4-Hexyl-1,3-phenylenediol, a nuclear factor-κB inhibitor, improves photodamaged skin and clinical signs of ageing in a double-blinded, randomized controlled trial.
BACKGROUND
The nuclear factor-κB (NF-κB) pathway is a key mediator of inflammation; however, few studies have examined the direct effects of NF-κB inhibition on the skin.


OBJECTIVE
To investigate NF-κB activity in cultured human fibroblasts and to investigate the effects of 4-hexyl-1,3-phenylenediol (an NF-κB inhibitor) on elastin and collagen gene expression in vitro and on the clinical appearance of photodamaged skin.


METHODS
The amount and activity of NF-κB in human fibroblasts obtained from donors (17-78 years old) was measured after transfection with a NF-κB reporter and a luciferase promoter system. The expression of extracellular matrix (ECM) genes was determined using quantitative polymerase chain reaction. Women with moderate skin photodamage were randomized to daily treatment with a topical lotion containing 4-hexyl-1,3-phenylenediol (n = 30) or vehicle (n = 29) for 8 weeks, with clinical assessments at baseline and weeks 2, 4 and 8.


RESULTS
Fibroblasts obtained from donors older than 50 years had higher NF-κB activity compared with cells from younger donors; inhibition of the NF-κB pathway with 4-hexyl-1,3-phenylenediol enhanced the expression of ECM genes. In women, treatment for 8 weeks with 4-hexyl-1,3-phenylenediol significantly improved crow's feet fine lines, cheek wrinkles, age spots, mottled pigmentation and radiance compared with both the vehicle and baseline. Furthermore, treatment with 4-hexyl-1,3-phenylenediol resulted in a twofold greater clinical improvement in overall photodamage compared with the vehicle group.


CONCLUSIONS
Inhibition of the proinflammatory NF-κB pathway resulted in increased expression of ECM proteins in vitro and significant clinical improvement in photodamaged skin.
Johnson and Johnson Skin Research Center, CPPW, A Division of Johnson and Johnson Consumer Companies, Inc., 199 Grandview Road, Skillman, NJ, 08558, U.S.A.
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Kaur
Johnson and Johnson Skin Research Center, CPPW, A Division of Johnson and Johnson Consumer Companies, Inc., 199 Grandview Road, Skillman, NJ, 08558, U.S.A.
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Kizoulis
Johnson and Johnson Skin Research Center, CPPW, A Division of Johnson and Johnson Consumer Companies, Inc., 199 Grandview Road, Skillman, NJ, 08558, U.S.A.
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Fantasia
Johnson and Johnson Skin Research Center, CPPW, A Division of Johnson and Johnson Consumer Companies, Inc., Val de Reuil, France.
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Oddos
Laboratoire Microenvironnement Cellulaire et Pathologies, (MILPAT) EA 4652, SFR ICORE 146 UCBN, UFR de Médecine, CHU Niveau 3, Avenue de la Côte de Nacre, 14032 CAEN, Cedex, France.
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Bigot
Laboratoire Microenvironnement Cellulaire et Pathologies, (MILPAT) EA 4652, SFR ICORE 146 UCBN, UFR de Médecine, CHU Niveau 3, Avenue de la Côte de Nacre, 14032 CAEN, Cedex, France.
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Galera
Johnson and Johnson Skin Research Center, CPPW, A Division of Johnson and Johnson Consumer Companies, Inc., 199 Grandview Road, Skillman, NJ, 08558, U.S.A.
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Tucker-Samaras
University of Pennsylvania Medical School, 415 Curie Blvd, Philadelphia, PA, 19104, U.S.A.
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Leyden
Johnson and Johnson Skin Research Center, CPPW, A Division of Johnson and Johnson Consumer Companies, Inc., 199 Grandview Road, Skillman, NJ, 08558, U.S.A.
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Southall
D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D003879:Dermatologic Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005148:Facial Dermatoses / Q000188:drug therapy*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010787:Photosensitivity Disorders / Q000188:drug therapy*; D012118:Resorcinols / Q000008:administration & dosage*; D015595:Skin Aging / Q000187:drug effects*; D016896:Treatment Outcome; D055815:Young Adult
C000596938:4-hexyl-1,3-phenylenediol; D024042:Collagen Type I; D003879:Dermatologic Agents; D016328:NF-kappa B; D012118:Resorcinols