Inhibitory effects of the standardized extract (DA‐9601) of Artemisia asiatica Nakai on phorbol ester–induced ornithine decarboxylase activity, papilloma formation, cyclooxygenase‐2 expression, inducible nitric oxide synthase expression and nuclear transcription factor κB activation in mouse skin

Abstract

Artemisia asiatica Nakai has been used in traditional Asian medicine for the treatment of inflammatory and other disorders. Previous studies have revealed that the formulated ethanol extract (DA-9601) of A. asiatica has pronounced antioxidative and antiinflammatory activities and exhibits cytoprotective effects against experimentally induced gastrointestinal, hepatic and pancreatic damage. In the present study, we assessed the inhibitory effect of DA-9601 on tumor promotion, which is closely linked to inflammatory tissue damage. As an initial approach to evaluating the possible antitumor-promoting potential of DA-9601, its effects on TPA-induced ear edema were examined in female ICR mice. Pretreatment of the inner surface of the mouse ear with DA-9601 30 min prior to topical application of TPA inhibited ear edema at 5 hr. TPA-stimulated expression of epidermal COX-2 and NOS was also mitigated by topical application of the same extract. Moreover, DA-9601 abrogated the TPA-mediated activation of NF-kappaB/Rel and AP-I in mouse epidermis. Suppression of epidermal NF-kappaB by DA-9601 appeared to be mediated in part through inhibition of IkappaBalpha degradation, thereby blocking the nuclear translocation of p65, the functional subunit of NF-kappaB. DA-9601 also significantly suppressed TPA-induced ODC activity and papilloma formation in mouse skin. Taken together, these findings suggest that DA-9601 derived from A. asiatica possesses potential chemopreventive activities. (C) 2002 Wiley-Liss, Inc.