Korean J Physiol Pharmacol.  2015 May;19(3):269-274. 10.4196/kjpp.2015.19.3.269.

Short-term Treatment of Daumone Improves Hepatic Inflammation in Aged Mice

• Park JH
• Ha H

• KMID: 1791429
• DOI: http://doi.org/10.4196/kjpp.2015.19.3.269

Abstract

Chronic inflammation has been proposed as one of the main molecular mechanisms of aging and age-related diseases. Although evidence in humans is limited, short-term calorie restriction (CR) has been shown to have anti-inflammatory effects in aged experimental animals. We reported on the long-term treatment of daumone, a synthetic pheromone secreted by Caenorhabditis elegans in an energy deficient environment, extends the life-span and attenuates liver injury in aged mice. The present study examined whether late onset short-term treatment of daumone exerts anti-inflammatory effects in the livers of aged mice. Daumone was administered orally at doses of 2 or 20 mg/kg/day for 5 weeks to 24-month-old male C57BL/6J mice. Increased liver macrophage infiltration and gene expression of proinflammatory cytokines in aged mice were significantly attenuated by daumone treatment, suggesting that short-term oral administration of daumone may have hepatoprotective effects. Daumone also dose-dependently suppressed tumor necrosis factor-alpha (TNF-alpha)-induced nuclear factor-kappaB (NF-kappaB) phosphorylation in HepG2 cells. The present data demonstrated that short-term treatment of daumone has anti-inflammatory effects in aged mouse livers possibly through suppression of NF-kappaB signaling and suggest that daumone may become a lead compound targeting aging and age-associated diseases.

Keyword

Aging; Hep G2 cells; Inflammation; Liver; Pheromones

MeSH Terms

Administration, Oral
Aging
Animals
Caenorhabditis elegans
Child, Preschool
Cytokines
Gene Expression
Hep G2 Cells
Humans
Inflammation*
Liver
Macrophages
Male
Mice*
NF-kappa B
Pheromones
Phosphorylation
Tumor Necrosis Factor-alpha
Cytokines
NF-kappa B
Pheromones
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Daumone treatment ameliorated proinflammatory cytokines in the livers of old mice. (A) Macrophage infiltration established by F4/80 immunohistochemical staining in the liver tissue. Brown, F4/80; Blue, hematoxylin. (B) F4/80 positive area was quantified by Image Pro and presented as the mean±SE of 3 mice/group. (C~G) Liver mRNA levels were determined by real-time qRT-PCR and are presented as the mean±SE of 10 mice/group. *p<0.05 vs. Y, †p<0.05 vs. O. Y, young mice; O, old mice. Magnification, 200x; scale bar, 50 µm.

• 

  Fig. 2 Daumone attenuated NF-κB signaling in Hep G2 cells. The cells were pretreated with daumone for 6 hours before the addition of TNF-α (5 ng/ml) for 1 hour. Protein levels of (B) nuclear factor-κB (NF-κB)-p65 and (C) IκBα phosphorylation were determined by Western blot analysis. (A) Presented immunoblots. Data are presented as the mean±SE of 4 experiments. *p<0.05 vs. control, †p<0.05 vs. TNF-α only. p65, nuclear factor-κB-p65; IκB, inhibitor of nuclear factor-κB.

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