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Eur J Pharmacol. 2009 Nov 10;622(1-3):52-7. doi: 10.1016/j.ejphar.2009.09.008. Epub 2009 Sep 16.

Anti-inflammatory action of mollugin and its synthetic derivatives in HT-29 human colonic epithelial cells is mediated through inhibition of NF-kappaB activation.

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1
College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan, South Korea.

Abstract

Mollugin is the active compound of Rubia cordifolia, which has been used as a traditional Chinese medicine for the treatment of various inflammatory diseases including arthritis and uteritis. In the present study, we investigated for the first time the inhibitory effects and the mechanisms of action of mollugin (M1) and its synthetic derivatives (M2-M4) on tumor necrosis factor (TNF)-alpha-induced inflammatory responses in HT-29 human colon epithelial cells. Treatment with M1 and its derivatives M2-M4 significantly inhibited TNF-alpha-induced attachment of U937 monocytic cells to HT-29 cells, which mimics the initial phase of colon inflammation. TNF-alpha-induced mRNA induction of the chemokines, monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8, and the intercellular cell adhesion molecule (ICAM)-1, which are involved in adhesion between leukocytes and epithelial cells, was suppressed by M1-M4, and M1 was the most efficacious. In addition, M1-M4 significantly suppressed TNF-alpha-induced NF-kappaB transcriptional activity. Such NF-kappaB inhibitory activity of M1-M4 (20 microM) correlated with their ability to suppress TNF-alpha-induced chemokine expression and U937 monocytic cell adhesion to HT-29 colonic epithelial cells. Treatment of HT-29 cells with M1 and PDTC, a NF-kappaB inhibitor, synergistically suppressed both TNF-alpha-induced NF-kappaB activation and monocytic cell adhesion to HT-29 cells. These results suggest that M1-M4 inhibit TNF-alpha-induced expression of inflammatory molecules via NF-kappaB, and that M1, a potent NF-kappaB inhibitor, may be a valuable new drug candidate for the treatment of colon inflammation.

PMID:
19765578
DOI:
10.1016/j.ejphar.2009.09.008
[Indexed for MEDLINE]

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