Effect of Chunghyuldan in Chronic Oxazolone-Induced Mouse Dermatitis
Biological and Pharmaceutical Bulletin
Psoriasis is a chronic and inflammatory skin disorder. Psoriasis patients have been shown to have the bias of interferon (IFN)-g producing Th1 and cyclooxygenase (COX)-induced macrophage in lesion skin and peripheral blood.     Cyclooxygenase (COX)-2 inhibitors non-steroidal anti-inflammatory drugs and corticosteroids and immunosuppressants FK-506 and cyclosporine A for Th1 cells have been used clinically for psoriasis. 5-9) Corticosteroids are well known to have potent
... tory effects, but topical use can cause intense skin atrophy, one of the serious side effects limiting their uses for chronic skin diseases. 5,7) Repeated application of corticosteroids on dorsal skin of rats also causes dramatic skin atrophy. FK-506 and cyclosporine A also exhibited side effects, such as severe nephrotoxicity and neurotoxicity. 6) Therefore, herbal medicines for clinical uses, such as Centella asiatica extract, Orengedokto and Sofusan, should be developed. 10,11) Nevertheless, antipsoriatic effects of these herbal medicines have not been thoroughly studied. During the screening program to discover such agents from herbal medicines, Chunghyuldan (CHD, Daio-Orengedokuto in Japanese) exhibited the anti-inflammatory effect. 12) Therefore, we evaluated the antipsoriatic effect of CHD in the oxazolone-induced mouse contact dermatitis model by topical administration and measured mRNA levels of COX-2 and some cytokines. MATERIALS AND METHODS Materials Oxazolone, lipopolysaccharide (LPS), dexamethasone and RNase-free DNase were purchased from Sigma Co. (St. Louis, MO, U.S.A). TRI reagent was purchased from Molecular Research Center Inc. (Cincinnati, Ohio, U.S.A.). CHD and metabolized CHD were prepared according to the previously reported methods of Cho et al. 12) Animals The female BALB/c mice (20-25 g) were supplied from Orient Experimental Animal Breeding Center (Seoul, Korea). All animals were housed in wire cages at 20-22°C and 50Ϯ10% humidity, fed standard laboratory chow (Orient Experimental Animal Breeding Center, To evaluate the antipsoriatic effect of Chunghyuldan (CHD, Daio-Orengedokuto in Japanese), which exhibited anti-inflammatory and antiischemic actions, the inhibitory activity of CHD metabolized with and without human intestinal microflora was investigated in oxazolone-induced mouse ear dermatitis. The CHD and metabolized CHD (MCHD) at concentrations of 0.1% also potently suppressed mouse ear swelling by 52.7% and 63.2% at 16 d, respectively. The antipsoriatic effect between CHD and MCHD was not significantly different, although that of CHD weakly increased by the metabolism of human intestinal microflora. Both CHD and MCHD also potently reduced the mRNA levels of cyclooxygenase (COX)-2, interferon (IFN)-g g and IL-4 increased in oxazoloneapplied mouse ears, but weakly inhibited that of IL-1b b and TNF-a a. Based on these findings, CHD may improve contact dermatitis or psoriasis by the regulation of COX-2 produced by macrophage cells and IFN-g g and IL-4 produced by Th cells.