Herbs as alternative cancer therapies have attracted a great deal of recent attention due to their low toxicity and costs. In this study, the antitumor activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb, were investigated in nude mice carrying a human esophageal cancer cell line YES-2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when injected into these mice. In this study, in vivo growth of YES-2 cells was not affected by an oral supplement containing the extract powder of C. rhizoma at a final concentration of 1% (CR supplement). However, in comparison with normal diet, CR supplement significantly attenuated weight loss of tumor-bearing mice without a change in food or water intake. Tumor IL-6 levels were significantly lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL-6 was detectable in four (50%) of eight control mice; IL-6 was not detected in mice treated with CR supplement. We also confirmed that berberine (8-32 microM), a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression. Our results suggest that C. rhizoma may have an anticachectic effect on esophageal cancer and an effect is associated with the ability of berberine to down-regulate tumor IL-6 production.