J Vet Sci.  2010 Mar;11(1):43-50. 10.4142/jvs.2010.11.1.43.

Ethanol extract of Angelica gigas inhibits croton oil-induced inflammation by suppressing the cyclooxygenase - prostaglandin pathway

• Shin S
• Joo SS
• Park D
• Jeon JH
• Kim TK
• Kim JS
• Park SK
• Hwang BY
• Kim YB

• KMID: 1106156
• DOI: http://doi.org/10.4142/jvs.2010.11.1.43

Abstract

The anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG) were investigated in vitro and in vivo using croton oil-induced inflammation models. Croton oil (20 microgram/mL) up-regulated mRNA expression of cyclooxygenase (COX)-I and COX-II in the macrophage cell line, RAW 264.7, resulting in the release of high concentrations of prostaglandin E2 (PGE2). EAG (1~10 microgram/mL) markedly suppressed croton oil-induced COX-II mRNA expression and PGE2 production. Application of croton oil (5% in acetone) to mouse ears caused severe local erythema, edema and vascular leakage, which were significantly attenuated by oral pre-treatment with EAG (50~500 mg/kg). Croton oil dramatically increased blood levels of interleukin (IL)-6 and PGE2 without affecting tumor-necrosis factor (TNF)-alpha and nitric oxide (NO) levels. EAG pre-treatment remarkably lowered IL-6 and PGE2, but did not alter TNF-alpha or NO concentrations. These results indicate that EAG attenuates inflammatory responses in part by blocking the COX-PGE2 pathway. Therefore, EAG could be a promising candidate for the treatment of inflammatory diseases.

Keyword

Angelica gigas; croton oil; cyclooxygenase-II; inflammation; prostaglandin E2

MeSH Terms

Angelica/*immunology
Animals
Cell Line
Cyclooxygenase 1/genetics/*immunology
Cyclooxygenase 2/genetics/*immunology
Dinoprostone/genetics/immunology
Inflammation/drug therapy/enzymology/*immunology
Interleukin-6/blood
Macrophages
Male
Mice
Mice, Inbred ICR
Nitric Oxide/blood
Phytotherapy/*methods
Plant Extracts/*pharmacology/therapeutic use
Plant Roots/immunology
RNA, Messenger/chemistry/genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha/blood

Figure

• 

  Fig. 1 Effects of ethanol extract of Angelica gigas (EAG) (1~10 µg/mL) on the mRNA expression of cyclooxygenase (COX)-I and COX-II in RAW 264.7 cells stimulated with interferon-γ (IFN-γ, 10 IU/mL) and croton oil (CO, 20 µg/mL). +: treated; -: non-treated.

• 

  Fig. 2 Effects of ethanol extract of Angelica gigas (EAG) (1~10 µg/mL) on prostaglandin E2 (PGE2) production from RAW 264.7 cells stimulated with IFN-γ (10 IU/mL) and croton oil (CO, 20 µg/mL). *Significantly different from IFN-γ alone (p < 0.05). †Significantly different from IFN-γ + croton oil (p < 0.05). +: treated;-:non-treat.

• 

  Fig. 3 Effects of 5-day pre-treatment with the ethanol extract of Angelica gigas (EAG) (50~500 mg/kg) on erythema (A), edema (ear weight, B) and vascular (Evan's blue, C) leakage of mouse ears applied with croton oil (CO, 50 µL as 5% in acetone). *Significantly different from vehicle (p < 0.05). †Significantly different from croton oil alone (p < 0.05).

• 

  Fig. 4 HPLC chromatogram (A) and content analysis (B) of decursin and decursinol angelate in ethanol extract of Angelica gigas (EAG) analyzed with a ChemcoPak Chemcobond 5-ODS-H column and eluted with acetonitrile-water-methanol gradient.

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