A (S)-(+)-decursin derivative, (S)-(+)-3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano[3,2-g]-chromen-3-yl-ester, attenuates the development of atopic dermatitis-like lesions in NC/Nga mice

Abstract

(S)-(+)-decursin is a biological coumarin compound isolated from Angelica gigas Nakai. (S)-(+)-decursin and its analogue have a variety of pharmacological activities. In the present study, the anti-inflammatory effect of a (S)-(+)-decursin derivative, (S)-(+)-3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano [3,2-g]-chromen-3-yl-ester (Compound 6, C6), on in vitro and in vivo atopic dermatitis was investigated. C6 suppressed the secretion of IL-6, IL-8, and monocyte chemotactic protein-1 increase by the house dust mite extract in the eosinophilic leukemia cell line and THP-1 cells. C6 inhibited the production of TARC, IL-6, and IL-8 increase by IFN-γ and TNF-α in the human keratinocyte cell line. In the in vivo experiment, NC/Nga mice were sensitized to 2,4-dinitrochlorobenzene, and then C6 or dexamethasone (Dex) were orally and dorsally administered for three weeks. C6 treatment reduced the skin severity score compared with that of the control group. C6 inhibited the thickening of the epidermis and inflammatory cell infiltration into the dermis by evaluating the histological examination. The serum immunoglobulin E (IgE) level decreased in the C6-treated group compared with that of the control group. The inhibitory effect of C6 on IgE concentration was similar to that of Dex. The levels of IL-4, IL-5, IL-13, and eotaxin increased after treatment with concanavalin A in mouse splenocytes. The cytokine levels of the C6-treated group were lower than those of the control group. Taken together, C6 may attenuate atopic dermatitis-like lesions through its anti-inflammatory effect, such as inhibition of IgE and inflammatory cytokines, and it may be valuable as a therapeutic drug for the treatment of atopic dermatitis.