cytokines. Plasma and intestinal lipid peroxidation was also not significantly changed 4 h after LPS injection; however, FA did reduce basal lipid peroxidation in the mesentery. Both phytochemical pretreatments protected against LPS-induced reduction in intestinal barrier integrity, but FA additionally reduced inflammatory cell infiltration even below negative control.

MeSH terms

  • Animals
  • Cytokines / blood
  • Diet*
  • Diynes / chemistry
  • Diynes / pharmacology
  • Diynes / therapeutic use*
  • Enzyme Induction / drug effects
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fatty Alcohols / chemistry
  • Fatty Alcohols / pharmacology
  • Fatty Alcohols / therapeutic use*
  • Gene Expression Regulation / drug effects
  • Heme Oxygenase-1 / biosynthesis*
  • Inflammation / drug therapy*
  • Inflammation / enzymology*
  • Inflammation / genetics
  • Inflammation / pathology
  • Intestines / pathology*
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology
  • Isothiocyanates / therapeutic use*
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism
  • Phytochemicals / pharmacology
  • Phytochemicals / therapeutic use
  • Signal Transduction / drug effects
  • Sulfoxides

Substances

  • Cytokines
  • Diynes
  • Fatty Alcohols
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Phytochemicals
  • Sulfoxides
  • falcarinol
  • Heme Oxygenase-1
  • sulforaphane