In Vitro 12(S)-HETE and Leukotriene Metabolism Inhibitory Activity of Sesquiterpenes of Warburgia ugandensis

Abstract

Twelve drimane and coloratane sesquiterpenes, isolated from the stem bark of Ethiopian Warburgia ugandensis, were evaluated for inhibition of 12(S)-HETE using human platelets and of leukotriene B₄ formation using activated human neutrophile granulocytes. Among the compounds examined for inhibition of 12-LOX, ugandensidial and muzigadial displayed potent inhibitory activity with IC₅₀ values of 3.3 and 20.2 μM, respectively, in comparison to the positive control baicalein with an IC₅₀ value of 20.0 μM. In the 5-LOX assay muzigadial and ugandensidial also exhibited a dose dependent and potent inhibitory effect on LTB₄ biosynthesis with an IC₅₀ value of 10.2 and 12.7 μM, respectively, compared to the well known 5-LOX inhibitor zileuton with an IC₅₀ value of 10.4 μM. In contrast, none of the other sesquiterpenoids showed significant inhibition of either 12(S)-HETE or LTB₄ metabolism.

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