Studies on the Antioxidative Activity of Phloroglucinol Derivatives Isolated from Hypericum Species

Abstract

Twenty-one phloroglucinol derivatives, belonging to 8 different carbon skeletons, were tested for their ability to influence the oxidative burst of polymorphonuclear cells (PMNs) after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP) or opsonized zymosan (OZ). Results revealed a strong reduction of oxygen production by PMNs after stimulation with FMLP for the compounds ialibinone E (5), hyperguinone B (15) and hyperforin (21). The IC₅₀ values obtained were 2.5 μM (5), 3.3 μM (15) and 1.8 μM (21), respectively. Slight modifications of the substituents or variation of the stereochemistry resulted in a significant loss of activity. None of the active compounds showed antioxidative activity after stimulation with OZ. The influence of compounds 5, 15 and 21 on the production of oxygen radicals in an H₂O₂/horseradish peroxidase system was investigated and revealed potent activity only for compound 5 (IC₅₀ 1 μM). The superoxide-scavenging properties of ialibinone E (5) and hyperguinone B (15) were additionally tested in a cytochrome c assay and only ialibinone E (5) was found to be significantly active at lower micromolar concentrations. Ialibinone E (5) was not active in a xanthine oxidase assay (urate formation) in concentrations up to 100 μM and its activity is therefore not attributable to the inhibition of this enzyme. It can be assumed that the activity of compounds 5 and 15 in the different cellular and enzymatic assays, is most likely caused by different and maybe specific mechanisms and cannot be explained by a radical scavenger activity alone. None of the active phloroglucinols showed cytotoxic effects against the PMNs.

Key words

Phloroglucinols - Hypericum - clusiaceae - antioxidative activity - reactive oxygen species

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