Systemic vitamin E metabolites have been proposed as signaling molecules, but their physiological role is unknown. Here we show, by library screening of potential human vitamin E metabolites, that long-chain ω-carboxylates are potent allosteric inhibitors of 5-lipoxygenase, a key enzyme in the biosynthesis of chemoattractant and vasoactive leukotrienes. 13-((2R)-6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoic acid (α-T-13′-COOH) can be synthesized from α-tocopherol in a human liver-on-chip, and is detected in human and mouse plasma at concentrations (8–49 nM) that inhibit 5-lipoxygenase in human leukocytes. α-T-13′-COOH accumulates in immune cells and inflamed murine exudates, selectively inhibits the biosynthesis of 5-lipoxygenase-derived lipid mediators in vitro and in vivo, and efficiently suppresses inflammation and bronchial hyper-reactivity in mouse models of peritonitis and asthma. Together, our data suggest that the immune regulatory and anti-inflammatory functions of α-tocopherol depend on its endogenous metabolite α-T-13′-COOH, potentially through inhibiting 5-lipoxygenase in immune cells.

Covering: the literature from the first reported isolation of isoflavonoids from non-leguminous families up to April 2005 This review provides a listing of isoflavonoids reported in non-leguminous families. Reviews published to date have principally focused on plants with the richest isoflavonoid contents, the family Leguminosae. After a brief recall of the structure of isoflavonoids, we present all isoflavonoid structures encountered in non-leguminous families which may, thereby, become new plant sources for these compounds. Articles reporting on their different functions in plants are presented, as well as a brief summary discussing their potential benefits for human health. A list of 135 references is given.