Epidermal anti-Inflammatory properties of 5,11,14 20:3: Effects on mouse ear edema, PGE(2 )levels in cultured keratinocytes, and PPAR activation

BACKGROUND: 5,11,14 20:3 is similar to 20:4n-6 but lacks the internal Δ8 double bond essential for prostaglandin and eicosanoid synthesis. When previously fed to laboratory animals as a gymnosperm seed oil component it has shown anti-inflammatory properties. RESULTS: Herein, topically applied Podocarpus nagi methyl esters (containing 26% 5,11,14 20:3) were incorporated into mouse ear phospholipids, reduced 20:4n-6, and reduced 20:4n-6- and TPA-induced mouse ear edema. Purified 5,11,14 20:3 was taken up by cultured human skin keratinocytes, reduced 20:4n-6, and reduced PGE(2 )levels dramatically. Purified 5,11,14 20:3 did not affect PPARα, PPARγ, or PPARδ transactivation. CONCLUSIONS: Topical application of 5,11,14 20:3 to skin surfaces can thus reduce inflammatory processes, most likely by displacing 20:4n-6 from phospholipid pools and reducing downstream inflammatory products derived from 20:4n-6 such as PGE(2 )and leukotrienes. It could have potential use in treating clinical skin disorders resulting from overproduction of 20:4n-6-derived eicosanoid products.