Nutr Res Pract.  2015 Aug;9(4):364-369. 10.4162/nrp.2015.9.4.364.

Anti-inflammatory and antioxidant effects of umbelliferone in chronic alcohol-fed rats

• Sim MO
• Lee HI
• Ham JR
• Seo KI
• Kim MJ
• Lee MK

• KMID: 2313852
• DOI: http://doi.org/10.4162/nrp.2015.9.4.364

Abstract

BACKGROUND/OBJECTIVES
Inflammation is associated with various types of acute and chronic alcohol liver diseases. In this study, we examined whether umbelliferone (7-hydroxycoumarin, UF) ameliorates chronic alcohol-induced liver damage by modulating inflammatory response and the antioxidant system.
METHODS
Rats were fed a Liber-Decarli liquid diet containing 5% alcohol with or without UF (0.05 g/L) for 8 weeks, while normal rats received an isocaloric carbohydrate liquid diet.
RESULTS
Chronic alcohol intake significantly increased serum tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 levels and decreased interleukin 10 level; however, UF supplementation reversed the cytokines related to liver damage. UF significantly suppressed hepatic lipopolysaccharide binding protein, toll-like receptor 4 (TLR4), nuclear factor kappa B, and TNF-alpha gene expression increases in response to chronic alcohol intake. Masson's trichrome staining revealed that UF improved mild hepatic fibrosis caused by alcohol, and UF also significantly increased the mRNA expressions and activities of superoxide dismutase and catalase in liver, and thus, decreased lipid peroxide and mitochondrial hydrogen peroxide levels.
CONCLUSIONS
The findings of this study indicate that UF protects against alcohol-induced liver damage by inhibiting the TLR4 signaling pathway and activating the antioxidant system.

Keyword

Alcohol; antioxidant; inflammation; TLR4 signaling; umbelliferone

MeSH Terms

Animals
Antioxidants*
Carrier Proteins
Catalase
Cytokines
Diet
Fibrosis
Gene Expression
Hydrogen Peroxide
Inflammation
Interleukin-10
Interleukin-6
Liver
Liver Diseases
NF-kappa B
Rats*
RNA, Messenger
Superoxide Dismutase
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha
Antioxidants
Carrier Proteins
Catalase
Cytokines
Hydrogen Peroxide
Interleukin-10
Interleukin-6
NF-kappa B
RNA, Messenger
Superoxide Dismutase
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Chemical structures of UF (Umbelliferone).

• 

  Fig. 2 Effects of umbelliferone on serum TNF-α (A), IL-6 (B), IL-10 (C), IFNγ and IL-1β (D) levels in chronic alcohol-fed rats. Values are expressed as the means ± SE. Values are significantly different between groups according to Student's t-test. *P < 0.05, **P < 0.01 NC : Al, ##P < 0.01 Al : Al-UF.

• 

  Fig. 3 Effects of umbelliferone on hepatic inflammatory genes expression (A) and Masson's trichrome stain (B) in chronic alcohol-fed rats. Values are expressed as the means ± SE. Values are significantly different between groups according to Student's t-test. * P < 0.05, *** P < 0.001 NC : Al, # P < 0.05, ### P < 0.001 Al : Al-UF. Relative mRNA expression of each gene was normalized to the GAPDH and compared with NC level. White arrows indicate collagen deposition (200× magnification).

• 

  Fig. 4 Effects of umbelliferone on hepatic antioxidant enzyme genes expression in chronic alcohol-fed rats. Values are expressed as the means ± SE. Values are significantly different between groups according to Student's t-test. *P < 0.05, **P < 0.01, ***P < 0.001 NC : Al, #P < 0.05, ##P < 0.01 Al : Al-UF. Relative mRNA expression of each gene was normalized to the GAPDH and compared with NC level.

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