title: Sodium dl-α-tocopheryl-6-O-phosphate inhibits PGE₂ production in keratinocytes induced by UVB, IL-1β and peroxidants.
abstract: The water-soluble vitamin E derivative, sodium dl-α-tocopheryl-6-O-phosphate (1), exhibits protective effects against skin damage. As reported herein, we investigated the actions of 1 on the formation of the inflammatory mediator, prostaglandin E(2) (PGE(2)), as compared to dl-α-tocopheryl acetate (2) and dipotassium glycyrrhizin acid (3). In a three-dimensional (3D) human skin model 1 was converted to α-tocopherol (Toc) to a greater extent than 2. Post-treatment using 2% 1 following ultraviolet B (UVB) irradiation for 2h significantly reduced photodamage as indicated by UVB-damaged cell formation and PGE(2) synthesis. In normal human epidermal keratinocytes stimulated with UVB irradiation, or exposed to interleukin-1 beta, tert-butylhydroperoxide or hydrogen peroxide, pre-treatment with 1 (0-2 μM) inhibited PGE(2) production in dose-dependent manner to a greater extent than 2 and 3. Increases in stimulator-induced cyclooxygenase 2 mRNA expression and p38 MAPK phosphorylation were suppressed by pre-treatment with 1. The vitamin C derivative, magnesium L-ascorbyl-2-phosphate, significantly and synergistically, enhanced the inhibitory effects of 1 on PGE(2) production. These results suggest that 1 is a highly potent protective when compared among the examined commercial human skin care products, and that it might be useful for therapeutic and preventive medicine.
authors.affiliation: Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Kato
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D016877:Oxidants / Q000494:pharmacology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011837:Radiation-Protective Agents / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016877:Oxidants; D012333:RNA, Messenger; D011837:Radiation-Protective Agents; C012552:alpha-tocopherol phosphate; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D024502:alpha-Tocopherol; D015232:Dinoprostone