Effects of methylated derivatives of luteolin isolated from Cyperus alopecuroides in rat H4IIE hepatoma cells

Abstract

Polyphenols are ubiquitous substances in human diet. Their antioxidative, antiinflammatory and antiviral effects are of interest for human health, and polyphenols such as luteolin are used at high concentrations in food supplements. Luteolin is metabolized to glucuronides, but also to methylated derivatives. For example, O-methylation of the catechol group mediated by the catechol-O-methyl transferase, is an important step in flavonoid metabolism. The aim of this project was to determine the effect of O-methylation on antioxidative capacity and cytotoxicity of luteolin in H4IIE rat hepatoma cells. Therefore we analyzed the effects of luteolin 5,3′-dimethylether, isolated from the flowers of foxtail flatsedge (Cyperus alopecuroides) and luteolin 5,7,3′,4′-tetramethylether compared to the non-methylated flavonoid luteolin. The antioxidative potential of luteolin was lowered by methylation, an effect that seems to be mediated by masking of the catechol moiety in the B ring. The cytotoxic potential of luteolin 5,3′- dimethylether is comparable to luteolin, but the tetramethylether showed no cytotoxic effect. The cytotoxic effect of luteolin but not luteolin 5,3′-dimethylether was mediated via apoptosis (caspase-3 activation). We conclude that the O-methylation of luteolin led to a decreased radical-scavenging activity and to a reduction in the apoptotic potential of the flavonoid. © Basic & Clinical Pharmacology & Toxicology 2006.