Formation and biological targets of botanical o-quinones

Abstract The formation of o -quinones from direct 2-electron oxidation of catechols and/or two successive one electron oxidations could explain the cytotoxic/genotoxic and/or chemopreventive effects of several phenolic botanical extracts. For example, poison ivy contains urushiol, an oily mixture, which is oxidized to various o -quinones likely resulting in skin toxicity through oxidative stress and alkylation mechanisms resulting in immune responses. Green tea contains catechins which are directly oxidized to o -quinones by various oxidative enzymes. Alternatively, phenolic botanicals could be o -hydroxylated by P450 to form catechols in vivo which are oxidized to o -quinones. Examples include, resveratrol which is oxidized to piceatannol and further oxidized to the o -quinone. Finally, botanical o -quinones can be formed by O -dealkylation of O- alkoxy groups or methylenedioxy rings resulting in catechols which are further oxidized to o -quinones. Examples include safrole, eugenol, podophyllotoxin and etoposide, as well as methysticin. Once formed these o -quinones have a variety of biological targets in vivo resulting in various biological effects ranging from chemoprevention -> no effect -> toxicity. This U-shaped biological effect curve has been described for a number of reactive intermediates including o -quinones. The current review summarizes the latest data on the formation and biological targets of botanical o -quinones.