Int. J. Mol. Sci. 2013, 14(6), 10926-10943; doi:10.3390/ijms140610926
Article

Mechanisms by Which Licochalcone E Exhibits Potent Anti-Inflammatory Properties: Studies with Phorbol Ester-Treated Mouse Skin and Lipopolysaccharide-Stimulated Murine Macrophages

1 Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea 2 WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea 3 Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea
* Author to whom correspondence should be addressed.
Received: 29 March 2013; in revised form: 15 May 2013 / Accepted: 15 May 2013 / Published: 24 May 2013
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Abstract: In this study we found that licochalcone E (LicE), a recently isolated retrochalcone from Glycyrrhiza inflata, exhibits potent anti-inflammatory effects in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage models. Topical application of LicE (0.5–2 mg) effectively inhibited TPA-induced (1) ear edema formation; (2) phosphorylation of stress-activated protein kinase/c-Jun-N-terminal kinase (SAPK/JNK), c-Jun, and extracellular signal regulated kinase 1/2; and (3) expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins in mouse skin. The treatment of RAW 264.7 cells with LicE (2.5–7.5 μmol/L) induced a profound reduction in LPS-induced (1) release of NO and prostaglandin E2; (2) mRNA expression and secretion of interleukin (IL)-6, IL-1β and tumor necrosis factor-α; (3) promoter activity of iNOS and COX-2 and expression of their corresponding mRNAs and proteins; (4) activation of AKT, p38 mitogen activated protein kinase (MAPK), SAPK/JNK and c-Jun; (5) phosphorylation of inhibitor of κB (IκB) kinase-αβ and IκBα, degradation of IκBα, translocation of p65 (RelA) to the nucleus and transcriptional activity of nuclear factor (NF)-κB; and (6) transcriptional activity of activator protein (AP)-1. These results indicate that the LicE inhibition of NF-κB and AP-1 transcriptional activity through the inhibition of AKT and MAPK activation contributes to decreases in the expression of pro-inflammatory cytokines and the inducible enzymes iNOS and COX-2.
Keywords: licochalcone E; inflammation; mouse skin

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MDPI and ACS Style

Lee, H.N.; Cho, H.J.; Lim, D.Y.; Kang, Y.-H.; Lee, K.W.; Park, J.H.Y. Mechanisms by Which Licochalcone E Exhibits Potent Anti-Inflammatory Properties: Studies with Phorbol Ester-Treated Mouse Skin and Lipopolysaccharide-Stimulated Murine Macrophages. Int. J. Mol. Sci. 2013, 14, 10926-10943.

AMA Style

Lee HN, Cho HJ, Lim DY, Kang Y-H, Lee KW, Park JHY. Mechanisms by Which Licochalcone E Exhibits Potent Anti-Inflammatory Properties: Studies with Phorbol Ester-Treated Mouse Skin and Lipopolysaccharide-Stimulated Murine Macrophages. International Journal of Molecular Sciences. 2013; 14(6):10926-10943.

Chicago/Turabian Style

Lee, Han N.; Cho, Han J.; Lim, Do Y.; Kang, Young-Hee; Lee, Ki W.; Park, Jung H.Y. 2013. "Mechanisms by Which Licochalcone E Exhibits Potent Anti-Inflammatory Properties: Studies with Phorbol Ester-Treated Mouse Skin and Lipopolysaccharide-Stimulated Murine Macrophages." Int. J. Mol. Sci. 14, no. 6: 10926-10943.

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