Differential Inhibition of Matrix Metalloproteinases-2, -9, and -13 Activities by Selected Anthraquinones

 

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Abstract

Matrix metalloproteinases (MMPs) play an important role in physiological and pathological matrix remodeling. Here, we report that the natural anthraquinones, emodin, emodic acid, chrysazin, physcion, and rhein differentially inhibit several members of this enzyme family, the gelatinases MMP-2 and -9, and the collagenase MMP-13. The IC₅₀ values determined by measuring the activities of human recombinant catalytic domains of these enzymes varied in the micromolar range. Emodin and emodic acid most potently inhibited MMP-9 with IC₅₀ values of 15 and 10 μM, respectively. With MMP-13, emodic acid was 3-times less potent than emodin which showed a similar IC₅₀ value (13 μM) as chrysazin. These results are of interest in view of the widespread medicinal use of anthraquinones and their derivatives.

Abbreviations

DMSO:dimethyl sulfoxide

MMP:matrix metalloproteinase

TIMP:tissue inhibitor of matrix metalloproteinases

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Rolf Gebhardt

Institute of Biochemistry

Medical Faculty

University of Leipzig

Johannisallee 30

04103 Leipzig

Germany

Fax: +49-341-972-2109

Email: rgebhardt@medizin.uni-leipzig.de