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Anti-inflammatory activity of 2,4, 6-trihydroxy-alpha-p-methoxyphenyl-acetophenone (compound D-58)
R Malaviya1, R Malaviya, F M Uckun
1Drug Discovery Program, Departments of Allergy and Inflammatory Diseases, Parker Hughes Institute, St. Paul, MN 55113, USA.
Background:
Active oxygen radicals as well as a variety of cytosolic protein tyrosine kinases play a role in the regulation of prostaglandin E(2) (PGE(2)), a key inflammatory mediator, released by skin cells in response to irradiation with ultraviolet B light (UVB). Identification of chemical compounds that can interrupt such events may provide a basis for the development of potent anti-inflammatory agents.
Objective:
To investigate the effect of a novel genistein analog, 2,4, 6-trihydroxy-alpha-p-methoxyphenylacetophenone, with antioxidant property (compound D-58), on UVB-induced inflammatory responses.
Methods:
Epidermal cell cultures were irradiated with UVB both in the presence and absence of compound D-58 and the PGE(2) released in the medium was determined by ELISA. For in vivo studies, skin inflammation was induced in mice either by carrageenan challenge of the air pouch or by an acute exposure of skin to UVB radiation. The resulting inflammatory mediator release, skin edema and the histological changes of the skin were determined both in the presence and absence of compound D-58.
Results:
Compound D-58 treatment effectively inhibited the development of edema and histological changes in the skin of UVB-irradiated mice as well as the release of PGE(2) in vitro as well as in vivo.
Conclusion:
Compound D-58 (2,4,6-trihydroxy-alpha-p-methoxyphenylacetophenone) has potent anti-inflammatory properties.
