Chemopreventive effects of the standardized extract (DA-9601) of Artemisia asiatica on azoxymethane-initiated and dextran sulfate sodium-promoted mouse colon carcinogenesis.

Dextran sulfate sodium (DSS) administration has been reported to cause inflammation in mouse colonic mucosa, which promotes colon carcinogenesis. When male ICR mice were treated with a single intraperitoneal dose (10 mg/kg body weight) of azoxymethane (AOM) followed by 2.5% DSS in drinking water for 7 consecutive days, all developed tumors at the 16th wk, mostly in the distal colon. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were markedly upregulated in the AOM-initiated and DSS-promoted colon tumors. The DNA binding activity of nuclear factor-kappaB (NF-kappa B) was also elevated in the colon tumors. In this study, we examined the chemopreventive effects of the standardized extract (DA-9601) of Artemisia asiatica that has been used in the traditional herbal medicine for the treatment of inflammatory disorders. Mice fed the chow diet containing 10% DA-9601 for 15 wk following DSS treatment displayed the significantly lower multiplicity of colon tumors. DA-9601 treatment suppressed the expression of COX-2 and iNOS as well as NF-kappa B DNA binding in the colonic tissues. It also downregulated the phosphorylation of extracellular, signal-regulated protein kinase and p38 mitogen-activated protein kinase that are upstream of NF-kappa B. Furthermore, DA-9601 reduced expression of beta-catenin in colonic mucosa of mice challenged with AOM plus DSS.