Inhibitory Effects of ent-Kauranes from the Stems of Annona squamosa on Superoxide Anion Generation by Human Neutrophils

Abstract

Eleven ent-kauranes, isolated from the fresh stems of Annona squamosa L. (Annonaceae), were subjected to assays on the generation of superoxide anion (O₂ ^·-) by human neutrophils. Except for ent-kaur-16-en-19-oic acid, 16β,17-dihydroxy-ent-kauran-19-al, and 16α,17-dihydroxy-ent-kauran-19-al, all ent-kauranes showed significant inhibitory effect on O₂ ^·- generation in response to formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP/CB). In contrast, phorbol myristate acetate (PMA)-induced O₂ ^·- generation was not suppressed by any ent-kauranes. Especially, ent-kaur-16-en-19-oic acid could significantly increase O₂ ^·- production. The structure-activity relationship of these compounds is also discussed herein. Furthermore, the effect of ent-kauranes on nitric oxide generation by NR8383 macrophages in response to lipopolysaccharide (LPS) was examined. None of the compounds showed an inhibitory effect on nitric oxide generation.

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