Anti-inflammatory and anti-virus potential of poxytrins, especially protectin DX

Abstract

Poxytrins (Pufa Oxygenated Trienes) are dihydroxy derivatives from polyunsaturated fatty acids (PUFA) with adjacent hydroxyl groups to a conjugated triene having the specific E,Z,E geometry. They are made by the double action of one lipoxygenase or the combined actions of two lipoxygenases, followed by reduction of the resulting hydroperoxides with glutathione peroxidase. Because of their E,Z,E conjugated triene, poxytrins may inhibit inflammation associated with cyclooxygenase (COX) activities, and reactive oxygen species (ROS) formation. In addition of inhibiting COX activities, at least one poxytrin, namely protectin DX (PDX) from docosahexaenoic acid (DHA), has also been reported as able to inhibit influenza virus replication by targeting its RNA metabolism.

Fig. 1

Structures of compounds related to leukotriene B4 synthesis as well as to its geometric and stereoisomer LTBX. 5/12-LOX: 5/12-lipoxygenase; GPx: glutathione peroxidase.

Fig. 2

Structures of double 15-lipoxygenase products from arachidonic (5,12- and 8,15-diOH-20:4), docosahexaenoic (protectin DX or PDX) and alpha-linolenic (9(S),16(S)- and 9(R),16(S)-diOH-18:3 or linotrins) acids, globally called poxytrins. They all show the characteristic configuration of the E,Z,E, conjugated triene between two secondary alcohols.

Fig. 3

Summary figure for potential bioactivities of poxytrins.