Dietary squalene supplementation improves DSS-induced acute colitis by downregulating p38 MAPK and NFkB signaling pathways

Mol Nutr Food Res. 2015 Feb;59(2):284-92. doi: 10.1002/mnfr.201400518. Epub 2014 Dec 12.


Scope: Squalene is a polyunsaturated triterpene, which has exhibited anticancer and antioxidant activities among others. We investigated dietary squalene supplementation effect on an acute colitis model induced by dextran sulfate sodium (DSS) in C57BL/6 mice.

Methods and results: Mice were fed from weaning with squalene at 0.02% and 0.1%. After 4 weeks, mice were exposed to 3% DSS for 5 days developing acute colitis. After DSS removal (5 days), colons were histological and biochemically processed. Our results showed that dietary squalene treatment exerts anti-inflammatory action in DSS-induced acute colitis. Western blot revealed that squalene downregulated COX-2 (where COX is cyclooxygenase) and inducible nitric oxide synthase system by inhibition of mitogen-activated protein kinase p38 and the nuclear factor-kappa B signaling pathways, preventing an increase in the cytokines levels. Under our experimental conditions, STAT3 and FOXP3 (where FOXP3 is forkhead box P3) were not modified and the transcriptional regulation of antioxidant and/or detoxifying enzymes, Nrf2 (where Nrf2 is nuclear factor (erythroid-derived 2)-like 2), was reduced in DSS-induced colitis. However, any change could be observed after squalene supplementation.

Conclusion: Squalene was able to improve the oxidative events and returned proinflammatory proteins expression to basal levels probably through p38 mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways. However, supplementary studies are needed in order to provide a basis for developing a new dietary supplementation strategy.

Keywords: Dextran sulfate sodium; MAPK; NFkB; Squalene; Ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colon / drug effects
  • Colon / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dextran Sulfate / adverse effects
  • Dietary Supplements*
  • Down-Regulation
  • Female
  • Interleukin-1beta / blood
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Signal Transduction*
  • Squalene / pharmacology*
  • Tumor Necrosis Factor-alpha / blood
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Anti-Inflammatory Agents
  • Antioxidants
  • Interleukin-1beta
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Squalene
  • Dextran Sulfate
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • p38 Mitogen-Activated Protein Kinases